Miracle-dz/UniFAR-FTUs huggingface dataset:
XenoCP: Cloud-based BAM cleansing tool for RNA and DNA from Xenograft

Summary Xenografts are important models for cancer research and the presence of mouse reads in xenograft next generation sequencing data can potentially confound interpretation of experimental results. We present an efficient, cloud-based BAM-to-BAM cleaning tool called XenoCP to remove mouse reads from xenograft BAM files. We show application of XenoCP in obtaining accurate gene expression quantification in RNA-seq and tumor heterogeneity in WGS of xenografts derived from brain and solid tumors. Availability and Implementation St. Jude Cloud (https://pecan.stjude.cloud/permalink/xenocp) and St. Jude Github (https://github.com/stjude/XenoCP) Contact jinghui.zhang@stjude.org
Morphological and molecular characterisation of Distolabrellus veechi (Rhabditida: Mesorhabditidae) from India

A redescription of Distolabrellus veechi (Rhabditida: Mesorhabditidae) from agricultural soils in Uttarakhand and Uttar Pradesh, India, is provided. Specimens were extracted from soil using the Galleria soil baiting technique, with two strains of nematodes named JP1 and JP2 being obtained. Morphological and morphometric studies on the species agree well with previous records. Molecular analyses are provided using 18S, 28S and ITS rRNA sequences, the ITS sequences being obtained for the first time in this species. These analyses show that the material examined agrees well with previously studied populations. Phylogenetic analyses showed Distolabrellus to be the sister group of Crustorhabditis and Teratorhabditis, all having the male spicules fused for more than 50% of their length. Illustrations and phylogenetic trees based on 18S, 28S and ITS rRNA sequences are provided.
Effects of olive pulp addition to broiler diets on performance, selected biochemical parameters and antioxidant enzymes

Olive oil production generates various by-products that can be used in animal nutrition. These by-products contain several polyphenolic compounds that may exhibit antioxidant properties. The present study was designed to evaluate the effects of adding olive pulp to the feed on broiler performance, carcass yield and antioxidant enzymes. Two hundred (200), as hatched, day-old, Cobb 500 broilers were reared in total for 42 days. There were 4 dietary treatments. In T1 treatment, no olive pulp was added to starter, grower and finisher diet. In T2 treatment, olive pulp was added to starter, grower and finisher diet at a level of 0, 2.5 and 5% respectively. In T3 treatment, olive pulp was added to starter, grower and finisher diet at a level of 0, 5 and 5% respectively. In T4 treatment, olive pulp was added to starter, grower and finisher diet at a level of 0, 5 and 8% respectively. Performance, carcass yield and a number of biochemical parameters were examined. Oleuropein and hydroxytyrosol were present in the olive pulp at 952 and 216 mg/kg respectively. Broilers performed well and no differences were observed between treatments on final body weight, carcass yield, total antioxidant activity and expression of selected antioxidant enzymes. Discriminant analysis was further applied and revealed that samples clustered according to added level of olive pulp. Samples from broilers fed T2 and T3 diet were located in the middle of the plot away from other treatments exhibiting high values of carcass, breast yield and most of the antioxidant enzyme activities. In conclusion, olive pulp can be used up to 5% in diets of broilers and future studies conducted on-farm conditions may pronounce its impact on growth performance and antioxidant potential.
Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

Bats account for ~20% of all extant mammal species and are considered exceptional given their extraordinary adaptations, including biosonar, true flight, extreme longevity, and unparalleled immune systems. To understand these adaptations, we generated reference-quality genomes of six species representing the key divergent lineages. We assembled these genomes with a novel pipeline incorporating state-of-the-art long-read and long-range sequencing and assembly techniques. The genomes were annotated using a maximal evidence approach, de novo predictions, protein/mRNA alignments, Iso-seq long read and RNA-seq short read transcripts, and gene projections from our new TOGA pipeline, retrieving virtually all (>99%) mammalian BUSCO genes. Phylogenetic analyses of 12,931 protein coding-genes and 10,857 conserved non-coding elements identified across 48 mammalian genomes helped to resolve bats’ closest extant relatives within Laurasiatheria, supporting a basal position for bats within Scrotifera. Genome-wide screens along the bat ancestral branch revealed (a) selection on hearing-involved genes (e.g LRP2, SERPINB6, TJP2), which suggest that laryngeal echolocation is a shared ancestral trait of bats; (b) selection (e.g INAVA, CXCL13, NPSR1) and loss of immunity related proteins (e.g. LRRC70, IL36G), including pro-inflammatory NF-kB signalling; and (c) expansion of the APOBEC family, associated with restricting viral infection, transposon activity and interferon signalling. We also identified unique integrated viruses, indicating that bats have a history of tolerating viral pathogens, lethal to other mammal species. Non-coding RNA analyses identified variant and novel microRNAs, revealing regulatory relationships that may contribute to phenotypic diversity in bats. Together, our reference-quality genomes, high-quality annotations, genome-wide screens and in-vitro tests revealed previously unknown genomic adaptations in bats that may explain their extraordinary traits.
Data architecture and visualization for a large-scale neuroscience collaboration

The International Brain laboratory (IBL) is a collaboration aiming to understand the neural basis of decision-making. Ten experimental labs use multiple neural recording modalities in diverse brain structures of mice making perceptual decisions. A primary requirement of IBL is to establish a data architecture that integrates data from all labs and modalities together. We have developed a system that allows users across 5 countries to automatically contribute data and metadata, search for relevant data, and share code for exploratory analysis. To accurately record metadata about subjects and experiments in a searchable and accessible way, we have developed a user-friendly, web-based electronic lab notebook system for colony and experiment management (Alyx). Alyx is a small relational metadatabase that records relevant information about each subject (age, strain, procedures), alongside information about experiments and their resulting data files. Once an experiment is completed, data registered in Alyx is automatically uploaded to a central server via Globus transfer. Users can search and access the data using a lightweight interface called the Open Neurophysiology Environment (ONE), implemented in Python and MATLAB. ONE defines a list of DatasetTypes, as arrays of predetermined shapes and units. Users search the database by running a command that returns an ID identifying experiments matching their criteria. A command one.load returns the requested DatasetTypes as a numerical array, downloading it from the central server and caching on the user’s machine to avoid repeated downloads. Additional commands provide further ways to list experiments on the server, and the dataset types they each contain. This system allows users to search, load and process data that was collected in laboratories spanning multiple geographical locations. To visualize these data, we have developed a pipeline for automated analysis, based on the DataJoint framework.
The proteome of small urinary extracellular vesicles after kidney transplantation as an indicator of renal cellular biology and a source for markers predicting outcome

Kidney transplantation is the preferred renal replacement therapy available. Yet, the biological processes during and after kidney transplantation and how they translate into the overall functional graft outcome are insufficiently understood. Recent developments in the field of extracellular vesicle research allow the deeper exploitation of this non-invasive source. We separated small urinary extracellular vesicles (suEVs) throughout the course of living donor kidney transplantation. SuEVs were collected longitudinally from both the donor and the recipient in 22 living donor kidney transplantations. Unbiased proteomic analysis revealed specific temporal patterns of suEV proteins indicative of the cellular processes involved in the allograft’s response after transplantation with proteins playing a role in complement activation being among the most dynamically regulated components. Using a leave-one-out cross validation model, we identified potential prognostic markers of kidney function at 1 year after transplantation. One of the proteins identified – phosphoenol pyruvate carboxykinase (PCK2) – could be confirmed in an independent validation cohort of another 22 donor-recipient pairs using targeted mass spectrometry. This study sheds the light on early molecular processes during the course of kidney transplantation and shows the future potential of suEVs as a source of biomarkers in this setting. The data set is provided as a unique resource directly accessible through an online tool that allows dynamic interrogation of this first comprising suEV proteome atlas after kidney transplantation. One Sentence Summary This study represents the first atlas of the proteomic changes in small urinary extracellular vesicles throughout living donor kidney transplantation identifying PCK2 abundance as a biomarker for renal function 12 months after transplantation
Structural Similarities between Some Common Fluorophores Used in Biology, Marketed Drugs, Endogenous Metabolites, and Natural Products

Background It is known that at least some fluorophores can act as ‘surrogate’ substrates for solute carriers (SLCs) involved in pharmaceutical drug uptake, and this promiscuity is taken to reflect at least a certain structural similarity. As part of a comprehensive study seeking the ‘natural’ substrates of ‘orphan’ transporters that also serve to take up pharmaceutical drugs into cells, we have noted that many drugs bear structural similarities to natural products. A cursory inspection of common fluorophores indicates that they too are surprisingly ‘drug-like’, and they also enter at least some cells. Some are also known to be substrates of efflux transporters. Consequently, we sought to assess the structural similarity of common fluorophores to marketed drugs, endogenous mammalian metabolites, and natural products. We used a set of some 150 fluorophores. Results The great majority of fluorophores tested exhibited significant similarity (Tanimoto similarity > 0.75) to at least one drug as judged via descriptor properties (especially their aromaticity, for identifiable reasons that we explain), by molecular fingerprints, by visual inspection, and via the “quantitative estimate of drug likeness” technique. It is concluded that this set of fluorophores does overlap a significant part of both drug space and natural products space. Consequently, fluorophores do indeed offer a much wider opportunity than had possibly been realised to be used as surrogate uptake molecules in the competitive or trans-stimulation assay of membrane transporter activities.
Vacuolar processing enzyme translocates to the vacuole through the autophagy pathway to induce programmed cell death

The caspase-like vacuolar processing enzyme (VPE) is a key factor in programmed cell death (PCD) associated with plant stress responses. Growth medium lacking a carbon source and dark conditions caused punctate labeling of 35S::VPE1-GFP (StVPE1-GFP) in potato leaves. Carbon starvation of BY-2 cells induced higher VPE activity and PCD symptoms. Growing VPE-RNAi BY-2 cells without sucrose reduced VPE activity and prevented PCD symptoms. During extended exposure to carbon starvation, VPE expression and activity levels peaked, with a gradual increase in BY-2 cell death. Histological analysis of StVPE1-GFP in BY-2 cells showed that carbon starvation induces its translocation from the endoplasmic reticulum to the central vacuole, through tonoplast engulfment. Exposure of BY-2 culture to the autophagy inhibitor concanamycin A caused autophagic bodies accumulation in the cell vacuole. Such accumulation did not occur in the presence of 3-methyladenine, an inhibitor of early-stage autophagy. BY-2 cells constitutively expressing StATG8IL-RFP, an autophagosome marker, showed colocalization with the StVPE1-GFP protein in the cytoplasm and vacuole. RNAi silencing of the core autophagy component ATG4 in BY-2 cells reduced VPE activity and cell death. These results are the first to suggest that VPE translocates to the cell vacuole through the autophagy pathway, leading to PCD. One sentence summary Carbon starvation induced programmed cell death by trafficking vacuolar processing enzyme through the autophagy pathway to the vacuole.
The effect of the mycorrhization on the content of macroelements in the soil and leaves of blueberry cultivated after replantation

Research on the impact of the mycorrhization on the content of selected macroelements (N, P, K and Mg) present in the soil and in the leaves of the highbush blueberry (Vaccinium corymbosum L.) cultivar ‘Bluecrop’ was carried out between 2009 and 2014. Plants were grown in the replanted soil (after 30 years of blueberry cultivation) and in the soil not used for blueberry cultivation (virgin soil). The mycorrhizal vaccine (mixture Vaccinium myrtillus L., V. vitis-idaea L. and Arctostaphylos uva-ursi L.) was used once when the plants were planted permanently. A varied effect of the use of mycorrhizal vaccine on the chemical composition of soil and plants was demonstrated. The application of this treatment significantly decreased the content of ammonium (N-NH4), phosphorus (P) and potassium (K) in the soil and increased nitrate (N-NO3) and magnesium (Mg) content in relation to the control treatment (without the mycorrhizal vaccine). Within the examined soils – soil after replantation as well as virgin soil – a significant effect of mycorrhizae on the increase of nitrogen (N), K and Mg content in blueberry leaves was demonstrated.
Long-term warming effects on the microbiome and nitrogen fixation associated with the moss Racomitrium lanuginosum in a subarctic alpine heathland

Bacterial communities form the basis of biogeochemical processes and determine plant growth and health. Mosses, an abundant plant group in many Arctic ecosystems, harbour diverse bacterial communities that are for instance involved in nitrogen fixation. Global climate change is causing changes in aboveground plant biomass and shifting species composition in the Arctic, but little is known about the response of the moss microbiome. Here, we study the bacterial community associated with the moss Racomitrium lanuginosum, a common species in the Arctic, in a 20-year in situ warming experiment in an Icelandic heathland. We evaluate changes in bacterial community composition and diversity. Further, we assess the consequences of warming for nifH gene copy numbers and nitrogen fixation rates. Our findings indicate an increase in the relative abundance of Proteobacteria and a decrease in the relative abundance of Cyanobacteria and Acidobacteria with warming. The nifH gene copy number decreases, while the rate of nitrogen fixation is not affected. This contradiction could be explained by a shift in the nitrogen fixing bacterial community. Although climate warming might not change the contribution of R. lanuginosum to nitrogen input in nitrogen-limited ecosystems, the microbial community resilience and the nitrogen fixing taxa may shift.
Unveiling the physiological mechanisms that drive the emergence of antibiotic resisters from antibiotic persister population of mycobacteria

The physiological mechanisms behind the emergence of antibiotic-resistant bacteria from their antibiotic-persister population are beginning to be explored. Here we delineate the sequential physiological events that drive the emergence of rifampin-resistant rpoB mutants from rifampin-persister population of mycobacteria during prolonged exposure. The rifampin-persister population generated elevated levels of hydroxyl radical, which inflicted mutations, enabling regrowth of the persister cells to form multi-septated, multi-nucleated elongated cells. These cells, through multiple divisions, produced multiple sister-daughter cells, causing an abrupt, unexpectedly high increase of rifampin-resistant colonies. Similar response was observed against moxifloxacin also. Earlier studies on the rifampin/moxifloxacin-exposed laboratory/clinical M. tuberculosis strains from in-vitro cultures and infected mouse-lung also showed cfu spurt, but went unnoticed/unreported. It is likely that these sequential physiological events may be driving the emergence of antibiotic-resistant tubercle bacilli in TB patients also. Escherichia coli also has been found to respond similarly against subminimal inhibitory concentrations of ciprofloxacin. Thus, the present findings attain broad significance as a general physiological mechanism used by diverse bacterial genera to emerge as drug-resistant strains against antibiotics.
CT Diagnosis of Atypical Liver Abscess

Objective:To analyze the CT appearances of atypical liver abscess and deepen the understanding of this disease.Methods:12 cases of atypical liver abscess proved by clinical or pathological data were reviewed,all of them were examined by plain CT scan and enhanced scan.Results:In plain CT scan,the atypical liver abscesses exhibited as hypodensity mass;enhanced CT showed peripheral enhancement sign,mass "diminution" sign,honeycomb enhancement and delayed enhancement.Conclusion:Atypical liver abscess is nonspecific on plain CT scan,the enhanced appearance is characteristic so helps to the diagnosis.
Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level

The neuronal basis of goal-directed behavior requires interaction of multiple separated brain regions. How subcortical regions and their interactions with brain-wide activity are involved in action selection is less understood. We have investigated this question by developing an assay based on whole-brain volumetric calcium imaging using light-field microscopy combined with an operant-conditioning task in larval zebrafish. We find global and recurring dynamics of brain states to exhibit pre-motor bifurcations towards mutually exclusive decision outcomes which arises from a spatially distributed network. Within this network the cerebellum shows a particularly strong pre-motor activity, predictive of both the timing and outcome of behavior up to ∼10 seconds before movement initiation. Furthermore, on the single-trial level, decision directions can be inferred from the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the decision time can be quantitatively predicted by the rate of bi-hemispheric population ramping activity. Our results point towards a cognitive role of the cerebellum and its importance in motor planning.
Establishment of STZ-Induced Diabetic Nephropathic Rat Model

Objective To establish a diabetic nephropathic rat model and to study it's kidney lesions. Methods 40 male Wistar rats were randomly divided into control and experimental diabetic groups, 20 per each group. Diabetic rats were induced by one intraperitoneal injection of streptozotocin (STZ) in a dose of 65 mg/kg. The rats were breed for 14 weeks. During the experiment, the blood glucose and urine glucose were measured and gross health status was observed. Finally, serum creatinine (SCr), blood urea nitrogen (BUN), urine protein and urine albumin were assayed, and renal pathological changes were examined by light and electron microscopy. Results The diabetic rats showed increased SCr, BUN, urine protein and urine albumin levels and hypertrophy of the kidneys. The renal pathology exhibited glomerular and tubulo-interstitial alterations. Conclusion The STZ-induced rat diabetic model have certain glomerulus and tubulo-interstitial lesions and can be used in diabetic nephropathy studies.
The paternally imprinted gene Snord116 regulates cortical neuronal activity

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in both humans and mice. Here, we further explore the processes of sleep regulation by studying the PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused on microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles within NREM sleep. While the former are thought to contribute to neuronal network formation early in brain development, the latter are markers of thalamocortical processes. Both signals are often compromised in neurodevelopmental disorders and influence functional properties of cortical neurons. Thus, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array (MEA) studies. Our results indicate that the Snord116 gene in mice selectively influences REM sleep properties, such as theta rhythms and the organization of REM episodes throughout sleep-wake cycles. Moreover, sleep spindles present specific abnormalities in PWS model systems, indicating that these features of sleep may translate as potential biomarkers in human PWS. We observed abnormalities in the synchronization of cortical neuronal activity that are accounted for by high levels of norepinephrine. In conclusion, our results provide support for an important role of Snord116 in regulating brain activity during sleep and, in particular, cortical neuronal properties, thereby opening new avenues for developing interventions in PWS. Significance Statement We found that the Snord116 gene, a major player in Prader-Willi syndrome (PWS), significantly impacts REM sleep and its regulation. Additionally, we found that sleep spindles, a subtle electroencephalography (EEG) marker that occurs during NREM sleep, are dysregulated in PWS mice that carry a paternal deletion of the Snord116 gene. Using a combination of in vivo and in vitro experiments, we identified sleep features at the network and molecular level that suggest that Snord116 is fundamental in the synchronization of neuronal networks. Our study also provides a new pre-clinical tool to investigate the pathophysiology of sleep in PWS.