Mudd, Philip A Crawford, Jeremy Chase Turner, Jackson S Souquette, Aisha Reynolds, Daniel Bender, Diane Bosanquet, James P Anand, Nitin J Striker, David A Martin, R Scott
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Science advances
We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decrease...
Sacco, Michael Dominic Ma, Chunlong Lagarias, Panagiotis Gao, Ang Townsend, Julia Alma Meng, Xiangzhi Dube, Peter Zhang, Xiujun Hu, Yanmei Kitamura, Naoya
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Science advances
The main protease (Mpro) of SARS-CoV-2 is a key antiviral drug target. While most Mpro inhibitors have a γ-lactam glutamine surrogate at the P1 position, we recently found that several Mpro inhibitors have hydrophobic moieties at the P1 site, including calpain inhibitors II and XII, which are also active against human cathepsin L, a host protease t...
Swann, Jeremy B Nusser, Anja Morimoto, Ryo Nagakubo, Daisuke Boehm, Thomas
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The onset of lymphocyte development in the vertebrate primordial thymus, about 500 million years ago, represents one of the foundational events of the emerging adaptive immune system. Here, we retrace the evolutionary trajectory of thymopoiesis, from early vertebrates to mammals, guided by members of the Foxn1/4 transcription factor gene family, wh...
Bhardwaj, Rajesh Lindinger, Sonja Neuberger, Arthur Nadezhdin, Kirill D Singh, Appu K Cunha, Micael R Derler, Isabella Gyimesi, Gergely Reymond, Jean-Louis Hediger, Matthias A
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Science advances
Epithelial calcium channel TRPV6 plays vital roles in calcium homeostasis, and its dysregulation is implicated in multifactorial diseases, including cancers. Here, we study the molecular mechanism of selective nanomolar-affinity TRPV6 inhibition by (4-phenylcyclohexyl)piperazine derivatives (PCHPDs). We use x-ray crystallography and cryo-electron m...
Menasche, Bridget L Davis, Eric M Wang, Shifeng Ouyang, Yan Li, Suzhao Yu, Haijia Shen, Jingshi
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Major histocompatibility complex (MHC)-unrestricted cytotoxic lymphocytes (CLs) such as natural killer (NK) cells can detect and destroy tumor and virus-infected cells resistant to T cell-mediated killing. Here, we performed genome-wide genetic screens to identify tumor-intrinsic genes regulating killing by MHC-unrestricted CLs. A group of genes id...
Wu, Qingqing Li, Yue Lyu, Mohan Luo, Yiwen Shi, Hui Zhong, Shangwei
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How mechanical forces regulate plant growth is a fascinating and long-standing question. After germination underground, buried seedlings have to dynamically adjust their growth to respond to mechanical stimulation from soil barriers. Here, we designed a lid touch assay and used atomic force microscopy to investigate the mechanical responses of seed...
Xu, Xue Zhou, Yuan Feng, Xiaowen Li, Xiong Asad, Mohammad Li, Derek Liao, Bo Li, Jianqiang Cui, Qinghua Wang, Edwin
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Science advances
There is an ongoing debate on the importance of genetic factors in cancer development, where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer cases are inheritable. By conducting a systematic analysis of germline genomes of 9712 cancer patients representing 22 common cancer types along with 16,670 noncancer individ...
Yang, Z Li, P Shang, Q Wang, Y He, J Ge, S Jia, R Fan, X
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Obesity drives the development of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis. Several bone morphogenetic proteins (BMPs) except BMP9 were reported related to metabolic syndrome. This study demonstrates that liver cytokine BMP9 is decreased in the liver and serum of NAFLD model mice and patients. BMP9 knockdown induc...
Raina, Deepak Bushan Matuszewski, Lucas-Maximilian Vater, Corina Bolte, Julia Isaksson, Hanna Lidgren, Lars Tägil, Magnus Zwingenberger, Stefan
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Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We d...
Fu, Yao Li, Feili Karstensen, Johannes Wang, Chunzai
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Science advances
The Atlantic Meridional Overturning Circulation (AMOC) is crucially important to global climate. Model simulations suggest that the AMOC may have been weakening over decades. However, existing array-based AMOC observations are not long enough to capture multidecadal changes. Here, we use repeated hydrographic sections in the subtropical and subpola...
