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Accurate prediction of TCR-pMHC binding is important for the development of cancer immunotherapies, especially TCR-based agents. Existing algorithms often experience diminished performance when dealing with unseen epitopes, primarily due to the complexity in TCR-pMHC recognition patterns and the scarcity of available data for training. We have developed a novel deep learning model, 'TCR Antigen Binding Recognition' based on BERT, named as TABR-BERT. Leveraging BERT's potent representation learning capabilities, TABR-BERT effectively captures essential information regarding TCR-pMHC interactions from TCR sequences, antigen epitope sequences and epitope-MHC binding. By transferring this knowledge to predict TCR-pMHC recognition, TABR-BERT demonstrated better results in benchmark tests than existing methods, particularly for unseen epitopes. [ABSTRACT FROM AUTHOR]

The occurrence of male feticide and/or infanticide represents an extreme case of sexual conflict: an adaptive strategy of male reproduction at the expense of females. Females are predicted to develop numerous countertactics; however, it has remained unclear whether countertactics can effectively shift the balance which likely depends on the social and mating system. We conducted a 15-year, detailed observation of female and male behavior during male replacement in free-ranging golden snub-nosed monkeys (Rhinopithecus roxellana) of a multilevel society. We have identified several potential countertactics against feticide and/or infanticide, including pregnant or lactating females staying with ousted males or transferring to stay with the ousted male after being attacked, which lead to 2 of 11 fetuses succumbing to feticide, and extra-unit mating, female joint defense and transferring with their infants to other social units, which lead to 6 of 34 infants succumbing to infanticide. Female joint defenses crucially delay infanticide, providing mothers the opportunity to transfer with their vulnerable infants to another social unit where they have previously mated with the male leader or where they have female relatives. Importantly, in response to mothers starting to transfer, some males cease attacking infants, a change in behavior that is likely to be beneficial to males because during their tenures they can sire future offspring of the mothers who remain. Our findings show how dynamic interactions between males and females can be and how the conditions in multilevel societies can shift the outcome of intersexual conflict from males to females. [ABSTRACT FROM AUTHOR]

Objective Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. Methods A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. Results After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048–0.715, P  = 0.014; HR = 0.435, CI: 0.234–0.812, P  = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P  = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. Conclusions Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation. [ABSTRACT FROM AUTHOR]

Bortezomib suppressing NF‐κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV‐1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV‐1 reactivation, and how bortezomib exacerbates HSV‐1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV‐1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV‐1‐infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV‐1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy‐induced leukocyte deficiency. [ABSTRACT FROM AUTHOR]

Motivation: In the past years, the long read (LR) sequencing technologies, such as Pacific Biosciences and Oxford Nanopore Technologies, have been demonstrated to substantially improve the quality of genome assembly and transcriptome characterization. Compared to the high cost of genome assembly by LR sequencing, it is more affordable to generate LRs for transcriptome characterization. That is, when informative transcriptome LR data are available without a high-quality genome, a method for de novo transcriptome assembly and annotation is of high demand. Results: Without a reference genome, IDP-denovo performs de novo transcriptome assembly, isoform annotation and quantification by integrating the strengths of LRs and short reads. Using the GM12878 human data as a gold standard, we demonstrated that IDP-denovo had superior sensitivity of transcript assembly and high accuracy of isoform annotation. In addition, IDP-denovo outputs two abundance indices to provide a comprehensive expression profile of genes/isoforms. IDPdenovo represents a robust approach for transcriptome assembly, isoform annotation and quantification for non-model organism studies. Applying IDP-denovo to a non-model organism, Dendrobium officinale, we discovered a number of novel genes and novel isoforms that were not reported by the existing annotation library. These results reveal the high diversity of gene isoforms in D.officinale, which was not reported in the existing annotation library. [ABSTRACT FROM AUTHOR]

Background Reliable stability and yield of RNA from breast cancer tissues are important for biobanking, clinical trials, and diagnostic testing. Methods Aliquots of fresh primary tumor tissue from 17 surgically resected invasive breast cancers were placed into RNAlater at room temperature after tumor removal (baseline) and up to 3 hours thereafter or were snap frozen at baseline and 40 minutes thereafter. Samples were stored at −80°C until gene expression profiling with Affymetrix Human Gene U133A microarrays. We evaluated the effects of cold ischemic time (the time from tumor specimen removal to sample preservation) and sample preservation method on RNA yield, Bioanalyzer-based RNA integrity number, microarray-based 3′/5′ expression ratios for assessing transcript integrity, and microarray-based measurement of single-gene and multigene expression signatures. The statistical significance of the effects was assessed using linear mixed effects regression models. All statistical tests were two-sided. Results Sample preservation in RNAlater statistically significantly improved RNA integrity compared with snap freezing as assessed by the RNA integrity number, which increased from 7.31 to 8.13 units (difference = 0.82 units, 95% confidence interval [CI] = 0.53 to 1.11 units, P < .001), and RNA yield, which increased threefold from 8.9 to 28.6 μg (difference = 19.7 μg, 95% CI = 14.1 to 25.3 μg, P < .001). Prolonged cold ischemic delay at room temperature before sample stabilization decreased the RNA integrity number by 0.12 units/h (95% CI = 0.02 to 0.23 units/h) compared with a projected average RNA integrity number of 7.39 if no delays were present (P = .008) and decreased the RNA yield by 1.5 μg/h (95% CI = 0 to 4 μg/h) from a baseline mean RNA yield of 33.5 μg if no delays were present (P = .019). Prolonged cold ischemia statistically significantly increased the 3′/5′ ratio of control gene transcripts, particularly of STAT1 (P < .001). Snap freezing statistically significantly increased the 3′/5′ ratio of three control transcripts (ACTB, GAPDH, and 18S rRNA). Expression levels of single genes and multigene signatures for breast cancer were largely unaffected by sample preservation method or cold ischemia. Conclusions Sample preservation in RNAlater improves RNA yield and quality, whereas cold ischemia increases RNA fragmentation as measured by the 3′/5′ expression ratio of control genes. However, expression levels of single genes and multigene signatures that are of diagnostic relevance in breast cancer were mostly unaffected by sample preservation method or prolonged cold ischemic duration. [ABSTRACT FROM AUTHOR]

A late Mesozoic belt of volcanicintrusive complexes occurs in SE China. Volcanic activity at Xiangshan in the NW of the belt took place mainly in the Late Jurassic (158135?Ma). The volcanic rocks from the Xiangshan volcanic complex include rhyolitic crystal tuffs, welded tuffs, rhyolite lavas, porphyritic lavas, and associated subvolcanic rocks. Mineral assemblages in these magmatic rocks include K-feldspar, plagioclase, quartz, Fe-rich biotite and minor amphibole, orthopyroxene and almandine. Mineral geothermometry indicates a high crystallization temperature (>850C) for the Xiangshan magmas. The volcanic rocks are generally peraluminous; SiO2 contents are between 654% and 768% and the samples have high alkalis, rare earth elements (REE), high field strength elements and Ga contents and high Ga/Al ratios, but are depleted in Ba, Sr and transition metals. Trace element geochemistry and SrNdO isotope systematics imply that the Xiangshan magmas were probably derived from partial melting of Middle Proterozoic metamorphic lower-crustal rocks that had been dehydrated during an earlier thermal event. These features suggest an A-type affinity. Quenched mafic enclaves, hosted by the subvolcanic rocks, consist mainly of alkali feldspar, plagioclase, clinopyroxene, phlogopite and amphibole. Geothermometry calculations indicate that the primary magmas that chilled to form the quenched enclaves had anomalously high temperatures (>1200C). The quenched enclaves have boninitic affinities; for example, intermediate SiO2 contents, high MgO and low TiO2 contents, high Mg-numbers and high concentrations of Sc, Ni, Co and V. However, they also have shoshonitic characteristics, e.g. enrichment in alkalis, high K2O contents with high K2O/Na2O ratios, high light REE and large ion lithophile element contents, low initial ?Nd values (-42) and high initial 87Sr/86Sr ratios (07081). We suggest a phlogopite-bearing spinel harzburgitic lithospheric mantle source for these high-Mg potassic magmas. Underplating of such anomalously high-temperature magmas could have induced granulite-facies lower-crustal rocks to partially melt and generate the Xiangshan A-type volcanic suite. A back-arc extensional setting, related to subduction of the Palaeo-Pacific plate, is favoured to explain the petrogenesis of the Xiangshan volcanic complex and quenched enclaves. [ABSTRACT FROM AUTHOR]

Interactions between plants and microbes are involved in biodiversity maintenance, community stability and ecosystem functioning. However, differences in the community and network structures between phyllosphere epiphytic and endophytic bacteria have rarely been investigated. Here, we examined phyllosphere epiphytic and endophytic bacterial communities of six mangrove species using Illumina MiSeq sequencing of the 16S rRNA gene. The results revealed that the community structure of epiphytic and endophytic bacteria was different. Plant identity significantly affected the diversity and community structure of both epiphytic and endophytic bacteria, with a greater effect on the community structure of the former than the latter. Network analysis showed that both plant–epiphytic and plant–endophytic bacterial network structures were characterized by significantly highly specialized and modular but lowly connected and anti-nested properties. Furthermore, the epiphytic bacterial network was more highly specialized and modular but less connected and more strongly anti-nested than the endophytic bacterial network. This study reveals that the phyllosphere epiphytic and endophytic bacterial community structures differ and plant identity has a greater effect on the epiphytic than on the endophytic bacteria, which may provide a comprehensive insight into the role of plant identity in driving the phyllosphere epiphytic and endophytic microbial community structures in mangrove ecosystems. [ABSTRACT FROM AUTHOR]

Summary: We developed a new algorithmic method, VirusSeq, for detecting known viruses and their integration sites in the human genome using next-generation sequencing data. We evaluated VirusSeq on whole-transcriptome sequencing (RNA-Seq) data of 256 human cancer samples from The Cancer Genome Atlas. Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity. VirusSeq can also perform this function using whole-genome sequencing data of human tissue.Availability: VirusSeq has been implemented in PERL and is available at http://odin.mdacc.tmc.edu/∼xsu1/VirusSeq.html.Contact: xsu1@mdanderson.orgSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]