IRIS3: integrated cell-type-specific regulon inference server from single-cell RNA-Seq

group of genes controlled as a unit, usually by the same repressor or activator gene, is known as a regulon. The ability to identify active regulons within a specific cell type, i.e., cell-type-specific regulons (CTSR), provides an extraordinary opportunity to pinpoint crucial regulators and target genes responsible for complex diseases. However, the identification of CTSRs from single-cell RNA-Seq (scRNA-Seq) data is computationally challenging. We introduce IRIS3, the first-of-its-kind web server for CTSR inference from scRNA-Seq data for human and mouse. IRIS3 is an easy-to-use server empowered by over 20 functionalities to support comprehensive interpretations and graphical visualizations of identified CTSRs. CTSR data can be used to reliably characterize and distinguish the corresponding cell type from others and can be combined with other computational or experimental analyses for biomedical studies. CTSRs can, therefore, aid in the discovery of major regulatory mechanisms and allow reliable constructions of global transcriptional regulation networks encoded in a specific cell type. The broader impact of IRIS3 includes, but is not limited to, investigation of complex diseases hierarchies and heterogeneity, causal gene regulatory network construction, and drug development

Durer-pentagon-based complex network

A novel Durer-pentagon-based complex network was constructed by adding a centre node. The properties of the complex network including the average degree, clustering coefficient, average path length, and fractal dimension were determined. The proposed complex network is small-world and fractal

A New and Efficient Boundary Element-Free Method for 2-D Crack Problems

An efficient boundary element-free method is established for 2-D crack problems by combining a pair of boundary integral equations and the moving-least square approximation. The displacement boundary integral equation is collated on the on-crack boundary, and a new traction boundary integral equation is applied on the crack surface without the separate consideration of the upper and lower sides. In virtue of integration by parts, only singularity in order 1/r is involved in the integral kernels of new traction boundary integral equation, which brings convenience to the numerical implementation. Meanwhile, the integration by parts produces the new variables, the displacement density, and displacement dislocation density, and they are the coexisting unknowns along with the displacement and displacement dislocation. With the high-order continuity of the moving-least square approximation, these new variables are directly approximated with the nodal displacement or displacement dislocation, and the final system of equations contains the unknowns of nodal displacements and displacement dislocations only. The boundary element-free computational scheme is established, and several examples show the efficiency and flexibility of the proposed method

Dynamic Behavior of RC Columns Confined with Micro-Expansive Concrete-Filled Steel Tubes Subjected to Lateral Low-Velocity Impact: Experimental and Numerical Study

In order to improve the anti-collision capacity of existing reinforced concrete (RC) columns under vehicle impact load, an experimental study on the anti-collision performance of RC columns strengthened with micro-expansive concrete filled steel tube was carried out. By combining an experiment and finite element calculation, the influence of steel tube strength, micro-expansive concrete strength and steel tube wall thickness on the anti-collision performance of strengthened RC columns were studied. The results showed that the peak displacement of an SM-RC column is 25.9% lower than that of an RC column, due to the increased stiffness, the peak impact force increased by 138.2%. The micro-expansive concrete filled steel tube reinforcement method can significantly improve the anti-collision performance of RC columns and reduce the lateral deformation. Increasing the strength grade of steel tube and thickness of steel tube can greatly improve the impact resistance of strengthened RC columns and reduce the lateral deflection deformation of short columns, compared with steel tube strength Q235, the displacement of Q690 is reduced 47.4%. the displacement of the 8-mm thick steel tube is reduced by 48.1% compared with the 4-mm one. while the strength grade of micro-expansive concrete has little effect on the impact resistance and lateral deflection deformation of strengthened RC columns

A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

Alzheimer's disease (AD) is a complex neurodegenerative disease, perturbing neuronal and non-neuronal cell populations. In this study, using single-cell transcriptomics, we mapped all non-immune, non-neuronal cell populations in wild-type and AD model (5xFAD) mouse brains. We identified an oligodendrocyte state that increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). In a murine model of amyloidosis, DOLs appear long after plaque accumulation, and amyloid-beta (Aβ) alone was not sufficient to induce the DOL signature in vitro. DOLs could be identified in a mouse model of tauopathy and in other murine neurodegenerative and autoimmune inflammatory conditions, suggesting a common response to severe pathological conditions. Using quantitative spatial analysis of mouse and postmortem human brain tissues, we found that oligodendrocytes expressing a key DOL marker (SERPINA3N/SERPINA3 accordingly) are present in the cortex in areas of brain damage and are enriched near Aβ plaques. In postmortem human brain tissue, the expression level of this marker correlated with cognitive decline. Altogether, this study uncovers a shared signature of oligodendrocytes in central nervous system pathologies

A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

International audienceAlzheimer's disease (AD) is a complex neurodegenerative disease, perturbing neuronal and non-neuronal cell populations. In this study, using single-cell transcriptomics, we mapped all non-immune, non-neuronal cell populations in wild-type and AD model (5xFAD) mouse brains. We identified an oligodendrocyte state that increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). In a murine model of amyloidosis, DOLs appear long after plaque accumulation, and amyloid-beta (Aβ) alone was not sufficient to induce the DOL signature in vitro. DOLs could be identified in a mouse model of tauopathy and in other murine neurodegenerative and autoimmune inflammatory conditions, suggesting a common response to severe pathological conditions. Using quantitative spatial analysis of mouse and postmortem human brain tissues, we found that oligodendrocytes expressing a key DOL marker (SERPINA3N/SERPINA3 accordingly) are present in the cortex in areas of brain damage and are enriched near Aβ plaques. In postmortem human brain tissue, the expression level of this marker correlated with cognitive decline. Altogether, this study uncovers a shared signature of oligodendrocytes in central nervous system pathologies

Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance

Summary: Bladder cancer (BLCA) is more common in men but more aggressive in women. Sex-based differences in cancer biology are commonly studied using a murine model with BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in the BBN model have been profiled, these profiles provide limited information on the tumor microenvironment. Here, we applied single-cell RNA sequencing to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. We found proportional and gene expression differences in epithelial and non-epithelial subpopulations between male and female tumors. Expression of several genes predicted sex-specific survival in several human BLCA datasets. We identified novel and clinically relevant sex-specific transcriptional signatures including immune cells in the tumor microenvironment and it validated the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in the development of new and accurate cancer markers

Sex-biased adaptive immune regulation in cancer development and therapy

Summary: The cancer research field is finally starting to unravel the mystery behind why males have a higher incidence and mortality rate than females for nearly all cancer types of the non-reproductive systems. Here, we explain how sex – specifically sex chromosomes and sex hormones – drives differential adaptive immunity across immune-related disease states including cancer, and why males are consequently more predisposed to tumor development. We highlight emerging data on the roles of cell-intrinsic androgen receptors in driving CD8+ T cell dysfunction or exhaustion in the tumor microenvironment and summarize ongoing clinical efforts to determine the impact of androgen blockade on cancer immunotherapy. Finally, we outline a framework for future research in cancer biology and immuno-oncology, underscoring the importance of a holistic research approach to understanding the mechanisms of sex dimorphisms in cancer, so sex will be considered as an imperative factor for guiding treatment decisions in the future