Showing papers in "Annals of the New York Academy of Sciences in 2012"
TL;DR: This paper outlines a model of the processes and neural systems involved in emotion generation and regulation and shows how the model can be generalized to understand the brain mechanisms underlying other emotion regulation strategies as well as a range of other allied phenomena.
Abstract: This paper reviews and synthesizes functional imaging research that over the past decade has begun to offer new insights into the brain mechanisms underlying emotion regulation. Toward that end, the first section of the paper outlines a model of the processes and neural systems involved in emotion generation and regulation. The second section surveys recent research supporting and elaborating the model, focusing primarily on studies of the most commonly investigated strategy, which is known as reappraisal. At its core, the model specifies how prefrontal and cingulate control systems modulate activity in perceptual, semantic, and affect systems as a function of one's regulatory goals, tactics, and the nature of the stimuli and emotions being regulated. This section also shows how the model can be generalized to understand the brain mechanisms underlying other emotion regulation strategies as well as a range of other allied phenomena. The third and last section considers directions for future research, including how basic models of emotion regulation can be translated to understand changes in emotion across the life span and in clinical disorders.
1,435 citations
TL;DR: To tackle the high prevalence of smoking among disadvantaged groups, a combination of tobacco control measures is required, and these should be delivered in conjunction with wider attempts to address inequalities in health.
Abstract: Smoking prevalence is higher among disadvantaged groups, and disadvantaged smokers may face higher exposure to tobacco's harms. Uptake may also be higher among those with low socioeconomic status (SES), and quit attempts are less likely to be successful. Studies have suggested that this may be the result of reduced social support for quitting, low motivation to quit, stronger addiction to tobacco, increased likelihood of not completing courses of pharmacotherapy or behavioral support sessions, psychological differences such as lack of self-efficacy, and tobacco industry marketing. Evidence of interventions that work among lower socioeconomic groups is sparse. Raising the price of tobacco products appears to be the tobacco control intervention with the most potential to reduce health inequalities from tobacco. Targeted cessation programs and mass media interventions can also contribute to reducing inequalities. To tackle the high prevalence of smoking among disadvantaged groups, a combination of tobacco control measures is required, and these should be delivered in conjunction with wider attempts to address inequalities in health.
1,190 citations
TL;DR: The effects of such nature experience on human cognitive function and mental health are reviewed, synthesizing work from environmental psychology, urban planning, the medical literature, and landscape aesthetics, and a system of categorization for different types of nature experience is proposed.
Abstract: Scholars spanning a variety of disciplines have studied the ways in which contact with natural environments may impact human well-being. We review the effects of such nature experience on human cognitive function and mental health, synthesizing work from environmental psychology, urban planning, the medical literature, and landscape aesthetics. We provide an overview of the prevailing explanatory theories of these effects, the ways in which exposure to nature has been considered, and the role that individuals' preferences for nature may play in the impact of the environment on psychological functioning. Drawing from the highly productive but disparate programs of research in this area, we conclude by proposing a system of categorization for different types of nature experience. We also outline key questions for future work, including further inquiry into which elements of the natural environment may have impacts on cognitive function and mental health; what the most effective type, duration, and frequency of contact may be; and what the possible neural mechanisms are that could be responsible for the documented effects.
753 citations
TL;DR: In this paper, a review focused on impaired glucocorticoid receptor (GR) function as a molecular mechanism of glucoc Corticoid resistance and showed that both genetic and environmental factors can contribute to impaired GR function.
Abstract: Enhanced susceptibility to inflammatory and autoimmune disease can be related to impairments in HPA axis activity and associated hypocortisolism, or to glucocorticoid resistance resulting from impairments in local factors affecting glucocorticoid availability and function, including the glucocorticoid receptor (GR). The enhanced inflammation and hypercortisolism that typically characterize stress-related illnesses, such as depression, metabolic syndrome, cardiovascular disease, or osteoporosis, may also be related to increased glucocorticoid resistance. This review focuses on impaired GR function as a molecular mechanism of glucocorticoid resistance. Both genetic and environmental factors can contribute to impaired GR function. The evidence that glucocorticoid resistance can be environmentally induced has important implications for management of stress-related inflammatory illnesses and underscores the importance of prevention and management of chronic stress. The simultaneous assessment of neural, endocrine, and immune biomarkers through various noninvasive methods will also be discussed.
562 citations
TL;DR: The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.
Abstract: Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity–cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity–cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.
509 citations
TL;DR: This overview surveys examples of biological roles of sialic acids in immunity, with emphasis on an evolutionary perspective, given the breadth of the subject.
Abstract: Sialic acids are a diverse family of monosaccharides widely expressed on all cell surfaces of vertebrates and so-called “higher” invertebrates, and on certain bacteria that interact with vertebrates. This overview surveys examples of biological roles of sialic acids in immunity, with emphasis on an evolutionary perspective. Given the breadth of the subject, the treatment of individual topics is brief. Subjects discussed include biophysical effects regulation of factor H; modulation of leukocyte trafficking via selectins; Siglecs in immune cell activation; sialic acids as ligands for microbes; impact of microbial and endogenous sialidases on immune cell responses; pathogen molecular mimicry of host sialic acids; Siglec recognition of sialylated pathogens; bacteriophage recognition of microbial sialic acids; polysialic acid modulation of immune cells; sialic acids as pathogen decoys or biological masks; modulation of immunity by sialic acid O-acetylation; sialic acids as antigens and xeno-autoantigens; antisialoglycan antibodies in reproductive incompatibility; and sialic-acid–based blood groups.
497 citations
TL;DR: It is concluded that craving has considerable utility for diagnosis and as a clinical outcome, and that findings from future research will likely expand the clinical potential of the craving construct in the domains of prognosis and craving as a treatment target.
Abstract: Although drug craving has received considerable research attention over the past several decades, to date there has been no systematic review of the general clinical significance of craving. This paper presents an overview of measurement issues of particular relevance to a consideration of use of craving in clinical settings. The paper then considers the relevance of craving across a broad array of clinical domains, including diagnosis, prognostic utility, craving as an outcome measure, and the potential value of craving as a direct target of intervention. The paper is both descriptive and prescriptive, informed by the current state of the science on craving with recommendations for the definition of craving, assessment practices, future research, and clinical applications. We conclude that craving has considerable utility for diagnosis and as a clinical outcome, and that findings from future research will likely expand the clinical potential of the craving construct in the domains of prognosis and craving as a treatment target.
405 citations
TL;DR: While the Asian vulture crisis has been largely linked to poisoning by diclofenac, vulture population declines in Africa have numerous causes, which have made conserving existing populations more difficult and in Africa there has been little government support to conserve vultures despite mounting evidence of the major threats.
Abstract: Vultures are nature’s most successful scavengers, and they provide an array of ecological, economic, and cultural services. As the only known obligate scavengers, vultures are uniquely adapted to a scavenging lifestyle. Vultures’ uniqueadaptationsincludesoaringflight,keeneyesight,andextremelylowpHlevelsintheirstomachs.Presently,14 of23(61%)vulturespeciesworldwidearethreatenedwithextinction,andthemostrapiddeclineshaveoccurredinthe vulture-rich regions of Asia and Africa. The reasons for the population declines are varied, but poisoning or human persecution, or both, feature in the list of nearly every declining species. Deliberate poisoning of carnivores is likely the most widespread cause of vulture poisoning. In Asia, Gyps vultures have declined by >95% due to poisoning by the veterinary drug diclofenac, which was banned by regional governments in 2006. Human persecution of vultures hasoccurredforcenturies,andshootinganddeliberatepoisoningarethemostwidelypracticedactivities.Ecological consequences of vulture declines include changes in community composition of scavengers at carcasses and an increased potential for disease transmission between mammalian scavengers at carcasses. There have been cultural and economic costs of vulture declines as well, particularly in Asia. In the wake of catastrophic vulture declines in Asia, regional governments, the international scientific and donor communities, and the media have given the crisis substantial attention. Even though the Asian vulture crisis focused attention on the plight of vultures worldwide, the situation for African vultures has received relatively little attention especially given the similar levels of population decline. While the Asian crisis has been largely linked to poisoning by diclofenac, vulture population declines in Africa have numerous causes, which have made conserving existing populations more difficult. And in Africa there has been little government support to conserve vultures despite mounting evidence of the major threats. In other regions with successful vulture conservation programs, a common theme is a huge investment of financial resources and highly skilled personnel, as well as political will and community support.
352 citations
TL;DR: Butyrate has a potential clinical application in the treatment of inflammatory bowel disease and may contribute to the restoration of the tight junction barrier in IBD by affecting the expression of claudin‐2, occludin, cingulin, and zonula occluda poteins.
Abstract: Butyrate production in the large intestine and ruminant forestomach depends on bacterial butyryl-CoA/acetate-CoA transferase activity and is highest when fermentable fiber and nonstructural carbohydrates are balanced. Gastrointestinal epithelia seem to use butyrate and butyrate-induced endocrine signals to adapt proliferation, apoptosis, and differentiation to the growth of the bacterial community. Butyrate has a potential clinical application in the treatment of inflammatory bowel disease (IBD; ulcerative colitis). Via inhibited release of tumor necrosis factor α and interleukin 13 and inhibition of histone deacetylase, butyrate may contribute to the restoration of the tight junction barrier in IBD by affecting the expression of claudin-2, occludin, cingulin, and zonula occludens poteins (ZO-1, ZO-2). Further evaluation of the molecular events that link butyrate to an improved tight junction structure will allow for the elucidation of the cofactors affecting the reliability of butyrate as a clinical treatment tool.
321 citations
TL;DR: For instance, the authors found that older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information than younger adults, compared with younger adults.
Abstract: This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults' ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults' avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, although age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences.
266 citations
TL;DR: Examination of the regulation and role of MLCK in tight junction dysfunction has helped to define pathological processes and characterize the role of barrier loss in disease pathogenesis, and may provide future therapeutic targets to treat intestinal disease.
Abstract: Dynamic regulation of paracellular permeability is essential for physiological epithelial function, while dysregulated permeability is common in disease. The recent elucidation of the molecular composition of the epithelial tight junction complex has been accompanied by characterization of diverse intracellular mediators of paracellular permeabiltiy. Myosin light chain kinase (MLCK), which induces contraction of the perijunctional actomyosin ring through myosin II regulatory light chain phosphorylation, has emerged as a key regulator of tight junction permeability. Examination of the regulation and role of MLCK in tight junction dysfunction has helped to define pathological processes and characterize the role of barrier loss in disease pathogenesis, and may provide future therapeutic targets to treat intestinal disease.
TL;DR: The discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases.
Abstract: Recent studies indicate that besides digestion and absorption of nutrients and water and electrolytes homeostasis, another key function of the intestine is to regulate the trafficking of environmental antigens across the host mucosal barrier. Intestinal tight junctions (TJs) create gradients for the optimal absorption and transport of nutrients and control the balance between tolerance and immunity to nonself antigens. To meet diverse physiological challenges, intestinal epithelial TJs must be modified rapidly and in a coordinated fashion by regulatory systems that orchestrate the state of assembly of the TJ multiprotein network. While considerable knowledge exists about TJ ultrastructure, relatively little is known about their physiological and pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led us to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases.
TL;DR: In this article, the timing and intensity of DBS stimulation are titrated according to biomarkers that capture current clinical state, such as bradykinesia and rigidity across patients.
Abstract: Feedback control of deep brain stimulation (DBS) in Parkinson's disease has great potential to improve efficacy, reduce side effects, and decrease the cost of treatment. In this, the timing and intensity of stimulation are titrated according to biomarkers that capture current clinical state. Stimulation may be at standard high frequency or intelligently patterned to directly modify specific pathological rhythms. The search for and validation of appropriate feedback signals are therefore crucial. Signals recorded from the DBS electrode currently appear to be the most promising source of feedback. In particular, beta-frequency band oscillations in the local field potential recorded at the stimulation target may capture variation in bradykinesia and rigidity across patients, but this remains to be confirmed within patients. Biomarkers that reliably reflect other impairments, such as tremor, also need to be established. Finally, whether brain signals are causally important needs to be established before stimulation can be specifically patterned rather than delivered at empirically defined high frequency.
TL;DR: Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high‐elevation refugia, which is the key to survival of many susceptible Hawaiian birds.
Abstract: Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease-free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand.
TL;DR: The goal of this collection of expert reviews is to highlight what is known about how carbohydrates and their binding partners—the microbial, tumor, and host—cooperate within the immune system, while also identifying areas of opportunity to those willing to take up the challenge of understanding more about how carbohydrate influence immune responses.
Abstract: Unlike their protein "roommates" and their nucleic acid "cousins," carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the nontemplate nature of their synthesis and the resulting heterogeneity. The goal of this collection of expert reviews is to highlight what is known about how carbohydrates and their binding partners-the microbial (non-self), tumor (altered-self), and host (self)-cooperate within the immune system, while also identifying areas of opportunity to those willing to take up the challenge of understanding more about how carbohydrates influence immune responses. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as are proteins, nucleic acids, and lipids. Here, we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs, and galectins) and their contributions to the biology of immune responses in physiologic and pathologic settings.
TL;DR: Current data on xenotransplantation of human cells into zebrafish is summarized, highlighting the advantages and limitations of this model in comparison to classical murine models of xenotranplantation.
Abstract: The zebrafish has become a powerful vertebrate model for genetic studies of embryonic development and organogenesis and increasingly for studies in cancer biology. Zebrafish facilitate the performance of reverse and forward genetic approaches, including mutagenesis and small molecule screens. Moreover, several studies report the feasibility of xenotransplanting human cells into zebrafish embryos and adult fish. This model provides a unique opportunity to monitor tumor-induced angiogenesis, invasiveness, and response to a range of treatments in vivo and in real time. Despite the high conservation of gene function between fish and humans, concern remains that potential differences in zebrafish tissue niches and/or missing microenvironmental cues could limit the relevance and translational utility of data obtained from zebrafish human cancer cell xenograft models. Here, we summarize current data on xenotransplantation of human cells into zebrafish, highlighting the advantages and limitations of this model in comparison to classical murine models of xenotransplantation.
TL;DR: Evidence is summarized showing how IL‐6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep‐related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL‐ 6 in the circulation.
Abstract: Chronic low-grade inflammation, in particular increased concentrations of proinflammatory cytokines such as interleukin (IL)-6 in the circulation, is observed with increasing age, but it is also as a consequence of various medical and psychological conditions, as well as life-style choices. Since molecules such as IL-6 have pleiotropic effects, consequences are wide ranging. This short review summarizes the evidence showing how IL-6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep-related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL-6 in the circulation. Research showing that acute as well as chronic psychological stress also increase concentrations of IL-6 supports the notion of a close link between an organism's response to physiological and psychological perturbations. The findings summarized here further underscore the particular importance of IL-6 as a messenger molecule that connects peripheral regulatory processes with the CNS.
TL;DR: Early expansion attempts are highlighted and recent development in the extrinsic control of HSPC fate in vitro is reviewed, suggesting that additional factors are required to improve ex vivo stem cell expansion protocols.
Abstract: Attempts to improve hematopoietic reconstitution and engraftment potential of ex vivo-expanded hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful due to the inability to generate sufficient stem cell numbers and to excessive differentiation of the starting cell population. Although hematopoietic stem cells (HSCs) will rapidly expand after in vivo transplantation, experience from in vitro studies indicates that control of HSPC self-renewal and differentiation in culture remains difficult. Protocols that are based on hematopoietic cytokines have failed to support reliable amplification of immature stem cells in culture, suggesting that additional factors are required. In recent years, several novel factors, including developmental factors and chemical compounds, have been reported to affect HSC self-renewal and improve ex vivo stem cell expansion protocols. Here, we highlight early expansion attempts and review recent development in the extrinsic control of HSPC fate in vitro.
TL;DR: Pediatric imaging and analysis tools and protocols are summarized and reviewed and neuroimaging protocols for young nonsedated children and infants are presented, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.
Abstract: Structural and functional magnetic resonance imaging (fMRI) has been used increasingly to investigate typical and atypical brain development. However, in contrast to studies in school-aged children and adults, MRI research in young pediatric age groups is less common. Practical and technical challenges occur when imaging infants and children, which presents clinicians and research teams with a unique set of problems. These include procedural difficulties (e.g., participant anxiety or movement restrictions), technical obstacles (e.g., availability of child-appropriate equipment or pediatric MR head coils), and the challenge of choosing the most appropriate analysis methods for pediatric imaging data. Here, we summarize and review pediatric imaging and analysis tools and present neuroimaging protocols for young nonsedated children and infants, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.
TL;DR: PGC‐1α appears to play a protective role against atrophy‐linked skeletal muscle deterioration and upregulating nuclear respiratory factors and mitochondrial transcription factor A leads to increased mitochondrial DNA replication and gene transcription.
Abstract: This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)–mediated pathway and discusses the role of PGC-1α in skeletal muscle atrophy caused by immobilization. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1α overexpression underline the importance of PGC-1α in atrophied skeletal muscle, demonstrate enhancement of the PGC-1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1α appears to play a protective role against atrophy-linked skeletal muscle deterioration.
TL;DR: The exposure to environmental pro‐oxidant agents leads to the formation of reactive oxygen species (ROS) and the generation of bioactive molecules that can damage skin cells.
Abstract: Living organisms are continuously exposed to environmental pollutants Because of its critical location, the skin is a major interface between the body and the environment and provides a biological barrier against an array of chemical and physical environmental pollutants The skin can be defined as our first defense against the environment because of its constant exposure to oxidants, including ultraviolet (UV) radiation and other environmental pollutants such as diesel fuel exhaust, cigarette smoke (CS), halogenated hydrocarbons, heavy metals, and ozone (O3) The exposure to environmental pro-oxidant agents leads to the formation of reactive oxygen species (ROS) and the generation of bioactive molecules that can damage skin cells This short review provides an overview of the effects and mechanisms of action of CS, O3, and UV on cutanous tissues
TL;DR: Following various mechanisms of gene duplication, genes are often retained or lost in a biased manner, which has suggested recent models for gene family evolution, such as functional buffering and the gene balance hypothesis in addition to now‐classical models, including neofunctionalization and subfunctionalization.
Abstract: With many plant genomes sequenced, it is now clear that one distinguishing feature of angiosperm (flowering plant) genomes is their high frequency of whole-genome duplication. Single-gene duplication is also widespread in angiosperm genomes. Following various mechanisms of gene duplication, genes are often retained or lost in a biased manner, which has suggested recent models for gene family evolution, such as functional buffering and the gene balance hypothesis in addition to now-classical models, including neofunctionalization and subfunctionalization. Evolutionary consequences of gene duplication, often studied through analyzing gene expression divergence, have enhanced understanding of the biological significance of different mechanisms of gene duplication.
TL;DR: Cognitive neuroscientists have a unique opportunity to study how an evolutionarily ancient response rooted in the chemical senses has expanded into a uniquely human social cognitive domain; many interesting research avenues remain to be explored.
Abstract: Disgust is characterized by a remarkably diverse set of stimulus triggers, ranging from extremely concrete (bad tastes and disease vectors) to extremely abstract (moral transgressions and those who commit them). This diversity may reflect an expansion of the role of disgust over evolutionary time, from an origin in defending the body against toxicity and disease, through defense against other threats to biological fitness (e.g., incest), to involvement in the selection of suitable interaction partners, by motivating the rejection of individuals who violate social and moral norms. The anterior insula, and to a lesser extent the basal ganglia, are implicated in toxicity‐ and disease‐related forms of disgust, although we argue that insular activation is not exclusive to disgust. It remains unclear whether moral disgust is associated with insular activity. Disgust offers cognitive neuroscientists a unique opportunity to study how an evolutionarily ancient response rooted in the chemical senses has expanded into a uniquely human social cognitive domain; many interesting research avenues remain to be explored.
TL;DR: The protective effects of helminths on expression of inflammatory bowel disease, multiple sclerosis, and animal models of these and other inflammatory diseases are reviewed and the immune pathways altered by helminth that may afford protection from these illnesses are reviewed.
Abstract: Exposure to commensal and pathogenic organisms strongly influences our immune system. Exposure to helminths was frequent before humans constructed their current highly hygienic environment. Today, in highly industrialized countries, contact between humans and helminths is rare. Congruent with the decline in helminth infections is an increase in the prevalence of autoimmune and inflammatory disease. It is possible that exclusion of helminths from the environment has permitted the emergence of immune-mediated disease. We review the protective effects of helminths on expression of inflammatory bowel disease, multiple sclerosis, and animal models of these and other inflammatory diseases. We also review the immune pathways altered by helminths that may afford protection from these illnesses. Helminth exposure tends to inhibit IFN-γ and IL-17 production, promote IL-4, IL-10, and TGF-β release, induce CD4+ T cell Foxp3 expression, and generate regulatory macrophages, dendritic cells, and B cells. Helminths enable protective pathways that may vary by specific species and disease model. Helminths or their products likely have therapeutic potential to control or prevent immune-mediated illness.
TL;DR: Even though Arctic species richness is increasing via immigration from the South, many Arctic vertebrates are expected to become increasingly threatened during this century, and adjustment via phenotypic plasticity is likely to dominate vertebrate responses in the short term.
Abstract: Climate change is taking place more rapidly and severely in the Arctic than anywhere on the globe, exposing Arctic vertebrates to a host of impacts. Changes in the cryosphere dominate the physical changes that already affect these animals, but increasing air temperatures, changes in precipitation, and ocean acidification will also affect Arctic ecosystems in the future. Adaptation via natural selection is problematic in such a rapidly changing environment. Adjustment via phenotypic plasticity is therefore likely to dominate Arctic vertebrate responses in the short term, and many such adjustments have already been documented. Changes in phenology and range will occur for most species but will only partly mitigate climate change impacts, which are particularly difficult to forecast due to the many interactions within and between trophic levels. Even though Arctic species richness is increasing via immigration from the South, many Arctic vertebrates are expected to become increasingly threatened during this century.
TL;DR: No human or animal models of defect in transmigration—the fourth and last phase of the cascade—has been described, and the genetic basis for LAD III has been revealed to involve mutations in kindlin‐3, a newly recognized essential component of integrin activation—the second phase ofThe adhesion cascade.
Abstract: Leukocyte trafficking from the blood stream to tissues is essential for continuous surveillance of foreign antigens. This dynamic process, designated as the leukocyte adhesion cascade, involves distinct steps. In leukocyte adhesion deficiency (LAD) I the firm adhesion of leukocyte to the endothelium is defective, due to mutations in the beta 2 integrin gene. LAD II is caused by mutations in the fucose transporter specific to the Golgi apparatus, leading to the absence of Sialyl Lewis X-the fucosylated ligand for the selectins-thus affecting the rolling phase, the first phase of the cascade. In LAD III, a primary activation defect occurs in beta integrins 1, 2, and 3. Recently, the genetic basis for LAD III has been revealed to involve mutations in kindlin-3, a newly recognized essential component of integrin activation-the second phase of the adhesion cascade. Until now, no human or animal models of defect in transmigration-the fourth and last phase of the cascade-has been described.
TL;DR: Although some of the molecular details are missing, studies summarized above point to modulating protein localization and dynamics that are common mechanisms for tight junction regulation.
Abstract: Increasing evidence suggests that the tight junction is a dynamically regulated structure. Cytoskeletal reorganization, particularly myosin light chain phosphorylation--induced actomyosin contraction, has increasingly been recognized as a mediator of physiological and pathophysiological tight junction regulation. However, our understanding of molecular mechanisms of tight junction modulation remains limited. Recent studies using live cell and live animal imaging techniques allowed us to peek into the molecular details of tight junction regulation. At resting conditions, the tight junction is maintained by dynamic protein-protein interactions, which may provide a platform for rapid tight junction regulation. Following stimulation, distinct forms of tight junction protein reorganization were observed. Tumor necrosis factor (TNF-α) causes a myosin light chain kinase (MLCK)--mediated barrier regulation by inducing occludin removal from the tight junction through caveolar endocytosis. In contrast, MLCK- and CK2-inhibition--caused tight junction regulation is mediated by altered zonula occludens (ZO)-1 protein dynamics and requires ZO-1--mediated protein-protein interaction, potentially through regulating claudin function. Although some of the molecular details are missing, studies summarized above point to modulating protein localization and dynamics that are common mechanisms for tight junction regulation.
TL;DR: Breakthroughs in improving outcome after stroke will only result from approaches that target not only the brain, but also systemic effects of stroke, and the highly successful concept of stroke units attests to the benefits of treating stroke comprehensively.
Abstract: Throughout the history of research on stroke pathophysiology, focus has shifted from purely vascular concepts to the insight that a complex interplay of biochemical and molecular mechanisms involving practically any cell type of the brain ("neurovascular unit") partakes in either salvage or demise of the tissue after a stroke. In addition, it was realized that peripheral immune cells play important roles, not only after their invasion into the brain but also because of stroke-induced effects on the immune system that can result in infections. Indeed, outcome of stroke patients is not only dictated by nonmodifiable factors, such as severity of stroke, age, or premorbidity, but also by modifiable factors largely related to medical complications, such as infections and possibly sarcopenia. The highly successful concept of stroke units attests to the benefits of treating stroke comprehensively. Breakthroughs in improving outcome after stroke will only result from approaches that target not only the brain, but also systemic effects of stroke.
TL;DR: The N‐linked glycans on the IgG Fc are absolutely required for initiating and suppressing inflammation, and the Fc glycan requirements to initiate and suppress inflammation will be discussed herein.
Abstract: IgG antibodies trigger leukocyte activation and inflammation by forming immune complexes that crosslink activating Fcγ receptors (FcγRs). This is essential to combat infection, but detrimental if antibodies target or cross-react with autoantigens. The high specificity and long serum half-life of IgG antibodies confers tremendous therapeutic potential. Indeed, antibodies have been successfully employed to target cancers, autoreactive B cells, and pro-inflammatory cytokines. Conversely, IgG antibodies can also initiate anti-inflammatory responses. In the form of intravenous immunoglobulin (IVIG), IgGs are routinely administered to treat inflammatory autoimmune diseases. Importantly, the N-linked glycans on the IgG Fc are absolutely required for initiating these IgG effector functions. In fact, the Fc glycan composition dictates IgG affinity to individual FcγRs, and in a broader sense, binding to different FcγRs classes: activating, inhibitory, and anti-inflammatory (dendritic cell-specific ICAM-3 grabbing nonintegrin, DC-SIGN). The Fc glycan requirements to initiate and suppress inflammation will be discussed herein.
TL;DR: In this article, the authors address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real-life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities.
Abstract: In the last 50 years, the average self-reported sleep duration in the United States has decreased by 1.5–2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta-analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism. This relationship is likely to be bidirectional and causal in nature, but many aspects remain to be elucidated. Sleep and the internal circadian clock influence a host of endocrine parameters. Sleep curtailment in humans alters multiple metabolic pathways, leading to more insulin resistance, possibly decreased energy expenditure, increased appetite, and immunological changes. On the other hand, psychological, endocrine, and anatomical abnormalities in individuals with obesity and/or diabetes can interfere with sleep duration and quality, thus creating a vicious cycle. In this review, we address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real-life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities.