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Mashup Score: 0GPnotebook: A pan-cancer glycoproteomic database and toolkit for analysis of protein glycosylation changes associated with cancer phenotypes - 3 hour(s) ago
Protein glycosylation plays a pivotal role in various biological processes, and the analysis of intact glycopeptides (IGPs) has emerged as a powerful approach for characterizing alterations in protein glycosylation associated with diseases. Despite the critical insights gained from IGP analysis, there is an evident scarcity of intact glycopeptide database and specialized tools for a comprehensive glycoproteomic examination. In response to this deficiency, we have developed a Python package, “GPnotebook,” which consolidates the intact glycopeptides identified from different cancer types by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and includes analytical tools for an in-depth characterization of glycopeptides. GPnotebook facilitates an array of functions including statistical profiling, differential expression analysis, glycosylation subtype categorization, investigation of glycosylation-phosphorylation interplay, survival analysis, and glycosylation enzyme assessment. We
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Mashup Score: 0A Futile Cycle? Tissue Homeostatic Trans-Membrane Water Co-Transport: Kinetics, Thermodynamics, Metabolic Consequences - 3 hour(s) ago
The phenomenon of active trans-membrane water cycling (AWC) has emerged in little over a decade. Here, we consider H2O transport across cell membranes from the origins of its study. Historically, trans-membrane water transport processes were classified into: A) compensating bidirectional fluxes (exchange), and B) unidirectional flux (net flow) categories. Recent literature molecular structure determinations and molecular dynamic (MD) simulations indicate probably all the many different hydrophilic substrate membrane co-transporters have membrane-spanning hydrophilic pathways and co-transport water along with their substrates, and that they individually catalyze category A and/or B water flux processes, although usually not simultaneously. The AWC name signifies that, integrated over the all the cell co-transporters, the rate of homeostatic, bidirectional trans cytolemmal water exchange (category A) is synchronized with the metabolic rate of the crucial Na+,K+ ATPase (NKA) enzyme. A lit
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Mashup Score: 0Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing - 3 hour(s) ago
5-Methylcytosine (m5C) is one of the major post-transcriptional modifications in mRNA and is highly involved in the pathogenesis of various diseases. However, the capacity of existing assays for accurately and comprehensively transcriptome-wide m5C mapping still needs improvement. Here, we develop a detection method named DRAM (deaminase and reader protein assisted RNA methylation analysis), in which deaminases (APOBEC1 and TadA-8e) are fused with m5C reader proteins (ALYREF and YBX1) to identify the m5C sites through deamination events neighboring the methylation sites. This antibody-free and bisulfite-free approach provides transcriptome-wide editing regions which are highly overlapped with the publicly available BS-seq datasets and allows for a more stable and comprehensive identification of the m5C loci. In addition, DRAM system even supports ultra-low input RNA (10ng) and monitor the dynamic accumulation of cellular m5C. We anticipate that the DRAM system could pave the way for un
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Mashup Score: 0Early-life scarcity adversity biases behavioral development toward a bipolar-like phenotype in mice heterozygous for CNTNAP2 - 10 hour(s) ago
The etiological complexity of psychiatric disorders arises from the dynamic interplay between genetic and environmental vulnerabilities. Among the environmental components, early-life adversities (ELA) are a major risk-factors for developing a psychiatric disorder. Yet, the mechanistic interaction between ELA and genetic vulnerability contributing to psychopathology is poorly understood. To fill this gap, we took advantage of the ideally controlled conditions of a pre-clinical approach. In this study we raised a mouse model with genetic predisposition to multiple psychiatric disorders (autism spectrum, schizophrenia, bipolar disorder), the Cntnap2+/- mouse, with limited bedding and nesting (LBN), a well-established paradigm to induce early-life stress in rodents. These mice were compared to LBN-raised Cntnap2+/+ littermates, as well as parallel groups of Cntnap2+/+ and Cntnap2+/- raised in standard conditions. Using a battery for behavioral phenotyping we show that ELA shapes non-overl
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Mashup Score: 1
Biological accounts of reinforcement learning posit that dopamine encodes reward prediction errors (RPEs), which are multiplied by a learning rate to update state or action values. These values are thought to be represented in synaptic weights in the striatum, and updated by dopamine-dependent plasticity, suggesting that dopamine release might reflect the product of the learning rate and RPE. Here, we leveraged the fact that animals learn faster in volatile environments to characterize dopamine encoding of learning rates. We trained rats on a task with semi-observable states offering different rewards, and rats adjusted how quickly they initiated trials across states using RPEs. Computational modeling and behavioral analyses showed that learning rates were higher following state transitions, and scaled with trial-by-trial changes in beliefs about hidden states, approximating normative Bayesian strategies. Notably, dopamine release in the nucleus accumbens encoded RPEs independent of le
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Mashup Score: 1Temporal variability enhances vocal learning - 10 hour(s) ago
Species-typical behaviors are organized into species-typical patterns, and deviations away from these patterns often diminish the strength of behavioral and sensory responses to such stimuli. In songbirds like the zebra finch, species-typical songs consist of acoustic elements (syllables) arranged into stereotyped (i.e., highly predictable) sequences with stereotyped timing. However, the degree to which deviations away from these stereotyped temporal patterns modulate the strength of vocal learning (i.e., the fidelity of vocal imitation) remains unknown. Here we tutored 127 juvenile zebra finches with stimuli that varied in the stereotypy of syllable sequencing and timing. In contrast to the prediction that deviations away from species-typical stereotypy would diminish vocal learning, deviations from sequence or timing stereotypy did not decrease how well juveniles imitated the acoustic structure of syllables. Moreover, presenting syllables in species-atypical sequences (i.e., randomiz
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Mashup Score: 3
Denisovans are an extinct group of humans whose morphology is mostly unknown. The scarcity of verified Denisovan fossils makes it challenging to study how they differed in their anatomy, and how well they were adapted to their environment. To gain insight into their evolutionary history, we used a genetic phenotyping approach, where predicted Denisovan anatomy was inferred by detecting gene regulatory changes that likely altered Denisovan skeletal morphology. We then scanned Middle Pleistocene skulls for unclassified specimens that match our Denisovan profile and thus might have been related to Denisovans. We found that the Harbin, Dali, and Kabwe specimens show a particularly good match to the predicted Denisovan profile. We conclude that our genetic phenotyping approach could help classify unidentified specimens, and that Harbin, Dali, and Kabwe likely belonged to individuals closely linked to the Denisovan lineage. ### Competing Interest Statement The authors have declared no compet
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Mashup Score: 0
Background: Ultra-high-resolution magnetic resonance imaging of the ex vivo brain is increasingly becoming an indispensable tool for studying the morphology and potential pathology of the brain. Despite the important role of the cerebellum in nervous system functions and motor control, as well as its potential damage in neurological diseases, it remains relatively understudied compared to other brain regions. One major reason is the even finer structures. Methods: A balanced steady state free precession approach with receiver bandwidths as low as 50Hz/pixel and long repetition times of 36ms is suggested and optimized, called “LoBa-bSSFP”, which enhances the signal-to-noise ratio and alleviates strain on the gradient system for the ultra-high spatial resolutions. A radiofrequency phase cycle scheme is used to reduce potential artifacts. Only 3T MRI standard equipment is utilized for acquisition and basic image reconstruction of the ex vivo brain immersed in perfluoropolyether. Results:
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Mashup Score: 0
It has been believed that platelet integrin αIIbβ3 recognizes fibrinogen and several ECM proteins, and we recently showed that αIIbβ3 binds to several inflammatory cytokines (e.g., CCL5, and CXCL12), which are stored in platelet granules. These ligands bind to the classical ligand (RGD)-binding site (site 1) of integrin αIIbβ3. Also, they bind to the allosteric site (site 2) of αIIbβ3, which is distinct from site 1, and allosterically activate αIIbβ3. Site 2 is known to be involved in allosteric integrin activation and inflammatory signaling. FGF2 is also stored in platelet granules and known to be pro-thrombotic, but it is unclear if FGF2 binds to αIIbβ3. We studied if FGF2 and its homologue FGF1 bind to αIIbβ3 and induce allosteric activation. FGF1 (not stored in platelet granules) is known to be anti-thrombotic. Mechanism of anti-thrombotic action of FGF1 is unknown. Here we describe that FGF1 and FGF2 bound to site 1 of αIIbβ3, indicating that αIIbβ3 is a new receptor for FGF1/2. N
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Mashup Score: 1A natural ANI gap that can define intra-species units of bacteriophages and other viruses - 14 hour(s) ago
Despite the importance of intra-species variants of viruses for causing disease and/or disrupting ecosystem functioning, there is no universally applicable standard to define these. A 95% whole-genome average nucleotide identity (ANI) gap is commonly used to define species, especially for bacteriophages, but whether a similar gap exists within species that can be used to define intra-species units has not been evaluated yet. Whole-genome comparisons among members of 1,016 bacteriophage species revealed a region of low frequency of pairs around 99.2-99.8% ANI, showing 3-fold or fewer pairs than expected for an even or normal distribution. This second gap is prevalent in viruses infecting various cultured or uncultured hosts, and from a variety of environments, although a few exceptions to this pattern were also observed (~3.7% of the total species evaluated) and are likely attributed to cultivation biases. Similar results were observed for a limited set of eukaryotic viruses that are ad
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GPnotebook: A pan-cancer glycoproteomic database and toolkit for analysis of protein glycosylation changes associated with cancer phenotypes https://t.co/mLUkXxHSGq #bioRxiv