The host plays an essential role in parasite transmission. The viability of the host–parasite relationship depends upon development of immune resistance and the induction of disease tolerance. Here I ...propose that pathogen coevolution of avirulence factors promoting host disease tolerance is an essential feature of the parasitic lifestyle.
Exercise and inflammation Metsios, George S.; Moe, Rikke H.; Kitas, George D.
Best practice & research. Clinical rheumatology,
April 2020, 2020-04-00, 20200401, Letnik:
34, Številka:
2
Journal Article
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Based on current knowledge deriving from studies in animals and humans (the general population and patients with non-communicable diseases), there is biological plausibility that exercise may have ...anti-inflammatory effects. This may be particularly important for patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMDs). The present review discusses the current state-of-the-art on exercise and inflammation, explores how exercise can moderate inflammation-dependent RMD outcomes and the most prevalent systemic manifestations and addresses the relationship between the dosage (particularly the intensity) of exercise and inflammation. We conclude that present data support potential beneficial effects of exercise on inflammation, however, the evidence specifically in RMDs is limited and inconclusive. More targeted research is required to elucidate the effects of exercise on inflammation in the context of RMDs.
Recent advancement in molecular techniques has spurred numerous studies on responses of microorganisms to lead exposure, leveraging detailed phylogenetic analyses and functional gene identification ...to discern the effects of lead toxicity on microbial communities. A comprehensive review of recent research is provided on (1) lead resistance mechanisms of microorganisms; (2) microbial community changes in contaminated aquatic sediments and terrestrial soils; and (3) lead resistance genes applied to lead biosensor development. Ample evidence in the literature, including both in vitro and in situ studies, indicates that exposure to lead inhibits microbial activities (such as respiration and metabolism), reduces biomass and alters microbial community structure. Even at sites where microbial communities do not vary compositionally with contaminant levels, functional differences between microbial communities are evident. The main mechanisms of lead resistance involve extracellular and intracellular biosorption, precipitation, complexation, and/or efflux pumps. The suites of genes associated with lead resistance mechanisms can serve, when considered with phylogenetic information, as indicators of lead contamination. This holds potential for development of next generation lead biosensors. To promote applications of advanced knowledge, molecular techniques, and lead biosensor technology, perspectives on using microbial indicators for site ecological assessment are presented.
cAMP is the original second messenger that is synthesized in response to a number of extracellular stimuli. Recent advances in cAMP reporter technology have given an insight into how cAMP signals ...retain their specificity. Spatial and temporal cAMP dynamics are regulated by discretely positioned phosphodiesterases that act as sinks to create simultaneous, multiple cAMP gradients in many cellular locations. Such gradients are sampled within microdomains that contain anchored cAMP effector proteins. Compartmentalization of proteins that produce, degrade and are activated by cAMP is crucial for the specificity of action required for normal cell function.
Rheumatoid arthritis (RA) is characterised by functional disability, pain, fatigue and body composition alterations that can further impact on the physical dysfunction seen in RA. RA is also ...associated with systemic manifestations, most notably an increased risk for cardiovascular disease. There is strong evidence to suggest that increasing physical activity and/or exercise can simultaneously improve symptoms and reduce the impact of systemic manifestations in RA. However, implementation of interventions to facilitate increased physical activity and/or exercise within routine clinical practice is slow because of not only patient-specific and healthcare professional-related barriers but also lack of relevant infrastructure and provision. We review the evidence supporting the physiological adaptations and beneficial effects occurring as a result of increased physical activity and/or exercise in RA and propose an implementation model for facilitating the long-term engagement of patients with RA. We propose that implementation should be led, in a pragmatic manner, by rheumatology healthcare practitioners and supported by social innovation.
This article investigates the dynamic relationship between human capital and energy consumption using Chinese provincial data over the period 1990–2010. Considering for cross-sectional dependence and ...parameter heterogeneity across space and over time, we identify a significant and negative human capital–energy consumption relationship in China. Specifically, we find that a 1% increase in human capital reduces energy consumption by a range between 0.18% and 0.45%. Furthermore, this negative relationship can be attributed to stronger accumulation of post-school human capital in eastern China. This finding suggests that energy conservation in China could be achieved by improving post-school human-capital components such as on-the-job training, experience and learning-by-doing.
•We investigate the impact of human capital on energy consumption in China.•We consider cross-sectional dependence and parameter heterogeneity.•Post-school human-capital accumulation improves energy conservation.•Heterogeneous human capital–energy consumption relationships across provinces.
Effect of micro pin-fin shapes on cooling of high heat flux electronic chips with a single hot spot was investigated numerically. Hydrothermal performances of different micro pin-fin shapes were ...evaluated. Circular shape, hydrofoil shape, modified hydrofoil shape, and symmetric convex shape were the cross section shapes used for micro pin-fins. All cooling configurations had the same staggered arrangements for micro pin-fins. An electronic chip with a 2.45 × 2.45 mm footprint having a hot spot of 0.5 × 0.5 mm at its centre was used for simulations. Uniform heat flux of 2000 W cm−2 was applied at the hot spot. The rest of the chip was exposed to 1000 W cm−2 uniform heat load. The cross section area of the circular shape and hydrofoil shape micro pin-fins was kept the same to have a fair comparison. Convex and hydrofoil shape designs showed significant reduction in the required pumping power as well as the maximum required pressure. In the last case, the height of micro pin-fins was increased from 200 μm to 400 μm to remove 100% of the total heat load via convection, and at the same time keep the maximum temperatures within an acceptable range.
•Maximum temperature of hot spots can be reduced using hydrodynamically shaped closely packed array of pin-fins.•Pumping power requirements can be reduced by reshaping and resizing pin-fins.•It is possible to remove all heat from a chip by using an array of micro pin-fins.•Larger cross section pin-fins should be under the hot spot to facilitate local heat conduction.•Multiobjective design optimization and high conductivity thin film coatings are recommended.
Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we ...optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.
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•Optimized CRISPR platform for identification of genome-wide genetic vulnerabilities•Catalog of genetic vulnerabilities in acute myeloid leukemia cell lines•KAT2A inhibition induces myeloid differentiation and apoptosis•KAT2A inhibition arrests the growth of primary AML cells, but not of normal progenitors
Tzelepis et al. optimize a CRISPR-Cas9-based platform for the performance of genome-wide recessive screens and apply it to identify genetic vulnerabilities of human AML cells. They identify several known therapeutic targets including BRD4, DOT1L, and MEN1, and numerous additional candidates. They provide data proposing KAT2A as a potential therapeutic target.
The separation of male and female flowers in maize provides the potential for independent regulation of traits that affect crop productivity. For example, tassel branch number controls pollen ...abundance and length of shedding time, whereas ear row number directly affects kernel yield. Mutations in duplicate SBP-box transcription factor genes unbranched2 ( ub2 ) and ub3 affect both of these yield traits. Double mutants display a decrease in tassel branch number and an increase in ear row number, both of which are enhanced by loss of a related gene called tasselsheath4 ( tsh4 ). Furthermore, triple mutants have more tillers and leaves—phenotypes seen in Corngrass1 mutants that result from widespread repression of SBP-box genes. Immunolocalization of UB2 and UB3 proteins revealed accumulation throughout the meristem but absence from the central domain of the meristem where cells regenerate. Thus, ub2 , ub3 , and tsh4 function as redundant factors that limit the rate of cell differentiation to the lateral domains of meristems. When these genes are mutated, cells are allocated to lateral primordia at a higher rate, causing a net loss of cells from the central domain and premature termination of the inflorescence. The ub3 locus is tightly linked to quantitative trait loci (QTL) for ear row number and tassel branch number in both the nested association mapping (NAM) and intermated B73 by Mo17 (IBM) populations of maize recombinant inbreds, indicating that this gene may be agronomically important. Analysis of ear and tassel QTL across biparental families suggests that multiple mutations in ub3 independently regulate male and female inflorescence development.
Significance Crop yields are dependent on the number of lateral primordia made by the inflorescence. In maize unbranched mutants, excess lateral primordia are made at the expense of the stem cells located in the center of the meristem. Ultimately, the unbranched mutant meristem lacks enough cells to regenerate and thus, terminates prematurely. This study shows that the duplicate transcription factors unbranched2 and unbranched3 function together to decrease the rate of lateral primordia initiation, thus giving the stem cells of the meristem enough time to regenerate. Variants of the unbranched3 gene affect different aspects of lateral primordia initiation that control crop yield.
Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late ...1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.
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