bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing large genomic contexts for accurately predicting enhancer-promoter interactions
Authors: Chen Ken , Zhao Huiying , Yang Yuedong 
Published: September 2021

AbstractAccurately identifying enhancer-promoter interactions (EPIs) is challenging because enhancers usually act on the promoters of distant target genes. Although a variety of machine learning and deep learning models have been developed, many of them are not designed to or could not be well applied to predict EPIs in cell types different from the training data. In this study, we develop the TransEPI model for EPI prediction based on datasets derived from Hi-C and ChIA-PET data. TransEPI compiles genomic features from large intervals harboring the enhancer-promoter pair and adopts a Transformer-based architecture to capture the long-range dependencies. Thus, TransEPI could achieve more accurate prediction by addressing the impact of other genomic loci that may competitively interact with the enhancer-promoter pair. We evaluate TransEPI in a challenging scenario, where the independent test samples are predicted by models trained on the data from different cell types and chromosomes. TransEPI robustly predicts cross-cell-type EPI prediction by achieving comparable performance in cross-validation and independent test. More importantly, TransEPI significantly outperforms the state-of-the-art EPI models on the independent test datasets, with the Area Under Precision-Recall Curve (auPRC) score increasing by 48.84 % on average. Hence, TransEPI is applicable for accurate EPI prediction in cell types without chromatin structure data. Moreover, we find the TransEPI framework could also be extended to identify the target gene of non-coding mutations, which may facilitate studying pathogenic non-coding mutations.
Novel insights on obligate symbiont lifestyle and adaptation to chemosynthetic environment as revealed by the giant tubeworm genome
Authors: de Oliveira André Luiz , Mitchell Jessica , Girguis Peter , Bright Monika 
Published: September 2021

AbstractThe mutualism between the giant tubewormRiftia pachyptilaand its endosymbiontCandidatusEndoriftia persephone has been extensively researched over the past 40 years. However, the lack of the host whole genome information has impeded the full comprehension of the genotype/phenotype interface inRiftia. Here we described the high-quality draft genome ofRiftia, its complete mitogenome, and tissue-specific transcriptomic data. TheRiftiagenome presents signs of reductive evolution, with gene family contractions exceeding expansions. Expanded gene families are related to sulphur metabolism, detoxification, anti-oxidative stress, oxygen transport, immune system, and lysosomal digestion, reflecting evolutionary adaptations to the vent environment and endosymbiosis. Despite the derived body plan, the developmental gene repertoire in the gutless tubeworm is extremely conserved with the presence of a near intact and complete Hox cluster. Gene expression analyses establishes that the trophosome is a multi-functional organ marked by intracellular digestion of endosymbionts, storage of excretory products and haematopoietic functions. Overall, the plume and gonad tissues both in contact to the environment harbour highly expressed genes involved with cell cycle, programmed cell death, and immunity indicating a high cell turnover and defence mechanisms against pathogens. We posit that the innate immune system plays a more prominent role into the establishment of the symbiosis during the infection in the larval stage, rather than maintaining the symbiostasis in the trophosome. This genome bridges four decades of physiological research inRiftia, whilst simultaneously provides new insights into the development, whole organism functions and evolution in the giant tubeworm.
Sex-specific divergent maturational trajectories in the postnatal rat basolateral amygdala
Authors: Guily Pauline , Lassalle Olivier , Chavis Pascale , Manzoni Olivier JJ 
Published: September 2021

AbstractThe basolateral amygdala (BLA), the part of the amygdala complex involved in the transduction of perceptual stimuli into emotion, undergoes profound reorganization at adolescence in rodents and humans. How cellular and synaptic plasticity evolve throughout postnatal development in both sexes is only partially understood. We used a cross-sectional approach to compare the morphology, neuronal, and synaptic properties of BLA neurons in rats of both sexes at adolescence and adulthood. While BLA pyramidal neurons from rats of both sexes displayed similar current-voltage relationships, rheobases, and resting potentials during pubescence, differences in these parameters emerged between sexes at adulthood: BLA neurons were more excitable in males than females. During pubescence, BLA neuron excitability was highest in females and unchanged in males; male action potentials were smaller and shorter than females and fast afterhyperpolarizations were larger in males. During post-natal maturation, no difference in spine density was observed between groups or sexes but spine length increased and decreased in females and males, respectively. A reduction in spine head diameter and volume was observed exclusively in females. Basic synaptic properties also displayed sex-specific maturational differences. Stimulus-response relationships and maximal fEPSP amplitudes where higher in male adolescents compared with adults but were similar in females of both ages. Spontaneous excitatory postsynaptic currents mediated by AMPA receptors were smaller in BLA neurons from adolescent female compared with their adult counterparts but were unchanged in males. These differences did not directly convert into changes in overall synaptic strength estimated from the AMPA/NMDA ratio, which was smaller in adolescent females. Finally, the developmental courses of long-term potentiation and depression (LTP, LTD) were sexually dimorphic. LTP was similarly present during the adolescent period in males and females but was not apparent at adulthood in females. In contrast, LTD followed an opposite development: present in adolescent females and expressed in both sexes at adulthood. These data reveal divergent maturational trajectories in the BLA of male and female rats and suggest cellular substrates to the BLA linked sex-specific behaviors at adolescence and adulthood.
Molecular phylogeny of fucoxanthin-chlorophyll a/c proteins from Chaetoceros gracilis and Lhcq/Lhcf diversity
Authors: Kumazawa Minoru , Nishide Hiroyo , Nagao Ryo , Inoue-Kashino Natsuko , Shen Jian-Ren , Nakano Takeshi , Uchiyama Ikuo , Kashino Yasuhiro , Ifuku Kentaro 
Published: September 2021

AbstractDiatoms adapt to various aquatic light environments and play major roles in the global carbon cycle using their unique light-harvesting system, i.e., fucoxanthin chlorophyll a/c binding proteins (FCPs). Structural analyses of photosystem II (PSII)-FCPII and photosystem I (PSI)-FCPI complexes from the diatom Chaetoceros gracilis have revealed the localization and interactions of many FCPs; however, the entire set of FCPs has not been characterized. Here, we identified 46 FCPs in the newly assembled genome and transcriptome of C. gracilis. Phylogenetic analyses suggested that these FCPs could be classified into five subfamilies: Lhcr, Lhcf, Lhcx, Lhcz, and novel Lhcq, in addition to a distinct type of Lhcr, CgLhcr9. The FCPs in Lhcr, including CgLhcr9 and some Lhcqs, had orthologous proteins in other diatoms, particularly those found in the PSI-FCPI structure. By contrast, the Lhcf subfamily, some of which were found in the PSII-FCPII complex, seemed to be diversified in each diatom species, and the number of Lhcqs differed among species, indicating that their diversification may contribute to species-specific adaptations to light. Further phylogenetic analyses of FCPs/light-harvesting complex (LHC) proteins using genome data and assembled transcriptomes of other diatoms and microalgae in public databases suggest that our proposed classification of FCPs was common among various red-lineage algae derived from secondary endosymbiosis of red algae, including Haptophyta. These results provided insights into the loss and gain of FCP/LHC subfamilies during the evolutionary history of the red algal lineage.One sentence summaryPhylogenetic analysis of fucoxanthin-chlorophyll a/c proteins in C. gracilis revealed five major subfamilies and one minor subfamily, providing insights into the diversification of light-harvesting systems in red algae.
USP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K
Authors: Prieto-Garcia Cristian , Hartmann Oliver , Reissland Michaela , Braun Fabian , Bozkurt Süleyman , Fuss Carmina , Schülein-Völk Christina , Buchberger Alexander , Calzado Canale Marco A. , Rosenfeldt Mathias , Dikic Ivan , Münch Christian , Diefenbacher Markus E. 
Published: September 2021

AbstractOncogenic transformation of lung epithelial cells is a multi-step process, frequently starting with the inactivation of tumor suppressors and subsequent activating mutations in proto-oncogenes, such as members of the PI3K or MAPK family. Cells undergoing transformation have to adjust to changes, such as metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors, which manifest these adjustments. Here, we report that the deubiquitylase USP28 enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes, such as c-JUN, c-MYC, NOTCH and ΔNP63, at early stages of malignant transformation. USP28 is increased in cancer compared to normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors, such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small molecule inhibitor reset the proteome of transformed cells towards a ‘pre-malignant’ state, and its inhibition cooperated with clinically established compounds used to target EGFRL858R, BRAFV600Eor PI3KH1047Rdriven tumor cells. Targeting USP28 protein abundance already at an early stage via inhibition of its activity therefore is a feasible strategy for the treatment of early stage lung tumours and the observed synergism with current standard of care inhibitors holds the potential for improved targeting of established tumors.
Inhibition of the SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity
Authors: Ben-Shmuel Aviad , Sabag Batel , Biber Guy , Puthenveetil Abhishek , Levy Moria , Jubany Tammir , Joseph Noah , Matalon Omri , Kivelevitz Jessica , Barda-Saad Mira 
Published: September 2021

AbstractNatural Killer (NK) cells play a crucial role in immunity, killing virally infected and cancerous cells. The balance of signals initiated upon engagement of activating and inhibitory NK receptors with cognate ligands determines killing or tolerance. Nevertheless, the molecular mechanisms regulating rapid NK cell discrimination between healthy and malignant cells in a heterogeneous tissue environment are incompletely understood. The SHP-1 tyrosine phosphatase is the central negative NK cell regulator, which dephosphorylates key activating signaling proteins. Though the mechanism by which SHP-1 mediates NK cell inhibition has been partially elucidated, the pathways by which SHP-1 is itself regulated remain unclear. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 “folded” state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in-vivo. This study reveals a molecular pathway that sustains the NK cell activation threshold through suppression of SHP-1 activity.
Geometrical Study of Virus RNA Sequences
Authors: Belinsky Alex , Kouzaev Guennadi 
Published: September 2021

AbstractIn this contribution, some applications of the earlier developed fast algorithm of calculating coordinates of single nucleotides and RNA fragments are considered to create multi-scale geometrical models of RNAs and their mutations. The algorithm allows to plot single nucleotides and RNA’s fragments on one figure and to track the RNA mutations of any level visually and numerically using interpolation formulas and point-to-point estimates of coordinates of ATG starting triplets and single nucleotides. The performed study of many samples of SARS CoV-2 viruses shows perturbations of ATG starting triplet coordinates in the vicinity of orf1ab gene end only.
CHAS, a deconvolution tool, infers cell type-specific signatures in bulk brain histone acetylation studies of neurological and psychiatric disorders
Authors: Murphy Kitty B. , Ye Yuqian , Tsalenchuk Maria , Nott Alexi , Marzi Sarah J. 
Published: September 2021

AbstractAcetylation of histone H3 lysine 27 (H3K27ac) has emerged as an informative disease-associated epigenetic mark. However, cell type-specific contributions to epigenetic dysregulation in disease are unclear as studies have often used bulk brain tissue. Therefore, methods for the deconvolution of bulk H3K27ac profiles are critical. Here we developed the Cell type-specific Histone Acetylation Score (CHAS), a computational tool for inferring cell type-specific signatures in bulk brain H3K27ac profiles. We applied CHAS to > 300 H3K27ac ChIP-seq samples from studies of Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, schizophrenia, and bipolar disorder in bulk post-mortem brain tissue. In addition to recapitulating known disease-associated shifts in cellular proportions, we identified novel cell type-specific biological insights into brain disorder associated regulatory variation. In most cases, genetic risk and epigenetic dysregulation targeted different cell types, thus suggesting independent mechanisms. For instance, Alzheimer’s disease genetic risk was exclusively enriched within microglia, while epigenetic dysregulation predominantly fell within oligodendrocyte-specific H3K27ac regions. In addition, reanalysis of the original datasets using CHAS enabled identification of biological pathways associated with each neurological and psychiatric disorder at cellular resolution.
Novel effector recognition capacity engineered into a paired NLR complex
Authors: Wang Shanshan , Huang Weijie , Duxbury Zane , Hogenhout Saskia A. , Jones Jonathan D. G. 
Published: September 2021

AbstractThe Arabidopsis RRS1-R Resistance gene confers recognition of the bacterial acetyltransferase PopP2 and another bacterial effector, AvrRps4. The RRS1-S allele recognizes AvrRps4 but not PopP2. RRS1- R/RRS1-S heterozygotes cannot recognize PopP2. RRS1-R and RRS1-S also suppress the constitutive RPS4-dependent autoactivity of RRS1-Rslh1. Phytoplasmas cause important plant diseases, and their effectors can cause degradation of specific host proteins. We tested whether attaching a pathogen effector-dependent degron to RRS1-R, enabling its degradation by phytoplasma effector SAP05, could derepress RRS1-Rslh1 autoactivity, resulting in SAP05-dependent resistance. In transient assays in tobacco, RRS1-R-derived constructs can confer a hypersensitive response (HR) to SAP05. However, phytoplasma infection assays in transgenic Arabidopsis resulted in delayed disease symptoms but not full resistance. We provide a proof-of-concept strategy utilizing the recessiveness of a plant immune receptor gene to engineer recognition of a pathogen effector that promotes degradation of a specific host protein.
Speech categorization reveals the role of early-stage temporal-coherence processing in auditory scene analysis
Authors: Viswanathan Vibha , Shinn-Cunningham Barbara G. , Heinz Michael G. 
Published: September 2021

AbstractTemporal coherence of sound fluctuations across spectral channels is thought to aid auditory grouping and scene segregation. Although prior studies on the neural bases of temporal-coherence processing focused mostly on cortical contributions, neurophysiological evidence suggests that temporal-coherence-based scene analysis may start as early as the cochlear nucleus (i.e., the first auditory region supporting cross-channel processing over a wide frequency range). Accordingly, we hypothesized that aspects of temporal-coherence processing that could be realized in early auditory areas may shape speech understanding in noise. We then explored whether physiologically plausible computational models could account for results from a behavioral experiment that measured consonant categorization in different masking conditions. We tested whether within-channel masking of target-speech modulations predicted consonant confusions across the different conditions, and whether predicted performance was improved by adding across-channel temporal-coherence processing mirroring the computations known to exist in the cochlear nucleus. Consonant confusions provide a rich characterization of error patterns in speech categorization, and are thus crucial for rigorously testing models of speech perception; however, to the best of our knowledge, they have not been utilized in prior studies of scene analysis. We find that within-channel modulation masking can reasonably account for category confusions, but that it fails when temporal fine structure (TFS) cues are unavailable. However, the addition of across-channel temporal-coherence processing significantly improves confusion predictions across all tested conditions. Our results suggest that temporal-coherence processing strongly shapes speech understanding in noise, and that physiological computations that exist early along the auditory pathway may contribute to this process.
Expectations boost the reconstruction of auditory features from electrophysiological responses to noisy speech
Authors: Corcoran Andrew W. , Perera Ricardo , Koroma Matthieu , Kouider Sid , Hohwy Jakob , Andrillon Thomas 
Published: September 2021

AbstractOnline speech processing imposes significant computational demands on the listening brain, the underlying mechanisms of which remain poorly understood. Here, we exploit the perceptual ‘pop-out’ phenomenon (i.e. the dramatic improvement of speech intelligibility after receiving information about speech content) to investigate the neurophysiological effects of prior expectations on degraded speech comprehension. We recorded electroencephalography and pupillometry from 21 adults while they rated the clarity of noise-vocoded and sine-wave synthesised sentences. Pop-out was reliably elicited following visual presentation of the corresponding written sentence, but not following incongruent or neutral text. Pop-out was associated with improved reconstruction of the acoustic stimulus envelope from low-frequency EEG activity, implying that improvements in perceptual clarity were mediated via top-down signals that enhance the quality of cortical speech representations. Spectral analysis further revealed that pop-out was accompanied by a reduction in theta-band power, consistent with predictive coding accounts of acoustic filling-in and incremental sentence processing. Moreover, delta-band power, alpha-band power, and pupil diameter were all increased following the provision of any written sentence information, irrespective of content. Together, these findings reveal distinctive profiles of neurophysiological activity that differentiate the content-specific processes associated with degraded speech comprehension from the context-specific processes invoked under adverse listening conditions.
Bee-associated fungi mediate effects of fungicides on bumble bees
Authors: Rutkowski Danielle , Litsey Eliza , Maalouf Isabelle , Vannette Rachel L. 
Published: September 2021

AbstractBumble bees are important pollinators that face threats from multiple sources, including agrochemical application. Declining bumble bee populations have been linked to fungicide application, which could directly affect the fungi often found in the stored food and GI tract of healthy bumble bees. Here, we test the hypothesis that fungicides impact bee health by disrupting bee-fungi interactions. We examine the interactive effects of the fungicide propiconazole and fungal supplementation on the survival, reproduction, and microbiome composition of microcolonies (queenless colonies) using two species,Bombus vosnesenskiiandB. impatiens. We found that both bee species benefitted from fungi, but were differentially affected by fungicides. InB. vosnesenskii, fungicide exposure decreased survival while fungal supplementation mitigated fungicide effects. ForB. impatiens, fungicide application had no effect, but fungal supplementation improved survival and offspring production. Fungicides reduced fungal abundance inB. vosnesenskiimicrocolonies, but not inB. impatiens, where instead fungal addition decreased fungal abundance. InB. vosnesenskii, the abundance of the pathogenAscosphaerawas negatively associated with survival, while the yeastZygosaccharomyceswas positively associated with survival. Our results highlight species-specific differences in response to fungicides and the nature of bee-fungi associations, and caution the use of results obtained using one species to predict responses of other species. These results demonstrate that fungicides can alter bee-fungi interactions with consequences for bee survival and reproduction, and suggest that exploring the mechanisms of such interactions, including interactions among fungi in the bee GI tract, may offer insights into bumble bee biology and conservation strategies.Significance statementWild bumble bee populations are declining globally, and a major predictor of these declines is agricultural fungicide application. We test the hypothesis that bee-associated fungi mediate fungicide effects on bees, examining how fungicide exposure and subsequent fungal supplementation impact bumble bee survival and microbiome. Fungal supplementation enhanced survival in both bumble bee species tested here, with fungi mediating effects of fungicide exposure in one species. Differences in bee survival were associated with changes in the gut mycobiome: negatively with the pathogenAscosphaeraand positively withZygosaccharomycesyeasts. This study highlights the importance of the mycobiome in bumble bee health both as a mechanism by which fungicides impact bumble bees and as an avenue of further research on beneficial bee-associated fungi.