A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission by Benjamin Sobkowiak, Patrick Cudahy, Melanie H. Chitwood, Taane G. Clark, Caroline Colijn, Louis Grandjean, Katharine S. Walter, Valeriu Crudu, Ted Cohen

“…Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samples from Mycobacterium tuberculosis short-read WGS data. …”
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DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer by Xiao Hong Zhao, Man Man Han, Qian Qian Yan, Yi Meng Yue, Kaihong Ye, Yuan Yuan Zhang, Liu Teng, Liang Xu, Xiao-Jing Shi, Ting La, Yu Chen Feng, Ran Xu, Vinod K. Narayana, David P. De Souza, Lake-Ee Quek, Jeff Holst, Tao Liu, Mark A. Baker, Rick F. Thorne, Xu Dong Zhang, Lei Jin

“…Abstract Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. …”
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Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: A Post Hoc Analysis of ORAL Surveillance by Bogdan Batko, Slawomir Jeka, Piotr Wiland, Agnieszka Zielińska, Maria Stopińska-Polaszewska, Marcin Stajszczyk, Magdalena Kosydar-Piechna, Mary Jane Cadatal, Jose L. Rivas

“…Abstract Introduction In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. …”
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Modeling the tropical fish community related to land uses and environmental determinants by N. Takarina, O. Chuan, M. Afifudin, L. Tristan, I. Arif, A. Adiwibowo

“…This information is urgently needed as fish is one of the most important food resources here. This study aims to assess and compare the environment and tropical fish community between disturbed and intact sites, represented by coasts dominated by settlements and coasts dominated by mangrove forests in West Java, Indonesia.METHODS: Fish sampling was carried out at two sites: Jakarta as the disturbed site and Subang as the intact site; water quality was also measured at these sites. …”
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Establishment of a CRISPR-Based Lentiviral Activation Library for Transcription Factor Screening in Porcine Cells by Yingjuan Liang, Xiaoxia Yao, Jingxin Han, Jinpeng Wang, Xiao Zhang, Donglin Zhao, Chaoqian Jiang, Lishuang Geng, Shihao Lv, Zhonghua Liu, Yanshuang Mu

“…A transcription-factor-scale activation library based on the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated endonuclease Cas9 (Cas9) system could facilitate the discovery and functional characterization of the transcription genes involved in a specific gene network. Here, we have designed and constructed a CRISPR activation (CRISPRa) sgRNA library, containing 5056 sgRNAs targeting the promoter region of 1264 transcription factors in pigs. …”
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Delivery determinants of an Acinetobacter baumannii type VI secretion system bifunctional peptidoglycan hydrolase by Valeriya Bezkorovayna, Brooke K. Hayes, Francesca N. Gillett, Amy Wright, David I. Roper, Marina Harper, Sheena McGowan, John D. Boyce

“…Each effector, Tse15, Tde16, and Tae17, is delivered via a non-covalent interaction with a specific T6SS VgrG protein (VgrG15, VgrG16, and VgrG17, respectively). Here we define the regions of interaction between Tae17 and its cognate delivery protein VgrG17 and identify that amino acids G1069 and W1075 in VgrG17 are essential for Tae17 delivery via the T6SS, the first time such specific delivery determinants of T6SS cargo effectors have been defined. …”
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Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers by James A. Oo, Timothy Warwick, Katalin Pálfi, Frederike Lam, Francois McNicoll, Cristian Prieto-Garcia, Stefan Günther, Can Cao, Yinuo Zhou, Alexey A. Gavrilov, Sergey V. Razin, Alfredo Cabrera-Orefice, Ilka Wittig, Soni Savai Pullamsetti, Leo Kurian, Ralf Gilsbach, Marcel H. Schulz, Ivan Dikic, Michaela Müller-McNicoll, Ralf P. Brandes, Matthias S. Leisegang

“…However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate that trans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. …”
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RETRACTED: The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model by Yukihiro Hiramatsu, Koichiro Suzuki, Takashi Nishida, Naoki Onoda, Takashi Satoh, Shizuo Akira, Masahito Ikawa, Hiroko Ikeda, Junzo Kamei, Sandra Derouiche, Makoto Tominaga, Yasuhiko Horiguchi

“…However, its etiological agent and the mechanism are totally unknown because of a lack of versatile animal models that reproduce the cough. Here, we present a mouse model that reproduces coughing after intranasal inoculation with the bacterium or its components and demonstrate that lipooligosaccharide (LOS), pertussis toxin (PTx), and Vag8 of the bacterium cooperatively function to cause coughing. …”
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High-resolution Cryo-EM Structure Determination of a-Synuclein—A Prototypical Amyloid Fibril by Juan Sanchez, Joshua Pierson, Collin Borcik, Chad Rienstra, Elizabeth Wright

“…The latest advances in cryo-EM structure determination and real-space helical reconstruction methods have resulted in over 60 in vitro structures of a-syn fibrils solved to date, with a handful of these reaching a resolution below 2.5 Å. Here, we provide a protocol for a-syn protein expression, purification, and fibrilization. …”
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Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis by Min-Na Zhang, Ran Duan, Gui-Hong Chen, Mei-Jun Chen, Chun-Gu Hong, Xin Wang, Zhi-Lin Pang, Chun-Yuan Chen, Hua-Feng Liu, Da Zhong, Hui Xie, Wen-Bao Hu, Zheng-Zhao Liu

“…However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy. …”
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Super-enhancer-driven SLCO4A1-AS1 is a new biomarker and a promising therapeutic target in glioblastoma by Yibo Wu, Fang Li, Chen Yang, Xuehai Zhang, Zhiwei Xue, Yanfei Sun, Xiaoying Lin, Xuemeng Liu, Zhimin Zhao, Bin Huang, Qibing Huang, Xingang Li, Mingzhi Han

“…However, the role of SE-associated long non-coding RNAs (lncRNAs) in GBM remains poorly understood. Here, we screened for an up-regulated lncRNA-SLCO4A1-AS1 expressed in GBM by analyzing data from GSE54791, GSE4536 and TCGA. …”
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Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation by Mathias Guayasamin, Lewis R Depaauw-Holt, Ifeoluwa I Adedipe, Ossama Ghenissa, Juliette Vaugeois, Manon Duquenne, Benjamin Rogers, Jade Latraverse-Arquilla, Sarah Peyrard, Anthony Bosson, Ciaran Murphy-Royal

“…Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. …”
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Digital Quantitative Detection for Heterogeneous Protein and mRNA Expression Patterns in Circulating Tumor Cells by Hao Li, Jinze Li, Zhiqi Zhang, Qi Yang, Hong Du, Qiongzhu Dong, Zhen Guo, Jia Yao, Shuli Li, Dongshu Li, Nannan Pang, Chuanyu Li, Wei Zhang, Lianqun Zhou

“…However, current detection methods lack the capacity for simultaneous quantification of multidimensional biomarkers, impeding a comprehensive understanding of tumor biology and dynamic changes. Here, the CTC Digital Simultaneous Cross‐dimensional Output and Unified Tracking (d‐SCOUT) technology is introduced, which enables simultaneous quantification and detailed interpretation of HCC transcriptional and phenotypic biomarkers. …”
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Single-molecule two- and three-colour FRET studies reveal a transition state in SNARE disassembly by NSF by Sudheer K. Cheppali, Chang Li, Wenjing Xing, Ruirui Sun, Mengyi Yang, Yi Xue, Si-Yao Lu, Jun Yao, Shan Sun, Chunlai Chen, Sen-Fang Sui

“…Recycling/disassembly of the protein machinery involved in membrane fusion is essential and is facilitated by an AAA+ ATPase, N-ethylmaleimide sensitive factor (NSF) in the presence of an adapter protein, α-SNAP. Here we use single-molecule fluorescence spectroscopy approaches to elucidate the chain of events that occur during the disassembly of SNARE complex by NSF. …”
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Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant by Antheia Kissopoulou, Eva Fernlund, Christina Holmgren, Eira Isaksson, Jan‐Erik Karlsson, Henrik Green, Jon Jonasson, Rada Ellegård, Hanna Klang Årstrand, Anneli Svensson, Cecilia Gunnarsson

“…Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.…”
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Activation of Delta-Opioid Receptor Protects ARPE19 Cells against Oxygen-Glucose Deprivation/Reoxygenation-Induced Necroptosis and Apoptosis by Inhibiting the Release of TNF-α by Runjie Guo, Ping Chen, Tiantian Fu, Ren Zhang, Yuan Zhu, Nange Jin, Hong Xu, Yong Xia, Xuesong Tian

“…However, the role of TNF-α and DOR in necroptosis and apoptosis of retinal pigment epithelial (RPE) cells remains largely unknown. Here, we explored the mechanisms of TNF-α and DOR in necroptosis and apoptosis using an oxygen-glucose deprivation/reoxygenation (OGD/R) model of adult retinal pigment epithelial cell line-19 (ARPE19) cells. …”
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Stereotactic aspiration alone or Ommaya placement and aspiration followed by stereotactic radiosurgery for cystic brain metastasis: A systematic review and meta-analysis by David R. Peters, Alfredo Conti, Marc Levivier, Luis Schiappacasse, Mohamed Faouzi, Mioara Florentina Trandafirescu, Constantin Tuleasca

“…Stereotactic cyst aspiration for volume reduction followed by stereotactic radiosurgery (SRS) is an alternative treatment modality that may benefit patients with large cystic BMs not favorable for SRS alone nor microsurgical resection. Research question: Here, we perform a systematic review and meta-analysis of stereotactic aspiration alone or reservoir (Ommaya) placement plus aspiration followed by SRS for cystic BMs. …”
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Taung and beyond: The mining history, geology and taphonomy of Australopithecus in South Africa by Rieneke Weij, Stephanie E. Baker, Tara R. Edwards, Job Kibii, Georgina Luti, Robyn Pickering

“…To understand this rich and diverse fossil record, we must understand how the landscape formed (cave formation processes) and changed (mining), when this happened (geochronology), and how the fossils were accumulated and modified (taphonomy). Here we provide a review of these themes to mark the centenary of the Taung Child discovery. …”
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Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide by Audrey Le Bas, Bradley R. Clarke, Tanisha Teelucksingh, Micah Lee, Kamel El Omari, Andrew M. Giltrap, Stephen A. McMahon, Hui Liu, John H. Beale, Vitaliy Mykhaylyk, Ramona Duman, Neil G. Paterson, Philip N. Ward, Peter J. Harrison, Miriam Weckener, Els Pardon, Jan Steyaert, Huanting Liu, Andrew Quigley, Benjamin G. Davis, Armin Wagner, Chris Whitfield, James H. Naismith

“…WzxE is part of the Wzx family and required in many glycan assembly systems, but an understanding of its molecular mechanism is hindered due to a lack of structural evidence. Here, we present the first X-ray structures of WzxE from Escherichia coli in complex with nanobodies. …”
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AlScN/GaN HEMTs with 4 A/mm on-current and maximum oscillation frequency >130 GHz by Kazuki Nomoto, Joseph Casamento, Thai-Son Nguyen, Lei Li, Hyunjea Lee, Chandrashekhar Savant, Austin Lee Hickman, Takuya Maeda, Jimy Encomendero, Ved Gund, Timothy Vasen, Shamima Afroz, Daniel Hannan, James C. M. Hwang, Debdeep Jena, Huili Grace Xing

“…Aluminum Scandium Nitride (AlScN) is an attractive material for use as a lattice-matched epitaxial barrier layer in GaN high-electron mobility transistors (HEMTs). Here we report the device fabrication, direct current (DC) and radio frequency (RF) characteristics of epitaxial AlScN/AlN/GaN HEMTs on SiC substrates with regrown ohmic contacts. …”
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