Search our Database of Scientific Publications and Authors

I’m looking for a

    48753 results match your criteria Annals of the New York Academy of Sciences[Journal]

    1 OF 976

    Factors associated with nutritional status and dietary practices of Bangladeshi adolescents in early pregnancy.
    Ann N Y Acad Sci 2018 Feb 18. Epub 2018 Feb 18.
    Department of Nutrition, University of California, Davis, Davis, California.
    Bangladesh has a high prevalence of adolescent pregnancy, but little is known about the nutritional status and dietary practices of Bangladeshi adolescents in early pregnancy or associated factors. We used the baseline data of 1552 pregnant adolescents from a longitudinal, cluster-randomized effectiveness trial conducted in northwest Bangladesh. Forty-four percent of the adolescents were short for their age, 36% had low body mass index, 28% were anemic, 10% had iron deficiency, and 32% had vitamin A deficiency. Read More

    A public health approach for preventing neural tube defects: folic acid fortification and beyond.
    Ann N Y Acad Sci 2018 Feb 16. Epub 2018 Feb 16.
    Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, Georgia.
    In this paper we review the evidence basis for prevention of folic acid-sensitive neural tube defects (NTDs) through public health interventions in women of reproductive age (WRA), the proven vehicles for delivery of folic acid, and what is needed to effectively scale these, and provide a snapshot of potential innovations that require future research. Our primary focus is on the global situation affecting large-scale food fortification (LSFF) with folic acid, in particular the fortification of wheat flour and maize meal. Our overarching conclusion is that folic acid fortification is an evidence-based intervention that reduces the prevalence of NTDs, and that LSFF with folic acid is underutilized. Read More

    The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics.
    Ann N Y Acad Sci 2018 Feb 15. Epub 2018 Feb 15.
    Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois.
    Multidrug resistant Gram-negative bacterial infections are on the rise, and there is a lack of new classes of drugs to treat these pathogens. This drug shortage is largely due to the challenge of finding antibiotics that can permeate and persist inside Gram-negative species. Efforts to understand the molecular properties that enable certain compounds to accumulate in Gram-negative bacteria based on retrospective studies of known antibiotics have not been generally actionable in the development of new antibiotics. Read More

    Toward a multifactorial model of expertise: beyond born versus made.
    Ann N Y Acad Sci 2018 Feb 15. Epub 2018 Feb 15.
    Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
    The debate over the origins of individual differences in expertise has raged for over a century in psychology. The "nature" view holds that expertise reflects "innate talent"-that is, genetically determined abilities. The "nurture" view counters that, if talent even exists, its effects on ultimate performance are negligible. Read More

    Biogeographic constraints to marine conservation in a changing climate.
    Ann N Y Acad Sci 2018 Feb 7. Epub 2018 Feb 7.
    Bren School of Environmental Science & Management, University of California, Santa Barbara, Santa Barbara, California.
    The siting of protected areas to achieve management and conservation objectives draws heavily on biogeographic concepts of the spatial distribution and connectivity of species. However, the marine protected area (MPA) literature rarely acknowledges how biogeographic theories underpin MPA and MPA network design. We review which theories from biogeography have been incorporated into marine spatial planning and which relevant concepts have yet to be translated to inform the next generation of design principles. Read More

    Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms.
    Ann N Y Acad Sci 2018 Feb;1413(1):104-110
    CNRS 8119, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
    The neuromuscular junction (NMJ) is a cholinergic synapse in vertebrates. This synapse connects motoneurons to muscles and is responsible for muscle contraction, a physiological process that is essential for survival. A key factor for the normal functioning of this synapse is the regulation of acetylcholine (ACh) levels in the synaptic cleft. Read More

    An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor-positive myasthenia gravis patients.
    Ann N Y Acad Sci 2018 Feb 24;1413(1):154-162. Epub 2018 Jan 24.
    UPMC Sorbonne Universities, Paris, France.
    A chronic autoimmune disease, myasthenia gravis (MG) is characterized in 85% of patients by antibodies directed against the acetylcholine receptor (AChR) located at the neuromuscular junction. The functional and effective balance between regulatory T cells (Tcells) and effector T cells (Tcells) is lost in the hyperplastic thymus of MG patients with antibodies specific for the AChR (AChRMG patients). The objective of this review is to describe how Tcells and inflammatory T cells participate in this imbalance and contribute to induce a chronic inflammatory state in the MG thymus. Read More

    Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications.
    Ann N Y Acad Sci 2018 Feb 5. Epub 2018 Feb 5.
    Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
    Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. Read More

    Developing treatment guidelines for myasthenia gravis.
    Ann N Y Acad Sci 2018 Jan;1412(1):95-101
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
    A task force of the Myasthenia Gravis Foundation of America recently published a formal consensus statement intended to be a treatment guide for clinicians caring for myasthenia gravis (MG) patients worldwide. Its development was stimulated by the fact that there is generally no accepted standard of care for MG, and no one treatment is best for all MG patients. Also, there are few randomized trials of treatments in current use, and the generalizability of the few trials that have been successful may be difficult. Read More

    Therapeutic strategies for congenital myasthenic syndromes.
    Ann N Y Acad Sci 2018 Jan;1412(1):129-136
    Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom.
    To date, more than 25 genes have been implicated in the etiology of the congenital myasthenic syndromes (CMS), and an ever-growing phenotypic landscape is now encountered in the CMS clinic. Unlike the autoimmune form of myasthenia, there is no role for immunomodulatory agents in the treatment of CMS. The present-day drug repertoire comprises acetylcholinesterase inhibitors (mainly pyridostigmine), 3,4-diaminopyridine (3,4-DAP), ephedrine, salbutamol/albuterol, open-channel blockers (fluoxetine, quinidine), or a combination of these. Read More

    Mechanisms underlying B cell immune dysregulation and autoantibody production in MuSK myasthenia gravis.
    Ann N Y Acad Sci 2018 Jan;1412(1):154-165
    Department of Neurology, Yale School of Medicine, New Haven, Connecticut.
    Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with myasthenia gravis (MG) who do not have detectable antibodies to the acetylcholine receptor. Although the autoantibody-mediated pathology is well understood, much remains to be learned about the cellular immunology that contributes to autoantibody production. To that end, our laboratory has investigated particular components associated with the cellular immunopathology of MuSK MG. Read More

    Western lifestyle and immunopathology of multiple sclerosis.
    Ann N Y Acad Sci 2018 Jan 27. Epub 2018 Jan 27.
    VIB Laboratory of Translational Immunomodulation, Center for Inflammation Research, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
    There is increasing evidence for a sudden and unprecedented rise in the incidence of multiple sclerosis (MS) in Westernized countries over the past decades, emphasizing the role of environmental factors. Among many candidates, rapid changes in dietary habits seem to play a role in the pathogenesis of MS. Here, we summarize and discuss the available evidence for the role of dietary nutrients, such as table salt, fatty acids, and flavonoids, in the development and pathogenesis of MS. Read More

    Should vitamin Bstatus be considered in assessing risk of neural tube defects?
    Ann N Y Acad Sci 2018 Jan 29. Epub 2018 Jan 29.
    School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.
    There is a strong biological premise for including vitamin Bwith folic acid in strategies to prevent neural tube defects (NTDs), due to the closely interlinked metabolism of these two vitamins. For example, reduction of Bdeficiency among women of reproductive age could enhance the capacity of folic acid to prevent NTDs by optimizing the cellular uptake and utilization of natural folate cofactors. Vitamin Bmight also have an independent role in NTD prevention, such that adding it in fortification programs might be more effective than fortifying with folic acid alone. Read More

    Update on management of diabetic foot ulcers.
    Ann N Y Acad Sci 2018 Jan;1411(1):153-165
    Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
    Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5-year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular assessment, and infection and glycemic control. Read More

    Cardiometabolic risk in obese children.
    Ann N Y Acad Sci 2018 Jan;1411(1):166-183
    Division of Pediatric Endocrinology and Diabetes, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC.
    Obesity in childhood remains a significant and prevalent public health concern. Excess adiposity in youth is a marker of increased cardiometabolic risk (CMR) in adolescents and adults. Several longitudinal studies confirm the strong association of pediatric obesity with the persistence of adult obesity and the future development of cardiovascular disease, diabetes, and increased risk of death. Read More

    Precision medicine in diabetes: an opportunity for clinical translation.
    Ann N Y Acad Sci 2018 Jan;1411(1):140-152
    Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
    Metabolic disorders present a public health challenge of staggering proportions. In diabetes, there is an urgent need to better understand disease heterogeneity, clinical trajectories, and related comorbidities. A pressing and timely question is whether we are ready for precision medicine in diabetes. Read More

    Piecing together the puzzle of pancreatic islet adaptation in pregnancy.
    Ann N Y Acad Sci 2018 Jan;1411(1):120-139
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, and the Comprehensive Diabetes Center, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
    Pregnancy places acute demands on maternal physiology, including profound changes in glucose homeostasis. Gestation is characterized by an increase in insulin resistance, counterbalanced by an adaptive increase in pancreatic β cell production of insulin. Failure of normal adaptive responses of the islet to increased maternal and fetal demands manifests as gestational diabetes mellitus (GDM). Read More

    Updates on obesity pharmacotherapy.
    Ann N Y Acad Sci 2018 Jan;1411(1):106-119
    Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts.
    Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short-term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. Read More

    Distinct patterns of gene expression in human cardiac fibroblasts exposed to rapamycin treatment or methionine restriction.
    Ann N Y Acad Sci 2018 Jan 28. Epub 2018 Jan 28.
    Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
    Both methionine restriction and rapamycin treatment are robust longevity-enhancing regimens for which the mechanisms remain unclear. Cellular senescence is a major contributor to the aging process, and we find that both the methionine and rapamycin regimens delay or prevent activation of the senescence program in human cells. Using a transcriptome-wide analysis, we examined the impact of methionine restriction and rapamycin treatment on senescence-associated gene expression in human cardiac fibroblasts. Read More

    Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):126-135. Epub 2018 Jan 28.
    Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
    Myasthenia gravis (MG) is a common disorder that affects the neuromuscular junction. It is caused by antibodies against acetylcholine receptor and muscle-specific tyrosine kinase; however, some MG patients do not have antibodies against either of the proteins. Recent studies have revealed antibodies against agrin and its receptor LRP4-both critical for neuromuscular junction formation and maintenance-in MG patients from various populations. Read More

    Acetylcholine receptor-specific immunosuppressive therapy of experimental autoimmune myasthenia gravis and myasthenia gravis.
    Ann N Y Acad Sci 2018 Feb 29;1413(1):76-81. Epub 2018 Jan 29.
    Department of Neuroscience, Medical School of the University of Pennsylvania, Philadelphia, Pennsylvania.
    Experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG) are caused by autoantibodies to the extracellular domain of muscle nicotinic acetylcholine receptors (AChRs). Autoantibodies to the cytoplasmic domain of AChRs do not cause EAMG because they cannot bind AChRs in vivo. The ideal MG therapy would quickly and permanently suppress only the pathological autoimmune response to AChRs. Read More

    Challenging the current model of early-onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):82-91. Epub 2018 Jan 28.
    Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
    The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. Read More

    Pathophysiological mechanisms of autoimmunity.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):59-68. Epub 2018 Jan 28.
    INSERM U974, Paris, France.
    Autoimmune diseases (AIDs) are chronic disorders characterized by inflammatory reactions against self-antigens that can be either systemic or organ specific. AIDs can differ in their epidemiologic features and clinical presentations, yet all share a remarkable complexity. AIDs result from an interplay of genetic and epigenetic factors with environmental components that are associated with imbalances in the immune system. Read More

    Therapeutic applications of betulinic acid nanoformulations.
    Ann N Y Acad Sci 2018 Jan 29. Epub 2018 Jan 29.
    Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
    Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad-spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half-life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half-life, and efficacy by using nanoscale drug delivery systems. Read More

    Sulfur amino acid restriction-induced changes in redox-sensitive proteins are associated with slow protein synthesis rates.
    Ann N Y Acad Sci 2018 Jan 29. Epub 2018 Jan 29.
    Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
    The mechanisms underlying life span extension by sulfur amino acid restriction (SAAR) are unclear. Cysteine and methionine are essential for the biosynthesis of proteins and glutathione (GSH), a major redox buffer in the endoplasmic reticulum (ER). We hypothesized that SAAR alters protein synthesis by modulating the redox milieu. Read More

    Serological and experimental studies in different forms of myasthenia gravis.
    Ann N Y Acad Sci 2018 Feb 29;1413(1):143-153. Epub 2018 Jan 29.
    Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
    Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Read More

    IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):92-103. Epub 2018 Jan 28.
    Departments of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
    Immunoglobulin 4 (IgG4) is one of four human IgG subclasses and has several unique functional characteristics. It exhibits low affinity for complement and for most Fc receptors. It furthermore has generally high affinity for its antigen, with binding occurring in a monovalent fashion, as IgG4 can exchange Fab-arms with other IgG4 molecules. Read More

    Comparative effectiveness clinical trials to advance treatment of myasthenia gravis.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):69-75. Epub 2018 Jan 28.
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
    Myasthenia gravis (MG) presents many challenges for establishing treatment efficacy through clinical trials. Among these are the rarity and heterogeneity of the disease, spontaneous fluctuations, prolonged latency to effect for many immunosuppressive drugs, and the uncertain generalizability of results from randomized controlled trials (RCTs). Prospective observational study designs may overcome some of these limitations, but attention is required to ensure that internal validity is not compromised. Read More

    Clinical trials for myasthenia gravis: a historical perspective.
    Ann N Y Acad Sci 2018 Feb 27;1413(1):5-10. Epub 2018 Jan 27.
    Department of Neurology, GW-Medical Faculty Associates, George Washington University, Washington, DC.
    Symposia dedicated to myasthenia gravis and related disorders date back to 1947 and serve as markers of the progress for the field. We provide a brief historical review of therapy development through the lens of the publications that arose from the close to quinquennial meetings that have been supported nearly since their inception by the Myasthenia Gravis Foundation of America and the New York Academy of Sciences. One can appreciate great advances, false starts, and dead ends that are found in all fields of medicine. Read More

    A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):119-125. Epub 2018 Jan 28.
    Department of Medicine and Rehabilitation, University of California Davis, Sacramento, California.
    We report a severe defect of neuromuscular transmission in a consanguineous patient with a homozygous variant in the laminin α5 subunit gene (LAMA5). The variant c.8046C > T (p. Read More

    Rationale for the clinical guidelines for myasthenia gravis in Japan.
    Ann N Y Acad Sci 2018 Feb 28;1413(1):35-40. Epub 2018 Jan 28.
    Medical Engineering Course, Department of Engineering, The Faculty of Engineering, Nagasaki Institute of Applied Science, Nagasaki, Japan.
    According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients' health-related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. Read More

    Cardioprotective effects of dietary rapamycin on adult female C57BLKS/J-Leprmice.
    Ann N Y Acad Sci 2018 Jan 29. Epub 2018 Jan 29.
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.
    Rapamycin (RAPA), an inhibitor of mTORC signaling, has been shown to extend life span in mice and other organisms. Recently, animal and human studies have suggested that inhibition of mTORC signaling can alleviate or prevent the development of cardiomyopathy. In view of this, we used a murine model of type 2 diabetes (T2D), BKS-Lepr, to determine whether RAPA treatment can mitigate the development of T2D-induced cardiomyopathy in adult mice. Read More

    Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.
    Ann N Y Acad Sci 2018 Jan 28. Epub 2018 Jan 28.
    Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, Michigan.
    The endoplasmic reticulum (ER) is broadly distributed throughout the cytoplasm of pancreatic beta cells, and this is where all proinsulin is initially made. Healthy beta cells can synthesize 6000 proinsulin molecules per second. Ordinarily, nascent proinsulin entering the ER rapidly folds via the formation of three evolutionarily conserved disulfide bonds (B7-A7, B19-A20, and A6-A11). Read More

    Framework for laboratory harmonization of folate measurements in low- and middle-income countries and regions.
    Ann N Y Acad Sci 2018 Jan 29. Epub 2018 Jan 29.
    Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
    The measurement of serum and red blood cell folate, two commonly used biomarkers of folate status in populations, is complicated by analytical and data interpretation challenges. Folate results show poor comparability across laboratories, even using the same analytical technique. The folate microbiologic assay produces accurate results and requires simple instrumentation. Read More

    Rituximab in myasthenia gravis: a "to be or not to be" inhibitor of T cell function.
    Ann N Y Acad Sci 2018 Feb 25;1413(1):41-48. Epub 2018 Jan 25.
    Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy.
    In recent years, rituximab (RTX), a monoclonal antibody that binds the B lymphocyte membrane protein CD20, has been increasingly used for the treatment of autoimmune diseases, with the rationale of destroying pathogenic B lymphocytes and decreasing autoantibody formation. Surprisingly, RTX has also proven effective in predominantly T cell-mediated diseases, raising the question whether additional mechanisms may play roles in determining the therapeutic response. Here, we review the current literature on the effects of RTX in autoimmune diseases, with special emphasis on myasthenia gravis (MG). Read More

    Revisiting the genomic hypomethylation hypothesis of aging.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
    The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans. We critically reviewed the publications on the effect of age on DNA methylation and the expression of the enzymes involved in DNA methylation to evaluate the validity of the hypomethylation hypothesis of aging. Read More

    Genetic constraints on adaptation: a theoretical primer for the genomics era.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    School of Biological Sciences, and Centre for Geometric Biology, Monash University, Clayton, Victoria, Australia.
    Genetic constraints are features of inheritance systems that slow or prohibit adaptation. Several population genetic mechanisms of constraint have received sustained attention within the field since they were first articulated in the early 20th century. This attention is now reflected in a rich, and still growing, theoretical literature on the genetic limits to adaptive change. Read More

    Quantitative genetic methods depending on the nature of the phenotypic trait.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    School of Biological Sciences, University of Auckland, Auckland, New Zealand.
    A consequence of the assumptions of the infinitesimal model, one of the most important theoretical foundations of quantitative genetics, is that phenotypic traits are predicted to be most often normally distributed (so-called Gaussian traits). But phenotypic traits, especially those interesting for evolutionary biology, might be shaped according to very diverse distributions. Here, I show how quantitative genetics tools have been extended to account for a wider diversity of phenotypic traits using first the threshold model and then more recently using generalized linear mixed models. Read More

    Gene regulatory mechanisms underlying sex differences in brain development and psychiatric disease.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
    The sexual differentiation of the mammalian nervous system requires the precise coordination of the temporal and spatial regulation of gene expression in diverse cell types. Sex hormones act at multiple developmental time points to specify sex-typical differentiation during embryonic and early development and to coordinate subsequent responses to gonadal hormones later in life by establishing sex-typical patterns of epigenetic modifications across the genome. Thus, mutations associated with neuropsychiatric conditions may result in sexually dimorphic symptoms by acting on different neural substrates or chromatin landscapes in males and females. Read More

    Toll-like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?
    Ann N Y Acad Sci 2018 Feb 24;1413(1):11-24. Epub 2018 Jan 24.
    Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan, Italy.
    Pathogen infections and dysregulated Toll-like receptor (TLR)-mediated innate immune responses are suspected to play key roles in autoimmunity. Among TLRs, TLR7 and TLR9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal B cell activation and survival. Recently, we provided evidence of Epstein-Barr virus (EBV) persistence and reactivation in the thymus of myasthenia gravis (MG) patients, suggesting an involvement of EBV in the intrathymic pathogenesis of the disease. Read More

    Lessons from animal nutritionists: dietary amino acid requirement studies and considerations for healthy aging studies.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Department of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, Ontario, Canada.
    Dietary restriction (DR) increases median life span and protects against age-related disease. Improved longevity can be achieved by restriction of dietary energy, protein, or amino acids (AAs), such as methionine (Met). Met requirements have been defined using methodologies that measure the dose response to Met when all other dietary variables are held constant and with outcomes focused on protein turnover. Read More

    The role of autophagy in the regulation of yeast life span.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Department of Biology, Orentreich Foundation for the Advancement of Science, Cold Spring, New York.
    The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disease. While organismal aging is a complex, multifactorial process, a popular theory is that cellular aging is a significant contributor to the progressive decline inherent to all multicellular organisms. To explore the molecular determinants that drive cellular aging, as well as how to retard them, researchers have utilized the highly genetically tractable budding yeast Saccharomyces cerevisiae. Read More

    The investment case for folic acid fortification in developing countries.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Division of Nutritional Sciences and Charles H. Dyson School of Applied Economics and Management, Cornell University, Ithaca, New York.
    There is compelling evidence that neural tube defects can be prevented through mandatory folic acid fortification. Why, then, is an investment case needed? At the core of the answer to this question is the notion that governments and individuals have limited resources for which there are many competing claims. An investment case compares the costs and benefits of folic acid fortification relative to alternative life-saving investments and informs estimates of the financing required for implementation. Read More

    Myasthenic syndromes due to defects in COL13A1 and in the N-linked glycosylation pathway.
    Ann N Y Acad Sci 2018 Feb 24;1413(1):163-169. Epub 2018 Jan 24.
    Nuffield Department of Clinical Neuroscience, Level 3 The West Wing, The John Radcliffe, Oxford, UK.
    The congenital myasthenic syndromes (CMS) are hereditary disorders of neuromuscular transmission. The number of cases recognized, at around 1:100,000 in the United Kingdom, is increasing with improved diagnosis. The advent of next-generation sequencing has facilitated the discovery of many genes that harbor CMS-associated mutations. Read More

    Oral bisphosphonate use and age-related macular degeneration: retrospective cohort and nested case-control study.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    Oxford NIHR Biomedical Research Centre, Musculoskeletal Theme, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK.
    Our objective here was to determine whether oral bisphosphonate (BP) use is associated with the incidence of age-related macular degeneration (AMD). We performed a population-based study using electronic health records from UK primary care (Clinical Practice Research Datalink). A cohort of 13,974 hip fracture patients (1999-2013) was used to conduct (1) a propensity score-matched cohort analysis and (2) a nested case-control analysis. Read More

    Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis.
    Ann N Y Acad Sci 2018 Jan 24. Epub 2018 Jan 24.
    World Health Organization Collaborating Centre for Community Genetics, UCL Centre for Health Informatics and Multiprofessional Education (CHIME), University College London, London, UK.
    Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under-5 mortality. Read More

    Understanding the determinants of hemoglobin and iron status: adolescent-adult women comparisons in SANHANES-1.
    Ann N Y Acad Sci 2018 Jan 23. Epub 2018 Jan 23.
    Population Health, Health Systems and Innovation, Human Sciences Research Council, Cape Town, South Africa.
    The study compared hemoglobin (Hb) and serum ferritin levels between adolescent and adult women with different body mass indices, dietary intake, and sociodemography. A secondary analysis of data for 3177 South African women ⩾15 years of age who participated in the SANHANES-1 study was undertaken. Abnormal Hb (≤12 g/dL) and serum ferritin (<15 μg/mL) were based on the World Health Organization's criteria for nonpregnant women aged ⩾15 years. Read More

    Passive transfer models of myasthenia gravis with muscle-specific kinase antibodies.
    Ann N Y Acad Sci 2018 Feb 21;1413(1):111-118. Epub 2018 Jan 21.
    Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
    Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is characterized by fluctuating fatigable weakness. In MuSK MG, involvement of bulbar muscles, neck, and shoulder and respiratory weakness are more prominent than in acetylcholine receptor (AChR) MG. MuSK autoantibodies are mainly of the IgG4 subclass, and as such are unable to activate complement, have low affinity for Fc receptors, and are functionally monovalent. Read More

    Acetylcholine receptor antibody-mediated animal models of myasthenia gravis and the role of complement.
    Ann N Y Acad Sci 2018 Feb 21;1413(1):136-142. Epub 2018 Jan 21.
    Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC.
    Because of the failure of many promising therapeutics identified in preclinical evaluation, funding sources have established guidelines for increased rigor in animal evaluations. The myasthenia gravis (MG) community of scientists has developed guidelines for preclinical assessment for potential MG treatments. Here, we provide a focused summary of these recommendations and the role of complement in disease development in experimental models of MG. Read More

    The unfolding landscape of the congenital myasthenic syndromes.
    Ann N Y Acad Sci 2018 Feb 21;1413(1):25-34. Epub 2018 Jan 21.
    Department of Neurology, Mayo Clinic, Rochester, Minnesota.
    Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is impaired by one or more specific mechanisms. Since the advent of next-generation sequencing methods, the discovery of novel CMS targets and phenotypes has proceeded at an accelerated rate. Here, we review the current classification of CMS and describe our findings in five of these targets identified and investigated in our laboratory in the past 5 years. Read More

    1 OF 976