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المؤلفون: Faux, Pierre, Ding, Li, Miguel Ramirez-Aristeguieta, Luis, Chacón-Duque, J. Camilo, 1988, Comini, Maddalena, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Jaramillo, Claudia, Arias, William, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Barquera, Rodrigo, Everardo-Martinez, Paola, Quinto-Sanchez, Mirsha, Gomez-Valdes, Jorge, Villamil-Ramirez, Hugo, Silva de Cerqueira, Caio C., Hunemeier, Tabita, Ramallo, Virginia, Gonzalez-Jose, Rolando, Schuler-Faccini, Lavinia, Bortolini, Maria-Catira, Acuna-Alonzo, Victor, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Rothhammer, Francisco, Rojas, Winston, Schmid, Annina B., Adhikari, Kaustubh, Bennett, David L., Ruiz-Linares, Andres
المصدر: Communications Biology. 6(1)
الوصف: The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of similar to 123kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function. Neanderthal-derived variants in the SCN9A gene (encoding the voltage gated sodium channel, Nav1.7) are associated with enhanced experimental mechanical pain sensitivity in modern humans.
وصف الملف: print
الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-225829Test
https://doi.org/10.1038/s42003-023-05286-zTest -
2دورية أكاديمية
المؤلفون: Themistocleous, Andreas C, Baskozos, Georgios, Blesneac, Iulia, Comini, Maddalena, Megy, Karyn, Chong, Sam, Deevi, Sri VV, Ginsberg, Lionel, Gosal, David, Hadden, Robert DM, Horvath, Rita, Mahdi-Rogers, Mohamed, Manzur, Adnan, Mapeta, Rutendo, Marshall, Andrew, Matthews, Emma, McCarthy, Mark I, Reilly, Mary M, Renton, Tara, Rice, Andrew SC, Vale, Tom A, van Zuydam, Natalie, Walker, Suellen M, Woods, Christopher Geoffrey, Bennett, David LH
المصدر: Brain Commun , 5 (2) , Article fcad037. (2023)
مصطلحات موضوعية: neuropathic pain, peripheral neuropathy, sodium channels, whole genome sequencing
الوصف: The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The ...
وصف الملف: text
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10166688/1/Investigating%20genotype-phenotype%20relationship%20of%20extreme%20neuropathic%20pain%20disorders%20in%20a%20UK%20national%20cohort.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10166688Test/
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3دورية أكاديمية
المؤلفون: Middleton, Steven J, Barry, Allison M, Comini, Maddalena, Li, Yan, Ray, Pradipta R, Shiers, Stephanie, Themistocleous, Andreas C, Uhelski, Megan L, Yang, Xun, Dougherty, Patrick M, Price, Theodore J, Bennett, David L
المساهمون: National Institutes of Health, Eugene McDermott Professorship, NIH, Thompson Family Foundation Initiative, H.E.B. Professorship, Wellcome clinical scientist, Wellcome Pain Consortium, European Commission Horizon 2020, International Diabetic Neuropathy Consortium, Novo Nordisk Foundation, Academy of Medical Sciences Starter, Diabetes UK, Medical Research Council, Wellcome, GTC MSDTC Scholarship
المصدر: Brain ; volume 144, issue 5, page 1312-1335 ; ISSN 0006-8950 1460-2156
الوصف: Chronic pain affects one in five of the general population and is the third most important cause of disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy and tolerability. There has been a failure in translating promising preclinical drug targets into clinic use. This reflects challenges across the whole drug development pathway, from preclinical models to trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes an important contribution to many chronic pain states, they are located outside the blood–brain barrier, and they are relatively specific. The past decade has seen significant advances in the techniques available to study human nociceptors, including: the use of corneal confocal microscopy and biopsy samples to observe nociceptor morphology, the culture of human nociceptors (either from surgical or post-mortem tissue or using human induced pluripotent stem cell derived nociceptors), the application of high throughput technologies such as transcriptomics, the in vitro and in vivo electrophysiological characterization through microneurography, and the correlation with pain percepts provided by quantitative sensory testing. Genome editing in human induced pluripotent stem cell-derived nociceptors enables the interrogation of the causal role of genes in the regulation of nociceptor function. Both human and rodent nociceptors are more heterogeneous at a molecular level than previously appreciated, and while we find that there are broad similarities between human and rodent nociceptors there are also important differences involving ion channel function, expression, and cellular excitability. These technological advances have emphasized the maladaptive plastic changes occurring in human nociceptors following injury that contribute to chronic pain. Studying human nociceptors has revealed new therapeutic targets for the suppression of chronic pain and enhanced repair. Cellular models of human nociceptors have enabled ...
الإتاحة: https://doi.org/10.1093/brain/awab048Test
http://academic.oup.com/brain/article-pdf/144/5/1312/38813696/awab048.pdfTest -
4دورية أكاديمية
المؤلفون: Fan, Xiaoming, Hendriks, Johnny, Comini, Maddalena, Katranidis, Alexandros, Büldt, Georg, Gensch, Thomas
المصدر: Methods and applications in fluorescence 8(2), 025008 (2020). doi:10.1088/2050-6120/ab7e0f
مصطلحات موضوعية: info:eu-repo/classification/ddc/530
جغرافية الموضوع: DE
الوصف: Single molecule localization microscopy (SMLM) allows the imaging of cellular structures with resolutions five to ten times below the diffraction limit of optical microscopy. It was originally introduced as a two-dimensional technique based on the localization of single emitters as projection onto the x-y imaging plane. The determination of the axial position of a fluorescent emitter is only possible by additional information. Here we report a method (spatial filter SMLM (SFSMLM)) that allows to determine the axial positions of fluorescent molecules and nanoparticles on the nanometer scale by the usage of two spatial filters, which are placed in two otherwise identical emission detection channels. SFSMLM allows axial localization in a range of ca. 1.5 μm with a localization precision of 15 - 30 nm in axial direction. The technique was utilized for localizing and imaging small cellular structures – e.g. actin filaments, vesicles and mitochondria - in three dimensions.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/pmid:32150730; info:eu-repo/semantics/altIdentifier/issn/2050-6120; info:eu-repo/semantics/altIdentifier/hdl/2128/24640; info:eu-repo/semantics/altIdentifier/wos/WOS:000521503100001; https://juser.fz-juelich.de/record/873802Test; https://juser.fz-juelich.de/search?p=id:%22FZJ-2020-01007%22Test
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5دورية أكاديمية
المؤلفون: Comini, Maddalena, Sierra-Marquez, Juan, Guzman, Gustavo, Franzen, Arne, Willuweit, Antje, Katona, Istvan, Hidalgo, Patricia, Fahlke, Christoph, Guzman, Raul E.
المصدر: The journal of neuroscience 42(15), 3080-3095 (2022). doi:10.1523/JNEUROSCI.2439-21.2022
جغرافية الموضوع: DE
العلاقة: info:eu-repo/semantics/altIdentifier/issn/1529-2401; info:eu-repo/semantics/altIdentifier/issn/0270-6474; info:eu-repo/semantics/altIdentifier/wos/WOS:000789016600003; info:eu-repo/semantics/altIdentifier/pmid/pmid:35241492; https://publications.rwth-aachen.de/record/889482Test; https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-250585%22Test
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6كتاب
المؤلفون: Comini, Maddalena, Zifarelli, Giovanni
المصدر: Studies of Epithelial Transporters and Ion Channels ; Physiology in Health and Disease ; page 523-546 ; ISSN 2625-252X 2625-2538 ; ISBN 9783030554538 9783030554545
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7مؤتمر
المؤلفون: Comini, Maddalena
المصدر: Europhysiology, London, UK, 2018-09-14 - 2018-09-16
جغرافية الموضوع: DE
العلاقة: https://juser.fz-juelich.de/record/851815Test; https://juser.fz-juelich.de/search?p=id:%22FZJ-2018-05315%22Test
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8رسالة جامعية
المؤلفون: Comini, Maddalena
وصف الملف: Text
العلاقة: https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=47929Test; urn:nbn:de:hbz:061-20181129-081755-8
