Previous work introduced the [11C]yohimbine as a suitable ligand of central α2-adrenoreceptors (α2-ARs) for PET imaging. However, reproducibility of [11C]yohimbine PET measurements in healthy humans estimated with a simplified modeling method with reference region, as well as sensitivity of [11C]yohimbine to noradrenergic competition were not evaluated. The objectives of the present study were therefore to fill this gap.

Thirteen healthy humans underwent two [

C]yohimbine 90-minute dynamic scans performed on a PET-MRI scanner. Seven had arterial blood sampling with metabolite assessment and plasmatic yohimbine free fraction evaluation at the first scan to have arterial input function and test appropriate kinetic modeling. The second scan was a simple retest for 6 subjects to evaluate the test-retest reproducibility. For the remaining 7 subjects the second scan was a challenge study with the administration of a single oral dose of 150µg of clonidine 90min before the PET scan. Parametric images of α2-ARs distvivo in the human brain. Trial registration EudraCT 2018-000380-82.

The results add experimental support for the suitability of [11C]yohimbine PET in the quantitative assessment of α2-ARs occupancy in vivo in the human brain. Trial registration EudraCT 2018-000380-82.Interest in understanding the organization of the brain has led to the application of graph theory methods across a wide array of functional connectivity studies. The fundamental basis of a graph is the node. Recent work has shown that functional nodes reconfigure with brain state. To date, all graph theory studies of functional connectivity in the brain have used fixed nodes. Here, using fixed-, group-, state-specific, and individualized- parcellations for defining nodes, we demonstrate that functional connectivity changes within the nodes significantly influence the findings at the network level. In some cases, state- or group-dependent changes of the sort typically reported do not persist, while in others, changes are only observed when node reconfigurations are considered. The findings suggest that graph theory investigations into connectivity contrasts between brain states and/or groups should consider the influence of voxel-level changes that lead to node reconfigurations; the fundamental building block of a graph.Marine rockpools are isolated patches of habitat in the supratidal environment (the so-called splash zone), at the transition between sea and land, found along the rocky shores worldwide and characterized by harsh conditions for life. Nonetheless, few specialized invertebrates successfully colonized this peculiar environment. Among them several members of the water beetles Ochthebius Leach, 1815, subgenus Cobalius Rey (1886), which are found almost exclusively in supratidal and upper-most intertidal marine rockpools from the eastern Atlantic Ocean (Cape Verde, Canary Islands and Morocco, Madeira, Azores) throughout the whole Mediterranean basin. The subgenus Cobalius before 2020 was considered to include ten valid species, based on morphological differences. In late 2020, four additional new species were described. However, recent molecular phylogenetic studies have uncovered further cryptic diversity suggesting the presence of multiple undetected species within this group, highlighting that the species boundputative species, most of them diverged during the Late Miocene, Pliocene and Pleistocene (6.0-0.11 Mya).Although there is general consensus that sampling of multiple genetic loci is critical in accurate reconstruction of species trees, the exact numbers and the best types of molecular markers remain an open question. In particular, the phylogenetic utility of sex-linked loci is underexplored. Here, we sample all species and 70% of the named diversity of the New World wren genus Campylorhynchus using sequences from 23 loci, to evaluate the effects of linkage on efficiency in recovering a well-supported tree for the group. At a tree-wide level, we found that most loci supported fewer than half the possible clades and that sex-linked loci produced similar resolution to slower-coalescing autosomal markers, controlling for locus length. By contrast, we did find evidence that linkage affected the efficiency of recovery of individual relationships; as few as two sex-linked loci were necessary to resolve a selection of clades with long to medium subtending branches, whereas 4-6 autosomal loci were necessary to achieve comparable results. These results support an expanded role for sampling of the avian Z chromosome in phylogenetic studies, including target enrichment approaches. Our concatenated and species tree analyses represent significant improvements in our understanding of diversification in Campylorhynchus, and suggest a relatively complex scenario for its radiation across the Miocene/Pliocene boundary, with multiple invasions of South America.Dated species-level phylogenies are crucial for understanding the origin and evolutionary history of modern faunas, yet difficult to obtain due to the frequent absence of suitable age calibrations at species level. Substitution rates of related or more inclusive clades are often used to overcome this limitation but the accuracy of this approach remains untested. We compared tree dating based on substitution rates with analyses implementing fossil data by direct node-dating and indirect root-age constraints for the New Zealand endemic Berosus water beetles (Coleoptera Hydrophilidae). The analysis based solely on substitution rates indicated a Miocene colonization of New Zealand and Pleistocene origin of species. By contrast, all analyses that implemented fossil data resulted in significantly older age estimates, indicating an ancient early Cenozoic origin of the New Zealand clade, diversification of species during or after the Oligocene transgression and Miocene-Pliocene origin of within-species population structure. Rate-calibrated time trees were incongruent with recently published Coleoptera time trees, the fossil record of Berosus and the distribution of outgroup species. Strong variation of substitution rates among Coleoptera lineages, as well as among lineages within the family Hydrophilidae, was identified as the principal reason for low accuracy of rate-calibrated analyses, resulting in underestimated node ages in Berosus. We provide evidence that Oligocene to Pliocene events, rather than the Pleistocene Glacial cycles, played an essential role in the formation of the modern New Zealand insect fauna.Human biological aging from maturity to senescence is associated with a gradual loss of muscle mass and neuromuscular function. It is not until very old age (>80 years) however, that these changes often manifest into functional impairments. A driving factor underlying the age-related loss of muscle mass and function is the reduction in the number and quality of motor units (MUs). A MU consists of a single motoneuron, located either in the spinal cord or the brain stem, and all of the muscle fibres it innervates via its peripheral axon. Throughout the adult lifespan, MUs are slowly, but progressively lost. The compensatory process of collateral reinnervation attempts to recapture orphaned muscle fibres following the death of a motoneuron. Whereas this process helps mitigate loss of muscle mass during the latter decades of adult aging, the neuromuscular system has fewer and larger MUs, which have lower quality connections between the axon terminal and innervated muscle fibres. Whether this process of MU death and degradation can be attenuated with habitual physical activity has been a challenging question of great interest. This review focuses on age-related alterations of the human neuromuscular system, with an emphasis on the MU, and presents findings on the potential protective effects of lifelong physical activity. Although there is some discrepancy across studies of masters athletes, if one considers all experimental limitations as well as the available literature in animals, there is compelling evidence of a protective effect of chronic physical training on human MUs. Our tenet is that high-levels of physical activity can mitigate the natural trajectory of loss of quantity and quality of MUs in old age.

The objective of this study was to use nationally-representative data on Americans greater than 50years of age to determine the association between grip strength and inflammation as independent predictors of incident disability, chronic multimorbidity and dementia.

Middle age and older adults (n=12,618) from the 2006-2008 waves of the Health and Retirement Study with 8-years of follow-up were included. Longitudinal modeling was performed to examine the association between baseline grip strength (normalized to body mass NGS) and high sensitivity C-reactive protein (hs-CRP) (≥3.0mg/L) with incident physical disabilities (i.e., ≥2 limitations to activities of daily living), chronic multimorbidity (≥2 of chronic conditions), and dementia.

The odds of incident disability were 1.25 (95% CI 1.20-1.30) and 1.31 (95% CI 1.26-1.36) for men and women respectively, for each 0.05-unit lower NGS. The odds of incident chronic multimorbidity were 1.14 (95% CI 1.08-1.20) and 1.14 (95% CI 1.07-1.21) for men and women res should implement measures of grip strength in routine health assessments and discuss the potential dangers of weakness as well as interventions to improve strength with their patients.Gene expression of SAP 4-6 based on the detection of mRNA was observed in Candida albicans isolates from HIV-positive patients with oral candidiasis and commensal from healthy individuals. The species of C. albicans strains were selectively isolated from both sources using CHROMagar Chromogenic Media. The obtained isolates were then induced to express SAP 4-6 using SAP 4-6 gene inducer media. Analysis of gene expression was performed on a molecular basis using the RT-PCR method. Molecular analysis of gene expression showed that the isolates CH3 from HIV-positive patients with oral candidiasis could express SAP 4-6 gene, while commensal isolates from healthy people could not. Based on the results of this study, it could be concluded that, in terms of molecular detection, only isolates from HIV-positive patients (CH3) could express their SAP 4-6 gene.Function of mTORC1 and mTORC2 has emerged as a driver of mesangial cell pathologies in diabetic nephropathy. The mechanism of mTOR activation is poorly understood in this disease. Deptor is a constitutive subunit and a negative regulator of both mTOR complexes. Mechanistic investigation in mesangial cells revealed that high glucose decreased the expression of deptor concomitant with increased mTORC1 and mTORC2 activities, induction of hypertrophy and, expression of fibronectin and PAI-1. shRNAs against deptor mimicked these pathologic outcomes of high glucose. Conversely, overexpression of deptor significantly inhibited all effects of high glucose. To determine the mechanism of deptor suppression, we found that high glucose significantly increased the expression of EZH2, resulting in lysine-27 tri-methylation of histone H3 (H3K27Me3). Employing approaches including pharmacological inhibition, shRNA-mediated downregulation and overexpression of EZH2, we found that EZH2 regulates high glucose-induced deptor suppression along with activation of mTOR, mesangial cell hypertrophy and fibronectin/PAI-1 expression.