Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiologically Based Pharmacokinetic Models Predicting Renal and Hepatic Concentrations of Industrial Chemicals after Virtual Oral Doses in Rats.

Recently developed high-throughput in vitro assays in combination with computational models could provide alternatives to animal testing. The purpose of the present study was to model the plasma, hepatic, and renal pharmacokinetics of approximately 150 structurally varied types of drugs, food components, and industrial chemicals after virtual external oral dosing in rats and to determine the relationship between the simulated internal concentrations in tissue/plasma and their lowest-observed-effect levels. The model parameters were based on rat plasma data from the literature and empirically determined pharmacokinetics measured after oral administrations to rats carried out to evaluate hepatotoxic or nephrotic potentials. To ensure that the analyzed substances exhibited a broad diversity of chemical structures, their structure-based location in the chemical space underwent projection onto a two-dimensional plane, as reported previously, using generative topographic mapping. A high-throughput in silico one-compartment model and a physiologically based pharmacokinetic (PBPK) model consisting of chemical receptor (gut), metabolizing (liver), central (main), and excreting (kidney) compartments were developed in parallel. For 159 disparate chemicals, the maximum plasma concentrations and the areas under the concentration-time curves obtained by one-compartment models and modified simple PBPK models were closely correlated. However, there were differences between the PBPK modeled and empirically obtained hepatic/renal concentrations and plasma maximal concentrations/areas under the concentration-time curves of the 159 chemicals. For a few compounds, lowest-observed-effect levels were available for hepatotoxicity and nephrotoxicity in the Hazard Evaluation Support System Integrated Platform in Japan. The areas under the renal or hepatic concentration-time curves estimated using PBPK modeling were inversely associated with these lowest-observed-effect levels. Using PBPK forward dosimetry could provide the plasma/tissue concentrations of drugs and chemicals after oral dosing, thereby facilitating estimates of nephrotoxic or hepatotoxic potential as a part of risk assessment.
Spatial variation in structural damage to a keystone plant species in the sub-Antarctic: interactions between Azorella selago and invasive house mice

Abstract On Southern Ocean islands the effects of the house mouse on plants are not well understood. In particular, its influence at the landscape scale has largely been overlooked. To address this issue, we systematically mapped the distribution of a keystone, cushion plant species, Azorella selago, and mouse damage to it across Marion Island. Mouse damage was observed in a third of the sampled sites from sea level to 548 m a.s. l. Damage to individual cushions ranged from single burrows to the disintegration of entire cushions. Mouse damage was high in sites with low A. selago density, suggesting that in areas of low cushion density the impact of mice may be substantial. Moreover, it is not simply direct impacts on the A. selago population that are ecologically significant. Azorella selago cushions serve as nurse plants for many epiphyte species, so increasing the altitudinal range of a variety of them, and also house high densities of invertebrates especially in fellfield landscapes. In consequence, this study demonstrates that mice are having a significant, negative impact at the landscape scale on Marion Island, so adding to the growing list of species and ecosystem-level effects attributable to this invasive rodent.
Diverse nucleosome Site-Selectivity among histone deacetylase complexes

Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Previously we reported the results of studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates which revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (Wu et al, 2018). Here we analyze the enzymatic properties of five class I HDAC complexes: CoREST, NuRD, Sin3B, MiDAC and SMRT with site-specific acetylated nucleosome substrates. Our results demonstrate that these HDAC complexes show a wide variety of deacetylase rates in a site-selective manner. A Gly13 in the histone H3 tail is responsible for a sharp reduction in deacetylase activity of the CoREST complex for H3K14ac. These studies provide a framework for connecting enzymatic and biological functions of specific HDAC complexes.
Effects of Deer Browsing on Native and Non-native Vegetation in a Mixed Oak-Beech Forest on the Atlantic Coastal Plain

Abstract We studied the effects of browsing by Odocoileus virginianus (white-tailed deer) on the native and non-native vegetation in a mixed oak-beech forest in Rock Creek Park, Washington, DC. We compared the thickness and cover of vegetation up to 2 m in height, and species richness of native and non-native plants in 17 exclosed (1 × 4 m) and 17 control plots from 2001–2004. Over the four-year period, foraging by deer suppressed the thickness of vegetation ≤ 1 m in height, reduced the cover of herbaceous, woody, and native plants, and generally decreased the species richness of native and woody plants. Browsing had no effects on the species richness of non-native plants, but generally reduced the prevalence of Celastrus orbiculatus (oriental bittersweet). Of the dominant canopy species, browsing affected Quercus spp. (oak) regeneration, but had no apparent effects on Fagus grandifolia (American beech). These results indicate that white-tailed deer are having a detrimental effect on the structure and species richness of native plants in this forest, and as a consequence, diminishing the value of the habitat for wildlife. In addition, white-tailed deer may help control the spread of oriental bittersweet in forest interiors, particularly where this species occurs at relatively low levels. If deer browsing is left uncontrolled in this forest, we predict that its future composition will shift towards one with fewer species and one dominated almost exclusively by American beech.
Connectivity and patch area in a coastal marine landscape: Disentangling their influence on local species richness and composition

Landscape ecology emerged as a terrestrial discipline to evaluate the effect of spatial configuration of natural systems on ecological patterns. The advances in marine systems have been comparatively scarce perhaps as a consequence of a long-standing view about the greater dispersal potential of marine species and its effect on the spatial homogenization of marine landscapes. Herein we used an intertidal rocky system as a model to analyse the effect of landscape attributes on local species richness and composition. We evaluated the effect of patch area, landscape connectivity and salinity gradient on local species richness of macro-invertebrates, and the effect of geographic distance on species similarity. We sampled 19 rocky patches along the Uruguayan Atlantic coast one time during the spring of 2003. The relative contribution of the variables assessed on specific richness of sessile, mobile and total macrofauna was analysed with a stepwise multiple linear regression. For the mobile macrofaunal richness, we also incorporated the sessile macrofaunal richness as another independent variable. The effect of geographic distance on biological similarity was assessed by a Mantel test. We showed that landscape connectivity, as a descriptor of the average physical isolation of a biological community in the landscape, is an important factor explaining the community species richness for sessile macrofauna, what indirectly increases the mobile macrofaunal richness. The geographic distance between sites was negatively related to species similarity. We suggest that at the landscape scale, connectivity among sites can be important to understand the local structure of marine communities, particularly in rocky intertidal systems. Also the distance-decay of similarity in community composition provides a useful descriptor of how biological composition varies along a physical gradient. Our results contribute to reinforce the view that mesoscale connectivity (101–2 km) in coastal marine landscapes plays a more important role in local community structure than previously assumed.
Association of CD8 T cell apoptosis and EGFR mutation in non‐small lung cancer patients

Background The abundance of tumor infiltrating CD8 T cells is an important parameter for antitumor effect of PD‐1/PD‐L1 immune checkpoint inhibitors, which is less in epidermal growth factor receptor (EGFR) mutation than wild‐type non‐small cell lung cancer (NSCLC). The mechanism still requires further study. Methods In total 190 surgical lung adenocarcinoma samples were included. EGFR mutation was detected using amplification‐refractory mutation system. CD8 T cells and apoptosis were assessed by immunohistochemistry and immunofluorescence staining in tumor samples. Exosomes extracted from lung cancer cell lines with and without EGFR mutation were used to test the function of promoting apoptosis in vitro. Results The ratio of CD8 tumor infiltration lymphocytes was significantly lower in EGFR‐mutant than in wild‐type patients (P = 0.026). A higher ratio of apoptosis was also prone to occur in EGFR‐mutant patients (P = 0.035). The distribution of apoptosis was not statistically associated with the ratio of CD8 TILs. An in vitro experiment indicated that exosomes secreted by EGFR‐mutant non‐small cell lung cancer cell lines PC9 and HCC827 were more capable of promoting CD8 T cell apoptosis than EGFR wild‐type cell lines H1299 and SK‐MES‐1 (P = 0.007 and P = 0.010, respectively). Conclusions Non‐small cell lung cancer EGFR mutation could promote CD8 T cell apoptosis more than wild‐type. Inhibiting CD8 + TILs apoptosis may strengthen immunotherapy effects in EGFR‐mutant NSCLC patients.
Microsporidia Can Acquire Lamin‐like Intermediate Filaments and Cell Adhesion Catenin‐cadherin Complexes from the Host (?)

On their spore surfaces, Microsporidia often develop a canopy of filaments with characteristics of intermediate filaments (IF), as we demonstrated in previous studies on Thelohania sp. , Ameson michaelis, and Spraguea lophii. Genomic studies indicate that among invertebrates, lamins that may localize in the cytoplasm or nucleus, are the only known IF type. These IFs can bind to the substrate containing cell adhesion molecules (CAMs) cadherins, associated with β and γ catenins. The objects of this study were to determine whether microsporidia have CAMs with the attached IFs on their envelopes and to find out if these proteins are provided by the host. An examination was made for localization of lamins and CAMs on the spores of the mentioned above species and Anncaliia algerae, plus in the host animals. Then, we determined whether the spores of A. michaelis and A. algerae could bind vertebrate nuclear lamin onto the spore surface. We also tested transgenic Drosophila melanogaster stocks bearing cadherin‐GFP to see whether developing A. algerae parasites in these hosts could acquire host CAMs. The tests were positive for all these experiments. We hypothesize that microsporidia are able to acquire host lamin IFs and cell adhesion catenin–cadherin complexes from the host.
Phylogeny of Trematomus (Notothenioidei: Nototheniidae) inferred from mitochondrial and nuclear gene sequences

Abstract The biota of Antarctica is amazingly rich and highly endemic. The phylogenetics of notothenioid fishes has been extensively investigated through analyses of morphological characters, DNA sequences from mitochondrial genes, and single copy nuclear genes. These phylogenetic analyses have produced reasonably similar phylogenetic trees of notothenioids, however a number of phylogenetic questions remain. The nototheniid clade Trematomus is an example of a group where phylogenetic relationships remain unresolved. In this paper we revisit the phylogenetic relationships of Trematomus using both increased taxon sampling and an expanded dataset which includes DNA sequences from two mitochondrial genes (ND2 and 16S rRNA) and one single-copy nuclear gene (RPS7). The Bayesian phylogeny resulting from the analysis of the combined mitochondrial and nuclear gene datasets was well resolved and contained more interspecific nodes supported with significant Bayesian posteriors than either the mitochondrial or nuclear gene phylogenies alone. This demonstrates that the addition of nuclear gene sequence data to mitochondrial data can enhance phylogenetic resolution and increase node support. Additionally, the results of the combined mitochondrial and nuclear Bayesian analyses provide further support for the inclusion of species previously classified as Pagothenia and Cryothenia in Trematomus.
Rate of the HIV transmission and associated factors among HIV-exposed infants in Guangxi , China: 2014-2019.

This study aims to evaluate the epidemiological characteristics of mother-to-child transmission (MTCT) of HIV and identify the possible factors leading to infant HIV infection using a retrospective cohort study of early infant diagnosis (EID). Information on a total of 3,145 exposed infant-mother pairs was collected from the EID platform from July/2014 to December/2019. The MTCT rate was 2.1%. Spatial-temporal maps showed that rates varied by year and by region, with four districts (Baise, Guigang, Guilin, and Hechi) maintaining rates of >2.0% in 2019. The rate of antiretroviral therapy (ART) use was 94.4%, with a gradual increase in prescriptions of highly active ART (HAART) was from 83.0% in 2014 to 92.4% in 2019. A majority, 99.5% of infants were receiving artificial feeding. Factors associated with MTCT were ART use (OR = 0.065, 95%CI = 0.035-0.121) and artificial feeding (OR = 0.091, 95%CI = 0.018-0.452). HAART was more helpful in decreasing the risk of MTCT as compared to monotherapy (OR = 0.115, 95%CI = 0.014-0.933). ART during the postpartum period correlated with an increased risk (OR = 11.579, 95%CI = 1.402-95.960), when compared to use of ART during pregnancy. This study indicates that MTCT rate of HIV is decreasing meaningfully in Guangxi. Some areas still face challenges in elimination of MTCT and need further resources and interventions. Future program planning should take into consideration the fact that ART use-in particular the use of HAART or ART during pregnancy-and replacement feeding may contribute to the prevention of MTCT.
Updated Strategies for Pulse Oximetry Screening for Critical Congenital Heart Disease

Newborn screening for CCHD significantly improves outcomes. New approaches can improve the efficiency of screening. BrightcoveDefaultPlayer10.1542/6138655260001PEDS-VA_2019-1650 Video Abstract Seven years after its addition to the US Recommended Uniform Screening Panel, newborn screening for critical congenital heart disease (CCHD) using pulse oximetry became mandatory in the United States. Although CCHD newborn screening reduces morbidity and mortality, there remain important opportunities to improve. An expert panel convened for a 1-day meeting in September 2018, including subject matter experts and representatives from stakeholder organizations. Presentations on CCHD outcomes, variations in approach to screening, and data and quality improvement helped identify improvement opportunities. The expert panel concluded that sufficient evidence exists to recommend modifying the current American Academy of Pediatrics algorithm by (1) requiring an oxygen saturation of at least 95% in both (formerly either) the upper and lower extremities to pass and (2) requiring only 1 repeat screen instead of 2 for cases that neither pass nor fail initially. The panel underscored the importance of improving public health reporting by further specifying the targets of screening and criteria for reporting outcomes (false-negative and false-positive cases). The panel also highlighted the need to ensure sufficient public health funding for CCHD newborn screening and opportunities for education and global implementation. Newborn screening for CCHD using pulse oximetry has led to significant improvements in child health outcomes. However, further important work is required to understand and improve the effectiveness and efficiency of screening.
Increasing host cellular receptor—angiotensin‐converting enzyme 2 expression by coronavirus may facilitate 2019‐nCoV (or SARS‐CoV‐2) infection

The ongoing outbreak of a new coronavirus (2019‐nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID‐19) in humans. SARS‐CoV‐2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS‐CoV‐1 and SARS‐CoV‐2 may use the same host cellular receptor, angiotensin‐converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS‐CoV‐2 S protein is much higher than that of ACE2 binding to the SARS‐CoV S protein, explaining why SARS‐CoV‐2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS‐CoV‐1 and SARS‐CoV‐2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS‐CoV‐2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high‐risk factors for developing COVID‐19, and the infection of other viruses may increase the risk of SARS‐CoV‐2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.
MULTISCALE ANALYSIS OF TYRANNID ABUNDANCES AND LANDSCAPE VARIABLES IN THE CENTRAL PLAINS, USA

Abstract Effects of scale on relationships between organisms and their environment are of considerable contemporary interest. We evaluated Breeding Bird Survey data and landscape measures derived from aerial photographs to examine how relationships changed over a continuous range of 16 spatial scales. Analyses incorporated 1985–1994 data (average number of birds/stop/yr) for eight flycatcher species (Tyrannidae) for each of 50 stops on 198 Breeding Bird Survey transects in the Central Plains. Associations of bird abundances with landscape variables changed gradually with small changes in scale. Edge density had significant associations with abundances of Eastern Phoebes (Sayornis phoebe), Great Crested Flycatchers (Myiarchus crinitus), and Western Kingbirds (Tyrannus verticalis) suggesting this landscape characteristic is important for certain breeding flycatcher species. Fractal dimension and principal component II, the latter reflecting amounts of closed forest versus open country, exhibited the highest correlations with abundances of the greatest number of species. Correlations of abundances and landscape variables were highest at larger spatial scales, 17- to 50-stop segments (i.e., 13.7 and 40.2 km in length, respectively). Evaluating more than 2–3 spatial scales can provide insight into relationships of abundance of a species with potentially influential environmental factors. These analyses allow the data to indicate the most appropriate scale or scales for a particular study, rather than depending entirely on a researcher's subjective perception of what scales are important to a given species.
Psychological distress during the 2019 Coronavirus Disease (COVID‐19) pandemic among cancer survivors and healthy controls

Centre for Psycho-Oncological Research and Training, Division of Behavioural Sciences, School of Public Health, The University of Hong Kong, Pok Fu Lam, Hong Kong Jockey Club Institute of Cancer Care, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong Department of Psychology, The University of Hong Kong, Pok Fu Lam, Hong Kong Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England School of Nursing, The University of Hong Kong, Pok Fu Lam, Hong Kong
Ultrastructure of protein bodies in mutant rice (Oryza sativa L.) with altered storage protein composition.

Many rice mutants with altered storage protein composition, which relate to protein body II (PB-II), have been produced in order to obtain rice with new cooking properties or lowered protein digestibility, but the PB structures in the endosperm of such mutants remain obscure. We examined the polypeptide composition and ultrastructure of the endosperm during seed development using rice mutants with the low-glutelin-content gene (Lgc1) and/or 26 kDa globulin deficient gene (glb1). Lgc1 and glb1 have deletions of a region including glutelin structural genes and 26 kDa globulin gene, respectively. Mutants with Lgc1 accumulated prolamin polypeptides from an early stage of seed development, and numerous intact PB-I and a few, small, chipped PB-II were observed in the endosperm. The glb1 mutant showed deformed PB-II structures, which had similar electron density to wild-type PB-II. Both glutelins and globulins accumulate in PB-II, but the influence of the change in their composition on PB-II structure would be different. The unique PB-II structure in the glb1 mutant may bring about new processing properties for rice.
CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis

Inflammatory Bowel Disease (IBD) is one of the most common gastrointestinal (GI) disorders around the world, and includes diagnoses such as Crohn’s disease and ulcerative colitis. The etiology of IBD is influenced by genetic and environmental factors. One environmental perturbagen that is not well studied within the intestines is microcystin-leucine arginine (MC-LR), which is a toxin produced by cyanobacteria in freshwater environments around the world. We recently reported that MC-LR has limited effects within the intestines of healthy mice, yet interestingly has significant toxicity within the intestines of mice with pre-existing colitis induced by dextran sulfate sodium (DSS). MC-LR was found to prolong DSS-induced weight loss, prolong DSS-induced bloody stools, exacerbate DSS-induced colonic shortening, exacerbate DSS-induced colonic ulceration, and exacerbate DSS-induced inflammatory cytokine upregulation. In addition, we previously reported a significant increase in expression of the pro-inflammatory receptor CD40 in the colons of these mice, along with downstream products of CD40 activation, including plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). In the current study, we demonstrate that knocking out CD40 attenuates the effects of MC-LR in mice with pre-existing colitis by decreasing the severity of weight loss, allowing a full recovery in bloody stools, preventing the exacerbation of colonic shortening, preventing the exacerbation of colonic ulceration, and preventing the upregulation of the pro-inflammatory and pro-fibrotic cytokines IL-1β, MCP-1, and PAI-1. We also demonstrate the promising efficacy of a CD40 receptor blocking peptide to ameliorate the effects of MC-LR exposure in a proof-of-concept study. Our findings suggest for the first time that MC-LR acts through a CD40-dependent mechanism to exacerbate colitis.