Miracle-dz/UniFAR-FTUs huggingface dataset:
Defensiveness measurement in honey bees (Apis mellifera) and brain expression of associated genes after noxious stimulus

Honey bee (Apis mellifera sp.) colonies and individuals respond variably to disturbances. In this study, we examined the role of neural modulation and metabolism in constitutive and experience-dependent differences in defensive response. We compared brain gene expression in bees of identified gentle and defensive colonies in a standard assay. For neuromodulation, we examined membrane receptor genes for the biogenic amines dopamine (DOPR2), octopamine (OAR), and serotonin (5HT2a), and the enzyme gene in the synthesis pathway (THR). To examine neural metabolism, we assessed the Oxidative Phosphorylation Pathway “OXPHOS” gene expression (i.e., ND51 and ND20-LIKE). Bees of defensive colonies had a significantly lower expression of amine receptor, synthesis genes, and OXPHOS genes. Experience differences or exposure to nociceptive neurons activated by nocive stimuli (electric shock) led to differences in the expression of all genes except 5HT2a. The same target genes demonstrated an increase in expression levels after electric shock and sting response. We discuss the convergence of neuromodulation, neural metabolism
High total water loss driven by low-fat diet in desert-adapted mice

Availability of food resources is an important driver of survival. Animals must either relocate or adapt to persist in environments where critical resource abundance is changing. An optimal diet balances energy gain, water regulation, and nutrition. We used flow-through respirometry to characterize metabolic phenotypes of the desert-adapted cactus mouse (Peromyscus eremicus) under diurnally variable environmental conditions that mimic the environment of the Sonoran Desert. We treated mice with two different energetically equivalent diets, a standard diet and a low-fat diet, and measured energy expenditure, water loss rate, respiratory quotient, weight, and electrolyte levels. Mice fed the low-fat diet lost significantly more water than those on the standard diet. Our results suggest that cactus mice may have limited capacity to tolerate water deprivation if optimal foods become less abundant. Given that climate change is predicted to modify the distribution of food items, understanding these links may have important implications for long-term population viability for desert and non-desert adapted animals alike.
Berberine Bridge Enzyme-Like Oligosaccharide Oxidases Act As Enzymatic Transducers Between Microbial Glycoside Hydrolases and Plant Peroxidases

OG-oxidases (OGOXs) and CD-oxidase (CELLOX) are plant berberine bridge enzyme-like oligosaccharide oxidases that oxidize oligogalacturonides (OGs) and cellodextrins (CDs), cell wall fragments with nature of damage-associated molecular patterns (DAMPs). The oxidation of OGs and CDs attenuates their elicitor activity by concomitantly releasing H2O2. Here, we demonstrate that the H2O2 generated downstream of the combined action between a fungal polygalacturonase and OGOX1 or an endoglucanase and CELLOX can be directed by plant peroxidases (PODs) either towards a reaction possibly involved in plant defence such as the oxidation of monolignol or a reaction possibly involved in a developmental event such as the oxidation of auxin (IAA), pointing to OGOX1 and CELLOX as enzymatic transducers between microbial glycoside hydrolases and plant PODs.
CD200R1 promotes IL-17 production by ILC3s, by enhancing STAT3 activation

Psoriasis is a common chronic inflammatory skin disease with no cure. It is driven by the IL-23/IL-17A axis and TH17 cells but, recently group 3 innate lymphoid cells (ILC3s) have also been implicated. However, the development, and factors regulating the activity of ILC3s remain incompletely understood. Immune regulatory pathways are particularly important at barrier sites such as the skin, gut and lung, which are exposed to environmental substances and microbes. CD200R1 is an immune regulatory cell surface receptor which inhibits proinflammatory cytokine production in myeloid cells. CD200R1 is also highly expressed on ILCs, where its function remains largely unexplored. We previously observed reduced CD200R1 signalling in psoriasis skin, suggesting that dysregulation may promote disease. Here we show that contrary to this, psoriasis models are less severe in CD200R1-deficient mice due to reduced IL-17 production. Here we uncover a key cell-intrinsic role for CD200R1 in promoting IL-23-driven IL-17A production by ILC3s, by promoting STAT3 activation. CD200R1 is expressed on ILC precursors and is particularly high on neonatal ILC3s, suggesting CD200R1 may function during ILC development. Therefore, CD200R1 is required on ILC3s, potentially during their development, to promote IL-23-stimulated STAT3 activation triggering optimal IL-17 production.
SATINN: an automated neural network-based classification of testicular sections allows for high-throughput histopathology of mouse mutants

Abstract Motivation The mammalian testis is a complex organ with a cellular composition that changes smoothly and cyclically in normal adults. While testis histology is already an invaluable tool for identifying and describing developmental differences in evolution and disease, methods for standardized, digital image analysis of testis are needed to expand the utility of this approach. Results We developed SATINN (Software for Analysis of Testis Images with Neural Networks), a multi-level framework for automated analysis of multiplexed immunofluorescence images from mouse testis. This approach uses residual learning to train convolutional neural networks (CNNs) to classify nuclei from seminiferous tubules into seven distinct cell types with an accuracy of 81.7%. These cell classifications are then used in a second-level tubule CNN, which places seminiferous tubules into one of 12 distinct tubule stages with 57.3% direct accuracy and 94.9% within ±1 stage. We further describe numerous cell- and tubule-level statistics that can be derived from wild-type testis. Finally, we demonstrate how the classifiers and derived statistics can be used to rapidly and precisely describe pathology by applying our methods to image data from two mutant mouse lines. Our results demonstrate the feasibility and potential of using computer-assisted analysis for testis histology, an area poised to evolve rapidly on the back of emerging, spatially resolved genomic and proteomic technologies. Availability and implementation The source code to reproduce the results described here and a SATINN standalone application with graphic-user interface are available from http://github.com/conradlab/SATINN. Supplementary information Supplementary data are available at Bioinformatics online.
BioAct: Biomedical Knowledge Base Construction using Active Learning

Creating and curating knowledge resources has been a paramount activity in the biomedical domain. In recent years, automated methods for knowledge base construction have flourished and have enabled large scale construction and curation of such resources. In the biological domain, techniques such as next generation sequencing produce new data at exponential rate, making mere manual curation of knowledge resources simply unfeasible. The major technology to automate knowledge base construction is Information Extraction — specifically tasks such as Named Entity Recognition or Relation Extraction. The major hurdle for IE methods is the availability of labelled data for training, which can be prohibitively expensive and challenging to obtain due to the need of domain experts. Active learning aims at minimizing the cost of manual labelling by only requiring it for smaller and more useful portions of the data. With this motivation, we devised a method to quickly construct highly curated datasets to enable biomedical knowledge base construction. The method, named BioAct, is based on a partnership between automatic annotation methods (leveraging SciBERT with other machine learning models) and subject matter experts and uses active learning to create training datasets in the biological domain. The main contribution of this work is twofold; in addition to the BioAct method itself, we publicly release an annotated dataset on antimicrobial resistance, produced by a team of subject matter experts using BioAct. Additionally, we simulate a knowledge base construction task using the MegaRes and CARD knowledge bases to provide insight and lessons learned about the usefulness of the annotated dataset for this task.
How does target lesion selection affect RECIST? A computer simulation study

RECIST is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection. Disagreement among readers, and between readers and total tumor burden was analyzed, as a function of the total number of lesions, affected organs, and lesion growth. Disagreement aggravates when the number of lesions increases, when lesions are concentrated on few organs, and when lesion growth borders the thresholds of progressive disease and partial response. An intrinsic methodological error is observed in the estimation of total tumor burden (TTB) via RECIST. In a metastatic setting, RECIST displays a non-linear, unpredictable behavior. Our results demonstrate that RECIST can deliver an accurate estimate of total tumor burden in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the “selection of the largest lesions”, which introduce a bias that makes it hardly possible to perform an accurate estimate of the total tumor burden. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.
Cross-activation of the FGF, TGF-β and WNT pathways constrains BMP4-mediated induction of the Totipotent state in mouse embryonic stem cells

Cell signaling induced cell fate determination is central to stem cell and developmental biology. Embryonic stem cells (ESC) are an attractive model for understanding the relationship between cell signaling and cell fates. Cultured mouse ESCs can exist in multiple cell states resembling distinct stages of early embryogenesis, such as Totipotent, Pluripotent, Primed and Primitive Endoderm. The signaling mechanisms regulating the Totipotent state acquisition and coexistence of these states are poorly understood. Here we identify BMP4 as an inducer of the Totipotent state. However, we discovered that BMP4-mediated induction of the Totipotent state is constrained by the cross-activation of FGF, TGF-β and WNT pathways. We exploited this finding to enhance the proportion of Totipotent cells in ESCs by rationally inhibiting these cross-activated pathways using small molecules. Single-cell mRNA-sequencing further revealed that induction of the Totipotent state is accompanied by the suppression of both the Primed and Primitive Endoderm states. Furthermore, the reprogrammed Totipotent cells generated in culture have a molecular and functional resemblance to Totipotent cell stages of preimplantation embryos. Our findings reveal a novel BMP4 signaling mechanism in ESCs to regulate multiple cell states, potentially significant for managing stem cell heterogeneity in differentiation and reprogramming.
Attentional rhythmic blink: Theta/Alpha balance in neural oscillations determines the rhythmicity in visual sampling

Brain oscillations in the theta (3–7 Hz) and alpha (7–13 Hz) bands are implicated in visual perception and attention. We show that in an attentional blink paradigm, where the task requires detecting two targets presented in rapid succession, perceptual performance varied with the rhythms at these two frequencies, which we name attentional rhythmic blink. In the absence of distractors, second target detection performance fluctuated at the theta rhythm, but the fluctuation frequency shifted toward alpha rhythm when distractors were interspersed with the targets. We further show, in magnetoencephalography experiments, that a change in the dominant frequency of ongoing neural oscillations accompanied those in perceptual performance, with the parietal theta being more pronounced in the no-distractor and the occipital alpha in the distractor conditions, respectively. We propose that perceptual rhythms may depend on the power balance between ongoing neural oscillations, determined by the task-specific demand.
Ganglioside enriched phospholipid vesicles induce cooperative Aβ oligomerization and membrane disruption

A major hallmark of Alzheimer disease (AD) is the accumulation of extracellular aggregates of amyloid-β (Aβ). Structural polymorphism observed among Aβ fibrils in AD brains seem to correlate with the clinical sub-types suggesting a link between fibril polymorphism and pathology. Since fibrils emerge from a templated growth of low-molecular weight oligomers, understanding the factors affecting oligomer generation is important. The membrane lipids are key factors that influence early stages of Aβ aggregation and oligomer generation, and cause membrane disruption. We have previously showed that conformationally discrete Aβ oligomers can be generated by modulating the charge, composition, chain length of lipids and surfactants. Here, we extend our studies into liposomal models by investigating Aβ oligomerization on large unilamellar vesicles (LUVs) of total brain extracts (TBE), reconstituted lipid rafts (LRs) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Specifically, we varied the vesicle composition by varying the amount of GM1 gangliosides added as a constituent. We found that liposomes enriched in GM1 induce the formation of toxic, low-molecular weight oligomers that are isolable in a lipid-complexed form. Importantly, the data indicate that the oligomer formation and membrane disruption are highly cooperative processes. Numerical simulations on the experimental data confirm cooperativity and reveal that GM1-enriched liposomes form twice as many numbers of pores as those without GM1. Overall, this study uncovers mechanisms of cooperativity between oligomerization and membrane disruption under specific lipid compositional bias, and refocuses the significance of the early stages of Aβ aggregation in polymorphism, propagation, and toxicity in AD.
Agrobacterium mediated transformation and deciphering SNPs in TaLr67 gene homeologs for gene editing in wheat

Diseases adversely affect grain yield of crop plants. Leaf rust is a major disease of wheat. As race-specific resistance breaks down, introduction of newer sources of resistance often from older accessions is necessary. Linkage drag from the donor accessions adversely impacts grain yield. As a result, CIMMYT breeding effort has shifted to using durable resistance, also referred to as race non-specific host resistance, which allows slow rusting but maintains grain yield. One of the key genes for durable resistance is Lr67 and the resistant form of this gene is absent in CIMMYT elite lines. Hence, we have initiated efforts to convert the susceptible copy of Lr67 into its resistant form directly in these elite lines using gene editing. This would eliminate backcrossing and thus save time as well as eliminate linkage drag that would accompany the resistant copy of the gene if it were to be introgressed from an older accession. As first steps, we have isolated and sequenced the genomic copies from each of the A, B, and D genome of the Lr67 gene from three elite lines and an experimental line. Identification of more than 50 single nucleotide polymorphisms (SNPs) in the open reading frames (ORF) among these lines would be useful in designing the guide RNA molecules with precision. Further, we have streamlined genetic transformation of these elite lines, a prerequisite step for gene editing.
MetaTrass: High-quality metagenome assembly on the human gut microbiome by co-barcoding sequencing reads

With the development of sequencing technologies and computational analysis in metagenomics, the genetic diversity of non-conserved regions has been receiving intensive attention to unravel the human gut microbial community. However, it remains a challenge to obtain enough microbial draft genomes at a high resolution from a single sample. In this work, we presented MetaTrass with a strategy of binning first and assembling later to assemble high-quality draft genomes based on metagenomics co-barcoding reads and the public reference genomes. We applied the tool to the single tube long fragment reads datasets for four human faecal samples, and generated more high-quality draft genomes with longer contiguity and higher resolution than the common combination strategies of genome assembling and binning. A total of 178 high-quality genomes was successfully assembled by MetaTrass, but the maximum of 58 was generated by the optimal common combination strategy in our tests. These high-quality genomes paved the way for genetic diversity and lineage analysis among different samples. With the high capability of assembling high-quality genomes of metagenomics datasets, MetaTrass will facilitate the study of spatial characters and dynamics of complex microbial communities at high resolution. The open-source code of MetaTrass is available at https://github.com/BGI-Qingdao/MetaTrass.
Grazing and Recovery of Kelp Gametophytes Under Ocean Warming

Kelp forests are economically important ecosystems that support a wealth of biodiversity but are declining globally. They are often replaced by biologically depauperate alternate stable states dominated by turfing algae. Hysteresis maintains algal turfs by inhibiting kelp recruitment, preventing the reestablishment of kelp forests. The mechanisms inhibiting kelp recruitment remain poorly understood as microscopic stages of kelp are difficult to study in situ. A potential mechanism contributing to the suppression of recruitment may be turf-facilitated grazing of kelp gametophytes, the haploid free-living reproductive life stage. Here we assess the resilience of kelp gametophytes to grazing pressure from a gastropod micrograzer commonly present in turf under current and future ocean warming scenarios. Gametophyte coverage and abundance were significantly reduced following grazing under all temperatures, however there was no significant effect of temperature on grazing rates. Once grazing pressure was removed, gametophyte abundance recovered to control levels, but the total coverage and length of gametophytes continued to decline in all treatments. Gametophytes were found to survive micrograzer ingestion and continued to grow in aggregations in the gastropod’s mucus trail and faeces, even producing sporophytes. Gametophyte survival post-ingestion may positively contribute to dispersal and sporophyte recruitment, however the lack of gametophyte recovery at elevated temperatures may counteract this effect under future ocean warming. Taken together, this study demonstrates complex interactions that take place in the turf micro-habitat of kelp gametophytes and highlights biotic factors influencing transitions between kelp forests and algal turfs.
Effectiveness of Prophylactic Use of Hepatoprotectants for Tuberculosis Drug-Induced Liver Injury: A Population-Based Cohort Analysis Involving 6,743 Chinese Patients

Background: Tuberculosis drug-induced liver injury (TB-DILI) is a common and potentially severe adverse drug reaction leading to treatment interruption and treatment failure. The real-world preventive effectiveness of hepatoprotective agents for DILI is not well described. The aim of the study was to evaluate the patterns of prophylactic therapies in real-world settings and risks of DILI among adult TB patients without known risk factors for DILI. Methods: This is a population-based retrospective cohort study of patients receiving first-line anti-tuberculosis drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to the Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020. The primary exposure was any use of chemopreventive agents including silymarin and/or glycyrrhetinic acid during the 30-day period prior to TB diagnosis (index date). The main outcome measure was the occurrence of newly onset DILI following TB treatment. Eligible patients were followed until the earliest of any DILI, treatment discontinuation, death, or end of the study period (30 June 2020). Marginal structural competing risk models and Cox models via inverse probability treatment weights using high-dimensional propensity scores were used to estimate subdistribution hazard risks (SHR) and 95% confidence intervals (CIs) for DILI risks, with adjustment for age, sex, TB-related characteristics, and comorbidities. Results: We identified a cohort of 6,743 adult patients with TB (mean age of 47.1 [SD 18.7] years; 65.80% male), of whom 2,886 (42.8%) patients received hepatoprotective agents. A total of 895 DILI events and 111 all-cause death events without DILI were observed over a median follow-up of 367 days post-TB diagnosis. The incidence rates of composite outcomes combining DILI and all-cause mortality were 248.9 and 222.3 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.35, 95% CI 1.11–1.64), respectively. The incidence rates of DILI were 223.7 and 196.1 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.38, 95% CI 1.12–1.71), respectively. Patients with any chemopreventive agent use had comparable liver function changes as evidenced by laboratory tests. Conclusion: A non-trivial number of adult patients received chemopreventive agents for TB-DILI. However, prophylactic utilization of hepatoprotective agents was not associated with a reduction in TB-DILI risks.
The SITE-100 Project: Site-Based Biodiversity Genomics for Species Discovery, Community Ecology, and a Global Tree-of-Life

Most insect communities are composed of evolutionarily diverse lineages, but detailed phylogenetic analyses of whole communities are lacking, in particular in species-rich tropical faunas. Likewise, our knowledge of the Tree-of-Life to document evolutionary diversity of organisms remains highly incomplete and especially requires the inclusion of unstudied lineages from species-rich ecosystems. Here we present the SITE-100 program, which is an attempt at building the Tree-of-Life from whole-community sampling of high-biodiversity sites around the globe. Combining the local site-based sets into a global tree produces an increasingly comprehensive estimate of organismal phylogeny, while also re-tracing evolutionary history of lineages constituting the local community. Local sets are collected in bulk in standardized passive traps and imaged with large-scale high-resolution cameras, which is followed by a parataxonomy step for the preliminary separation of morphospecies and selection of specimens for phylogenetic analysis. Selected specimens are used for individual DNA extraction and sequencing, usually to sequence mitochondrial genomes. All remaining specimens are bulk extracted and subjected to metabarcoding. Phylogenetic analysis on the mitogenomes produces a reference tree to which short barcode sequences are added in a secondary analysis using phylogenetic placement methods or backbone constrained tree searches. However, the approach may be hampered because (1) mitogenomes are limited in phylogenetic informativeness, and (2) site-based sampling may produce poor taxon coverage which causes challenges for phylogenetic inference. To mitigate these problems, we first assemble nuclear shotgun data from taxonomically chosen lineages to resolve the base of the tree, and add site-based mitogenome and DNA barcode data in three hierarchical steps. We posit that site-based sampling, though not meeting the criterion of “taxon-completeness,” has great merits given preliminary studies showing representativeness and evenness of taxa sampled. We therefore argue in favor of site-based sampling as an unorthodox but logistically efficient way to construct large phylogenetic trees.