Exerkines in health, resilience and disease Chow, Lisa S; Gerszten, Robert E; Taylor, Joan M ...
Nature reviews. Endocrinology,
05/2022, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular ...mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.
We aimed to evaluate changes to measles-containing vaccine (MCV) provision and subsequent measles disease cases in low- and lower-middle income countries (LICs, LMICs) in relation to the COVID-19 ...pandemic.
A systematic search was conducted of MEDLINE, OVID EMBASE and PubMed records. Primary quantitative and qualitative research studies published from January 2020 were included if they reported on COVID-19 impact on MCV provision and/or measles outbreak rates within LICs and LMICs.
45 studies were included. The change in MCV1 vaccination coverage in national and international regions ranged -13% to +44.4% from pre-COVID time periods. In local regions, the median MCV1 and overall EPI rate changed by -23.3% and -28.5% respectively. Median MCV2 rate was disproportionally impacted in local areas during COVID-interruption time-periods (-48.2%) with ongoing disruption in early-recovery time-periods (-17.7%). 8.9% of studies reported on vaccination status of confirmed measles cases; from these, 71%-91% had received no MCV dose.
MCV vaccination coverage experienced ongoing disruption during the recovery periods after initial COVID-19 disruption. Vaccination in local area datasets notably experienced longer-term disruption compared to nationally reported figures.
Agassiz's desert tortoise (Gopherus agassizii) is a long-lived species native to the Mojave Desert and is listed as threatened under the US Endangered Species Act. To aid conservation efforts for ...preserving the genetic diversity of this species, we generated a whole genome reference sequence with an annotation based on deep transcriptome sequences of adult skeletal muscle, lung, brain, and blood. The draft genome assembly for G. agassizii has a scaffold N50 length of 252 kbp and a total length of 2.4 Gbp. Genome annotation reveals 20,172 protein-coding genes in the G. agassizii assembly, and that gene structure is more similar to chicken than other turtles. We provide a series of comparative analyses demonstrating (1) that turtles are among the slowest-evolving genome-enabled reptiles, (2) amino acid changes in genes controlling desert tortoise traits such as shell development, longevity and osmoregulation, and (3) fixed variants across the Gopherus species complex in genes related to desert adaptations, including circadian rhythm and innate immune response. This G. agassizii genome reference and annotation is the first such resource for any tortoise, and will serve as a foundation for future analysis of the genetic basis of adaptations to the desert environment, allow for investigation into genomic factors affecting tortoise health, disease and longevity, and serve as a valuable resource for additional studies in this species complex.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The influence of spin-orbit coupling (SOC) on the physical properties of the 5
d
2
system Sr
2
MgOsO
6
is probed via a combination of magnetometry, specific heat measurements, elastic and ...inelastic neutron scattering and density functional theory calculations. Although a significant degree of frustration is expected, we find that Sr
2
MgOsO
6
orders in a type I antiferromagnetic structure at the remarkably high temperature of 108 K. The measurements presented allow for the first accurate quantification of the size of the magnetic moment in a 5
d
2
system of 0.60(2) μ
B
–a significantly reduced moment from the expected value for such a system. Furthermore, significant anisotropy is identified via a spin excitation gap and we confirm by first principles calculations that SOC not only provides the magnetocrystalline anisotropy, but also plays a crucial role in determining both the ground state magnetic order and the size of the local moment in this compound. Through comparison to Sr
2
ScOsO
6
, it is demonstrated that SOC-induced anisotropy has the ability to relieve frustration in 5
d
2
systems relative to their 5
d
3
counterparts, providing an explanation of the high
T
N
found in Sr
2
MgOsO
6
.
To assess production animal medicine veterinarians' prescription practices and identify factors influencing their use of antimicrobial drugs (AMDs) and their perceptions of and attitudes toward ...antimicrobial resistance (AMR).
157 production animal veterinarians in the United States.
An online cross-sectional survey and digital diary were used to gather information regarding perceptions on AMD use and AMR and on treatment recommendations for production setting-specific disease scenarios. Results were compared across respondents grouped by their selected production setting scenarios and reported years as veterinarians.
The most commonly selected production setting disease scenarios were dairy cattle (96/157 61.1%), backgrounding cattle (32/157 20.4%), and feedlot cattle (20/157 12.7%). Because few respondents selected swine (5/157 3.2%) or poultry (4/157 2.5%) scenarios, those responses were excluded from statistical analysis of AMD prescription practices. Most remaining respondents (147/148 99.3%) reported that they would recommend AMD treatment for an individual ill animal; however, responses differed for respondents grouped by their selected production setting scenarios and reported years as veterinarians when asked about AMD treatment of an exposed group or high-risk disease-free group. Most respondents reported that government regulations influenced their AMD prescribing, that owner and producer compliance was a veterinary-related factor that contributed to AMR, and that environmental modifications to prevent disease could be effective to mitigate AMR.
Results of the present study helped fill important knowledge gaps pertaining to prescription practices and influencing factors for AMD use in production animal medicine and provided baseline information for future assessments. This information could be used to inform future interventions and training tools to mitigate the public health threat of AMR.
Distance, environmental heterogeneity and local adaptation can strongly influence population structure and connectivity. Understanding how these factors shape the genomic landscape of threatened ...species is a major goal in conservation genomics and wildlife management. Herein, we use thousands (6,859) of single nucleotide polymorphism markers and spatial data from hundreds of individuals (n = 646) to re-evaluate the population structure of Agassiz's desert tortoise (Gopherus agassizii). Analyses resolve from 4 to 8 spatially well-defined clusters across the range. Western, central, and southern populations within the Western Mojave recovery unit are consistent throughout, while analyses sometimes merge other recovery units depending on the level of clustering. Causal modeling consistently associates genetic connectivity with least-cost distance, based on multiple landscape features associated with tortoise habitat, better than geographic distance. Some features include elevation, soil depth, rock volume, precipitation, and vegetation coverage, suggesting that physical, climatic, and biotic landscape features have played a strong evolutionary role restricting gene flow between populations. Further, 12 highly differentiated outlier loci have associated functions that may be involved with neurogenesis, wound healing, lipid metabolism, and possibly vitellogenesis. Together, these findings have important implications for recovery programs, such as translocations, population augmentation, reproduction in captivity and the identification of ecologically important genes, opening new venues for conservation genomics in desert tortoises.
Abstract
Targeted DNA sequencing approaches will improve how the size of short tandem repeats is measured for diagnostic tests and preclinical studies. The expansion of these sequences causes dozens ...of disorders, with longer tracts generally leading to a more severe disease. Interrupted alleles are sometimes present within repeats and can alter disease manifestation. Determining repeat size mosaicism and identifying interruptions in targeted sequencing datasets remains a major challenge. This is in part because standard alignment tools are ill-suited for repetitive and unstable sequences. To address this, we have developed Repeat Detector (RD), a deterministic profile weighting algorithm for counting repeats in targeted sequencing data. We tested RD using blood-derived DNA samples from Huntington’s disease and Fuchs endothelial corneal dystrophy patients sequenced using either Illumina MiSeq or Pacific Biosciences single-molecule, real-time sequencing platforms. RD was highly accurate in determining repeat sizes of 609 blood-derived samples from Huntington’s disease individuals and did not require prior knowledge of the flanking sequences. Furthermore, RD can be used to identify alleles with interruptions and provide a measure of repeat instability within an individual. RD is therefore highly versatile and may find applications in the diagnosis of expanded repeat disorders and in the development of novel therapies.
There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a ...second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.
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