Flynnpihl7772

Cardiac resident macrophages are self-maintaining and originate from embryonic hematopoiesis. After myocardial infarction, cardiac resident macrophages are responsible for the efficient clearance and degradation of apoptotic cardiomyocytes (efferocytosis). This process is required for inflammation resolution and tissue repair; however, the underlying molecular mechanisms remain unknown. Therefore, we aimed to identify the mechanisms of the continued clearance and degradation of phagolysosomal cargo by cardiac resident macrophages during myocardial infarction.

Multiple transgenic mice such as Lgmn

, Lgmn

 ; LysM

, Lgmn

 ; Cx3cr1

, Lgmn

 ; Lyve

, and cardiac macrophage Lgmn overexpression by adenovirus gene transfer were used to determine the functional significance of Lgmn in myocardial infarction. Immune cell filtration and inflammation were examined by flow cytometry and quantitative real-time polymerase chain reaction. Moreover, legumain (Lgmn) expression was analyzed by immunohistochemistry and qua.

Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.

Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.

The impact of laryngeal dysfunction on airflow has not been well characterized in motor neuron disease (MND). This study aimed to detect and characterize extreme airflow oscillations informally observed during volitional cough and forced vital capacity (FVC) tasks in individuals with MND who demonstrated neurolaryngeal impairments including reduced speed and extent of vocal fold abduction compared to healthy controls during volitional cough expulsion. The extreme airflow oscillations in the MND group, when viewed as a flow-volume loop, appeared similar to the "sawtooth-sign." If the airflow oscillations are periodic in a range similar to phonation, they may reflect reduced laryngeal patency.

Volitional cough and FVC airflow data (3 trials each) from 12 participants with MND with bulbar/laryngeal involvement (3 F; ages 45-76) and 12 healthy controls (6 F; ages 41-68) were analyzed for periodicity. Percent and absolute durations of periodicity of the flow oscillations were calculated by an algorithm appliedignificantly larger-magnitude, lower-kurtosis, and more prominent presence of sawtooth-like airflow periodicity within a frequency range similar to phonation observed in individuals with MND with neurolaryngeal impairments suggests glottic airflow resistance during forced expiration.Thermoplasmatota have been widely reported in a variety of ecosystems, but their distribution and ecological role in marine sediments are still elusive. Here, we obtained four draft genomes affiliated with the former RBG-16-68-12 clade, which is now considered a new order, "Candidatus Yaplasmales," of the Thermoplasmatota phylum in sediments from the South China Sea. The phylogenetic trees based on the 16S rRNA genes and draft genomes showed that "Ca. Yaplasmales" archaea are composed of three clades A, B, and C. Among them, clades A and B are abundantly distributed (up to 10.86%) in the marine anoxic sediment layers (>10-cm depth) of six of eight cores from 1,200- to 3,400-m depths. Metabolic pathway reconstructions indicated that all clades of "Ca. Yaplasmales" have the capacity for alkane degradation by predicted alkyl-succinate synthase. AG 825 nmr Clade A of "Ca. Yaplasmales" might be mixotrophic microorganisms for the identification of the complete Wood-Ljungdahl pathway and putative genes involved in the degradatdiated recycling of complex organic carbon is still largely unknown, which is an important question for carbon budget in global oceans and maintenance of the deep-sea ecosystem. In this study, we report the prevalence (up to 10.86% of the microbial community) of archaea from a novel order of Thermoplasmatota, "Ca. Yaplasmales," in six of eight cores from 1,200- to 3,400-m depths in the South China Sea. We provide genomic evidence of "Ca. Yaplasmales" in the anaerobic microbial degradation of alkanes, aliphatic and monoaromatic hydrocarbons, and halogenated organic compounds. Our study identifies the key archaeal players in anoxic marine sediments, which are probably critical in recycling the complex organic carbon in global oceans.In his 1972 paper 'The apportionment of human diversity', Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low FST values. However, when we analyse haplotypes defined by these SNPs (which define 'HLA alleles'), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.Lewontin's 1972 paper (RC Lewontin, 1972 The apportionment of human diversity, in Evolutionary biology, vol. 6 (eds T Dobzhansky, MK Hecht, WC Steere), pp. 381-398) can be viewed as one foray in his battle against biological determinism. Our paper shows where Lewontin, The apportionment of human diversity, fits in the debate over human classification that it stimulated. We outline three assumptions inherent in the biological deterministic view of human phenotypic diversity and show how the 1972 paper, as well as Lewontin's papers in 1970 and 1974 on the problems with the heritability statistic and his 1979 criticism of naive pan-selectionism, invalidate these assumptions. These papers were crucial components of his campaign against biological determinism and the racism with which it was associated. In the current climate of widespread racism and the rise of sociogenomics, it is important to revisit Lewontin's writings and to disseminate the messages they contain. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.Lewontin's 1972 article 'The apportionment of human diversity' described a key feature of human genetic diversity that would have profound impacts on conversations regarding genetics and race the typical genetic locus varies much less between classical human race groupings than one might infer from inspecting the features historically used to define those races, like skin pigmentation. From this, Lewontin concluded 'Human racial classification … is now seen to be of virtually no genetic or taxonomic significance' (p. 397). Here, 50 years after the paper's publication, the goal is to understand the origins and legacy of the paper. Aided by insights from published papers and interviews with several of Lewontin's contemporaries, I review the 1972 paper, asking about the intellectual background that led to the publication of the paper, the development of its impact, the critiques of the work and the work's application and limitations today. The hope is that by gaining a clearer understanding of the origin and reasoning of the paper, we might dispel various confusions about the result and sharpen an understanding of the enduring value and insight the result provides. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.'The Apportionment of Human Diversity' stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontin's conclusion that racial classification is of 'virtually no genetic or taxonomic significance', the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontin's work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.Given the many small-effect loci uncovered by genome-wide association studies (GWAS), polygenic scores have become central to genomic medicine, and have found application in diverse settings including evolutionary studies of adaptation. Despite their promise, polygenic scores have been found to suffer from limited portability across human populations. This at first seems in conflict with the observation that most common genetic variation is shared among populations. We investigate one potential cause of this discrepancy stabilizing selection on complex traits. Counterintuitively, while stabilizing selection constrains phenotypic evolution, it accelerates the loss and fixation of alleles underlying trait variation within populations (GWAS loci). Thus even when populations share an optimum phenotype, stabilizing selection erodes the variance contributed by their shared GWAS loci, such that predictions from GWAS in one population explain less of the phenotypic variation in another. We develop theory to quantify how stabilizing selection is expected to reduce the prediction accuracy of polygenic scores in populations not represented in GWAS samples. In addition, we find that polygenic scores can substantially overstate average genetic differences of phenotypes among populations. We emphasize stabilizing selection around a common optimum as a useful null model to connect patterns of allele frequency and polygenic score differentiation. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.