Lovisa Franzén, Martina Olsson Lindvall, Michael Hühn, Victoria Ptasinski, Laura Setyo, Benjamin P. Keith, Astrid Collin, Steven Oag, Thomas Volckaert, Annika Borde, Joakim Lundeberg, Julia Lindgren, Graham Belfield, Sonya Jackson, Anna Ollerstam, Marianna Stamou, Patrik L. Ståhl, Jorrit J. Hornberg <<<

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. Here we generated spatially resolved transcriptome maps of human IPF (n = 4) and bleomycin-induced mouse pulmonary fibrosis (n = 6) to address these limitations. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by transforming growth factor beta signaling alongside predicted regulators, such as TP53 and APOE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF. <<<

ABSTRACT Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl 3 ) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella , indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella , a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella ( S. flexneri 2a , Shigella dysenteriae , and Shigella sonnei ) using our present mouse model and Salmonella ( Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral S higella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella . <<<

Ting Liu, Jianan Rao, Wenting Hu, Bowen Cui, Jiaoyang Cai, Yuhan Liu, Huiying Sun, Xiaoxiao Chen, Yanjing Tang, Jing Chen, Xiang Wang, Han Wang, Wubin Qian, Binchen Mao, Sheng Guo, Ronghua Wang, Yu Liu, Shuhong Shen <<<

AbstractStudies have revealed key genomic aberrations in pediatric acute myeloid leukemia (AML) based on Western populations. It is unknown to what extent the current genomic findings represent populations with different ethnic backgrounds. Here we present the genomic landscape of driver alterations of Chinese pediatric AML and discover previously undescribed genomic aberrations, including the XPO1-TNRC18 fusion. Comprehensively comparing between the Chinese and Western AML cohorts reveal a substantially distinct genomic alteration profile. For example, Chinese AML patients more commonly exhibit mutations in KIT and CSF3R, and less frequently mutated of genes in the RAS signaling pathway. These differences in mutation frequencies lead to the detection of previously uncharacterized co-occurring mutation pairs. Importantly, the distinct driver profile is clinical relevant. We propose a refined prognosis risk classification model which better reflected the adverse event risk for Chinese AML patients. These results emphasize the importance of genetic background in precision medicine. <<<

Abstract NPBS (Natural Products & Biological Sources) database is a chemical data resource with relational data between natural products and biological sources, manually curated from literatures of natural product researches. The relational data link a specific species and all the natural products derived from it and contrarily link a specific natural product and all the biological sources. The biological sources cover diverse species of plant, bacterial, fungal and marine organisms; the natural molecules have proper chemical structure data and computable molecular properties and all the relational data have corresponding references. NPBS database provides a wider choice of biological sources and can be used for dereplication to prevent re-isolation and re-characterization of already known natural products. Database URL: http://www.organchem.csdb.cn/scdb/NPBS <<<

Mari Järve, Lehti Saag, Christiana Lyn Scheib, Ajai K. Pathak, Francesco Montinaro, Luca Pagani, Rodrigo Flores, Meriam Guellil, Lauri Saag, Kristiina Tambets, Alena Kushniarevich, Anu Solnik, Liivi Varul, Stanislav Zadnikov, Oleg Petrauskas, Maryana Avramenko, Boris Magomedov, Serghii Didenko, Gennadi Toshev, Igor Bruyako, Denys Grechko, Vitalii Okatenko, Kyrylo Gorbenko, Oleksandr Smyrnov, Anatolii Heiko, Roman Reida, Serheii Sapiehin, Sergey Sirotin, Aleksandr Tairov, Arman Beisenov, Maksim Starodubtsev, Vitali Vasilev, Alexei Nechvaloda, Biyaslan Atabiev, Sergey Litvinov, Natalia Ekomasova, Murat Dzhaubermezov, Sergey Voroniatov, Olga Utevska, Irina Shramko, Elza Khusnutdinova, Mait Metspalu, Nikita Savelev, Aivar Kriiska, Toomas Kivisild, Richard Villems <<<

Xia Wang, Qun Yang, Sukriti Singh, Horst Borrmann, Vicky Hasse, Changjiang Yi, Yongkang Li, Marcus Schmidt, Xiaodong Li, Gerhard H. Fecher, Dong Zhou, Binghai Yan, Claudia Felser <<<

AbstractElectrocatalytic water splitting is a promising approach for clean hydrogen production, but the process is hindered by the sluggish kinetics of the anodic oxygen evolution reaction (OER) owing to the spin-dependent electron transfer process. Efforts to control spin through chirality and magnetization have shown potential in enhancing OER performance. Here we harnessed the potential of topological chiral semimetals (RhSi, RhSn and RhBiS) and their spin-polarized Fermi surfaces to promote the spin-dependent electron transfer in the OER, addressing the traditional volcano-plot limitations. We show that OER activities follow the trend RhSi < RhSn < RhBiS, corresponding to the increasing extent of spin–orbit coupling (SOC). The chiral single crystals outperform achiral counterparts (RhTe2, RhTe and RuO2) in alkaline electrolyte, with RhBiS exhibiting a specific activity two orders of magnitude higher than RuO2. Our work reveals the pivotal roles of chirality and SOC in spin-dependent catalysis, facilitating the design of ultra-efficient chiral catalysts. <<<

Caroline C. Escoubas, Leah C. Dorman, Phi T. Nguyen, Christian Lagares-Linares, Haruna Nakajo, Sarah R. Anderson, Beatriz Cuevas, Ilia D. Vainchtein, Nicholas J. Silva, Yinghong Xiao, Peter V. Lidsky, Ellen Y. Wang, Sunrae E. Taloma, Hiromi Nakao-Inoue, Bjoern Schwer, Raul Andino, Tomasz J. Nowakowski, Anna V. Molofsky <<<

SummaryMicroglia are brain resident phagocytes that can engulf synaptic components and extracellular matrix as well as whole neurons. However, whether there are unique molecular mechanisms that regulate these distinct phagocytic states is unknown. Here we define a molecularly distinct microglial subset whose function is to engulf neurons in the developing brain. We transcriptomically identified a cluster of Type I interferon (IFN-I) responsive microglia that expanded 20-fold in the postnatal day 5 somatosensory cortex after partial whisker deprivation, a stressor that accelerates neural circuit remodeling.In situ, IFN-I responsive microglia were highly phagocytic and actively engulfed whole neurons. Conditional deletion of IFN-I signaling (Ifnar1fl/fl) in microglia but not neurons resulted in dysmorphic microglia with stalled phagocytosis and an accumulation of neurons with double strand DNA breaks, a marker of cell stress. Conversely, exogenous IFN-I was sufficient to drive neuronal engulfment by microglia and restrict the accumulation of damaged neurons. IFN-I deficient mice had excess excitatory neurons in the developing somatosensory cortex as well as tactile hypersensitivity to whisker stimulation. These data define a molecular mechanism through which microglia engulf neurons during a critical window of brain development. More broadly, they reveal key homeostatic roles of a canonical antiviral signaling pathway in brain development. <<<

Qiming Sun, Timothy C. Berkelbach, Nick S. Blunt, George H. Booth, Sheng Guo, Zhendong Li, Junzi Liu, James McClain, Elvira R. Sayfutyarova, Sandeep Sharma, Sebastian Wouters, Garnet Kin-Lic Chan <<<

PySCF is a general-purpose electronic structure platform designed from theground up to emphasize code simplicity, both to aid new method development, aswell as for flexibility in computational workflow. The package provides a widerange of tools to support simulations of finite size systems, extended systemswith periodic boundary conditions, low dimensional periodic systems, and customHamiltonians, using mean-field and post-mean-field methods with standardGaussian basis functions. To ensure easy of extensibility, PySCF uses thePython language to implement almost all its features, while computationallycritical paths are implemented with heavily optimized C routines. Using thiscombined Python/C implementation, the package is as efficient as the bestexisting C or Fortran based quantum chemistry programs. In this paper wedocument the capabilities and design philosophy of the current version of thePySCF package. <<<

AbstractUnderstanding the structure of a problem, such as the relationships between stimuli, supports fast learning and flexible reasoning. Recent theoretical suggestions have highlighted the usefulness of explicit structural representations that are fully divorced from sensory details for generalisation. Rodent work has suggested that abstraction of structure occurs gradually, over time, in cortex. However, direct evidence of such explicit relational representations in humans is scarce, and its relationship to consolidation mechanisms is underexplored. Here, we use a graph-learning paradigm to find such a relational map in the human medial prefrontal cortex. Importantly, this representation was absent early after learning but emerged on the time scale of days. These results shed new light on neural representations underlying the remarkable human ability to draw accurate inferences from little data. <<<

Chengzhi Jiao, Xiaoming Xie, Chenyang Hao, Liyang Chen, Yuxin Xie, Vanika Garg, Li Zhao, Zihao Wang, Yuqi Zhang, Tian Li, Junjie Fu, Annapurna Chitikineni, Jian Hou, Hongxia Liu, Girish Dwivedi, Xu Liu, Jizeng Jia, Long Mao, Xiue Wang, Rudi Appels, Rajeev K. Varshney, Weilong Guo, Xueyong Zhang <<<