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Hu, B.

Publications and source records attributed to Hu, B..

At least 91 records · Page 5Linked to original sources
bioRxiv2024

African Swine Fever Virus Protein B263R Inhibits Autophagy by Promoting Proteasomal Degradation of Beclin1

African swine fever (ASF) is a highly contagious viral disease that affects both domestic and wild pigs, leading to substantial economic losses in the swine industry. However,the precise role of ASFV-encoded viral protein in viral replication and disease has remained elusive. In our study, we elucidated that B263R inhibited autophagy by interacting with Beclin1. Mechanistically, the binding of B263R to Beclin1 promotes its degradation through the mediation of K48-linked ubiquitination at site K31. Notably, the knockdown of Beclin1 mitigated the effect of B263R on reducing the levels of LC3-II, thus further affirming the pivotal role of Beclin1 in B263R-mediated autophagy inhibition. The proliferation of recombinant adenovirus inherently expressing B263R significantly decreased, underscoring the inherent role of B263R-mediated autophagy in virus replication. These findings shed light on the molecular mechanisms employed by ASFV to evade host cell autophagic defenses and offered potential targets for therapeutic interventions against ASFV infection. IMPORTANCEUnderstanding the mechanisms underlying the evasion of host cellular defenses by the African swine fever virus (ASFV) is of pivotal significance owing to its profound impact on the global swine industry. The precise functional roles of ASFV proteins in virus replication and disease remain incompletely characterized. In this study, it is demonstrated that a specific ASFV protein, B263R, acts to inhibit autophagy by interacting with Beclin1, thereby facilitating its degradation. The elucidation of this molecular pathway not only advances our comprehension of ASFV pathogenesis but also furnishes potential targets for therapeutic interventions against ASFV infection. By unraveling the intricate interplay between ASFV and host cell autophagy, this scholarly endeavor contributes invaluable insights to the development of strategies aimed at mitigating the spread of ASFV and minimizing its adverse repercussions on the swine industry.

microbiology↗
bioRxiv2024

Learning the language of proteins and predicting the impact of mutations

Mutations in proteins directly impact their structure and function. Understanding the "language" of proteins, or the sequence to function (genotype-phenotype) relationship has many real-world applications. One set of applications includes those in biodefense, such as biological threat detection and biosurveillance, antibody engineering, and medical countermeasure development. In this study, we present a novel language model-based approach that can rapidly analyze vast collections of sequences, and make near real-time functional predictions that compare favorably to those made using conventional bioinformatic and experimental methods. Our findings reveal that tailored protein language models can predict protein mutation phenotypes, such as binding affinity or level of expression, when they are trained with high-throughput functional data. Protein language models applied to viral genomes can also discern the lineage within a family (e.g., sarbecovirus sequences). Coupled with sequenced-based biosurveillance, this type of model may provide early warning signals of potential zoonotic spillovers (i.e. host jumping) or "escape" from existing medical countermeasures posed by novel mutations. This research not only underscores the potential of ML and language models in addressing pressing challenges in understanding the mapping of sequence to function, but further elucidates their potential application in accelerating the response to biological threats as they evolve.

bioinformatics↗
bioRxiv2024

Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the epithelial and myeloid cells. Along with the diminished inflammatory response, the absence of TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza components in myeloid cells including monocytes and macrophages rendering them highly inflammatory. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/-mice. Further, we show elevated TLR9 activation in the plasma samples of patients with influenza and its association with the disease severity in hospitalized patients, demonstrating its clinical relevance. Overall, we demonstrate an essential role of damage sensing through TLR9 in promoting anti-influenza immunity and inflammatory response. Author SummaryTissue damage is an inevitable outcome of clinically relevant lung infections, but the host mechanisms for detecting such damage during infection are not well understood. We investigated the role of Toll-like receptor 9 (TLR9) in sensing tissue damage caused by influenza. Since influenza lacks TLR9 ligands, we hypothesized that TLR9 signaling is driven by tissue damage molecules like mitochondrial DNA (mtDNA). Our data indicate that TLR9 reduces early inflammatory lung injury but impairs viral clearance, resulting in extensive immune cell infection, persistent inflammation, and delayed recovery. Myeloid-specific TLR9 deletion ameliorated late-stage inflammatory responses. In humans, influenza-infected individuals exhibited elevated TLR9 activity and mtDNA levels in plasma compared to healthy controls, with higher TLR9 activation potential correlating with severe disease requiring ICU admission. These findings suggest that TLR9-mediated damage sensing triggers both inflammatory tissue injury and viral clearance. These data indicate that TLR9 activity can serve as a crucial biomarker and therapeutic target to limit influenza induced tissue injury.

immunology↗
bioRxiv2024

Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis

Non-small cell lung cancer (NSCLC) cells with oncogenic mutant p53 alleles (Onc-p53) exhibit significantly higher levels of proteasome activity, indicating that Onc-p53 induces proteotoxic stress which may be leveraged as a therapeutic vulnerability. Proteasome inhibitors (PIs), such as bortezomib (BTZ), can induce toxic levels of oxidative stress in cancer cells and thus we investigated whether PIs exhibit preferential cytotoxicity in Onc-p53 NSCLC cells. Indeed, BTZ and other PIs exhibited the IC50 6-7-fold lower in Onc-p53 cells vs. wild-type (WT) p53 cells. BTZ cytotoxic effects in Onc-p53 cells were nearly completely rescued by antioxidants such as N-acetyl cysteine, indicating that oxidative stress is the critical driver of BTZ-dependent cytotoxic effects in Onc-p53 cells. Importantly, we observed oxidative stress-dependent transcriptional induction of the pro-apoptotic NOXA with downstream cleaved caspase-3, consistent with apoptotic cell death in Onc-p53 but not in WT p53 cells treated with BTZ, and BTZ-generated oxidative stress was linked to nuclear translocation of NRF2 and transcriptional activation of ATF3, which in turn was required for NOXA induction. Validating BTZs translational potential in Onc-p53 NSCLC, BTZ and carboplatin or the BH3-mimetic navitoclax were synergistically cytotoxic in Onc-p53 but not WT p53 cells in vitro, and BTZ effectively limited growth of Onc-p53 NSCLC xenografts when combined with either carboplatin or navitoclax in vivo. Our data therefore support further investigation of the therapeutic utility of PIs combined with carboplatin or BH3-mimetics in Onc-p53 human NSCLC as novel therapeutic strategies. SignificanceNon-small cell lung cancer (NSCLC) is the leading cause of cancer death due, in part, to a lack of active therapies in advanced disease. We demonstrate that proteasome inhibitor/BH3-mimetic combination therapy is an active precision therapy in NSCLC cells and tumors expressing oncogenic mutant p53 alleles (Onc-p53).

cancer biology↗
bioRxiv2024

Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters

This study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the viruss lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections. Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies. Significance StatementOur research work explores groundbreaking insights that could reshape our understanding of COVID-19 and pave the way for targeted therapies. We use golden hamster models to express the possibility of different animal models could contribute to human diseases. We hope this finding could clarify some conflicts existed, and help further development of medication for COVID.

immunology↗
bioRxiv2024

In vivo affinity maturation of the HIV-1 Env-binding domain of CD4

Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice. After immunization, transferred B cells proliferated, class switched, affinity matured, and efficiently produced D1D2-presenting antibodies. Somatic hypermutations found in the D1D2-encoding region of engrafted B cells improved binding affinity of CD4-Ig-v0 for the HIV-1 envelope glycoprotein (Env) and the neutralization potency of CD4-Ig-v0 by more than ten-fold across a global panel of HIV-1 isolates, without impairing its pharmacokinetic properties. Thus, affinity maturation of non-antibody protein biologics in vivo can guide development of more effective therapeutics.

bioengineering↗
bioRxiv2024

The role of m6A methyltransferase WTAP in inflammatory response of atherosclerosis through NF-κB/NLRP3 mediated pyroptosis

BackgroundPyroptosis is a new form of pro-inflammatory programmed cell death that has been linked to the development of atherosclerosis (AS). However, its exact mechanisms are not known. N6-methyladenosine (m6A) methylation is the commonest and most abundant epigenetic modification of eukaryotic mRNAs. m6A methylation modulates pathological and physiological processes involved in cardiovascular diseases. However, the exact mechanism by which it regulates inflammation in AS is unclear. MethodsIn this study, the level of m6A and WTAP in CHD was explored. To determine the effect of WTAP on the release of pyrolysis-related proteins and pro-inflammatory cytokines, the expression of WTAP in lipopolysaccharide (LPS)-treated endothelial cells was silenced. Pyroptosis-related proteins and pro-inflammatory cytokines were quantified in the presence of NLRP3 shRNA (shNLRP3) and NF-kB shRNA (shNF-kB(p50)). The interaction of NF-kB and NLRP3 was examined through immunoprecipitation (CO-IP), immunofluorescence (IF) and GST-pull down assays. ResultIt was observed that lipopolysaccharide (LPS) induced Nod-like receptor protein 3 (NLRP3)-mediated pyroptosis and inflammation, both of which were abolished through the knockdown of WTAP. Interestingly, our results indicated that WTAP enhanced the function of nuclear factor {kappa}B (NF-{kappa}B) p50 (an NF-{kappa}B subunit) and that p50 could interact with NLRP3 in endothelial cells. ConclusionIn conclusion, these results suggested that WTAP in the formation of pyroptosis and inflammation in endothelial cells exposed to LPS stress by activating the NF-{kappa}B/NLRP3 signaling pathway. These findings demonstrate the mechanism of WTAP regulation during the progression of AS.

immunology↗
bioRxiv2023

H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs

Polycomb Repressive Complex 2 (PRC2)-mediated histone H3K27 tri-methylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochromatin. In early development, polycomb-regulated genes are connected through long-range 3D interactions which resolve upon differentiation. Here, we report that polycomb looping is controlled by H3K27me3 spreading and regulates target gene silencing and cell fate specification. Using glioma-derived H3 Lys-27-Met (H3K27M) mutations as tools to restrict H3K27me3 deposition, we show that H3K27me3 confinement concentrates the chromatin pool of cPRC1, resulting in heightened 3D interactions mirroring chromatin architecture of pluripotency, and stringent gene repression that maintains cells in progenitor states to facilitate tumor development. Conversely, H3K27me3 spread in pluripotent stem cells, following neural differentiation or loss of the H3K36 methyltransferase NSD1, dilutes cPRC1 concentration and dissolves polycomb loops. These results identify the regulatory principles and disease implications of polycomb looping and nominate histone modification-guided distribution of reader complexes as an important mechanism for nuclear compartment organization. Highlights{square} The confinement of H3K27me3 at PRC2 nucleation sites without its spreading correlates with increased 3D chromatin interactions. {square}The H3K27M oncohistone concentrates canonical PRC1 that anchors chromatin loop interactions in gliomas, silencing developmental programs. {square}Stem and progenitor cells require factors promoting H3K27me3 confinement, including H3K36me2, to maintain cPRC1 loop architecture. {square}The cPRC1-H3K27me3 interaction is a targetable driver of aberrant self-renewal in tumor cells.

molecular biology↗
bioRxiv2023

Recommendations For a Standardized Approach to Histopathologic Evaluation of Synovial Membrane in Murine Models of Experimental Osteoarthritis

BackgroundSynovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for synovial histopathology in mouse models of OA. MethodsCoronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T- Blue) and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations in the medial and lateral compartments. Inter-reader reliability of each feature was determined. ResultsThere was acceptable to very good agreement between raters. After DMM, increased hyperplasia and cellularity and a trend towards increased fibrosis were observed 6 weeks after DMM in the medial locations, and persisted up to 16 weeks. In the PMX model, cellularity and hyperplasia were evident in both medial and lateral compartments while fibrotic changes were largely seen on the medial side. Synovial changes were consistent from section to section in the mid-joint area mice. H&E, T-blue, and Saf-O stains resulted in comparable reliability. ConclusionsTo allow for a standard evaluation that can be implemented and compared across labs and studies, we recommend using 3 readers to evaluate a minimum set of 3 pathological features at standardized anatomic areas. Pre-defining areas to be scored, and reliability for each pathologic feature should be considered.

pathology↗
bioRxiv2023

Systematic perturbations of SETD2, NSD1, NSD2, NSD3 and ASH1L reveals their distinct contributions to H3K36 methylation

BackgroundMethylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development, disease, and cancer, how the molecular agents collectively shape the H3K36me landscape is unclear. ResultsWe use a mouse mesenchymal stem cell model to perturb the H3K36me deposition machinery and infer the activities of the five most prominent players: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most abundant within exons and are positively correlated with gene expression. We demonstrate that while SETD2 deposits most H3K36me3, it also deposits H3K36me2 within transcribed genes. Additionally, loss of SETD2 results in an increase of exonic H3K36me1, suggesting other H3K36 methyltransferases (K36MTs) prime gene bodies with lower methylation states ahead of transcription. Through a reductive approach, we uncover the distribution patterns of NSD3- and ASH1L-catalyzed H3K36me2. While NSD1/2 establish broad intergenic H3K36me2 domains, NSD3 deposits H3K36me2 peaks on active promoters and enhancers. Meanwhile, the activity of ASH1L is restricted to the regulatory elements of developmentally relevant genes, and our analyses implicate PBX2 as a potential recruitment factor. ConclusionsWithin genes, SETD2 deposits both H3K36me2/3, while the other K36MTs are capable of depositing H3K36me1/2 independently of SETD2 activity. For the deposition of H3K36me1/2, we find a hierarchy of K36MT activities where NSD1>NSD2>NSD3>ASH1L. While NSD1 and NSD2 are responsible for most genome-wide propagation of H3K36me2, the activities of NSD3 and ASH1L are confined to active regulatory elements.

genomics↗
bioRxiv2023

Adaptive Functions of Structural Variants in Human Brain Development

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV atlas in a population of 562 rhesus macaques, verified by two public SV benchmarks, an inhouse benchmark of eight macaque genomes with long-read sequencing and another inhouse benchmark of one macaque genome with whole-genome assembly. This accurate, quantitative SV map indicates stronger purifying selection on inversions, one type of poorly-clarified SVs to date, especially for those located on regulatory regions, suggesting a strategy for prioritizing inversions with the most important functions. Based on the distribution and the evolutionary features of these inversions in macaque population, we then identified 75 human-specific inversions, clarified their functional effects and prioritized them. Notably, the top-ranked inversions have substantially shaped the human transcriptome, through their dual-effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof-of-concept, we linked APCDD1, located on one of these inversions with the highest rank score and downregulated in human brains, to neuronal maturation. The accumulation of human-specific mutations on its promoter region, accelerated by the formation of the inversion, contributed to the decreased expression in humans. Notably, the overexpression of APCDD1 could accelerate the neuronal maturation, while its depletion in mice delays the neuronal maturation. This study thus highlights the contribution of SVs, especially the inversions, to the distinct features in human brain development.

evolutionary biology↗
bioRxiv2023

Diversity and distribution of viruses inhabiting the oil reservoirs

Oil reservoirs, being one of the most significant subsurface repositories of energy and carbon, have long hosted diverse microorganisms affecting energy production and carbon emissions. Viruses play crucial roles in the ecology of microbiomes, however, their distribution and ecological significance in oil reservoirs remain undetermined. Here, we assembled an extensive catalogue encompassing viral and prokaryotic genomes sourced from oil reservoirs. The catalogue comprises 7,229 prokaryotic genomes and 6,218 viral genomes from 182 oil reservoir metagenomes, respectively. Based on sequence clustering we identified 3,886 Operational Taxonomic Units (vOTUs) approximately at species level, 94.80% of which were not found in any other environments. The results showed that viruses were widely distributed in oil reservoirs, and oil reservoirs contain a significant number of unique and unexplored viruses. We also constructed a catalogue of 322,060 viral gene clusters including 105 virus-encoded putative auxiliary metabolic genes (AMGs) that participate in host metabolism and adaptation to the environment. Furthermore, our investigation has yielded a total of 7,197 putative virus-host pairs based on CRISPR and tRNA profiles. Viruses within oil reservoirs profoundly infected bacterial Actinobacteriota, Desulfobacterota, as well as archaeal Halobacteriota and Methanobacteriota. Combined microcosm enrichment experiments and bioinformatics analysis, we validated the ecological roles of viruses in regulating the community structure of sulfate reduction microorganisms, primarily through the predation of virulent viruses. Collectively, these findings have unveiled a rich diversity of novel viruses and their ecological functions within oil reservoirs. This study provides a comprehensive understanding of the role of viral communities in the biogeochemical cycle of the deep biosphere. It also facilitates microbial applications aimed at addressing challenges related to fossil-fuel production and carbon emissions in the petroleum industry.

microbiology↗
bioRxiv2023

Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens

The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.

systems biology↗
bioRxiv2023

The Role and Mechanism of TEAD4 in Preimplantation Embryonic Development in Mice and Cattle

Tead4, a critical transcription factor expressed during preimplantation development, is essential for the expression of trophectoderm-specific genes in mice. However, the functional mechanism of Tead4 in mouse preimplantation development and its conservation across mammals remain unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption of Tead4 through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes in Tead4 knockout embryos. As anticipated, Tead4 knockout leads to a decrease in trophectoderm genes Cdx2 and Gata3. Intriguingly, we observed a reduction in Krt8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a dramatic decrease in nuclear Yap in outside cells for Tead4-deficient morula, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos with TEAD4 depletion could still develop to blastocysts with normal expression of CDX2, GATA3, and SOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.

developmental biology↗
bioRxiv2023

Learning Complete Protein Representation by Deep Coupling of Sequence and Structure

Learning effective representations is crucial for understanding proteins and their biological functions. Recent advancements in language models and graph neural networks have enabled protein models to leverage primary or tertiary structure information to learn representations. However, the lack of practical methods to deeply co-model the relationships between protein sequences and structures has led to suboptimal embeddings. In this work, we propose CoupleNet, a network that couples protein sequence and structure to obtain informative protein representations. CoupleNet incorporates multiple levels of features in proteins, including the residue identities and positions for sequences, as well as geometric representations for tertiary structures. We construct two types of graphs to model the extracted sequential features and structural geometries, achieving completeness on these graphs, respectively, and perform convolution on nodes and edges simultaneously to obtain superior embeddings. Experimental results on a range of tasks, such as protein fold classification and function prediction, demonstrate that our proposed model outperforms the state-of-the-art methods by large margins.

bioinformatics↗
bioRxiv2023

Increasing the reliability of functional connectivity by predicting long-scan functional connectivity based on short-scan functional connectivity: model exploration, explanation, validation, and application.

Functional connectivity (FC) is a widely used imaging parameter of functional magnetic resonance imaging (fMRI). However, low reliability has been a concern among researchers, particularly in small-sample-size studies. Previous studies have shown that FC based on longer fMRI scans was more reliable, therefore, a feasible solution is to predict long-scan FCs using existing short-scan FCs. This study explored three different generalized linear models (GLMs) using the human connectome project (HCP) dataset. We found that the GLM based on individual short-scan FC could effectively predict long-scan individual FC value, while GLMs based on whole-brain FCs and dynamic FC performed better in predicting long-scan summed FC value of whole brain. The models were explained through visualization of weights in models. Besides, the differences in three GLMs could be explained as differences in distribution features of FC matrices predicted by them. Results were validated in different datasets, including the Consortium for Reliability and Reproducibility (CoRR) project and our local dataset. These models could be applied to improve the test-retest reliability of FC and to improve the performance of connectome-based predictive models (CPM). In conclusion, we developed three GLMs that could be used to predict long-scan FC from short-scan FC, and these models were robust across different datasets and could be applied to improve the test-retest reliability of FC and the performance of CPM.

neuroscience↗
bioRxiv2023

A mutation-mediated host shift drives Avian paramyxovirus type 1 evolution

PPMV-1, an antigenic variant of APMV-1, associated with specific pigeon host species. However, its evolutionary strategy and underlying drivers of host specificity remain unknown. In this study, we collect the outbreak data on a global scale to investigate its evolutionary dynamics, and provide an evidence-supported analysis the host shift of PPMV-1 from chickens to pigeons, and this shift is driven by the P protein. Our data indicated that the viruses in the United States and China have undergone convergent evolution. We find that three mutations of P protein, especially R163G, can significantly affect the adaptation of APMV-1 in pigeons. Mechanistically, sensor LSm14A inhibits the replication APMV-1 in DF-1 cells, and R163G substitutionon P protein increase LSm14A degradation. We propose the host shift drive the evolution of PPMV-1 and the underlying mechanism, offering new insights into the adaptive evolutionary process of the virus.

microbiology↗