Protein-protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease ...treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein-protein interactions and produce high-quality multimeric structural models.
Application of our method to the Human and Yeast genomes yield protein-protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2's non-structural protein 3. We also produced models of SARS-CoV2's spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor and dipeptidyl peptidase-4.
The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation. The interactome modeling pipeline is available at usegalaxy.org and usegalaxy.eu.
This study sought to examine mortality, health-related quality of life, and physical function among sepsis survivors who developed chronic critical illness.
Single-institution, prospective, ...longitudinal, observational cohort study assessing 12-month outcomes.
Two surgical/trauma ICUs at an academic tertiary medical and level 1 trauma center.
Adult critically ill patients that survived 14 days or longer after sepsis onset.
None.
Baseline patient characteristics and function, sepsis severity, and clinical outcomes of the index hospitalization were collected. Follow-up physical function (short physical performance battery; Zubrod; hand grip strength) and health-related quality of life (EuroQol-5D-3L, Short Form-36) were measured at 3, 6, and 12 months. Hospital-free days and mortality were determined at 12 months. We compared differences in long-term outcomes between subjects who developed chronic critical illness (≥ 14 ICU days with persistent organ dysfunction) versus those with rapid recovery. The cohort consisted of 173 sepsis patients; 63 (36%) developed chronic critical illness and 110 (64%) exhibited rapid recovery. Baseline physical function and health-related quality of life did not differ between groups. Those who developed chronic critical illness had significantly fewer hospital-free days (196 ± 148 vs 321 ± 65; p < 0.0001) and reduced survival at 12-months compared with rapid recovery subjects (54% vs 92%; p < 0.0001). At 3- and 6-month follow-up, chronic critical illness patients had significantly lower physical function (3 mo: short physical performance battery, Zubrod, and hand grip; 6 mo: short physical performance battery, Zubrod) and health-related quality of life (3- and 6-mo: EuroQol-5D-3L) compared with patients who rapidly recovered. By 12-month follow-up, chronic critical illness patients had significantly lower physical function and health-related quality of life on all measures.
Surgical patients who develop chronic critical illness after sepsis exhibit high healthcare resource utilization and ultimately suffer dismal long-term clinical, functional, and health-related quality of life outcomes. Further understanding of the mechanisms driving the development and persistence of chronic critical illness will be necessary to improve long-term outcomes after sepsis.
BACKGROUND
Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity ...could prevent major mobility disability (MMD) in sedentary older adults.
METHODS
We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE‐Pilot Study, and the LIFE Study.
RESULTS
The planning phase and the LIFE‐Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69‐0.98; P = .03), and that the intervention was cost‐effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer‐reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov).
CONCLUSIONS
The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872–881, 2020
See related editorial by LaCroix et al. in this issue.
Abstract
HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting a broad range of evolutionary models to multiple sequence alignments, and for conducting ...subsequent parameter estimation and hypothesis testing, primarily in the maximum likelihood statistical framework. It has become a popular choice for characterizing various aspects of the evolutionary process: natural selection, evolutionary rates, recombination, and coevolution. The 2.5 release (available from www.hyphy.org) includes a completely re-engineered computational core and analysis library that introduces new classes of evolutionary models and statistical tests, delivers substantial performance and stability enhancements, improves usability, streamlines end-to-end analysis workflows, makes it easier to develop custom analyses, and is mostly backward compatible with previous HyPhy releases.
Nutrition and Exercise in Sarcopenia Anton, Stephen D; Hida, Azumi; Mankowski, Robert ...
Current protein & peptide science,
01/2018, Letnik:
19, Številka:
7
Journal Article
Recenzirano
Sarcopenia is a debilitating condition that involves loss of muscle mass and function, which affects virtually everyone as they age, and can lead to frailty and ultimately disability. In growing ...recognition of the importance of both muscle strength and muscle mass relative to body size in contributing to functional decline, recent definitions have now incorporated grip strength and a correction for body mass as part of the key criteria that define sarcopenia. With this new definition, a much larger population of older adults are now at risk of sarcopenia. In the present article, we reviewed the literature for studies which tested the effects of diet or exercise interventions on changes in lean mass and/or functional outcomes in individuals with either sarcopenia and/or frailty and identified 19 clinical trials. There were a few key findings. First, dietary interventions involving protein supplementation improved functional and/or strength outcomes in a few trials; however, other dietary approaches were less effective. Exercise interventions and combined diet and exercise interventions produced consistent improvements in lower body muscle strength but had less consistent effects on walking speed and grip strength. Lifestyle interventions not involving calorie restriction generally did not induce significant changes in body composition. There were a limited number of trials in which participants with sarcopenia were specifically targeted, and thus there is an important need for more research to determine the appropriate types of intervention approaches for the high risk population of sarcopenic older adults.
Adaptive responses to exercise training (ET) are crucial in maintaining physiologic homeostasis and health span. Exercise-induced aerobic bioenergetic reactions in the mitochondria and cytosol ...increase production of reactive oxygen species, where excess of reactive oxygen species can be scavenged by enzymatic and nonenzymatic antioxidants (AO) to protect against deleterious oxidative stress. Free radicals, however, have recently been recognized as crucial signaling agents that promote adaptive mechanisms to ET, such as mitochondrial biogenesis, AO enzyme activity defense system upregulation, insulin sensitivity, and glucose uptake in the skeletal muscle. Commonly used nonenzymatic AO supplements, such as vitamins C and E, α-lipoic acid, and polyphenols, in combination with ET, have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training.
During the PubMed search, we selected studies that examined and compared ET effects with and without administration of commonly used AO supplements.
Preclinical and clinical studies to date have shown inconsistent results indicating either positive or negative effects of endurance training combined with different blends of AO supplements (mostly vitamins C and E and α-lipoic acid) on redox status, mitochondrial biogenesis pathways, and insulin sensitivity. Preclinical reports on ET combined with resveratrol, however, have shown consistent positive effects on exercise performance, mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting mixed effects. Relevant clinical studies have been few and have used inconsistent results and methodology (types of compounds, combinations, and supplementation time).
The future studies should investigate the effects of specific AO and other popular supplements, such as α-lipoic acid and resveratrol, on training effects in humans. Of particular importance are older adults who may be at higher risk of age-related increased oxidative stress, an impaired AO enzyme defense system, and comorbidities such as hypertension, insulin resistance, and diabetes.
Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. ...We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73±7years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300mg/day), and (3) high dose resveratrol (1000mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps<0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300mg/day and 1000mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials.
•Doses of 300 & 1000mg/d of resveratrol are well tolerated in overweight older adults.•Doses of 300 & 1000mg/d of resveratrol did not produce changes in metabolic parameters.•Older adults show high levels of adherence to 90 days of resveratrol supplementation.•Studies are needed to confirm optimal dosage of resveratrol and long-term safety.
Long-Term Adherence to Health Behavior Change Middleton, Kathryn R.; Anton, Stephen D.; Perri, Michal G.
American journal of lifestyle medicine,
11/2013, Letnik:
7, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The utility of lifestyle-based health promotion interventions is directly affected by participant adherence to prescribed behavior changes. Unfortunately, poor adherence to behaviors recommended in ...lifestyle interventions is widespread, particularly over the long term; thus, the “adherence problem” represents a significant challenge to the effectiveness of these interventions. The current review provides an overview of the adherence problem and describes a theoretical framework through which the factors that affect adherence can be understood. To further understand the difficulties individuals face when adhering to health behavior changes, we focus our discussion on the challenges associated with adherence to lifestyle behaviors recommended for weight loss and healthy weight management (ie, reductions in dietary intake and increases in physical activity). We describe strategies that improve long-term adherence to health behaviors related to healthy weight management, including the provision of extended care, skills training, improving social support, and strategies specific to maintaining changes in dietary intake and physical activity. Finally, we discuss difficulties involved in implementing long-term weight management programs and suggest practical solutions for providers.
Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, ...and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death. The effect vascular calcification has on function during aging is not well understood. Emerging findings suggest vascular calcification can impact skeletal muscle perfusion, negatively affecting nutrient and oxygen delivery to skeletal muscle, ultimately accelerating muscle loss and functional decline. The present review summarizes existing evidence on the biological mechanisms linking vascular calcification with sarcopenia during aging.
•Aging is associated with inflammation, oxidative stress and hormonal changes, which may contribute to vascular calcification.•Age-related vascular calcification leads to arterial stiffness, which may decrease muscle perfusion.•Aging-related vascular calcification may precede and contribute to sarcopenia.
Abstract Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the ...strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.
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