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Annals of the New York Academy of Sciences

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https://www.readbyqxmd.com/read/29341125/gut-microbiota-and-probiotics-novel-immune-system-modulators-in-myasthenia-gravis
#1
REVIEW
Elena Rinaldi, Alessandra Consonni, Elena Guidesi, Marina Elli, Renato Mantegazza, Fulvio Baggi
Gut microorganisms (microbiota) live in symbiosis with the host and influence human nutrition, metabolism, physiology, and immune development and function. The microbiota prevents pathogen infection to the host, and in turn the host provides a niche for survival. The alteration of gut bacteria composition (dysbiosis) could contribute to the development of immune-mediated diseases by influencing the immune system activation and driving the pro- and anti-inflammatory responses in order to promote or counteract immune reactions...
January 17, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29315608/clinical-and-research-strategies-for-limb-girdle-congenital-myasthenic-syndromes
#2
REVIEW
Emily O'Connor, Ana Töpf, René Zahedi, Sally Spendiff, Daniel Cox, Andreas Roos, Hanns Lochmüller
Congenital myasthenic syndromes (CMS) are a group of rare disorders that cause fatigable muscle weakness due to defective signal transmission at the neuromuscular junction, a specialized synapse between peripheral motor neurons and their target muscle fibers. There are now over 30 causative genes that have been reported for CMS. Of these, there are 10 that are associated with a limb-girdle pattern of muscle weakness and are thus classed as LG-CMS. Next-generation sequencing and advanced methods of data sharing are likely to uncover further genes that are associated with similar clinical phenotypes, contributing to better diagnosis and effective treatment of LG-CMS patients...
January 5, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29291259/age-related-changes-in-the-structure-and-function-of-mammalian-neuromuscular-junctions
#3
REVIEW
Silvia Willadt, Mark Nash, Clarke Slater
As mammals age, their neuromuscular junctions (NMJs) change their form, with an increasingly complex system of axonal branches innervating increasingly fragmented regions of postsynaptic differentiation. It has been suggested that this remodeling is associated with impairment of neuromuscular transmission and that this contributes to age-related muscle weakness in mammals, including humans. Here, we review previous work on NMJ aging, most of which has focused on either structure or function, as well as a new study aimed at seeking correlation between the structure and function of individual NMJs...
December 31, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29291257/aire-a-missing-link-to-explain-female-susceptibility-to-autoimmune-diseases
#4
REVIEW
Sonia Berrih-Aknin, Rozen Le Panse, Nadine Dragin
Women are more susceptible to autoimmune diseases than men. Autoimmunity results from tolerance breakdown toward self-components. Recently, three transcription modulators were identified in medullary thymic epithelial cells that orchestrate immune central tolerance processes: the autoimmune regulator (AIRE), FEZ family zinc finger 2 (FEZF2 or FEZ1), and PR domain zinc finger protein 1 (PRDM1). Interestingly, these three transcription modulators regulate nonredundant tissue-specific antigen subsets and thus cover broad antigen diversity...
December 31, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29291255/efficient-long-term-depletion-of-cd20-b-cells-by-rituximab-does-not-affect-gut-resident-plasma-cells
#5
Mathieu Uzzan, Huaibin M Ko, Adam K Rosenstein, Kamron Pourmand, Jean-Frederic Colombel, Saurabh Mehandru
The vast majority of antibody-producing B cells are located within the gastrointestinal tract and are key players in maintaining homeostasis. The failure of rituximab, a potent B cell-depleting agent, to ameliorate ulcerative colitis in a single clinical trial has dampened enthusiasm to study B cells in patients with inflammatory bowel disease (IBD). However, several lines of evidence suggest that intestinal B cells may be affected in IBD. Additionally, the pathophysiological mechanisms underlying rituximab's lack of efficacy in IBD remain unclear...
December 31, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29266270/cyp21a2-genetic-profile-in-14-egyptian-children-with-suspected-congenital-adrenal-hyperplasia-a-diagnostic-challenge
#6
Fatma Elmougy, Sahar Sharaf, Mona Hafez, Ahmed Khattab, Hazem Abou-Yousef, Marwa Elsharkawy, Heba Baz, Sherif Ekladious, Balsam Sherif, Noha Musa, Yasmin Elshiwy, Alaa Afif, Mona Abdullatif, Ghada Thabet, Normeen Rady, Amany Ibrahim, Hend Soliman
CYP21A2 genotyping remains an important element in the diagnosis and management of congenital adrenal hyperplasia, and establishing accurate genotype-phenotype correlations has facillitated adequate genetic counseling and prenatal management for at-risk families. Despite extensive efforts to establish a clear genotype-phenotype correlation, some discordance remains. Establishing a diagnosis of congenital adrenal hyperplasia on the basis of biochemical and clinical data is occasionally challenging, and the identification of CYP21A2 mutations may help confirm the diagnosis...
December 21, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29266255/myasthenia-gravis-with-antibodies-to-musk-an-update
#7
REVIEW
Amelia Evoli, Paolo E Alboini, Valentina Damato, Raffaele Iorio, Carlo Provenzano, Emanuela Bartoccioni, Mariapaola Marino
Myasthenia gravis with antibodies to the muscle-specific tyrosine kinase (MuSK+ MG) is a rare disease with distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very common and highly suggestive of the disease. On the other hand, a more indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. Though MuSK+ MG is still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment...
December 21, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29266249/myasthenia-gravis-the-role-of-complement-at-the-neuromuscular-junction
#8
REVIEW
James F Howard
Generalized myasthenia gravis (gMG) is a rare autoimmune disorder characterized by skeletal muscle weakness caused by disrupted neurotransmission at the neuromuscular junction (NMJ). Approximately 74-88% of patients with gMG have acetylcholine receptor (AChR) autoantibodies. Complement plays an important role in innate and antibody-mediated immunity, and activation and amplification of complement results in the formation of membrane attack complexes (MACs), lipophilic proteins that damage cell membranes. The role of complement in gMG has been demonstrated in animal models and patients...
December 21, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29194650/evolution-on-the-bright-side-of-life-microorganisms-and-the-evolution-of-mutualism
#9
REVIEW
Kristina Linnea Hillesland
Mutualistic interactions, where two interacting species have a net beneficial effect on each other's fitness, play a crucial role in the survival and evolution of many species. Despite substantial empirical and theoretical work in past decades, the impact of these interactions on natural selection is not fully understood. In addition, mutualisms between microorganisms have been largely ignored, even though they are ecologically important and can be used as tools to bridge the gap between theory and empirical work...
November 30, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29155442/safety-of-folic-acid
#10
Martha S Field, Patrick J Stover
There is a large body of literature demonstrating the efficacy of maternal folic acid intake in preventing birth defects, as well as investigations into potential adverse consequences of consuming folic acid above the upper intake level (UL). Recently, two authoritative bodies convened expert panels to assess risks from high intakes of folic acid: the U.S. National Toxicology Program and the UK Scientific Advisory Committee on Nutrition. Overall, the totality of the evidence examined by these panels, as well as studies published since the release of their reports, have not established risks for adverse consequences resulting from existing mandatory folic acid fortification programs that have been implemented in many countries...
November 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29148577/mouse-models-to-evaluate-the-role-of-estrogen-receptor-%C3%AE-in-skeletal-maintenance-and-adaptation
#11
REVIEW
Amanda M Rooney, Marjolein C H van der Meulen
Estrogen signaling and mechanical loading have individual and combined effects on skeletal maintenance and adaptation. Previous work investigating estrogen signaling both in vitro and in vivo using global estrogen receptor α (ERα) gene knockout mouse models has provided information regarding the role of ERα in regulating bone mass and adaptation to mechanical stimulation. However, these models have inherent limitations that confound interpretation of the data. Therefore, recent studies have focused on mice with targeted deletion of ERα from specific bone cells and their precursors...
November 17, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29139138/folate-status-in-women-of-reproductive-age-as-basis-of-neural-tube-defect-risk-assessment
#12
Lynn B Bailey, Dorothy B Hausman
Reliable folate status data for women of reproductive age (WRA) to assess global risk for neural tube defects (NTDs) are needed. We focus on a recent recommendation by the World Health Organization that a specific "optimal" red blood cell (RBC) folate concentration be used as the sole indicator of NTD risk within a population and discuss how to best apply this guidance to reach the goal of assessing NTD risk globally. We also emphasize the importance of using the microbiologic assay (MBA) as the most reliable assay for obtaining comparable results for RBC folate concentration across time and countries, the need for harmonization of the MBA through use of consistent key reagents and procedures within laboratories, and the requirement to apply assay-matched cutoffs for folate deficiency and insufficiency...
November 15, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125190/lambert-eaton-myasthenic-syndrome-mouse-passive-transfer-model-illuminates-disease-pathology-and-facilitates-testing-therapeutic-leads
#13
REVIEW
Stephen D Meriney, Tyler B Tarr, Kristine S Ojala, Man Wu, Yizhi Li, David Lacomis, Adolfo Garcia-Ocaña, Mary Liang, Guillermo Valdomir, Peter Wipf
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder caused by antibodies directed against the voltage-gated calcium channels that provide the calcium ion flux that triggers acetylcholine release at the neuromuscular junction. To study the pathophysiology of LEMS and test candidate therapeutic strategies, a passive-transfer animal model has been developed in mice, which can be created by daily intraperitoneal injections of LEMS patient serum or IgG into mice for 2-4 weeks. Results from studies of the mouse neuromuscular junction have revealed that each synapse has hundreds of transmitter release sites but that the probability for release at each one is likely to be low...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125188/the-mouse-passive-transfer-model-of-musk-myasthenia-gravis-disrupted-musk-signaling-causes-synapse-failure
#14
REVIEW
Nazanin Ghazanfari, Sofie Trajanovska, Marco Morsch, Simon X Liang, Stephen W Reddel, William D Phillips
While the majority of myasthenia gravis patients express antibodies targeting the acetylcholine receptor, the second most common cohort instead displays autoantibodies against muscle-specific kinase (MuSK). MuSK is a transmembrane tyrosine kinase found in the postsynaptic membrane of the neuromuscular junction. During development, MuSK serves as a signaling hub, coordinating the alignment of the pre- and postsynaptic components of the synapse. Adult mice that received repeated daily injections of IgG from anti-MuSK(+) myasthenia gravis patients developed muscle weakness, associated with neuromuscular transmission failure...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125186/evolutionary-dynamics-of-interactions-between-plants-and-their-enemies-comparison-of-herbivorous-insects-and-pathogens
#15
REVIEW
Kerry Wininger, Nathan Rank
Plants colonized land over 400 million years ago. Shortly thereafter, organisms began to consume terrestrial plant tissue as a nutritional resource. Most plant enemies are plant pathogens or herbivores, and they impose natural selection for plants to evolve defenses. These traits generate selection pressures on enemies. Coevolution between terrestrial plants and their enemies is an important element of the evolutionary history of both groups. However, coevolutionary studies of plant-pathogen interactions have tended to focus on different research topics than plant-herbivore interactions...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125185/thymus-involvement-in-early-onset-myasthenia-gravis
#16
REVIEW
Mélanie A Cron, Solène Maillard, José Villegas, Frédérique Truffault, Muriel Sudres, Nadine Dragin, Sonia Berrih-Aknin, Rozen Le Panse
It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125182/circulating-micrornas-as-potential-biomarkers-in-myasthenia-gravis-patients
#17
REVIEW
Anna Rostedt Punga, Tanel Punga
MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR(+) ) or muscle-specific tyrosine kinase (MuSK(+) ) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125180/exosomes-biology-therapeutic-potential-and-emerging-role-in-musculoskeletal-repair-and-regeneration
#18
REVIEW
Neil J Cobelli, Daniel J Leong, Hui B Sun
Exosomes are nanovesicles secreted from cells that play key roles in intercellular communication. They carry unique content derived from parental cells and are capable of transferring this cargo between cells. The role and function of exosomes largely depends on the origin and functional status of the parental cells. Emerging evidence indicates that exosomes are associated with biological processes and pathogenesis of certain diseases. These nanovesicles offer great potential as biomarkers, enabling the monitoring and diagnosis of various diseases in a noninvasive manner...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29125179/the-impact-of-sociodemography-diet-and-body-size-on-serum-retinol-in-women-16-35-years-of-age-sanhanes-1
#19
Whadi-Ah Parker, Zandile J Mchiza, Ronel Sewpaul, Nophiwe Job, Lumbwe Chola, Moses Sithole, Demetre Labadarios
To determine the current vitamin A status of a nationally representative sample of women aged 16-35 years, compare it with previous national data, and determine the impact of sociodemography, diet, and body size on vitamin A status, we performed secondary analysis of data on South African women who participated in the first South African National Health and Nutrition Examination Survey (SANHANES-1). Vitamin A status was assessed by serum retinol, and the findings are reported as means and prevalences with corresponding 95% confidence intervals...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29121404/the-association-of-british-neurologists-myasthenia-gravis-guidelines
#20
Jon Sussman, Maria E Farrugia, Paul Maddison, Marguerite Hill, M Isabel Leite, David Hilton-Jones
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence-based medicine. Despite the basic principles of treatment being well known, patients continue to receive suboptimal treatment. A myasthenia gravis guidelines group was therefore established under the aegis of the Association of British Neurologists. These guidelines attempt to steer a path between evidence-based practice where available and established best practice where evidence is unavailable...
November 9, 2017: Annals of the New York Academy of Sciences
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