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Walther Hickman opublikował 5 miesięcy, 1 tydzień temu
The results of this study provide a basis for the cost-effective and technically undemanding fabrication of high-energy-density LIBs.
The mental health and well-being of gender and sexuality diverse (GSD) people needs to be understood within a socio-political and cultural context.
In this paper, an intersectional, social and system-based framework for understanding the mental health and well-being of GSD people is presented, for practitioners within this field to consider GSD mental health experiences and challenges within context.
Starting with a consideration of the current landscape of understanding, pivotal theories and understandings within the field are outlined. The need for a framework that centralises intersectionality and broader systemic considerations is presented.
The framework provided has an explicit focus on four key features (1) intersectionality, (2) institutions, policies and laws, (3) people and groups and (4) social stories.
Consideration of each of these 'circles of influence’ can help practitioners to understand the multi-layered and intersectional experience of GSD folk and allows for an understanding of potential intervention at both an individual and systemic and societal level.
Use of such a framework in practice goes above and beyond what is currently available by centralising the role and impact of such wider systemic variables through an intersectional lens. The framework can be applicable worldwide given its flexibility to consider and apply pertinent policies, laws, people, groups and social stories within a particular country or culture.
Use of such a framework in practice goes above and beyond what is currently available by centralising the role and impact of such wider systemic variables through an intersectional lens. The framework can be applicable worldwide given its flexibility to consider and apply pertinent policies, laws, people, groups and social stories within a particular country or culture.The Bis-T series of compounds comprise some of the most potent inhibitors of dynamin GTPase activity yet reported, e. g., (2E,2’E)-N,N’-(propane-1,3-diyl)bis(2-cyano-3-(3,4-dihydroxyphenyl)acrylamide) (2), Bis-T-22. The catechol moieties are believed to limit cell permeability, rendering these compounds largely inactive in cells. To solve this problem, a prodrug strategy was envisaged and eight ester analogues were synthesised. The shortest and bulkiest esters (acetate and butyl/tert-butyl) were found to be insoluble under physiological conditions, whilst the remaining five were soluble and stable under these conditions. These five were analysed for plasma stability and half-lives ranged from ∼2.3 min (propionic ester 4), increasing with size and bulk, to greater than 24 hr (dimethyl carbamate 10). Similar profiles where observed with the rate of formation of Bis-T-22 with half-lives ranging from ∼25 mins (propionic ester 4). Propionic ester 4 was chosen to undergo further testing and was found to inhibit endocytosis in a dose-dependent manner with IC50 ∼8 μM, suggesting this compound is able to effectively cross the cell membrane where it is rapidly hydrolysed to the desired Bis-T-22 parent compound.Liquid metal catalysts have recently attracted attention for synthesizing high-quality 2D materials facilitated via the catalysts’ perfectly smooth surface. However, the microscopic catalytic processes occurring at the surface are still largely unclear because liquid metals escape the accessibility of traditional experimental and computational surface science approaches. Hence, numerous controversies are found regarding different applications, with graphene (Gr) growth on liquid copper (Cu) as a prominent prototype. In this work, novel in situ and in silico techniques are employed to achieve an atomic-level characterization of the graphene adsorption height above liquid Cu, reaching quantitative agreement within 0.1 Å between experiment and theory. The results are obtained via in situ synchrotron X-ray reflectivity (XRR) measurements over wide-range q-vectors and large-scale molecular dynamics simulations based on efficient machine-learning (ML) potentials trained to first-principles density functional theory (DFT) data. The computational insight is demonstrated to be robust against inherent DFT errors and reveals the nature of graphene binding to be highly comparable at liquid Cu and solid Cu(111). Transporting the predictive first-principles quality via ML potentials to the scales required for liquid metal catalysis thus provides a powerful approach to reach microscopic understanding, analogous to the established computational approaches for catalysis at solid surfaces.Different modes of reproduction evolve rapidly, with important consequences for genome composition. Selfing species often occupy a similar niche as their outcrossing sister species with which they are able to mate and produce viable hybrid progeny, raising the question of how they maintain genomic identity. Here, we investigate this issue by using the nematode Caenorhabditis briggsae, which reproduces as a hermaphrodite, and its outcrossing sister species Caenorhabditis nigoni We hypothesize that selfing species might develop some barriers to prevent gene intrusions through gene regulation. We therefore examined gene regulation in the hybrid F2 embryos resulting from reciprocal backcrosses between F1 hybrid progeny and C. nigoni or C. briggsae F2 hybrid embryos with ∼75% of their genome derived from C. briggsae (termed as bB2) were inviable, whereas those with ∼75% of their genome derived from C. nigoni (termed as nB2) were viable. Misregulation of transposable elements, coding genes, and small regulatory RNAs was more widespread in the bB2 compared with the nB2 hybrids, which is a plausible explanation for the differential phenotypes between the two hybrids. Our results show that regulation of the C. briggsae genome is strongly affected by genetic exchanges with its outcrossing sister species, C. nigoni, whereas regulation of the C. nigoni genome is more robust on genetic exchange with C. briggsae The results provide new insights into how selfing species might maintain their identity despite genetic exchanges with closely related outcrossing species.High-throughput short-read sequencing has taken on a central role in research and diagnostics. Hundreds of different assays take advantage of Illumina short-read sequencers, the predominant short-read sequencing technology available today. Although other short-read sequencing technologies exist, the ubiquity of Illumina sequencers in sequencing core facilities and the high capital costs of these technologies have limited their adoption. Among a new generation of sequencing technologies, Oxford Nanopore Technologies (ONT) holds a unique position because the ONT MinION, an error-prone long-read sequencer, is associated with little to no capital cost. Here we show that we can make short-read Illumina libraries compatible with the ONT MinION by using the rolling circle to concatemeric consensus (R2C2) method to circularize and amplify the short library molecules. This results in longer DNA molecules containing tandem repeats of the original short library molecules. This longer DNA is ideally suited for the ONT MinION, and after sequencing, the tandem repeats in the resulting raw reads can be converted into high-accuracy consensus reads with similar error rates to that of the Illumina MiSeq. We highlight this capability by producing and benchmarking RNA-seq, ChIP-seq, and regular and target-enriched Tn5 libraries. We also explore the use of this approach for rapid evaluation of sequencing library metrics by implementing a real-time analysis workflow.As expansions of CGG short tandem repeats (STRs) are established as the genetic etiology of many neurodevelopmental disorders, we aimed to elucidate the inheritance patterns and role of CGG STRs in autism-spectrum disorder (ASD). By genotyping 6063 CGG STR loci in a large cohort of trios and quads with an ASD-affected proband, we determined an unprecedented rate of CGG repeat length deviation across a single generation. Although the concept of repeat length being linked to deviation rate was solidified, we show how shorter STRs display greater degrees of size variation. We observed that CGG STRs did not segregate by Mendelian principles but with a bias against longer repeats, which appeared to magnify as repeat length increased. Through logistic regression, we identified 19 genes that displayed significantly higher rates and degrees of CGG STR expansion within the ASD-affected probands (P less then 1 × 10-5). This study not only highlights novel repeat expansions that may play a role in ASD but also reinforces the hypothesis that CGG STRs are specifically linked to human cognition.Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. mtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation, and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we use Saccharomyces yeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates of Saccharomyces paradoxus and Saccharomyces cerevisiae Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but the recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which led to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism, and the emergence of reproductive isolation.Aging is associated with changes in a variety of biological processes at the transcriptomic level, including gene expression. Two types of aging occur during a lifetime chronological and physiological aging. However, dissecting the difference between chronological and physiological ages at the transcriptomic level has been a challenge because of its complexity. We analyzed the transcriptomic features associated with physiological and chronological aging using Caenorhabditis elegans as a model. Many structural and functional transcript elements, such as noncoding RNAs and intron-derived transcripts, were up-regulated with chronological aging. In contrast, mRNAs with many biological functions, including RNA processing, were down-regulated with physiological aging. We also identified an age-dependent increase in the usage of distal 3′ splice sites in mRNA transcripts as a biomarker of physiological aging. Our study provides crucial information for dissecting chronological and physiological aging at the transcriptomic level.