Biology subjects

Zhang, R.

Publications and source records attributed to Zhang, R..

At least 343 records · Page 19Linked to original sources

bioRxiv2023

Prominent elevation of extracellular matrix molecules in intracerebral hemorrhage

BackgroundIntracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurological conditions, the deposition of extracellular matrix (ECM) molecules is a prominent obstacle for regenerative processes and an enhancer of neuroinflammation. Whether ECM molecules alter in composition after ICH, and which ECM members may inhibit repair, remain unknown in hemorrhagic stroke. MethodsThe collagenase-induced ICH mouse model and an autopsied human ICH specimen were investigated for expression of ECM members by immunofluorescence microscopy. Confocal image z-stacks were analyzed with Imaris 3D to assess the association of immune cells and ECM molecules. Sections from a mouse model of multiple sclerosis were used as disease controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs). ResultsAmongst the lectican chondroitin sulphate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in murine ICH. Fibrinogen, fibronectin and heparan sulphate proteoglycan (HSPG) were also elevated after murine ICH while thrombospondin was not. Confocal microscopy with Imaris 3D rendering co-localized neurocan, fibrinogen, fibronectin and HSPG molecules to Iba1+ microglia/macrophages or GFAP+ astrocytes. Marked differentiation from the multiple sclerosis model was observed, the latter with high versican-V1 and negligible neurocan. In culture, purified neurocan inhibited adhesion and process outgrowth of OPCs, which are early steps in myelination in vivo. The prominent expression of neurocan in murine ICH was corroborated in human ICH sections. ConclusionICH caused distinct alterations in ECM molecules. Amongst CSPG members, neurocan was selectively upregulated in both murine and human ICH. In tissue culture, neurocan impeded the properties of oligodendrocyte lineage cells. Alterations to the ECM in ICH may adversely affect reparative outcomes after stroke. What is already known on this topic - CSPGs are known to be elevated in multiple sclerosis and intraventricular hemorrhage, where they act as inhibitors of repair by hindering remyelination and axonal regeneration, as well as promoting neuroinflammation. However, there is currently no literature available regarding the role of CSPGs in ICH. What this study adds - Our findings demonstrate the elevation of specific ECM molecules, particularly neurocan, in murine and human ICH. These matrix molecules will likely affect subsequent reparative processes such as remyelination, as suggested by the result that purified neurocan impairs the process outgrowth and maturation of oligodendrocyte precursor cells. How this study might affect research, practice or policy - The targeting of ECM molecules represents a promising strategy to promote remyelination and control neuroinflammation, with the potential to improve prognosis following ICH.

neuroscience↗

bioRxiv2023

scGHOST: Identifying single-cell 3D genome subcompartments

New single-cell Hi-C (scHi-C) technologies enable probing of the genome-wide cell-to-cell variability in 3D genome organization from individual cells. Several computational methods have been developed to reveal single-cell 3D genome features based on scHi-C data, including A/B compartments, topologically-associating domains, and chromatin loops. However, no scHi-C analysis method currently exists for annotating single-cell subcompartments, which are crucial for providing a more refined view of large-scale chromosome spatial localization in single cells. Here, we present SCGHOST, a single-cell subcompartment annotation method based on graph embedding with constrained random walk sampling. Applications of SCGHOST to scHi-C data and single-cell 3D genome imaging data demonstrate the reliable identification of single-cell subcompartments and offer new insights into cell-to-cell variability of nuclear subcompartments. Using scHi-C data from the human prefrontal cortex, SCGHOST identifies cell type-specific subcompartments that are strongly connected to cell type-specific gene expression, suggesting the functional implications of single-cell subcompartments. Overall, SCGHOST is an effective new method for single-cell 3D genome subcompartment annotation based on scHi-C data for a broad range of biological contexts.

bioinformatics↗

bioRxiv2023

Seasonal Variation in Bacterial Community Structures of Mangrove Sediments

Climate change globally and sea level rise affect the mangrove ecosystem. The high diversity and temporal heterogeneity of the mangrove ecosystem will lead to a high diversity of sediment bacterial community structure and function. However, seasonal variations and potential assembly mechanisms of sediment bacterial communities in mangrove ecosystems remain to be discovered. We collected rhizosphere sediments and bulk sediments from Kandelia obovata and Aegiceras corniculatum at three locations covering Dongzhai Harbour in spring, summer, autumn, and winter, and sequenced 16S rRNAs. The results indicated that the alpha and beta diversity of bacterial communities in mangrove sediments differed significantly between seasons, and the bacterial communities in rhizosphere sediments had smaller seasonal changes and were more stable than those in bulk sediment bacterial communities. The seasonal changes in carbon, nitrogen content, and pH were the main influencing factors. The stochastic process dominated the assembly of bacterial communities in mangrove sediments. The assembly of bacterial communities varies between seasons. We found that the proportion of dispersal limitation was significantly negatively correlated with the carbon and nitrogen content in the sediment. Compared with bulk components, the dispersal limitation of bacterial communities in rhizosphere sediments accounted for a lower proportion of community construction, which might be caused by higher carbon and nitrogen content conditions in rhizosphere sediments. We found that beta diversity based on Bray-Curtis distance was significantly positively correlated with dispersal limitation, which explained why the beta diversity of bacterial communities in rhizosphere sediments was significantly lower than that of bulk components. This study increases the understanding of the responses of mangrove bacterial communities to seasonal change and may be beneficial for the protection of mangrove ecosystems in the face of climate change.

ecology↗

bioRxiv2023

Discovery of new deaminase functions by structure-based protein clustering

The elucidation of protein function and its exploitation in bioengineering have greatly contributed to the development of the life sciences. Existing protein mining efforts generally rely on amino acid sequences rather than protein structures due to technical difficulties in structural elucidation. We describe here for the use of AlphaFold2 to predict and subsequently cluster an entire protein family based on predicted structure similarities. We selected the deaminase family of proteins to analyze and through this approach identified many previously unknown deaminase properties. We applied these new deaminases to the development of new cytosine base editors with distinct features. Although we found many new double-stranded DNA deaminases from the DddA-like protein clade, we were surprised to find that most of the proteins in this family were not actually double-stranded DNA cytidine deaminases. From this protein clade, we engineered the smallest single-strand specific cytidine deaminase, which facilitates the first efficient cytosine base editor to be packaged into a single AAV vector. Importantly, we also profiled a deaminase from this clade that edits robustly in soybean plants, which previously suffered from poor editing by cytosine base editors. These newly discovered deaminases based on AI-assisted structural predictions greatly expand the utility of base editors for therapeutic and agricultural applications.

molecular biology↗

bioRxiv2023

Rotten to the core - a neurofunctional signature of subjective core disgust generalizes to socio-moral contexts

While disgust originates in the hard-wired mammalian distaste response, the conscious experience of disgust in humans strongly depends on subjective appraisal and may even extend to sociomoral contexts. In a series of studies, we combined functional magnetic resonance imaging (fMRI) with machine-learning based predictive modeling to establish a comprehensive neurobiological model of subjective disgust. The developed neurofunctional signature accurately predicted momentary self-reported subjective disgust across discovery (n=78) and pre-registered validation (n=30) cohorts and generalized across core disgust (n=34 and n=26), gustatory distaste (n=30), and sociomoral (unfair offers; n=43) contexts. Disgust experience was encoded in distributed cortical and subcortical systems, and exhibited distinct and shared neural representations with subjective fear or negative affect in interoceptive-emotional awareness and conscious appraisal systems while the signatures most accurately predicted the respective target experience. We provide an accurate fMRI-signature for disgust with a high potential to resolve ongoing evolutionary debates.

neuroscience↗

bioRxiv2023

A comparison of behavior paradigms assessing spatial memory in tree shrew

Spatial cognition enables animals to navigate the environment. Impairments in spatial navigation are often preclinical signs of Alzheimers disease (AD) in human. Therefore, evaluating spatial memory deficits is valuable when assessing incipient AD in animal models. The Chinese tree shrew, a close relative of primates, possesses many features that make it suitable for AD research. However, there is a scarcity of reliable behavior paradigms to monitor changes in spatial cognition in this species. To address this, we established reward-based paradigms in the radial-arm maze and the cheeseboard maze for tree shrew, and tested spatial memory of a group of twelve male animals in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and their task performance improved gradually until reaching a plateau in all three mazes. After the lesion, spatial learning was compromised in both newly-developed tasks, whereas memory retrieval was impaired in the water maze. Furthermore, individual task performance in both dry-land paradigms depended heavily on the size of remaining hippocampal tissue. Notably, all lesioned animals displayed spatial memory deficits in the cheeseboard task, but not in the other two paradigms. Our results suggest that the cheeseboard task currently represents the most sensitive paradigm for assessing spatial memory in tree shrew, with the potential to monitor progressive cognitive declines in aged or genetically modified animals developing AD-like symptoms. Significance StatementCognitive tests that monitor impairments in spatial memory play a crucial role in evaluating animal models with early-stage Alzheimers disease (AD). The Chinese tree shrew possesses many features suitable for an AD model, yet behavior tests assessing spatial cognition in this species are lacking. Here we developed novel behavior paradigms tailored to measure spatial memory in tree shrews and evaluated their sensitivity to changes in spatial learning by examining a group of hippocampus-lesioned animals. Our results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring the progressive cognitive decline in aged or genetically modified tree shrews that develop AD-like symptoms. This research may facilitate the use of tree shrew model in AD research.

animal behavior and cognition↗

bioRxiv2023

Deciphering molecular heterogeneity and dynamics of neural stem cells in human hippocampal development, aging, and injury

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are re-activated following stroke injury. Together, our findings provide valuable insights into the development, aging, and re-activation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

neuroscience↗

bioRxiv2023

Automated model building and protein identification in cryo-EM maps

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention. We present ModelAngelo, a machine-learning approach for automated atomic model building in cryo-EM maps. By combining information from the cryo-EM map with information from protein sequence and structure in a single graph neural network, ModelAngelo builds atomic models for proteins that are of similar quality as those generated by human experts. For nucleotides, ModelAngelo builds backbones with similar accuracy as humans. By using its predicted amino acid probabilities for each residue in hidden Markov model sequence searches, ModelAngelo outperforms human experts in the identification of proteins with unknown sequences. ModelAngelo will thus remove bottlenecks and increase objectivity in cryo-EM structure determination.

molecular biology↗

bioRxiv2023

Cardiac Effects of a Novel pH-Insensitive Sodium-Calcium Exchanger Mouse

BACKGROUNDCardiac sodium-calcium exchange (NCX1) is the dominant calcium (Ca) efflux mechanism in cardiomyocytes and is strongly regulated by pH. However, the role of NCX1 pH sensitivity in normal cardiac function is unknown. METHODSWe used CRISPR/Cas9 to produce a pH-resistant NCX1 mouse by replacing the histidine at position 165 of NCX1 with an alanine (H165A). Hearts were studied using echocardiography and ECG. RNA and protein expression levels were assessed using qPCR and Western blotting. Isolated ventricular cardiomyocytes were loaded with Ca indicators and patch clamped to record intracellular Ca transients and membrane current and voltage. RESULTSH165A mice live into adulthood with slightly reduced LV systolic function, normal heart rate and shortened QT interval. Both male and female animals exhibit reduced growth, but females eventually reach normal body weight. In patch clamped myocytes, NCX current (INCX) evoked by voltage ramps was reduced by 35% (at +80 mV). Lowering pHi to 6.5 using Na-Acetate had no effect on INCX in H165A myocytes, whereas the same intervention in wildtype (WT) inhibited INCX by 69% (at +80 mV, p<0.01). There was no change in H165A ventricular cardiomyocyte Ca transients measured with fura-2 AM. However, action potential duration was reduced 68%, consistent with the shorter QT interval. This coincided with a 37% reduction in L-type Ca current and increased expression of repolarizing K+ channels. H165A mice are also resistant to ischemia/reperfusion injury. CONCLUSIONSThe H165A mutation attenuates pH regulation of NCX1 in mice, is associated with reduced growth and accelerates cardiac repolarization without compromising excitation-contraction coupling. The mutation also confers cardioprotection. The H165A mouse is the first evidence that pH regulation of NCX1 affects cardiac physiology and is a potential model for studying the role of NCX1 pH-sensitivity on both physiological and pathophysiological cardiac function.

biophysics↗

bioRxiv2023

SKP2 knockout in Rb1/p53 deficient mouse models of osteosarcoma induces immune infiltration and drives a transcriptional program with a favorable prognosis

PurposeOsteosarcoma (OS) is an aggressive bone malignancy with a poor prognosis. One putative proto-oncogene in OS is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase. We previously demonstrated that SKP2 knockout in murine OS improved survival and delayed tumorigenesis. Here we aim to define the SKP2 drives transcriptional program and its clinical implication in OS. Experimental DesignWe performed RNA-sequencing (RNA-seq) on tumors from a transgenic OS mouse model with conditional Trp53 and Rb1 knockouts in the osteoblast lineage ("DKO": Osx1-Cre;Rb1lox/lox;p53lox/lox) and a triple-knockout model with additional Skp2 germline knockout ("TKO": Osx1-Cre;Rb1lox/lox;p53lox/lox;SKP2-/-). We validated our RNA-seq findings using qPCR and immunohistochemistry. To investigate the clinical implications of our results, we analyzed a human OS patient cohort ("NCI-TARGET OS") with RNA-seq and clinical data. ResultsWe found large differences in gene expression after SKP2 knockout. Strikingly, we observed increased expression of genes related to immune microenvironment infiltration in TKO tumors. We observed significant increases in signature genes for macrophages and to a lesser extent, T cells, B cells and vascular cells. We also uncovered a set of relevant transcription factors that may mediate the changes. In OS patient cohorts, high expression of genes upregulated in TKO was correlated with favorable overall survival, which was largely explained by the macrophage gene signatures. This relationship was further supported by our finding that SKP2 expression was negatively correlated with macrophage infiltration in the NCI-TARGET OS and the TCGA Sarcoma cohort. ConclusionOur findings indicate that SKP2 may mediate immune exclusion from the OS tumor microenvironment, suggesting that SKP2 modulation in OS may induce anti-tumor immune activation. Translational RelevanceOsteosarcoma (OS) is an aggressive bone malignancy. Standard care treatment involving chemotherapy and surgery remains unchanged for decades. OS prognosis remains poor and targeted therapies are critically needed. Immunotherapy failed in clinical trials despite extensive genomic instability, suggesting OS tumors employ active immune exclusion. One putative oncogene in OS is SKP2, which activates cell proliferation. SKP2 is correlated with worse prognosis in patients and knockout of SKP2 improved survival in murine OS. Here, we performed comparative transcriptomic analysis between transgenic OS murine models with SKP2 knockout and controls. We showed that SKP2 knockout dramatic increased immune gene expression largely due to macrophage, and to a lesser extent lymphocytes, infiltration. Interestingly, we found that the increased gene program uncovered from our SKP2 knockout model was correlated with improved survival in OS patients. Our findings indicate a completely new function for SKP2 in mediating immune exclusion in sarcoma and suggest that SKP2 inhibition may lead to improved immune activation and potential treatment.

cancer biology↗

bioRxiv2023

Lipid-anchored Proteasomes Control Membrane Protein Homeostasis

Protein degradation in eukaryotic cells is mainly carried out by the 26S proteasome, a macromolecular complex not only present in the cytosol and nucleus but also associated with various membranes. How proteasomes are anchored to the membrane and the biological meaning thereof have been largely unknown in higher organisms. Here we show that N-myristoylation of the Rpt2 subunit is a general mechanism for proteasome-membrane interaction. Loss of this modification in the Rpt2-G2A mutant cells leads to profound changes in the membrane-associated proteome, perturbs the endomembrane system and undermines critical cellular processes such as cell adhesion, endoplasmic reticulum-associated degradation (ERAD) and membrane protein trafficking. Rpt2G2A/G2A homozygous mutation is embryonic lethal in mice and is sufficient to abolish tumor growth in a nude mice xenograft model. These findings have defined an evolutionarily conserved mechanism for maintaining membrane protein homeostasis and underscored the significance of compartmentalized protein degradation by myristoyl-anchored proteasomes (MAPs) in health and disease.

biochemistry↗

bioRxiv2023

Dimeric Transmembrane Structure of the SARS-CoV-2 E Protein

The SARS-CoV-2 E protein is a transmembrane (TM) protein with its N-terminus exposed on the external surface of the virus. Here, the TM structure of the E protein is characterized by oriented sample and magic angle spinning solid-state NMR in lipid bilayers and refined by molecular dynamics simulations. This protein has been found to be a pentamer, with a hydrophobic pore that appears to function as an ion channel. We identified only a symmetric helix-helix interface, leading to a dimeric structure that does not support channel activity. The two helices have a tilt angle of only 6{degrees}, resulting in an extended interface dominated by Leu and Val sidechains. While residues Val14-Thr35 are almost all buried in the hydrophobic region of the membrane, Asn15 lines a water-filled pocket that potentially serves as a drug-binding site. The E and other viral proteins may adopt different oligomeric states to help perform multiple functions.

biophysics↗

bioRxiv2023

Acetyl transferase EP300 deficiency leads to chronic replication stress mediated by defective fork protection at stalled replication forks

Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a model to study EP300 deficiency and an p300-selective PROTAC degrader, degrader as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, accumulation of cytosolic DNA and transmission of unrepaired inherited DNA lesions in the subsequent G1-phase in EP300-deficient cells. We demonstrate that the DNA replication dynamics of EP300-mutated cells ATLL cells recapitulate features of BRCA-deficient cancers. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress and defective replication fork restart results in persistent genomic instability that underlie aggressive chemo-resistant tumorigenesis in humans.

cancer biology↗

bioRxiv2023

Plasma-free samples for transcriptomic analysis: a potential alternative to whole blood samples

RNA sequencing (RNAseq) technology has become increasingly important in precision medicine and clinical diagnostics and emerged as a powerful tool for identifying protein-coding genes, performing differential gene analysis, and inferring immune cell composition. Human peripheral blood samples are widely used for RNAseq, providing valuable insights into individual biomolecular information. Blood samples can be classified as whole blood (WB), plasma, serum, and remaining sediment samples, including plasma-free blood (PFB) and serum-free blood (SFB) samples. However, the feasibility of using PFB and SFB samples for transcriptome analysis remains unclear. In this study, we aimed to assess the viability of employing PFB or SFB samples as substitute RNA sources in transcriptomic analysis and performed a comparative analysis of WB, PFB, and SFB samples for different applications. Our results revealed that PFB samples exhibit greater similarity to WB samples in terms of protein-coding gene expression patterns, differential expression gene profiling, and immunological characterizations, suggesting that PFB can be a viable alternative for transcriptomic analysis. This contributes to the optimization of blood sample utilization and the advancement of precision medicine research.

bioinformatics↗

bioRxiv2023

REVEILLE2 Thermosensitive Splicing: A Molecular Basis for the Integration of Nocturnal Temperature Information by the Arabidopsis Circadian Clock

O_LICold stress is one of the major environmental factors that limit growth and yield of plants. However, it is still not fully understood how plants account for daily temperature fluctuations, nor how these temperature changes are integrated with other regulatory systems such as the circadian clock. C_LIO_LIWe demonstrate that REVEILLE2, a MYB-like transcription factor, exhibits a cold-induced alternative splicing switch from a non-translatable isoform at ambient temperature to a translatable isoform upon cold exposure. We explore the biological function of REVEILLE2 using a combination of molecular genetics, transcriptomics, and physiology. C_LIO_LIDisruption of the REVEILLE2 cooling switch alters regulatory gene expression, impairs circadian timing, and improves photosynthetic capacity. Changes in nuclear gene expression are particularly apparent in the initial hours following chilling, with chloroplast gene expression subsequently up-regulated. C_LIO_LIThe REVEILLE2 cold switch extends our understanding of plants immediate response to cooling. We propose that the circadian component REVEILLE2 restricts plants responses to nocturnal reductions in temperature, thereby enabling appropriate responses to daily environmental changes. C_LI Plain language summaryPlants need to respond appropriately to temperature, accounting for the expected daily patterns of reduced temperatures that occur every night relative to the day. Here, we show that a gene expressed at night fulfils this function.

plant biology↗

bioRxiv2023

Discovery of microRNA-derived RNAs and proteins in human cells

MicroRNAs (miRNAs) are short noncoding RNAs that can regulate gene expression through the binding of their 5-ends to mRNAs. However, the biological effects of miRNA binding via their 3-ends remain unclear. Here, we discover that the exact reverse pairing of the 3-ends of miRNAs or miRNA-like RNAs, collectively termed microsized RNAs (msRNAs), with template RNAs can initiate the production of msRNA-derived RNAs (msdRs), which can subsequently be translated into polypeptides (msdPs). Using 2,632 human msRNAs from miRBase, 11,121 msdRs and 1,239 msdPs were predicted based on a 15-nucleotide pairing threshold, and the presence of representative msdRs and msdPs was confirmed in human cells. Of clinical relevance, msdP0188 is highly expressed in human lung and breast cancers, and its corresponding msRNAs and msdRs represent novel anti-cancer targets. Notably, inhibiting telomerase reverse transcriptase, a putative RNA-dependent RNA polymerase identified by bioinformatic screening, led to reduced levels of msdP0188 in human cancer cells. Our findings reveal a novel "msRNA [->] msdR [->] msdP" axis, expanding the classical central dogma and predicting many previously unrecognized RNAs and polypeptides with potential biological functions in human cells and other systems.

cell biology↗

bioRxiv2023

Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death

Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells. Surprisingly, overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. Synaptic plasticity normally declines as animals age, but in our system, functional cross-neuron plasticity can be induced at different time points, whereas structural cross-neuron plasticity can only be induced at early stages. Our work uncovers a novel role for glial Draper signaling in cross-neuron plasticity that may enhance nervous system function during neurodegeneration and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.

neuroscience↗

bioRxiv2023

asmbPLS: Adaptive Sparse Multi-block Partial Least Square for Survival Prediction using Multi-Omics Data

BackgroundAs high-throughput studies advance, more and more high-dimensional multi-omics data are available and collected from the same patient cohort. Using multi-omics data as predictors to predict survival outcomes is challenging due to the complex structure of such data. ResultsIn this article, we introduce an adaptive sparse multi-block partial least square (asmbPLS) regression method by assigning different penalty factors to different blocks in different PLS components for feature selection and prediction. We compared the proposed method with several competitive algorithms in many aspects including prediction performance, feature selection and computation efficiency. The performance and the efficiency of our method were demonstrated using both the simulated and the real data. ConclusionsIn summary, asmbPLS achieved a competitive performance in prediction, feature selection, and computation efficiency. We anticipate asmbPLS to be a valuable tool for multi-omics research. An R package called asmbPLS implementing this method is made publicly available on GitHub.

bioinformatics↗