Article
Clinical Neurology
Arlette L. Bruijstens, Sandy Molenaar, Yu Yi M. Wong, Robert Kraaij, Rinze F. Neuteboom
Summary: This study investigated the gut microbiota composition and functional pathways in pediatric-onset multiple sclerosis (MS) patients and found that obese children had lower microbiota diversity and higher abundance of certain microbes and functional pathways.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Jiajia Wang, Lijun Yang, Mingqing Jiang, Chuntao Zhao, Xuezhao Liu, Kalen Berry, Ari Waisman, Abraham J. Langseth, Bennett G. Novitch, Dwight E. Bergles, Akiko Nishiyama, Q. Richard Lu
Summary: Through multiple experiments, it is shown that Olig2 is essential for the differentiation, myelination, and repair of immature OLs, contrary to previous findings. Additionally, the study highlights the importance of using Cre-dependent reporter genes in studying cell state progression.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Sharon A. Sagan, Zahra Moinfar, Carson E. Moseley, Ravi Dandekar, Collin M. Spencer, Alan S. Verkman, Ole Petter Ottersen, Raymond A. Sobel, John Sidney, Alessandro Sette, Mark S. Anderson, Lawrence Steinman, Michael R. Wilson, Joseph J. Sabatino, Scott S. Zamvil
Summary: This study investigates the role of AQP4-specific Th17 cells in the pathogenesis of neuromyelitis optica (NMO). The research shows that AQP4-specific T cells have a high affinity for binding to MHC II, and their clonal expansion is observed in AQP4-deficient mice. Thymic negative selection alone does not account for the tolerance to AQP4 in wild-type (WT) mice. AQP4-specific Th17 cells can cause paralysis followed by recovery, associated with apoptosis of donor T cells. However, these cells can persist and cause persistent paralysis in mice deficient in both T and B cells or lacking T cells only. In contrast, MOG-specific T cells survive and cause sustained disease in WT mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Clinical Neurology
Prateek Malik, Manohar Shroff
Summary: The central nervous system (CNS) is constantly under immune surveillance, which involves specialized mechanisms such as selectively permissive barriers and modifications to innate and adaptive immune systems. These mechanisms detect and eliminate inciting triggers, leading to varied endpoints of brain injury and edema. Recognizable patterns in these endpoints are often the result of underlying immune drivers, such as infection, inflammation, and genetics. Imaging provides insights into these patterns, which arise from unique interactions between these factors. Through case examples, we review the current understanding of these interactions and highlight how infection and inflammation can challenge the CNS in children.
Article
Neurosciences
Sitong Yang, Jingjing Ma, Han Zhang, Laiqiang Chen, Yuxuan Li, Mingtian Pan, Hongcheng Zhu, Jun Liang, Dajian He, Shihua Li, Xiao-Jiang Li, Xiangyu Guo
Summary: Huntington's disease (HD) is characterized by late-onset neurodegeneration caused by expanded CAG repeats in the huntingtin gene (HTT). This study investigated whether mutant HTT affects the development of glial cells during early brain development. The results showed that the numbers of astrocytes and oligodendrocytes in postnatal HD KI mice were not significantly altered compared to wild type (WT) mice, but myelin protein expression was reduced at 3 months of age. These findings suggest that cytoplasmic mutant HTT mediates myelination defects in the early stages of HD without impacting glial cell differentiation and maturation.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Nutrition & Dietetics
Ruth Gutierrez-Aguilar, Bernadette E. Grayson, Dong-Hoon Kim, Suma Yalamanchili, Mario L. Calcagno, Stephen C. Woods, Randy J. Seeley
Summary: GNPDA2 has been associated with obesity and type-2 diabetes, while its expression is high in the hypothalamus and adipose tissue. It plays a role in regulating glucose homeostasis, but not appetite. Inhibition of GFAT, on the other hand, affects appetite and body weight due to visceral illness.
FRONTIERS IN NUTRITION
(2021)
Article
Multidisciplinary Sciences
Kyla A. McKay, Ronny Wickstrom, Jan Hillert, Virginija Danylaite Karrenbauer
Summary: This study found that CSF markers were not associated with relapse rate but were related to higher disability scores in pediatric-onset multiple sclerosis patients. Pediatric-onset multiple sclerosis patients more commonly exhibit evidence of IgG production in the CSF compared to adult-onset cases.
SCIENTIFIC REPORTS
(2021)
Review
Clinical Neurology
Duriel Hardy
Summary: Acquired demyelinating syndromes of the central nervous system can affect the brain, optic nerves, and spinal cord, and have become increasingly recognized in children. Advances in imaging techniques, diagnostic testing, research, and collaborative efforts have contributed to this awareness. Identification of autoantibodies has helped in determining the clinical course, prognosis, and treatment approach. Understanding the unique clinical features, disease course, and treatments in pediatric patients is crucial for timely diagnosis and optimal outcomes. This article reviews the epidemiology, clinical features, diagnosis, treatment, and outcomes of the most common monophasic acquired demyelinating syndromes in children. Semin Pediatr Neurol 46:101050 Published by Elsevier Inc.
SEMINARS IN PEDIATRIC NEUROLOGY
(2023)
Article
Cell Biology
Bridget Shafit-Zagardo, Simone Sidoli, James E. Goldman, Juwen C. DuBois, John R. Corboy, Stephen M. Strittmatter, Hillary Guzik, Ukuemi Edema, Anita G. Arackal, Yair M. Botbol, Emilio Merheb, Rashed M. Nagra, Sarah Graff
Summary: During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. This study found that the insoluble protein TMEM106B, normally lysosome-associated, is insoluble in MS plaques relative to normal-appearing white matter from individuals with Alzheimer's disease and non-neurologic controls. Hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following experimental autoimmune encephalomyelitis.
Article
Multidisciplinary Sciences
Piet M. Bouman, Martijn D. Steenwijk, Jeroen J. G. Geurts, Laura E. Jonkman
Summary: Artificially generated DIR images from different MRI sequences were used to detect cortical multiple sclerosis lesions, showing potential as a substitute when conventional DIR images are unavailable. Incorporation of histopathological feedback improved accuracy in lesion detection.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Ruud L. van den Brink, Peter R. Murphy, Kobe Desender, Nicole de Ru, Sander Nieuwenhuis
Summary: Temporal expectations can speed up non-decisional processes but do not affect decision formation, as shown by modeling of behavioral data and electrophysiological recordings. Anticipatory x band power is modulated by temporal expectation and correlates with trial-by-trial variability in onset latency of the decision process in both behavioral and neural signatures.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Spring Flores Johnson, Pamela S. Klonoff, Ramaswamy Kavitha Perumparaichallai
Summary: This study examines the long-term outcomes of survivors with pediatric onset versus adult onset Acquired Brain Injury (ABI) who completed holistic milieu-oriented neurorehabilitation up to 30 years ago. It found that survivors, regardless of onset age, could benefit positively and enduringly from holistic neurorehabilitation. The study highlights the importance of early engagement in rehabilitative therapies for ABI survivors.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Saba Jafarpour, Abhik Banerjee, Natalie K. Boyd, Benjamin N. Vogel, Kelli C. Paulsen, Nusrat Ahsan, Wendy G. Mitchell, Shafali S. Jeste, Jonathan D. Santoro
Summary: This study identified rare gene variants implicated in immune dysregulation in pediatric autoimmune CNS diseases. Pathway analysis revealed an enrichment of NOD2-receptor signaling, suggesting a potential involvement of this pathway in these conditions.
JOURNAL OF NEUROLOGY
(2022)
Article
Immunology
Michelle Broekhuizen, Emilie Hitzerd, Thierry P. P. van den Bosch, Jasper Dumas, Robert M. Verdijk, Bas B. van Rijn, A. H. Jan Danser, Casper H. J. van Eijck, Irwin K. M. Reiss, Dana A. M. Mustafa
Summary: This study revealed distinct immunological alterations in early-onset preeclampsia compared to late-onset preeclampsia, with reduced expression of complement and Toll-like receptor associated genes, as well as decreased numbers of mast cells and M2 macrophages in early-onset preeclampsia placentas. Tailored treatments for each subtype may be desirable based on the differing immune profiles observed.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Giuseppe Locatelli, Filipa Marques-Ferreira, Antonis Katsoulas, Vasileia Kalaitzaki, Martin Krueger, Barbara Ingold-Heppner, Sabrina Walthert, Roman Sankowski, Olivia Prazeres da Costa, Amalia Dolga, Magdalena Huber, Maike Gold, Carsten Culmsee, Ari Waisman, Ingo Bechmann, Vladislava Milchevskaya, Marco Prinz, Achim Tresch, Burkhard Becher, Thorsten Buch
Summary: Research suggests that insulin-like growth factor 1 (IGF-1) signaling is not necessary for the function and survival of mature oligodendrocytes (ODCs) in the central nervous system (CNS). Lack of IGF-1 receptor in ODCs does not affect ODC survival and myelin status in toxin-induced and autoimmune demyelination models. Surprisingly, the absence of IGF-1 receptor in ODCs protects against clinical neuroinflammation in the autoimmune demyelination model.
Review
Cardiac & Cardiovascular Systems
Eloisa Arbustini, Elijah R. Behr, Lucie Carrier, Cornelia van Duijn, Paul Evans, Valentina Favalli, Pim van der Harst, Kristina Hermann Haugaa, Guillaume Jondeau, Stefan Kaab, Juan Pablo Kaski, Maryam Kavousi, Bart Loeys, Antonis Pantazis, Yigal Pinto, Heribert Schunkert, Alessandro Di Toro, Thomas Thum, Mario Urtis, Johannes Waltenberger, Perry Elliott
Summary: This article describes the importance of clinical criteria in interpreting genetic variants, using heritable Mendelian cardiomyopathies as an example. By conducting clinical family screening, clinicians can establish the relationship between genetic variants and phenotypes, thereby addressing the limitations of genetic testing. Collaboration between clinicians and patients plays a crucial role in resolving uncertainties and providing reliable and clinically useful information.
EUROPEAN HEART JOURNAL
(2022)
Article
Gastroenterology & Hepatology
Suk Yee Lam, Michiel C. Mommersteeg, Bingting Yu, Linda Broer, Manon C. W. Spaander, Fabian Frost, Stefan Weiss, Henry Voelzke, Markus M. Lerch, Ben Schoettker, Yan Zhang, Hannah Stocker, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Raitis Peculis, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, Andre Uitterlinden, Ernst J. Kuipers, Gwenny M. Fuhler, Georg Homuth, Maikel P. Peppelenbosch
Summary: The association between anti-H pylori IgG titers and the TLR1/6/10 locus was not replicated across different populations, and the variation at this locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes and neutrophils.
Article
Genetics & Heredity
R. J. Longchamps, S. Y. Yang, C. A. Castellani, W. Shi, J. Lane, M. L. Grove, T. M. Bartz, C. Sarnowski, C. Liu, K. Burrows, A. L. Guyatt, T. R. Gaunt, T. Kacprowski, J. Yang, P. L. De Jager, L. Yu, A. Bergman, R. Xia, M. Fornage, M. F. Feitosa, M. K. Wojczynski, A. T. Kraja, M. A. Province, N. Amin, F. Rivadeneira, H. Tiemeier, A. G. Uitterlinden, L. Broer, J. B. J. Van Meurs, C. M. Van Duijn, L. M. Raffield, L. Lange, S. S. Rich, R. N. Lemaitre, M. O. Goodarzi, C. M. Sitlani, A. C. Y. Mak, D. A. Bennett, S. Rodriguez, J. M. Murabito, K. L. Lunetta, N. Sotoodehnia, G. Atzmon, K. Ye, N. Barzilai, J. A. Brody, B. M. Psaty, K. D. Taylor, J. I. Rotter, E. Boerwinkle, N. Pankratz, D. E. Arking
Summary: Mitochondrial DNA copy number (mtDNA-CN) is a minimally invasive marker of mitochondrial function that can vary between individuals and cells. Through a genome-wide association study involving 465,809 White individuals, 133 SNPs associated with mtDNA-CN were identified across 100 loci. These SNPs were enriched for genes related to mitochondrial DNA depletion syndromes, mtDNA metabolism, and mtDNA replication. By leveraging pleiotropy between mtDNA-CN associated SNPs and various phenotypes, functional domains were identified, revealing three distinct groups of biological processes related to platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Furthermore, causal relationships were established between mitochondrial function and blood cell-related traits, kidney function, liver function, and overall and non-cancer mortality.
Review
Neurosciences
Giovanni B. Frisoni, Daniele Altomare, Dietmar Rudolf Thal, Federica Ribaldi, Rik van der Kant, Rik Ossenkoppele, Kaj Blennow, Jeffrey Cummings, Cornelia van Duijn, Peter M. Nilsson, Pierre-Yves Dietrich, Philip Scheltens, Bruno Dubois
Summary: The amyloid hypothesis has long been the leading model for the pathogenesis of Alzheimer's disease, but a probabilistic model is proposed as an alternative due to the increasing understanding of the complex biology of Alzheimer's disease. This new model suggests that genetic factors, environmental exposures, and lower-risk genes play significant roles in different types of Alzheimer's disease, leading to a better understanding of disease pathophysiology and potentially accelerating the development of prevention and treatment strategies.
NATURE REVIEWS NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Natalia Trpchevska, Maxim B. Freidin, Linda Broer, Berthe C. Oosterloo, Shuyang Yao, Yitian Zhou, Barbara Vona, Charles Bishop, Argyro Bizaki-Vallaskangas, Barbara Canlon, Fabio Castellana, Daniel I. Chasman, Stacey Cherny, Kaare Christensen, Maria Pina Concas, Adolfo Correa, Ran Elkon, Jonas Mengel-From, Yan Gao, Anne B. S. Giersch, Giorgia Girotto, Alexander Gudjonsson, Vilmundur Gudnason, Nancy L. Heard-Costa, Ronna Hertzano, Jacob v.B. Hjelmborg, Jens Hjerling-Leffler, Howard J. Hoffman, Jaakko Kaprio, Johannes Kettunen, Kristi Krebs, Anna K. Kahler, Francois Lallemend, Lenore J. Launer, I-Min Lee, Hampton Leonard, Chuan-Ming Li, Hubert Lowenheim, Patrik K. E. Magnusson, Joyce van Meurs, Lili Milani, Cynthia C. Morton, Antti Makitie, Mike A. Nalls, Giuseppe Giovanni Nardone, Marianne Nygaard, Teemu Palviainen, Sheila Pratt, Nicola Quaranta, Joel Ramo, Elmo Saarentaus, Rodolfo Sardone, Claudia L. Satizabal, John M. Schweinfurth, Sudha Seshadri, Eric Shiroma, Eldad Shulman, Eleanor Simonsick, Christopher Spankovich, Anke Tropitzsch, Volker M. Lauschke, Patrick F. Sullivan, Andre Goedegebure, Christopher R. Cederroth, Frances M. K. Williams, Andries Paul Nagtegaal
Summary: Hearing loss is a significant contributor to disability and a risk factor for dementia. By analyzing genetic data and mapping it to specific cells in the cochlea, this study identifies novel loci and highlights the importance of the stria vascularis in hearing impairment, offering potential targets for therapeutic intervention.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Obstetrics & Gynecology
Loes M. E. Moolhuijsen, Yvonne Louwers, Anke McLuskey, Linda Broer, Andre G. Uitterlinden, Renee M. G. Verdiesen, Ryan K. Sisk, Andrea Dunaif, Joop S. E. Laven, Jenny A. Visser
Summary: A novel AMH promoter polymorphism rs10406324 is associated with lower serum AMH levels in patients with PCOS, suggesting its role in the regulation of AMH gene expression.
HUMAN REPRODUCTION
(2022)
Article
Psychology, Clinical
Nicole Senft Everson, William M. P. Klein, Scott S. Lee, Rebecca Selove, Maureen Sanderson, William J. Blot, Rachel F. Tyndale, Stephen King, Karen Gilliam, Suman Kundu, Mark Steinwandel, Sarah J. Sternlieb, Shaneda Warren Andersen, Debra L. Friedman, Erin Connors, Mary Kay Fadden, Matthew S. Freiberg, Quinn S. Wells, Juan Canedo, Robert P. Young, Raewyn J. Scott, Ebele M. Umeukeje, Derek M. Griffith, Hilary A. Tindle
Summary: This study examines the different impacts of dispositional optimism and optimistic bias on smoking treatment engagement. The results show that dispositional optimism is associated with favorable outcomes, while optimistically-biased risk perception is associated with unfavorable outcomes. These findings highlight the distinct importance of these two constructs in smoking treatment.
Article
Rheumatology
Bahar Sedaghati-Khayat, Cindy G. Boer, Jos Runhaar, Sita M. A. Bierma-Zeinstra, Linda Broer, M. Arfan Ikram, Eleftheria Zeggini, Andre G. Uitterlinden, Jeroen G. J. van Rooij, Joyce B. J. van Meurs
Summary: This study examined the association between polygenic risk scores (PRS) and hip and knee osteoarthritis (OA) using data from population-based and clinical cohorts. The results showed a stronger association between PRS and clinically defined OA compared to radiographic OA phenotypes, with the highest risk stratification observed for total hip replacement (THR) or total knee replacement (TKR). These findings suggest that PRS-based risk assessment could play a role in preventing OA, but further studies are needed to test its integration in diverse healthcare settings.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Nutrition & Dietetics
Joelle E. Vergroesen, Tosca O. E. de Crom, Cornelia M. van Duijn, Trudy Voortman, Caroline C. W. Klaver, Wishal D. Ramdas
Summary: The study found that adherence to the MIND diet was associated with a lower incidence of open-angle glaucoma (iOAG), while adherence to the Mediterranean diet or Dutch dietary guidelines did not show significant associations with iOAG. Specifically, a higher intake of green leafy vegetables, berries, and fish was found to be protective against iOAG.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Cardiac & Cardiovascular Systems
Alexandra M. M. Filipkowski, Suman Kundu, Svetlana K. K. Eden, Charles W. W. Alcorn, Amy C. C. Justice, Kaku A. A. So-Armah, Hilary A. A. Tindle, Quinn S. S. Wells, Joshua A. A. Beckman, Matthew S. S. Freiberg, Aaron W. W. Aday
Summary: Compared with individuals without HIV infection, people with HIV do not have an increased risk of abdominal aortic aneurysm (AAA), but the risk of AAA is increased among HIV-infected individuals with low CD4+ T-cell counts or high HIV viral load.
Article
Endocrinology & Metabolism
Shylaja Srinivasan, Peitao Wu, Josep M. Mercader, Miriam S. Udler, Bianca C. Porneala, Traci M. Bartz, James S. Floyd, Colleen Sitlani, Xiquing Guo, Jeffrey Haessler, Charles Kooperberg, Jun Liu, Shahzad Ahmad, Cornelia van Duijn, Ching-Ti Liu, Mark O. Goodarzi, Jose C. Florez, James B. Meigs, Jerome Rotter, Stephen S. Rich, Josee Dupuis, Aaron Leong
Summary: In large biobank samples, a common variant polygenic score (PS) for type 1 diabetes (T1D) was not consistently associated with the prevalence of type 2 diabetes (T2D). However, possible heterogeneity in T2D cannot be ruled out and future studies are needed to further investigate subphenotyping.
JOURNAL OF THE ENDOCRINE SOCIETY
(2023)
Article
Genetics & Heredity
Stephanie L. Battle, Daniela Puiu, Eric Boerwinkle, Kent D. Taylor, Jerome Rotter, Stephan S. Rich, Megan L. Grove, Nathan Pankratz, Jessica L. Fetterman, Chunyu Liu, Dan E. Arking, Joost Verlouw, Linda Broer
Summary: This article presents a bioinformatics pipeline for identifying mitochondrial DNA variations and quantifying mitochondrial copy number, which more accurately captures the genetic features of mitochondria. The pipeline improves accuracy through methods such as remapping data, recovering reads, and using consensus chrM sequences.
NAR GENOMICS AND BIOINFORMATICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jeroen van Rooij, Annemieke Verkerk, Bahar Sedaghati-khayat, Linda Broer, Jard de Vries, Gaby van Dijk, Joyce van Meurs, Andre Uitterlinden
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Annemieke J. M. H. Verkerk, Jeroen van Rooij, Jard de Vries, Ans M. W. van de Ouweland, Maartje J. Hooning, Linda Broer, Willemina R. R. Geurts-Giele, Robert M. van der Helm, Robert M. W. Hofstra, Marieke F. van Dooren, J. Margriet Collee, E. H. Hoefsloot, Andre G. Uitterlinden, Joyce B. van Meurs
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Natalia Trpchevska, Neelke B. C. Oosterloo, Maxim B. Freydin, Linda Broer, Paul A. Nagtegaal, Andre Goedegebure, Christopher R. Cederroth, Frances M. K. Williams
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
