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  • 1. Abbara, Aula
    et al.
    Al-Harbat, Nizar
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Abo-Yahya, Bashar
    El-Amin, Wael
    Hatcher, James
    Gabbar, Omar
    Antimicrobial Drug Resistance among Refugees from Syria, Jordan2017In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 23, no 5, p. 885-886Article in journal (Refereed)
  • 2. Abbasi, Arshad Mehmood
    et al.
    Khan, Mir Ajab
    Khan, Nadeem
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Shah, Munir H
    Ethnobotanical survey of medicinally important wild edible fruits species used by tribal communities of Lesser Himalayas-Pakistan2013In: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 148, no 2, p. 528-536Article in journal (Refereed)
    Abstract [en]

    Ethnopharmacological relevance: Present survey was conducted to explore ethnomedicinal uses and cultural importance of wild edible fruits species by the inhabitants of Lesser Himalayas-Pakistan. Materials and methods: Information was obtained through informed consent semi-structured interviews, questionnaires, market survey, focus group conversation, unceremonious dialogue and village walks with key informants. Cultural significance of each species was calculated based on use report by participants at each study site. Results: A total of 35 wild edible fruits belonging to 21 genera and 17 families were used for the treatment of various ailments and consumed. Rosaceae was found dominating family with (8 spp.), followed by Moraceae (6 spp.), Rhamnaceae (5 spp.), Palmae and Vitaceae (2 spp. each) and remaining families were represented by one species each. Fruits (48%) were found highly utilized plant parts, followed by leaves (34%), bark, flowers and seeds (4% each), branches, latex and roots (2% each). Water was used as a medium for preparation while milk, ghee, oil, egg and butter are used for application. Modes of preparation were fall into seven categories like fresh parts eaten raw (38%), powder (24%), decoction (20%), extract (12 %), paste (4%), juice and latex (2% each). Based on cultural important index (CI) Morus nigra was found most significant species within top ten fruit plants followed by Morus alba, Olea ferruginea, Berberis lycium, Pyrus pashia, Ficus carica, Ficus palmata, Ziziphus mauritiana, Diospyros lotus and Ziziphus nummularia. Conclusions: Traditional uses of wild edible plant depend mainly on socio-economic factors rather than climatic conditions or wealth of flora. Use reports and citation demonstrated that there is a common cultural heritage regarding the gathered food plants. Further investigation is required for Antioxidant study, essential and toxic components, pharmacological applications; dietary requirements and biotechnological techniques to improve yields.

    (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 3.
    Abbood, Maab Mohammed Abbood
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bildning av ett elektroaktivt lipiddubbelskikt för studie av membranfördelningsbeteendet hos joniska läkemedel_ En laborativ studie2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 4.
    Abdalla, Souad
    Umeå University, Faculty of Medicine, Department of Medical and Translational Biology.
    HEALTH ECONOMIC EVALUATION OF THE IMPLEMENTATION OF FARICIMAB IN WET AGE-RELATED MACULAR DEGENERATION2024Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 5.
    Abdelrahim, Nada A.
    et al.
    Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Nile University, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fadl-Elmula, Imad M.
    Department of Pathology and Clinical Genetics, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan; Assafa Academy, Kartoum, Sudan.
    Human herpes virus type-6 is associated with central nervous system infections in children in Sudan2022In: African Journal of Laboratory Medicine, ISSN 2225-2002, E-ISSN 2225-2010, Vol. 11, no 1, article id a1718Article in journal (Refereed)
    Abstract [en]

    Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.

    Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.

    Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.

    Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.

    Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

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  • 6.
    Abdelrahim, Nada Abdelghani
    et al.
    Department of Pathology-Medical Microbiology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fadl-Elmula, Imad Mohammed
    Department of Pathology & Clinical Genetics, Al-Neelain University & Assafa Academy, Khartoum, Sudan.
    Viral meningitis in Sudanese children: differentiation, etiology and review of literature2022In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 101, no 46, article id e31588Article, review/survey (Refereed)
    Abstract [en]

    Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

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  • 7.
    Abdel-Shafi, Seham
    et al.
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Serwy, Heba
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Zawahry, Yehia
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    Zaki, Maysaa
    Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sitohy, Mahmoud
    Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
    The Association between icaA and icaB Genes, Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Staphylococci spp.2022In: Antibiotics, E-ISSN 2079-6382, Vol. 11, no 3, article id 389Article in journal (Refereed)
    Abstract [en]

    Sixty-six (66) Staphylococcus bacterial isolates were withdrawn from separate clinical samples of hospitalized patients with various clinical infections. Conventional bacteriological tests identified the species of all isolates, and standard microbiological techniques differentiated them into CoPS or CoNS. Their biofilm development was followed by an analysis via the MTP (microtiter tissue culture plates) technique, and we then investigated the presence/absence of icaA and icaB, which were qualified in the top-30 potent biofilm-forming isolates. Thirteen isolates (46.7%) showed the presence of one gene, six (20%) isolates exhibited the two genes, while ten (33.3%) had neither of them. The formation of staphylococci biofilms in the absence of ica genes may be related to the presence of other biofilm formation ica-independent mechanisms. CoPS was the most abundant species among the total population. S. aureus was the sole representative of CoPS, while S. epidermidis was the most abundant form of CoNS. Antibiotic resistance was developing against the most frequently used antimicrobial drugs, while vancomycin was the least-resisted drug. The totality of the strong and medium-strength film-forming isolates represented the majority proportion (80%) of the total investigated clinical samples. The biochemical pattern CoPS is associated with antibiotic resistance and biofilm formation and can be an alarming indicator of potential antibiotic resistance.

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  • 8.
    Abdollahi, Nyayesh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Modifierad constraint-induced movement therapy förbättrar livskvalitet hos unga stroke-patienter2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 9.
    Abdul Rahim, Esra
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    EFFEKT OCH SÄKERHET AV CENOBAMAT_Med fokus på behandling vid fokal epilepsi2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 10.
    Abdulamir, Dalia
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Evaluation of the Role of Histidines Regarding the Self-assembly and Fibrillar Stability of Amyloid βeta2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 11.
    Abdulbasid Samad, Delan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Farmaceut-patientkommunikation på öppenvårdsapotek i Kurdistan: En observationsstudie som undersöker i vilken omfattning apotekspersonalen informerar om läkemedelsanvändningen och dess verkan.2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Apotekens riktlinjer har utvecklats från att ha begränsat farmaceuter ideras utdelning av medicin till att ge råd eller erbjuda rådgivning om patientens medicinering. Det är viktigt att farmaceuter ger rådgivning kring patienters medicinering då det ger effektivt behandlingsresultat, ökad följsamhet och minskar konfusion och osäkerhet hos patienten. Studier har visat att den farmaceutiska rådgivningen varierar mycket på apotek. En svensk studie har visat att samtalet mellan farmaceut och patient fokuserar mer på ekonomi och regelverk än att ge farmaceutiskrådgivning. Det har tidigare inte gjorts studier på hur kommunikation samt den farmaceutiska rådgivningen fungerar i mellanöstern.

    Syfte: Syftet med den här studien är att undersöka kommunikationen mellan farmaceut och patient på öppenvårdsapotek i Kurdistan, Irak. Kommunikationen kommer att undersökas utifrån hur lång tid patientmötena tar och innehåll. Det som studeras är i vilken utsträckning apotekspersonalen konsulterar patienter samt den information som tillhandahålls till patienterna ur ett farmaceutiskt perspektiv.

    Metod: En kvantitativ och icke- deltagande observationsstudie där patientmöten observerades utifrån innehåll och tidsmätning av mötet. Observatören bockade avämnen som tas upp under mötet utefter en empirisk fastställd observationsmall.

    Resultat: 4 apotek deltog i studien och det gjordes sammanlagt 90 observationer varav 85 stycken inkluderades i studien. Apotekmiljön har en negativ påverkan på patientmötena, exempelvis att det saknas ett avskilt ställe för ett privatsamtal medpatienter, bullret i omgivningen och dålig organiserad läkemedel. Den stora delen av den medicinska konsulteringen är information om administrering, lite om läkemedelsverkan och nästan inget om biverkningar. Det icke-medicinska innehållet var frågor om pris och tillgänglighet av läkemedel.

    Diskussion: Det finns säkert många anledningar för varför kommunikationen inte är fokuserad på konsultering till patienter. En orsak kan vara otillräcklig kunskap bland informatörerna som konsultering kring biverkningar och läkemedels verkan exkluderas i kommunikationen. En annan förklaring kan vara att rådgivningen tar mer tid och at tapoteksägare upplever rådgivning som en dyr tjänst och av den anledningen inteprioriterar sin uppmärksamhet på läkemedelsrådgivning. Försäljningen som uppenbarligen inte ligger i att ge läkemedelsrådgivning till patienterna.

    Slutsats: Den här observationsstudien visade att mycket lite tid (medeltid 125,5 smin7 s/max 427 s) tillägnas till rådgivning kring patientens medicinering. Läkemedel är en stor behandlingsmetod inom hälso- och sjukvården av den orsaken borde farmaceutisk rådgivning vara tillgänglig för personer som besöker apotek. Resultatet avden här studien visar att dagens patientmöten på öppenvårdapotek i Kurdistan inte fokuserar på konsultering kring läkemedel. Eventuellt kommer patienten inte få ett nyttigt behandlingsresultat.

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  • 12.
    Abdullah Nasir, Ahmad
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herdenberg, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Oncology Research Laboratory, NUS M31, Umeå, Sweden.
    Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 8585Article in journal (Refereed)
    Abstract [en]

    Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.

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  • 13.
    Abdulsalam Muhammednouri, Hevi
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kvalitetsindikatorer på apotek. Patienters syn på apotekstjänster - ett enkätutvärderingsprojekt2021Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 14.
    Abed, Ala
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Polyfarmaci och fall hos äldre2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 15. Abel, Olubunmi
    et al.
    Powell, John F.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics2012In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 33, no 9, p. 1345-1351Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is the commonest adult onset motor neuron disease, with a peak age of onset in the seventh decade. With advances in genetic technology, there is an enormous increase in the volume of genetic data produced, and a corresponding need for storage, analysis, and interpretation, particularly as our understanding of the relationships between genotype and phenotype mature. Here, we present a system to enable this in the form of the ALS Online Database (ALSoD at http://alsod.iop.kcl.ac.uk), a freely available database that has been transformed from a single gene storage facility recording mutations in the SOD1 gene to a multigene ALS bioinformatics repository and analytical instrument combining genotype, phenotype, and geographical information with associated analysis tools. These include a comparison tool to evaluate genes side by side or jointly with user configurable features, a pathogenicity prediction tool using a combination of computational approaches to distinguish variants with nonfunctional characteristics from disease-associated mutations with more dangerous consequences, and a credibility tool to enable ALS researchers to objectively assess the evidence for gene causation in ALS. Furthermore, integration of external tools, systems for feedback, annotation by users, and two-way links to collaborators hosting complementary databases further enhance the functionality of ALSoD. Hum Mutat 33:1345-1351, 2012. (c) 2012 Wiley Periodicals, Inc.

  • 16.
    Abidine, Yara
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Liu, Lifeng
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Wallén, Oskar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Trybala, Edward
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Olofsson, Sigvard
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Bally, Marta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Cellular Chondroitin Sulfate and the Mucin-like Domain of Viral Glycoprotein C Promote Diffusion of Herpes Simplex Virus 1 While Heparan Sulfate Restricts Mobility2022In: Viruses, E-ISSN 1999-4915, Vol. 14, no 8, article id 1836Article in journal (Refereed)
    Abstract [en]

    The diffusion of viruses at the cell membrane is essential to reach a suitable entry site and initiate subsequent internalization. Although many viruses take advantage of glycosaminoglycans (GAG) to bind to the cell surface, little is known about the dynamics of the virus–GAG interactions. Here, single-particle tracking of the initial interaction of individual herpes simplex virus 1 (HSV-1) virions reveals a heterogeneous diffusive behavior, regulated by cell-surface GAGs with two main diffusion types: confined and normal free. This study reports that different GAGs can have competing influences in mediating diffusion on the cells used here: chondroitin sulfate (CS) enhances free diffusion but hinders virus attachment to cell surfaces, while heparan sulfate (HS) promotes virus confinement and increases entry efficiency. In addition, the role that the viral mucin-like domains (MLD) of the HSV-1 glycoprotein C plays in facilitating the diffusion of the virus and accelerating virus penetration into cells is demonstrated. Together, our results shed new light on the mechanisms of GAG-regulated virus diffusion at the cell surface for optimal internalization. These findings may be extendable to other GAG-binding viruses.

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  • 17.
    Abo Allneaj, Razan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Antidepressiva läkemedelsförskrivning för barn och ungdomar: Effektivitet och säkerhet av fluoxetin och sertralin2021Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 18. Abraham, Nabil M.
    et al.
    Liu, Lei
    Jutras, Brandon Lyon
    Yadav, Akhilesh K.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Narasimhan, Sukanya
    Gopalakrishnan, Vissagan
    Ansari, Juliana M.
    Jefferson, Kimberly K.
    Cava, Felipe
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Jacobs-Wagner, Christine
    Fikrig, Erol
    Pathogen-mediated manipulation of arthropod microbiota to promote infection2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 5, p. E781-E790Article in journal (Refereed)
    Abstract [en]

    Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood. Ixodes scapularis ticks harbor numerous human pathogens, including Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We now demonstrate that A. phagocytophilum modifies the I. scapularis microbiota to more efficiently infect the tick. A. phagocytophilum induces ticks to express Ixodes scapularis antifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation. IAFGP thereby perturbs the tick gut microbiota, which influences the integrity of the peritrophic matrix and gut barrier-critical obstacles for Anaplasma colonization. Mechanistically, IAFGP binds the terminal D-alanine residue of the pentapeptide chain of bacterial peptidoglycan, resulting in altered permeability and the capacity of bacteria to form biofilms. These data elucidate the molecular mechanisms by which a human pathogen appropriates an arthropod antibacterial protein to alter the gut microbiota and more effectively colonize the vector.

  • 19.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Outcome of microdialysis sampling on liver surface and parenchyma2016In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 200, no 2, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.

    Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.

    Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.

    Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.

  • 20.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Detection of myocardial ischaemia using surface microdialysis on the beating heart2011In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 31, no 3, p. 175-181Article in journal (Refereed)
    Abstract [en]

    Microdialysis (MD) can be used to study metabolism of the beating heart. We investigated whether microdialysis results obtained from epicardial (surface) sampling reflect acute changes in the same way as myocardial sampling from within the substance of the ventricular wall. In anaesthetized open-thorax pigs a coronary snare was placed. One microdialysis probe was placed with the sampling membrane intramyocardially (myocardial), and a second probe was placed with the sampling membrane epicardially (surface), both in the area which was made ischaemic. Ten minutes collection intervals were used for microdialysis samples. Samples from 19 pigs were analysed for lactate, glucose, pyruvate and glycerol during equilibration, baseline, ischaemia and reperfusion periods. For both probes (surface and myocardial), a total of 475 paired simultaneous samples were analysed. Results from analyses showed no differences in relative changes for glucose, lactate and glycerol during baseline, ischaemia and reperfusion. Surface microdialysis sampling is a new application of the microdialysis technique that shows promise and should be further studied.

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  • 21.
    Abramsson, Linnea
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Följsamhet till behandling med bisfosfonater: En intervjustudie på ortopedavdelningen vid Norrlands Universitetssjukhus, Umeå2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Följsamhet till behandling med bisfosfonater: En intervjustudie på ortopedavdelningen vid Norrlands Universitetssjukhus, Umeå
  • 22.
    Abramsson, Linnea
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    PREVALENCE OF DRUG RELATED PROBLEMS STOPP/START in elderly people with dementia2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 23.
    Abrudan, Teresa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Psykiska biverkningar av hormonella preventivmedel: En litteraturstudie om samband och riskfaktorer2021Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 24. Abu-Elyazeed, R R
    et al.
    Heineman, T
    Dubin, G
    Fourneau, M
    Leroux-Roels, I
    Leroux-Roels, G
    Richardus, J H
    Ostergaard, L
    Diez-Domingo, J
    Poder, A
    Van Damme, P
    Romanowski, B
    Blatter, M
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, J
    Josefsson, A
    Cunningham, A L
    Flodmark, C E
    Tragiannidis, A
    Dobson, S
    Olafsson, J
    Puig-Barbera, J
    Mendez, M
    Barton, S
    Bernstein, D
    Mares, J
    Ratner, P
    Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial2013In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, no 51, p. 6136-6143Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

    METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

    RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

    CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

  • 25.
    Abzhandadze, Tamar
    et al.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lundström, Erik
    Department of Neuroscience, Neurology, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.
    Buvarp, Dongni
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Quinn, Terence J
    Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
    S Sunnerhagen, Katharina
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Neurocare, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Development of a short-form Swedish version of the Montreal Cognitive Assessment (s-MoCA-SWE): Protocol for a cross-sectional study2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 5, article id e049035Article in journal (Refereed)
    Abstract [en]

    Introduction: Short forms of the Montreal Cognitive Assessment (MoCA) have allowed quick cognitive screening. However, none of the available short forms has been created or validated in a Swedish sample of patients with stroke.

    The aim is to develop a short-form Swedish version of the MoCA (s-MoCA-SWE) in a sample of patients with acute and subacute stroke. The specific objectives are: (1) to identify a subgroup of MoCA items that have the potential to form the s-MoCA-SWE; (2) to determine the optimal cut-off value of s-MoCA-SWE for predicting cognitive impairment and (3) and to compare the psychometric properties of s-MoCA-SWE with those of previously developed MoCA short forms.

    Methods and analysis: This is a statistical analysis protocol for a cross-sectional study. The study sample will comprise patients from Väststroke, a local stroke registry from Gothenburg, Sweden and Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS), a randomised controlled trial in Sweden. The s-MoCA-SWE will be developed by using exploratory factor analysis and the boosted regression tree algorithm. The cut-off value of s-MoCA-SWE for impaired cognition will be determined based on binary logistic regression analysis. The psychometric properties of s-MoCA-SWE will be compared with those of other MoCA short forms by using cross-tabulation and area under the receiving operating characteristic curve analyses.

    Ethics and dissemination: The Väststroke study has received ethical approval from the Regional Ethical Review Board in Gothenburg (346-16) and the Swedish Ethical Review Authority (amendment 2019-04299). The handling of data generated within the framework of quality registers does not require written informed consent from patients. The EFFECTS study has received ethical approval from the Stockholm Ethics Committee (2013/1265-31/2 on 30 September 2013). All participants provided written consent. Results will be published in an international, peer-reviewed journal, presented at conferences and communicated to clinical practitioners in local meetings and seminars.

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  • 26.
    Abzhandadze, Tamar
    et al.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lundström, Erik
    Department of Medical Sciences, Neurology, Akademiska Sjukhuset, Uppsala, Sweden.
    Buvarp, Dongni
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Quinn, Terence J.
    Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
    Sunnerhagen, Katharina S.
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Neurocare, Rehabilitation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Development of a Swedish short version of the montreal cognitive assessment for cognitive screening in patients with stroke2023In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 55, article id jrm4442Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The primary objective was to develop a Swedish short version of the Montreal Cognitive Assessment (s-MoCA-SWE) for use  with patients with stroke. Secondary objectives were to identify an optimal cut-off value for the s-MoCA-SWE to screen for cognitive impairment and to compare its sensitivity with that of previously developed short forms of the Montreal Cognitive Assessment.

    DESIGN: Cross-sectional study.

    SUBJECTS/PATIENTS: Patients admitted to stroke and rehabilitation units in hospitals across Sweden.

    METHODS: Cognition was screened using the Montreal Cognitive Assessment. Working versions of the s-MoCA-SWE were developed using supervised and unsupervised algorithms.

    RESULTS: Data from 3,276 patients were analysed (40% female, mean age 71.5 years, 56% minor stroke at admission). The suggested s-MoCA-SWE comprised delayed recall, visuospatial/executive function, serial 7, fluency, and abstraction. The aggregated scores ranged from 0 to 16. A threshold for impaired cognition ≤ 12 had a sensitivity of 97.41 (95% confidence interval, 96.64-98.03) and positive predictive value of 90.30 (95% confidence interval 89.23-91.27). The s-MoCA-SWE had a higher absolute sensitivity than that of other short forms.

    CONCLUSION: The s-MoCA-SWE (threshold ≤ 12) can detect post-stroke cognitive issues. The high sensitivity makes it a potentially useful "rule-out" tool that may eliminate severe cognitive impairment in people with stoke.

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  • 27.
    Achour, Cyrinne
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Aguilo, Francesca
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Long non-coding RNA and Polycomb: an intricate partnership in cancer biology2018In: Frontiers in Bioscience, ISSN 1093-9946, E-ISSN 1093-4715, Vol. 23, p. 2106-2132Article in journal (Refereed)
    Abstract [en]

    High-throughput analyses have revealed that the vast majority of the transcriptome does not code for proteins. These non-translated transcripts, when larger than 200 nucleotides, are termed long non-coding RNAs (lncRNAs), and play fundamental roles in diverse cellular processes. LncRNAs are subject to dynamic chemical modification, adding another layer of complexity to our understanding of the potential roles that lncRNAs play in health and disease. Many lncRNAs regulate transcriptional programs by influencing the epigenetic state through direct interactions with chromatin-modifying proteins. Among these proteins, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) have been shown to be recruited by lncRNAs to silence target genes. Aberrant expression, deficiency or mutation of both lncRNA and Polycomb have been associated with numerous human diseases, including cancer. In this review, we have highlighted recent findings regarding the concerted mechanism of action of Polycomb group proteins (PcG), acting together with some classically defined lncRNAs including X-inactive specific transcript (XIST), antisense non-coding RNA in the INK4 locus (ANRIL), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), and HOX transcript antisense RNA (HOTAIR).

  • 28.
    Achour, Cyrinne
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Aguilo, Francesca
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Long Noncoding RNAs as Players in Breast Tumorigenesis2020In: The chemical biology of long noncoding RNAs / [ed] Stefan Jurga, Jan Barciszewski, Springer, 2020, , p. 19p. 385-403Chapter in book (Refereed)
    Abstract [en]

    Comprehensive analysis of the mammalian genome uncovered the discovery of pervasive transcription of large RNA transcripts that do not code for proteins, namely, long noncoding RNAs (lncRNAs). LncRNAs play important roles in the regulation of gene expression from integration of chromatin remodeling complexes to transcriptional and posttranscriptional regulation of protein-coding genes. Application of next-generation sequencing technologies to cancer transcriptomes has revealed that aberrant expression of lncRNAs is associated with tumor progression and metastasis. Although thousands of lncRNAs have been shown to be dysregulated in different cancer types, just few of them have been fully characterized. In this book chapter, we aim to highlight recent findings of the mechanistic function of lncRNAs in breast cancer and summarize key examples of lncRNAs that are misregulated during breast tumorigenesis. We have categorized breast cancer–associated lncRNA according to their contribution to tumor suppression or tumor progression based on recent studies. Because some of them are expressed in a specific molecular breast cancer subtype, we have outlined lncRNAs that can potentially serve as diagnostic and prognostic markers, in which expression is linked to chemotherapy resistance. Finally, we have discussed current limitations and perspectives on potential lncRNA targets for use in therapies against breast cancer.

  • 29.
    Adams, David
    et al.
    CHU Bicêtre, APHP, French Reference Centre For FAP (NNERF), LE KREMLIN-BICETRE, France.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Conceicao, Isabel
    Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Department of Neurology, Lisbon, Portugal.
    Waddington-Cruz, Marcia
    Hospital Universitario Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil.
    Schmidt, Hartmut
    University Hospital of Münster, Department of Transplantation, Münster, Germany.
    Buades, Juan
    Hospital Son Llatzer, Servicio de Medicina Interna, Palma de Mallorca, Spain.
    Campistol, Josep
    Hospital Clinic Barcelona, Instituto Clinic de Nefrologia y Urologia (ICNU), Barcelona, Spain.
    Coehlo, Teresa
    Hospital de Santo Antonio, Unidade Clinica de Paramiloidose, Porto, Portugal.
    Phase 2 open-label extention (OLE) study of patisiran, an investigational siRNA agent for familial amyloidotic polyneuropathy (FAP)2015In: Orphanet Journal of Rare Diseases, E-ISSN 1750-1172, Vol. 10, article id O20Article in journal (Refereed)
    Abstract [en]

    Background: Familial amyloidotic polyneuropathy (FAP) is a progressive and fatal, autosomal dominant disease caused by deposition of mutant and wild-type transthyretin (TTR). Patisiran is an investigational, systemically administered lipid nanoparticle (LNP) formulation of a small interfering RNA (siRNA) targeting wild-type and mutant TTR. This formulation delivers the siRNA predominantly to the liver, thereby inhibiting synthesis of TTR at the primary site of production. A recently completed multi-center, multi-dose Phase 2 trial of patisiran in FAP patients (N=29) showed >80% sustained mean knockdown of serum TTR when administered at a dose of 0.3 mg/kg every 3 weeks with a generally favorable safety profile (Suhr O, ISA 2014).

    Methods: A Phase 2 open-label extension (OLE) study of patisiran in patients with FAP who participated in the aforementioned trial, was initiated in October 2013. The primary objective of the study is to evaluate the safety and tolerability of 0.3 mg/kg patisiran administered intravenously once every 3 weeks for up to 2 years. Secondary objectives include assessment of patisiran's effect on serum TTR levels, as well as evaluation every 6 months of its impact on clinical measures, including the mNIS+7 composite neurologic impairment score and quality of life (QOL).

    Results: Twenty-seven patients were enrolled; median age 64 years (range: 29-77 years). Chronic dosing with patisiran has been generally well tolerated. Three patients experienced serious adverse events unrelated to study drug. Flushing and infusion-related reactions were observed in 22.2% and 18.5% of the patients, respectively; these were mild in severity, and did not result in any discontinuations. Sustained mean serum TTR lowering of approximately 80% was achieved, with further mean nadir of up to 88% between doses for approximately 16 months. Stabilization of quality of life (QOL) measures was observed. Among the 20 evaluable patients at the time of data cutoff, neuropathy impairment scores were stable through 12 months with a mean change in mNIS+7 and NIS of -2.5 and 0.4 points, respectively; this compares favorably to the 10-18 point increase in neurologic impairment scores estimated at 12 months from prior FAP studies in a patient population with similar baseline NIS.

    Conclusion: Data from this Phase 2 OLE study demonstrate that 12-months of patisiran administration was well-tolerated, resulted in sustained mean serum TTR lowering, and has the potential to halt neuropathy progression. As of March 2015, dosing continues for all patients; 18-month results will be presented.

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  • 30. Adams, Hieab H. H.
    et al.
    Hibar, Derrek P.
    Chouraki, Vincent
    Stein, Jason L.
    Nyquist, Paul A.
    Renteria, Miguel E.
    Trompet, Stella
    Arias-Vasquez, Alejandro
    Seshadri, Sudha
    Desrivieres, Sylvane
    Beecham, Ashley H.
    Jahanshad, Neda
    Wittfeld, Katharine
    Van der Lee, Sven J.
    Abramovic, Lucija
    Alhusaini, Saud
    Amin, Najaf
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Arfanakis, Konstantinos
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Athanasiu, Lavinia
    Axelsson, Tomas
    Beiser, Alexa
    Bernard, Manon
    Bis, Joshua C.
    Blanken, Laura M. E.
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chauhan, Ganesh
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Filippi, Irina
    Ge, Tian
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Greven, Corina U.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Hass, Johanna
    Haukvik, Unn K.
    Hilal, Saima
    Hofer, Edith
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liao, Jiemin
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    Mazoyer, Bernard
    Mckay, David R.
    McWhirter, Rebekah
    Milaneschi, Yuri
    Mirza-Schreiber, Nazanin
    Muetzel, Ryan L.
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pappa, Irene
    Pirpamer, Lukas
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Puetz, Benno
    Rajan, Kumar B.
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    Van der Meer, Dennis
    Van Donkelaar, Marjolein M. J.
    Van Eijk, Kristel R.
    Van Erp, Theo G. M.
    Van Rooij, Daan
    Walton, Esther
    Westlye, Lars T.
    Whelan, Christopher D.
    Windham, Beverly G.
    Winkler, Anderson M.
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Xu, Bing
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Aggarwal, Neelum T.
    Almasy, Laura
    Ames, David
    Amouyel, Philippe
    Andreassen, Ole A.
    Arepalli, Sampath
    Assareh, Amelia A.
    Barral, Sandra
    Bastin, Mark E.
    Becker, Diane M.
    Becker, James T.
    Bennett, David A.
    Blangero, John
    van Bokhoven, Hans
    Boomsma, Dorret I.
    Brodaty, Henry
    Brouwer, Rachel M.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Bulayeva, Kazima B.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cannon, Dara M.
    Cavalleri, Gianpiero L.
    Chen, Christopher
    Cheng, Ching -Yu
    Cichon, Sven
    Cookson, Mark R.
    Corvin, Aiden
    Crespo-Facorro, Benedicto
    Curran, Joanne E.
    Czisch, Michael
    Dale, Anders M.
    Davies, Gareth E.
    De Geus, Eco J. C.
    De Jager, Philip L.
    de Zubicaray, Greig I.
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita L.
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Espeseth, Thomas
    Evans, Denis A.
    Fedko, Iryna
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Grabe, Hans J.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hardy, John
    Hartman, Catharina A.
    Hashimoto, Ryota
    Hegenscheid, Katrin
    Heinz, Andreas
    Le Hellard, Stephanie
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Ho, Beng-Choon
    Hoekstra, Pieter J.
    Hoffmann, Wolfgang
    Hofman, Albert
    Holsboer, Florian
    Homuth, Georg
    Hosten, Norbert
    Hottenga, Jouke-Jan
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Ikram, M. Kamran
    Jack, Clifford R., Jr.
    Jenldnson, Mark
    Johnson, Robert
    Jonsson, Erik G.
    Jukema, J. Wouter
    Kahn, Rene S.
    Kanai, Ryota
    Kloszewska, Iwona
    Knopman, David S.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Lemaitre, Herve
    Liu, Xinmin
    Longo, Dan L.
    Longstreth, W. T., Jr.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Katie L.
    McMahon, Francis J.
    Mecocci, Patrizia
    Melle, Ingrid
    Meyer-Lindenberg, Andreas
    Mohnke, Sebastian
    Montgomery, Grant W.
    Morris, Derek W.
    Mosley, Thomas H.
    Muhleisen, Thomas W.
    Mueller-Myhsok, Bertram
    Nalls, Michael A.
    Nauck, Matthias
    Nichols, Thomas E.
    Niessen, Wiro J.
    Noethen, Markus M.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ohi, Kazutaka
    Olvera, Rene L.
    Ophoff, Roel A.
    Pandolfo, Massimo
    Paus, Tomas
    Pausova, Zdenka
    Penninx, Brenda W. J. H.
    Pike, G. Bruce
    Potkin, Steven G.
    Psaty, Bruce M.
    Reppermund, Simone
    Rietschel, Marcella
    Roffman, Joshua L.
    Romanczuk-Seiferth, Nina
    Rotter, Jerome I.
    Ryten, Mina
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Schmidt, Reinhold
    Schofield, Peter R.
    Sigurdsson, Sigurdur
    Simmons, Andy
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hindu.
    Srikanth, Velandai
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Tiemeier, Henning
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    Van der Lugt, Aad
    Van der Wee, Nic J. A.
    Van Duijn, Cornelia M.
    Van Haren, Neeltje E. M.
    Van't Ent, Dennis
    Van Tol, Marie Jose
    Vardarajan, Badri N.
    Veltman, Dick J.
    Vernooij, Meike W.
    Voelzke, Henry
    Walter, Henrik
    Wardlaw, Joanna M.
    Wassink, Thomas H.
    Weale, Michael E.
    Weinberger, Daniel R.
    Weiner, Michael W.
    Wen, Wei
    Westman, Eric
    White, Tonya
    Wong, Tien Y.
    Wright, Clinton B.
    Zielke, H. Ronald
    Zonderman, Alan B.
    Deary, Ian J.
    DeCarli, Charles
    Schmidt, Helena
    Martin, Nicholas G.
    De Craen, Anton J. M.
    Wright, Margaret J.
    Launer, Lenore J.
    Schumann, Gunter
    Fornage, Myriam
    Franke, Barbara
    Debette, Stephanie
    Medland, Sarah E.
    Ikram, M. Arfan
    Thompson, Paul M.
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, no 12, p. 1569-1582Article in journal (Refereed)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 31. Adderley, Jack D.
    et al.
    von Freyend, Simona John
    Jackson, Sarah A.
    Bird, Megan J.
    Burns, Amy L.
    Anar, Burcu
    Metcalf, Tom
    Semblat, Jean-Philippe
    Billker, Oliver
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
    Wilson, Danny W.
    Doerig, Christian
    Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 4015Article in journal (Refereed)
    Abstract [en]

    Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum. We used arrays of 878 antibodies directed against human signaling proteins to interrogate the activation status of host erythrocyte phospho-signaling pathways at three blood stages of parasite asexual development. This analysis reveals a dynamic modulation of many host signalling proteins across parasite development. Here we focus on the hepatocyte growth factor receptor (c-MET) and the MAP kinase pathway component B-Raf, providing a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.

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  • 32.
    Adey, Brett N.
    et al.
    Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Cooper-Knock, Johnathan
    Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.
    Al Khleifat, Ahmad
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Fogh, Isabella
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    van Damme, Philip
    Department of Neurosciences, KU Leuven-University of Leuven, Experimental Neurology, Leuven Brain Institute (LBI), Leuven, Belgium; VIB, Center for Brain and Disease Research, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
    Corcia, Philippe
    UMR 1253, Université de Tours, Inserm, Tours, France; Centre de référence sur la SLA, CHU de Tours, Tours, France.
    Couratier, Philippe
    Centre de référence sur la SLA, CHRU de Limoges, Limoges, France; UMR 1094, Université de Limoges, Inserm, Limoges, France.
    Hardiman, Orla
    Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
    McLaughlin, Russell
    Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
    Gotkine, Marc
    Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Agnes Ginges Center for Human Neurogenetics, Department of Neurology, Hadassah Medical Center, Jerusalem, Israel.
    Drory, Vivian
    Department of Neurology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Silani, Vincenzo
    Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy.
    Ticozzi, Nicola
    Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, Università degli Studi di Milano, Milan, Italy.
    Veldink, Jan H.
    Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
    van den Berg, Leonard H.
    Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
    de Carvalho, Mamede
    Instituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
    Pinto, Susana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Instituto de Fisiologia, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
    Mora Pardina, Jesus S.
    ALS Unit, Hospital San Rafael, Madrid, Spain.
    Povedano Panades, Mónica
    Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, Barcelona, L’Hospitalet de Llobregat, Spain.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Weber, Markus
    Neuromuscular Diseases Unit/ALS Clinic, St. Gallen, Switzerland.
    Başak, Nazli A.
    Koc University School of Medicine, Translational Medicine Research Center, NDAL, Istanbul, Turkey.
    Shaw, Christopher E.
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Shaw, Pamela J.
    Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.
    Morrison, Karen E.
    School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom.
    Landers, John E.
    Department of Neurology, University of Massachusetts Medical School, MA, Worcester, United States.
    Glass, Jonathan D.
    Department of Neurology, Emory University School of Medicine, GA, Atlanta, United States.
    Vourc’h, Patrick
    Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Service de Biochimie et Biologie molécularie, CHU de Tours, Tours, France.
    Dobson, Richard J. B.
    Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London, Maudsley NHS Foundation Trust, King’s College London, London, United Kingdom; Institute of Health Informatics, University College London, London, United Kingdom; NIHR Biomedical Research Centre at University College London Hospitals, NHS Foundation Trust, London, United Kingdom.
    Breen, Gerome
    Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Al-Chalabi, Ammar
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; King’s College Hospital, London, United Kingdom.
    Jones, Ashley R.
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Iacoangeli, Alfredo
    Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London, Maudsley NHS Foundation Trust, King’s College London, London, United Kingdom.
    Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival2023In: Frontiers in Cellular Neuroscience, E-ISSN 1662-5102, Vol. 17, article id 1112405Article in journal (Refereed)
    Abstract [en]

    Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.

    Methods: Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.

    Results: We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.

    Discussion: These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.

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  • 33.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    On dopamine neurons: nerve fiber outgrowth and L-DOPA effects2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease is a disorder mainly characterized by progressive degeneration of dopamine producing neurons in the substantia nigra of the midbrain. The most commonly used treatment strategy is to pharmacologically restore the lost function by the administration of the dopaminergic precursor L-DOPA. Another treatment strategy is to replace the degenerated neurons with immature fetal ventral mesencephalic tissue, or ultimately stem cell-derived tissue. Grafting trials have, however, revealed poor reinnervation capacity of the grafts, leaving much of the striata dopamine-denervated. An additional drawback is the upcoming of dyskinesia (involuntary movements), a phenomenon also observed during L-DOPA treatment of Parkinson’s disease patients. Attempts to characterize nerve fiber formation from dopamine neurons have demonstrated that the nerve fibers are formed in two morphologically diverse outgrowth patterns, one early outgrowth seen in the absence of astrocytes and one later appearing outgrowth seen in co-existence with astrocytes.

    The overall objective of this thesis has been to study the dopaminergic outgrowth including guidance of nerve fiber formation, and to look into the mechanisms of L-DOPA-induced dyskinesia. The first paper in this thesis characterizes the different outgrowth patterns described above and their relation to different glial cells. The study demonstrated the two different outgrowth patterns to be a general phenomenon, applying not only to dopamine neurons. Attempts of characterization revealed no difference of origin in terms of dopaminergic subpopulations, i.e. A9 or A10, between the outgrowth patterns. Furthermore, the “roller-drum” technique was found optimal for studying the dual outgrowth sequences.

    The second and the third paper also utilized the “roller-drum” technique in order to promote both patterns of neuronal fiber formation. The effects of glial cell line-derived neurotrophic factor (GDNF) on the formation of dopamine nerve fibers, was investigated. Cultures prepared from gdnf knockout mice revealed that dopaminergic neurons survive and form nerve fiber outgrowth in the absence of GDNF. The dopaminergic nerve fibers exhibited an outgrowth pattern consistent with that previous observed in rat. GDNF was found to exert effect on the glial-associated outgrowth whereas the non-glial-associated was not affected. Astrocytic proliferation was inhibited using cytosine β-D-arabinofuranoside, resulting in reduced glial-associated outgrowth. The non-glial-associated dopaminergic outgrowth was on the other hand promoted, and was retained over longer time in culture. Furthermore, the non-glial-associated nerve fibers were found to target the fetal frontal cortex. Different developmental stages were shown to promote and affect the outgrowths differently. Taken together, these data indicate and state the importance of astrocytes and growth factors for neuronal nerve fiber formation and guidance. It also stresses the importance of fetal donor age at the time for transplantation.

    The fourth and fifth studies focus on L-DOPA dynamics and utilize in vivo chronoamperometry. In study four, 6-OHDA dopamine-depleted rats were exposed to chronic L-DOPA treatment and then rated as dyskinetic or non-dyskinetic. The electrochemical recordings demonstrated reduced KCl-evoked release in the intact striatum after chronic L-DOPA treatment. Time for maximal dopamine concentration after L-DOPA administration was found to be shorter in dyskinetic animals than in non-dyskinetic animals. The serotonergic nerve fiber content in the striatum was evaluated and brains from dyskinetic animals were found to exhibit significantly higher nerve fiber density compared to non-dyskinetic animals. Furthermore, the mechanisms behind the conversion of L-DOPA to dopamine in 6-OHDA dopamine-depleted rats were studied. Local administration of L-DOPA in the striatum increased the KCl-evoked dopamine release in the intact striatum. Acute application of L-DOPA resulted sometimes in a rapid conversion to dopamine, probably without vesicle packaging. This type of direct conversion is presumably occurring in non-neuronal tissue. Furthermore, KCl-evoked dopamine releases were present upon local application of L-DOPA in the dopamine-depleted striatum, suggesting that the conversion to dopamine took place elsewhere, than in dopaminergic nerve fibers. In conclusion, these studies state the importance of astrocytes for neuronal nerve fiber formation and elucidate the complexity of L-DOPA conversion in the brain.

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  • 34.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Barkander, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pelegrina-Hidalgo, Noelia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Gerhardt, Greg A
    Virel, Ana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance2019In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 131, article id 104551Article in journal (Refereed)
    Abstract [en]

    In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

  • 35.
    Agarkova, Irina
    et al.
    ETH-Zurich Hoenggerberg.
    Schoenauer, Roman
    ETH-Zurich Hoenggerberg.
    Ehler, Elisabeth
    King×s College London,.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carlsson, Eva
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Perriard, Jean-Claude
    ETH-Zurich Hoenggerberg.
    The molecular composition of the sarcomeric M-band correlates with muscle fiber type2004In: European Journal of Cell Biology, ISSN 0171-9335, Vol. 83, no 5, p. 193-204Article in journal (Refereed)
    Abstract [en]

    The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle types.

  • 36.
    Agerhäll, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Henrikson, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Johansson Söderberg, Jenny
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gylfe, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    High prevalence of pharyngeal bacterial pathogens among healthy adolescents and young adults2021In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 129, no 12, p. 711-716Article in journal (Refereed)
    Abstract [en]

    The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.

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  • 37.
    Aggett, Peter
    et al.
    Lancashire School of Health and Postgraduate Medicine, University of Central Lancashire, Preston, United Kingdom.
    Nordberg, Gunnar F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Nordberg, Monica
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Essential metals: assessing risks from deficiency and toxicity2022In: Handbook on the toxicology of metals: volume I: general considerations / [ed] Gunnar F. Nordberg; Max Costa, London: Academic Press, 2022, 5, p. 385-406Chapter in book (Refereed)
    Abstract [en]

    Recommendations aimed at protecting the public from toxicity of essential elements including essential metals have usually been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in the evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach, including a balanced consideration of nutritional and toxicological data. In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is a risk of developing deficiency, and another interval of (high) dietary intakes at which toxicity may occur. In most instances, there is a third set of intakes in between, which represents the acceptable range of oral intake (AROI), in which no adverse effects occur. This range determined from a homeostatic or biologically based (BBM) approach, which is discussed here, would be expected to apply to the general population. It must be noted, however, that this range would not protect all persons from adverse effects: this applies to those with genetically determined sensitivity, who may require higher intakes to avoid deficiency or lower intakes to avoid toxicity than those defined by the AROI. Nonetheless, AROI could be derived to protect 95% of the general human population from minimal adverse effects of deficiency or toxicity arising from inadequate and excessive intakes. As such the correspondence of these values to current Health-Based Guidance Values (HBGVs) and reference intakes of essential metals (EMs), and the roles of the BBM/Homeostatic Approach in Risk Assessment of EMs are of important public health interest.

  • 38.
    Aglago, Elom K.
    et al.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Kim, Andre
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Evangelou, Marina
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Ren, Yu
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Morrison, John
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Barry, Elizabeth L.
    Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
    Baurley, James W.
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Bien, Stephanie A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bishop, D Timothy
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Bouras, Emmanouil
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Buchanan, Daniel D.
    Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, VIC, Parkville, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Parkville, Australia.
    Budiarto, Arif
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
    Carreras-Torres, Robert
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
    Casey, Graham
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Cenggoro, Tjeng Wawan
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
    Chen, Xuechen
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Conti, David V.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Devall, Matthew
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Diez-Obrero, Virginia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Drew, David
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Figueiredo, Jane C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Gallinger, Steven
    Lunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia.
    Gruber, Stephen B.
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Gsur, Andrea
    Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Hampel, Heather
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hidaka, Akihisa
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Huyghe, Jeroen R.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Jenkins, Mark A.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
    Jordahl, Kristina
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Joshi, Amit D.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Kawaguchi, Eric S.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Larsson, Susanna C.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Marchand, Loic Le
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lewinger, Juan Pablo
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lynch, Brigid M.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
    Mahesworo, Bharuno
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Mandic, Marko
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Obón-Santacana, Mireia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Moreno, Victor
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Nan, Hongmei
    Department of Epidemiology, Richard M. Fairbanks School of Public Health, IN, Indianapolis, United States; IU Melvin and Bren Simon Cancer Center, Indiana University, IN, Indianapolis, United States.
    Nassir, Rami
    Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Ogino, Shuji
    Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States.
    Ose, Jennifer
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Pai, Rish K.
    Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States.
    Palmer, Julie R.
    Department of Medicine, Boston University School of Medicine, Slone Epidemiology Center, Boston University, MA, Boston, United States.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Peoples, Anita R.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Prentice, Ross L.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States.
    Sakoda, Lori C.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Scacheri, Peter C.
    Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Schmit, Stephanie L.
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Shcherbina, Anna
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Slattery, Martha L.
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Stern, Mariana C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Su, Yu-Ru
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Thibodeau, Stephen N.
    Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, Rochester, United States.
    Thomas, Duncan C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Tian, Yu
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    van Duijnhoven, Franzel Jb
    Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Wang, Jun
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
    Wu, Anna H.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Zemlianskaia, Natalia
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Gauderman, W James
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Campbell, Peter T.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk2023In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 83, no 15, p. 2572-2583Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.

    SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

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  • 39. Agostinelli, Emilio
    et al.
    Gonzalez-Velandia, Kevin Y.
    Hernandez-Clavijo, Andres
    Maurya, Devendra Kumar
    Neurobiology Group, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
    Xerxa, Elena
    Lewin, Gary R.
    Dibattista, Michele
    Menini, Anna
    Pifferi, Simone
    A Role for STOML3 in Olfactory Sensory Transduction2021In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 2, article id ENEURO.0565-20.2021Article in journal (Refereed)
    Abstract [en]

    Stomatin-like protein-3 (STOML3) is an integral membrane protein expressed in the cilia of olfactory sensory neurons (OSNs), but its functional role in this cell type has never been addressed. STOML3 is also expressed in dorsal root ganglia neurons, where it has been shown to be required for normal touch sensation. Here, we extended previous results indicating that STOML3 is mainly expressed in the knob and proximal cilia of OSNs. We additionally showed that mice lacking STOML3 have a morphologically normal olfactory epithelium. Because of its presence in the cilia, together with known olfactory transduction components, we hypothesized that STOML3 could be involved in modulating odorant responses in OSNs. To investigate the functional role of STOML3, we performed loose patch recordings from wild-type (WT) and Stoml3 knock-out (KO) OSNs. We found that spontaneous mean firing activity was lower with additional shift in interspike intervals (ISIs) distributions in Stoml3 KOs compared with WT neurons. Moreover, the firing activity in response to stimuli was reduced both in spike number and duration in neurons lacking STOML3 compared with WT neurons. Control experiments suggested that the primary deficit in neurons lacking STOML3 was at the level of transduction and not at the level of action potential generation. We conclude that STOML3 has a physiological role in olfaction, being required for normal sensory encoding by OSNs.

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  • 40. Agrawal, Ganesh Kumar
    et al.
    Sarkar, Abhijit
    Agrawal, Raj
    Ndimba, Bongani Kaiser
    Tanou, Georgia
    Dunn, Michael J
    Kieselbach, Thomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Cramer, Rainer
    Wienkoop, Stefanie
    Chen, Sixue
    Rafudeen, Mohammed Suhail
    Deswal, Renu
    Barkla, Bronwyn J
    Weckwerth, Wolfram
    Heazlewood, Joshua L
    Renaut, Jenny
    Job, Dominique
    Chakraborty, Niranjan
    Rakwal, Randeep
    Boosting the Globalization of Plant Proteomics through INPPO: Current Developments and Future Prospects2012In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 12, no 3, p. 359-368Article in journal (Refereed)
    Abstract [en]

    The International Plant Proteomics Organization (INPPO) is a non-profit-organization consisting of people who are involved or interested in plant proteomics. INPPO is constantly growing in volume and activity, which is mostly due to the realization among plant proteomics researchers worldwide for the need of such a global platform. Their active participation resulted in the rapid growth within the first year of INPPO's official launch in 2011 via its website (www.inppo.com) and publication of the 'Viewpoint paper' in a special issue of PROTEOMICS (May 2011). Here, we will be highlighting the progress achieved in the year 2011 and the future targets for the year 2012 and onwards. INPPO has achieved a successful administrative structure, the Core Committee (CC; composed of President, Vice-President, and General Secretaries), Executive Council (EC), and General Body (GB) to achieve INPPO objectives. Various committees and subcommittees are in the process of being functionalized via discussion amongst scientists around the globe. INPPO's primary aim to popularize the plant proteomics research in biological sciences has also been recognized by PROTEOMICS where a section dedicated to plant proteomics has been introduced starting January 2012, following the very first issue of this journal devoted to plant proteomics in May 2011. To disseminate organizational activities to the scientific community, INPPO has launched a biannual (in January and July) newsletter entitled 'INPPO Express: News & Views' with the first issue published in January 2012. INPPO is also planning to have several activities in 2012, including programs within the Education Outreach committee in different countries, and the development of research ideas and proposals with priority on crop and horticultural plants, while keeping tight interactions with proteomics programs on model plants such as Arabidopsis thaliana, rice, and Medicago truncatula. Altogether, the INPPO progress and upcoming activities are because of immense support, dedication, and hard work of all members of the INPPO community, and also due to the wide encouragement and support from the communities (scientific and non-scientific).

  • 41. Aguilo, Francesca
    et al.
    Avagyan, Serine
    Labar, Amy
    Sevilla, Ana
    Lee, Dung-Fang
    Kumar, Parameet
    Lemischka, Ihor R
    Zhou, Betty Y
    Snoeck, Hans-Willem
    Prdm16 is a physiologic regulator of hematopoietic stem cells.2011In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 117, no 19Article in journal (Refereed)
    Abstract [en]

    Fetal liver and adult bone marrow hematopoietic stem cells (HSCs) renew or differentiate into committed progenitors to generate all blood cells. PRDM16 is involved in human leukemic translocations and is expressed highly in some karyotypically normal acute myeloblastic leukemias. As many genes involved in leukemogenic fusions play a role in normal hematopoiesis, we analyzed the role of Prdm16 in the biology of HSCs using Prdm16-deficient mice. We show here that, within the hematopoietic system, Prdm16 is expressed very selectively in the earliest stem and progenitor compartments, and, consistent with this expression pattern, is critical for the establishment and maintenance of the HSC pool during development and after transplantation. Prdm16 deletion enhances apoptosis and cycling of HSCs. Expression analysis revealed that Prdm16 regulates a remarkable number of genes that, based on knockout models, both enhance and suppress HSC function, and affect quiescence, cell cycling, renewal, differentiation, and apoptosis to various extents. These data suggest that Prdm16 may be a critical node in a network that contains negative and positive feedback loops and integrates HSC renewal, quiescence, apoptosis, and differentiation.

  • 42.
    Aguilo, Francesca
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Departments of Structural and Chemical Biology, Genetics and Genomic Sciences and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Di Cecilia, Serena
    Walsh, Martin J
    Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease2016In: Long non-coding RNAs in human disease, Springer, 2016, Vol. 394, p. 29-39Chapter in book (Refereed)
    Abstract [en]

    The long non-coding RNA CDKN2B-AS1, commonly referred to as the Antisense Non-coding RNA in the INK4 Locus (ANRIL), is a 3.8-kb-long RNA transcribed from the short arm of human chromosome 9 on p21.3 that overlaps a critical region encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide association studies have identified this region with a remarkable and growing number of disease-associated DNA alterations and single nucleotide polymorphisms, which corresponds to increased susceptibility to human disease. Recent attention has been devoted on whether these alterations in the ANRIL sequence affect its expression levels and/or its splicing transcript variation, and in consequence, global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not only can regulate their immediate genomic neighbors in cis, but also has the capacity to regulate additional loci in trans. This action would further increase the complexity for mechanisms imposed through ANRIL and furthering the scope of this lncRNA in disease pathogenesis. In this chapter, we summarize the most recent findings on the investigation of ANRIL and provide a perspective on the biological and clinical significance of ANRIL as a putative biomarker, specifically, its potential role in directing cellular fates leading to cancer and cardiovascular disease.

  • 43.
    Aguilo, Francesca
    et al.
    Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Li, SiDe
    Balasubramaniyan, Natarajan
    Sancho, Ana
    Benko, Sabina
    Zhang, Fan
    Vashisht, Ajay
    Rengasamy, Madhumitha
    Andino, Blanca
    Chen, Chih-hung
    Zhou, Felix
    Qian, Chengmin
    Zhou, Ming-Ming
    Wohlschlegel, James A
    Zhang, Weijia
    Suchy, Frederick J
    Walsh, Martin J
    Deposition of 5-Methylcytosine on Enhancer RNAs Enables the Coactivator Function of PGC-1α2016In: Cell Reports, E-ISSN 2211-1247, Vol. 14, no 3, p. 479-492Article in journal (Refereed)
    Abstract [en]

    The Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a transcriptional co-activator that plays a central role in adapted metabolic responses. PGC-1α is dynamically methylated and unmethylated at the residue K779 by the methyltransferase SET7/9 and the Lysine Specific Demethylase 1A (LSD1), respectively. Interactions of methylated PGC-1α[K779me] with the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex, the Mediator members MED1 and MED17, and the NOP2/Sun RNA methytransferase 7 (NSUN7) reinforce transcription, and are concomitant with the m(5)C mark on enhancer RNAs (eRNAs). Consistently, loss of Set7/9 and NSun7 in liver cell model systems resulted in depletion of the PGC-1α target genes Pfkl, Sirt5, Idh3b, and Hmox2, which was accompanied by a decrease in the eRNAs levels associated with these loci. Enrichment of m(5)C within eRNA species coincides with metabolic stress of fasting in vivo. Collectively, these findings illustrate the complex epigenetic circuitry imposed by PGC-1α at the eRNA level to fine-tune energy metabolism.

  • 44.
    Aguilo, Francesca
    et al.
    Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Zakirova, Zuchra
    Nolan, Katie
    Wagner, Ryan
    Sharma, Rajal
    Hogan, Megan
    Wei, Chengguo
    Sun, Yifei
    Walsh, Martin J.
    Kelley, Kevin
    Zhang, Weijia
    Ozelius, Laurie J.
    Gonzalez-Alegre, Pedro
    Zwaka, Thomas P.
    Ehrlich, Michelle E.
    THAP1: role in mouse embryonic stem cell survival and differentiation2017In: Stem Cell Reports, ISSN 2213-6711, Vol. 9, no 1, p. 92-107Article in journal (Refereed)
    Abstract [en]

    THAP1 (THAP [Thanatos-associated protein] domain-containing, apoptosis-associated protein 1) is a ubiquitously expressed member of a family of transcription factors with highly conserved DNA-binding and protein-interacting regions. Mutations in THAP1 cause dystonia, DYT6, a neurologic movement disorder. THAP1 downstream targets and the mechanism via which it causes dystonia are largely unknown. Here, we show that wild-type THAP1 regulates embryonic stem cell (ESC) potential, survival, and proliferation. Our findings identify THAP1 as an essential factor underlying mouse ESC survival and to some extent, differentiation, particularly neuroectodermal. Loss of THAP1 or replacement with a disease-causing mutation results in an enhanced rate of cell death, prolongs Nanog, Prdm14, and/or Rex1 expression upon differentiation, and results in failure to upregulate ectodermal genes. ChIP-Seq reveals that these activities are likely due in part to indirect regulation of gene expression.

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  • 45. Aguilo, Francesca
    et al.
    Zhang, Fan
    Sancho, Ana
    Fidalgo, Miguel
    Di Cecilia, Serena
    Vashisht, Ajay
    Lee, Dung-Fang
    Chen, Chih-Hung
    Rengasamy, Madhumitha
    Andino, Blanca
    Jahouh, Farid
    Roman, Angel
    Krig, Sheryl R
    Wang, Rong
    Zhang, Weijia
    Wohlschlegel, James A
    Wang, Jianlong
    Walsh, Martin J
    Coordination of m(6)A mRNA Methylation and Gene Transcription by ZFP217 Regulates Pluripotency and Reprogramming.2015In: Cell Stem Cell, ISSN 1934-5909, E-ISSN 1875-9777, Vol. 17, no 6, p. 689-704Article in journal (Refereed)
    Abstract [en]

    Epigenetic and epitranscriptomic networks have important functions in maintaining the pluripotency of embryonic stem cells (ESCs) and somatic cell reprogramming. However, the mechanisms integrating the actions of these distinct networks are only partially understood. Here we show that the chromatin-associated zinc finger protein 217 (ZFP217) coordinates epigenetic and epitranscriptomic regulation. ZFP217 interacts with several epigenetic regulators, activates the transcription of key pluripotency genes, and modulates N6-methyladenosine (m(6)A) deposition on their transcripts by sequestering the enzyme m(6)A methyltransferase-like 3 (METTL3). Consistently, Zfp217 depletion compromises ESC self-renewal and somatic cell reprogramming, globally increases m(6)A RNA levels, and enhances m(6)A modification of the Nanog, Sox2, Klf4, and c-Myc mRNAs, promoting their degradation. ZFP217 binds its own target gene mRNAs, which are also METTL3 associated, and is enriched at promoters of m(6)A-modified transcripts. Collectively, these findings shed light on how a transcription factor can tightly couple gene transcription to m(6)A RNA modification to ensure ESC identity.

  • 46. Aguilo, Francesca
    et al.
    Zhou, Ming-Ming
    Walsh, Martin J
    Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression.2011In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 71, no 16Article in journal (Refereed)
    Abstract [en]

    Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15(INK4b), p14(ARF), and p16(INK4a), and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development.

  • 47. Aguiló, Francesca
    et al.
    Camarero, Nuria
    Relat, Joana
    Marrero, Pedro F
    Haro, Diego
    Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma.2010In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 427, no 2Article in journal (Refereed)
    Abstract [en]

    In the cytosol of lipogenic tissue, ketone bodies are activated by AACS (acetoacetyl-CoA synthetase) and incorporated into cholesterol and fatty acids. AACS gene expression is particularly abundant in white adipose tissue, as it is induced during adipocyte differentiation. In order to elucidate the mechanism controlling the gene expression of human AACS and to clarify its physiological role, we isolated the human promoter, characterized the elements required to initiate transcription and analysed the expression of the gene in response to PPARgamma (peroxisome-proliferator-activated receptor gamma), an inducer of adipogenesis. We show that the human AACS promoter is a PPARgamma target gene and that this nuclear receptor is recruited to the AACS promoter by direct interaction with Sp1 (stimulating protein-1).

  • 48.
    Ahlgren, Ulf
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Gotthardt, Martin
    Department of Nuclear Medicine, Nijmegen, Netherlands.
    Approaches for imaging islets2010In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 654, p. 39-57Article in journal (Refereed)
    Abstract [en]

    The establishment of improved technologies for imaging of the pancreas is a key element in addressing several aspects of diabetes pathogenesis. In this respect, the development of a protocol that allows for non-invasive scoring of human islets, or islet beta-cells, is of particular importance. The development of such a technology would have profound impact on both clinical and experimental medicine, ranging from early diagnosis of diabetes to the evaluation of therapeutic regimes. Another important task is the development of modalities for high-resolution imaging of experimental animal models for diabetes. Rodent models for diabetes research have for decades been instrumental to the diabetes research community. The ability to image, and to accurately quantify, key players of diabetogenic processes with molecular specificity will be of great importance for elucidating mechanistic aspects of the disease. This chapter aims to overview current progress within these research areas.

  • 49.
    Ahmad, Irfan
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet; Department of Allied Health Sciences, University of Health Sciences.
    Cimdins, Annika
    Beske, Timo
    Römling, Ute
    Detailed analysis of c-di-GMP mediated regulation of csgD expression in Salmonella typhimurium2017In: BMC Microbiology, E-ISSN 1471-2180, Vol. 17, article id 27Article in journal (Refereed)
    Abstract [en]

    Background: The secondary messenger cyclic di-GMP promotes biofilm formation by up regulating the expression of csgD, encoding the major regulator of rdar biofilm formation in Salmonella typhimurium. The GGDEF/EAL domain proteins regulate the c-di-GMP turnover. There are twenty-two GGDEF/EAL domain proteins in the genome of S. typhimurium. In this study, we dissect the role of individual GGDEF/EAL proteins for csgD expression and rdar biofilm development. Results: Among twelve GGDEF domains, two proteins upregulate and among fifteen EAL domains, four proteins down regulate csgD expression. We identified two additional GGDEF proteins required to promote optimal csgD expression. With the exception of the EAL domain of STM1703, solely, diguanylate cyclase and phosphodiesterase activities are required to regulate csgD mediated rdar biofilm formation. Identification of corresponding phosphodiesterases and diguanylate cyclases interacting in the csgD regulatory network indicates various levels of regulation by c-di-GMP. The phosphodiesterase STM1703 represses transcription of csgD via a distinct promoter upstream region. Conclusion: The enzymatic activity and the protein scaffold of GGDEF/EAL domain proteins regulate csgD expression. Thereby, c-di-GMP adjusts csgD expression at multiple levels presumably using a multitude of input signals.

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  • 50.
    Ahmad, Irfan
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nadeem, Aftab
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 1, article id e0210082Article in journal (Refereed)
    Abstract [en]

    Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.

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