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Annals of the New York Academy of Sciences

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https://www.readbyqxmd.com/read/29155442/safety-of-folic-acid
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/29106710/investigating-metabolic-regulation-using-targeted-neuromodulation
#12
REVIEW
Kavya Devarakonda, Sarah Stanley
The central nervous system (CNS) plays a vital role in regulating energy balance and metabolism. Over the last 50 years, studies in animal models have allowed us to identify critical CNS regions involved in these processes and even crucial cell populations. Now, techniques for genetically and anatomically targeted manipulation of specific neural populations using light (optogenetic), ligands (chemogenetic), or magnetic fields (radiogenetic/magnetogenetic) allow detailed investigation of circuits involved in metabolic regulation...
November 6, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29090837/biological-plausibility-of-the-gut-brain-axis-in-autism
#13
Alex Vasquez
Organic abnormalities with neuroinflammatory and psychiatric consequences involving abnormal kynurenine and purine metabolism, neurotransmitter and cytokine imbalances, and altered levels of nutrients and metabolites are noted in autism, and many of these abnormalities-specifically including increased intestinal permeability, microbial metabolites, and heightened serum levels of endotoxin-originate from the gut.
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29090836/recent-developments-on-intramedullary-nailing-a-biomechanical-perspective
#14
REVIEW
Natacha Rosa, Miguel Marta, Mário Vaz, S M O Tavares, Ricardo Simoes, Fernão D Magalhães, Antonio Torres Marques
Combining contributions from engineering and medicine, we highlight the biomechanical turning points in the historical evolution of the intramedullary nailing stabilization technique and discuss the recent innovations concerning increase in bone-implant system stability. Following the earliest attempts, where stabilization of long bone fractures was purely based on intuition, intramedullary nailing evolved from allowing alignment and translational control through press-fit fixation to current clinical widespread acceptance marked by the mechanical linkage between nail and bone with interlocking screws that allow alignment, translation, rotation, and length control...
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29090833/equivalence-and-regulatory-approaches-of-nonbiological-complex-drug-products-across-the-united-states-the-european-union-and-turkey
#15
REVIEW
Z Gulsen Oner, Sarah L J Michel, James E Polli
Regulatory agencies around the world may have different standards and approaches to evaluate and approve drug products and biological products. We describe the U.S. Food and Drug Administration's (FDA) Generic Drug User Fee Act program, as well as their approach to complex products. We discuss regulatory approaches for the development of nonbiological complex drug follow-ons and approval pathways in the United States. We compare FDA policies with other regulatory agencies (i.e., the European Medicines Agency and the Turkish Medicines and Medical Devices Agency)...
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29090832/sustaining-attention-to-simple-visual-tasks-a-central-deficit-in-schizophrenia-a-systematic-review
#16
REVIEW
Marc Hoonakker, Nadège Doignon-Camus, Anne Bonnefond
Impairments in sustained attention, that is, the ability to achieve and maintain the focus of cognitive activity on a given stimulation source or task, have been described as central to schizophrenia. Today, sustained attention deficit is still considered as a hallmark of schizophrenia. Nevertheless, current findings on this topic are not consistent. To clarify these findings, we attempt to put these results into perspective according to the type of assessment (i.e., overall and over time assessment), the participants' characteristics (i...
November 1, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29068559/neuromuscular-synapse-electrophysiology-in-myasthenia-gravis-animal-models
#17
REVIEW
Jaap J Plomp, Maartje G M Huijbers, Jan J G M Verschuuren
The neuromuscular junction (NMJ) forms the synaptic connection between a motor neuron and a skeletal muscle fiber. In order to achieve a sustained muscle contraction, this synapse has to reliably transmit motor neuronal action potentials onto the muscle fiber. To guarantee successful transmission even during intense activation of the NMJ, a safety factor of neuromuscular transmission exists. In the neuromuscular disorder myasthenia gravis (MG), autoantibodies are directed against acetylcholine receptors or, in the rarer variants, against other postsynaptic NMJ proteins...
October 25, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29068555/diagnostic-utility-of-cortactin-antibodies-in-myasthenia-gravis
#18
REVIEW
Isabel Illa, Elena Cortés-Vicente, María Ángeles Martínez, Eduard Gallardo
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG). We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG. We then designed an in-house enzyme-linked immunosorbent assay as a screening assay and confirmed these results by western blot...
October 25, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29068540/the-molecular-cross-talk-of-the-dystrophin-glycoprotein-complex
#19
REVIEW
Marta Gawor, Tomasz J Prószyński
The proper function of skeletal muscles relies on their ability to process signals derived from motor neurons, transmit stimuli along the muscle fibers, contract, and regenerate efficiently after injury. The dystrophin-glycoprotein complex (DGC; also called the dystrophin-associated protein complex) plays a central role in all of these processes. It acts as a transmembrane platform that anchors the extracellular matrix (ECM) to the intracellular cytoskeleton and makes muscle fibers more resistant to injury...
October 25, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29068534/freezing-does-not-alter-multiscale-tendon-mechanics-and-damage-mechanisms-in-tension
#20
Andrea H Lee, Dawn M Elliott
It is common in biomechanics to use previously frozen tissues, where it is assumed that the freeze-thaw process does not cause consequential mechanical or structural changes. We have recently quantified multiscale tendon mechanics and damage mechanisms using previously frozen tissue, where damage was defined as an irreversible change in the microstructure that alters the macroscopic mechanical parameters. Because freezing has been shown to alter tendon microstructures, the objective of this study was to determine if freezing alters tendon multiscale mechanics and damage mechanisms...
October 25, 2017: Annals of the New York Academy of Sciences
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