Cellular proteins are decorated with a wide range of acetyl and other acyl modifications. Many studies have demonstrated regulation of site-specific acetylation by acetyltransferases and ...deacetylases. Acylation is emerging as a new type of lysine modification, but less is known about its overall regulatory role. Furthermore, the mechanisms of lysine acylation, its overlap with protein acetylation, and how it influences cellular function are major unanswered questions in the field. In this review, we discuss the known roles of acetyltransferases and deacetylases and the sirtuins as a conserved family of a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacylases that are important for response to cellular stress and homeostasis. We also consider the evidence for an emerging idea of nonenzymatic protein acylation. Finally, we put forward the hypothesis that protein acylation is a form of protein “carbon stress” that the deacylases evolved to remove as a part of a global protein quality-control network.
The sirtuins are protein deacylases that regulate cellular homeostasis and response to stress. In this review, Wagner and Hirschey highlight recent findings on new types of acyl lysine modifications and propose a model for protein acylation as a “carbon stress” that sirtuins remove as part of protein quality control.
Host genotype affects microbiome composition in many plants, but the mechanisms and implications of this phenomenon are understudied. New work in PLOS Biology illustrates how host genotype leads to ...differential gene expression and fitness in bacteria of the barley rhizosphere.
Recent terminations of clinical trials of myostatin inhibitors in muscular dystrophy have raised questions about the predictiveness of mouse models for this therapeutic strategy.
A variety of ...myostatin inhibitors have been developed for preclinical and clinical studies. These inhibitors have ameliorated the phenotype of many but not all mouse models of muscular dystrophy. However, randomized double-blinded placebo controlled trials in both pediatric and adult muscular dystrophies have, as of yet, not demonstrated functional improvement.
The present article will review the preclinical promise of myostatin inhibitors, the clinical trial experience to date of these inhibitors in muscular dystrophy, and the potential reasons for the lack of observed translation.
Muscular dystrophies are a group of genetic muscle disorders that cause progressive muscle weakness and degeneration. Within this group, Duchenne muscular dystrophy (DMD) is the most common and one ...of the most severe. DMD is an X chromosome linked disease that occurs to 1 in 3500 to 1 in 5000 boys. The cause of DMD is a mutation in the dystrophin gene, whose encoded protein provides both structural support and cell signaling capabilities. So far, there are very limited therapeutic options available and there is no cure for this disease. In this review, we discuss the existing cell therapy research, especially stem cell-based, which utilize myoblasts, satellite cells, bone marrow cells, mesoangioblasts and CD133+ cells. Finally, we focus on human pluripotent stem cells (hPSCs) which hold great potential in treating DMD. hPSCs can be used for autologous transplantation after being specified to a myogenic lineage. Over the last few years, there has been a rapid development of isolation, as well as differentiation, techniques in order to achieve effective transplantation results of myogenic cells specified from hPSCs. In this review, we summarize the current methods of hPSCs myogenic commitment/differentiation, and describe the current status of hPSC-derived myogenic cell transplantation.
•Myogenic progenitor cells could provide a source for cell therapy for DMD to regenerate and replace the diseased tissue•An orchestration of signaling molecules directing the lineage determination sets the basis for PSC differentiation in vitro•There is a need to develop more cell therapy options (e.g iPSC) for DMD due to limited success of current ones•The review describes the most recent studies of hiPSC muscle lineage specification and the potential of their application
Since the publication of the Duchenne muscular dystrophy (DMD) care considerations in 2010, multidisciplinary care of this severe, progressive neuromuscular disease has evolved. In conjunction with ...improved patient survival, a shift to more anticipatory diagnostic and therapeutic strategies has occurred, with a renewed focus on patient quality of life. In 2014, a steering committee of experts from a wide range of disciplines was established to update the 2010 DMD care considerations, with the goal of improving patient care. The new care considerations aim to address the needs of patients with prolonged survival, to provide guidance on advances in assessments and interventions, and to consider the implications of emerging genetic and molecular therapies for DMD. The committee identified 11 topics to be included in the update, eight of which were addressed in the original care considerations. The three new topics are primary care and emergency management, endocrine management, and transitions of care across the lifespan. In part 1 of this three-part update, we present care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management.
Variation in the availability and distribution of food resources is a strong selective pressure on wild primates. We explored variation in Tibetan macaque gut microbiota composition during winter and ...spring seasons. Our results showed that gut microbial composition and diversity varied by season. In winter, the genus Succinivibrio, which promotes the digestion of cellulose and hemicellulose, was significantly increased. In spring, the abundance of the genus Prevotella, which is associated with digestion of carbohydrates and simple sugars, was significantly increased. PICRUSt analysis revealed that the predicted metagenomes related to the glycan biosynthesis and metabolic pathway was significantly increased in winter samples, which would aid in the digestion of glycan extracted from cellulose and hemicellulose. The predicted metagenomes related to carbohydrate and energy metabolic pathways were significantly increased in spring samples, which could facilitate a monkey's recovery from acute energy loss experienced during winter. We propose that shifts in the composition and function of the gut microbiota provide a buffer against seasonal fluctuations in energy and nutrient intake, thus enabling these primates to adapt to variations in food supply and quality.
Feeding a growing world population amidst climate change requires optimizing the reliability, resource use, and environmental impacts of food production. One way to assist in achieving these goals is ...to integrate beneficial plant microbiomes-i.e., those enhancing plant growth, nutrient use efficiency, abiotic stress tolerance, and disease resistance-into agricultural production. This integration will require a large-scale effort among academic researchers, industry researchers, and farmers to understand and manage plant-microbiome interactions in the context of modern agricultural systems. Here, we identify priorities for research in this area: (1) develop model host-microbiome systems for crop plants and non-crop plants with associated microbial culture collections and reference genomes, (2) define core microbiomes and metagenomes in these model systems, (3) elucidate the rules of synthetic, functionally programmable microbiome assembly, (4) determine functional mechanisms of plant-microbiome interactions, and (5) characterize and refine plant genotype-by-environment-by-microbiome-by-management interactions. Meeting these goals should accelerate our ability to design and implement effective agricultural microbiome manipulations and management strategies, which, in turn, will pay dividends for both the consumers and producers of the world food supply.
Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant's genetic control over its microbiota is of great interest to crop breeders and ...evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots of Boechera stricta (Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome is evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.
Climate change is driving rapid changes in environmental conditions and affecting population and species' persistence across spatial and temporal scales. Integrating climate change assessments into ...biological resource management, such as conserving endangered species, is a substantial challenge, partly due to a mismatch between global climate forecasts and local or regional conservation planning. Here, we demonstrate how outputs of global climate change models can be downscaled to the watershed scale, and then coupled with ecophysiological metrics to assess climate change effects on organisms of conservation concern. We employed models to estimate future water temperatures (2010-2099) under several climate change scenarios within the large heterogeneous San Francisco Estuary. We then assessed the warming effects on the endangered, endemic Delta Smelt, Hypomesus transpacificus, by integrating localized projected water temperatures with thermal sensitivity metrics (tolerance, spawning and maturation windows, and sublethal stress thresholds) across life stages. Lethal temperatures occurred under several scenarios, but sublethal effects resulting from chronic stressful temperatures were more common across the estuary (median >60 days above threshold for >50% locations by the end of the century). Behavioral avoidance of such stressful temperatures would make a large portion of the potential range of Delta Smelt unavailable during the summer and fall. Since Delta Smelt are not likely to migrate to other estuaries, these changes are likely to result in substantial habitat compression. Additionally, the Delta Smelt maturation window was shortened by 18-85 days, revealing cumulative effects of stressful summer and fall temperatures with early initiation of spring spawning that may negatively impact fitness. Our findings highlight the value of integrating sublethal thresholds, life history, and in situ thermal heterogeneity into global change impact assessments. As downscaled climate models are becoming widely available, we conclude that similar assessments at management-relevant scales will improve the scientific basis for resource management decisions.
The year 2010 featured a widespread drought in the Amazon rain forest, which was more severe than the “once‐in‐a‐century” drought of 2005. Water levels of major Amazon tributaries fell drastically to ...unprecedented low values, and isolated the floodplain population whose transportation depends upon on local streams which completely dried up. The drought of 2010 in Amazonia started in early austral summer during El Niño and then was intensified as a consequence of the warming of the tropical North Atlantic. An observed tendency for an increase in dry and very dry events, particularly in southern Amazonia during the dry season, is concomitant with an increase in the length of the dry season. Our results suggest that it is by means of a longer dry season that warming in the tropical North Atlantic affects the hydrology of the Amazon Rivers at the end of the recession period (austral spring). This process is, sometimes, further aggravated by deficient rainfall in the previous wet season.
Key Points
New results based on an observed extreme in Amazonia
Similar behaviour is detected in climate change projections in Amazonia
A longer dry season has been observed in southern Amazonia during last 10 years
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