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作者：Krueger, Ryan K.; Engel, Megan C.; Hausen, Ryan; Brenner, Michael P.
作者单位：Harvard University; University of Calgary; Johns Hopkins University; Harvard University
摘要：Developing physics-based models for molecular simulation requires fitting many unknown parameters to diverse experimental datasets. Traditionally, this process is piecemeal and difficult to reproduce, leading to a fragmented landscape of models. Here, we establish a systematic framework for fitting coarse-grained molecular models to macroscopic experimental data by leveraging recently developed methods for computing low-variance gradient estimates with automatic differentiation. Using a widely...
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作者：Leimar, Olaf
作者单位：Stockholm University
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作者：Waild, Nicole C.; Ciesla, Jessica H.; Schafer, Xenia L.; Munger, Joshua; Knipe, David M.
作者单位：University of Rochester
摘要：CRISPR screening is a powerful approach to identify genetic perturbations that impact viral infection. However, most virus-focused CRISPR screens utilize selection strategies that limit the ability to identify genes important for infection. Here, we developed a CRISPR screening pipeline to identify cellular determinants of human cytomegalovirus (HCMV) infection based on virally induced remodeling of cellular antibody affinity (VIRCAA), which is scalable for large libraries and can identify cel...
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作者：Winstone, Helena; Stillwell, Helen; Tan, Li Hui; Cohen, Noam A.; Perera, Ranawaka A. P. M.; Weiss, Susan R.
作者单位：University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine
摘要：Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a lethal pathogen with pandemic potential. Clade A and B MERS-CoV viruses have caused outbreaks in the Middle East since 2012 when they initially spilled over from camels to humans. Clade C viruses, however, are only found in camels across Africa and the spillover potential of these viruses seems to be lower than for clade A/B strains but remains to be fully understood. Here, we report that clade C spikes are less well-cleaved at the S...
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作者：Fresard, Sara; Pangburn, Sarah J.; Leiss, Kayla; Boodwa-Ko, Daphne; Kovacsics, Daniella; Schoenherr, Chris J.; Rabinowitz, Jeremy S.; Economides, Aris N.; Li, Li; Qiu, Weigang; Gonzalez-Baradat, Bernardo; Rosa, Alessandro; Thomson, Russell; Raper, Jayne; Verdi, Joseph
作者单位：City University of New York (CUNY) System; City University of New York (CUNY) System; Hunter College (CUNY); Regeneron
摘要：Some primates are immune to infection by most African trypanosome parasites due to apolipoprotein L-1 (APOL1), a primate-specific ion channel-forming protein. Our long-term objective has been to reduce African trypanosomiasis in livestock by genetic bioengineering of cattle with primate APOL1. To select which primate APOL1, we analyzed Papio ssp. APOL1 proteins and found that Papio hamadryasAPOL1 was a strong candidate for transgenic animal production based on its trypanosome-killing capacity,...
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作者：Katsumura, Takafumi; Sato, Suguru; Yamashita, Kana; Oda, Shoji; Gakuhari, Takashi; Tanaka, Shodai; Fujitani, Kazuko; Nishimaki, Toshiyuki; Imai, Tadashi; Yoshiura, Yasutoshi; Takeshima, Hirohiko; Hashiguchi, Yasuyuki; Sekita, Yoichi; Mitani, Hiroshi; Ogawa, Motoyuki; Takeuchi, Hideaki; Oota, Hiroki
作者单位：Kitasato University; Okayama University; Kyushu University; Kitasato University; University of Tokyo; Kanazawa University; Kitasato University; Japan Fisheries Research & Education Agency (FRA); Fukui Prefectural University; Tokai University; Osaka Medical & Pharmaceutical University; Kitasato University; Tohoku University; University of Tokyo
摘要：Phenotypic plasticity allows organisms to adapt traits in response to environmental changes, yet the molecular basis by which such plastic traits become genetically fixed remains unclear. Here, we investigated gut-length plasticity in medaka fish (Oryzias latipes) through genome-wide methylation profiling, CRISPR/Cas9-mediated deletion, and population genomic analyses. We found that seasonal methylation of CpG sites upstream of the Plxnb3 is correlated with gut-length plasticity, and deletion ...
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作者：Morgenstern, Travis J.; Ota, Naruhisa; Lin, Zhonghua; Lechermann, Laura M.; Gill, Herman; Ogasawara, Annie; Williams, Simon; Marroquin, Kevin A.; Scherl, Alexis; Davies, Christopher W.; Byrnes, James R.; Seshasayee, Dhaya; Koerber, James T.
作者单位：Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
摘要：Cytokines are critical signaling molecules, but their therapeutic potential remains unrealized due to pleiotropic effects across cell types. Current strategies to develop conditionally active cytokines involve complex engineering and production, limiting their application to a select few cytokines and receptors. Here, we describe a simple, highly modular format called Sterically Masked Activated Cytokine (SMACk) via facile assembly of a targeting Fab/VHH, cytokine, and Fc. We first develop an ...
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作者：Mosconi, Michele; Leonardi, Chiara; -Garb, Zev Armour; Rocutto, Beatrice; Beeg, Marten; Meisl, Georg; Ortigosa-Pascual, Lei; Broggini, Luca; Salmona, Mario; Ricagno, Stefano; Knowles, Tuomas P. J.; Diomede, Luisa
作者单位：University of Cambridge; Lund University; University of Milan; Harvard University; University of London; King's College London
摘要：Interactions between amyloidogenic proteins are emerging as critical drivers of neurodegenerative diseases. Among others, in Alzheimer's disease (AD) and severe forms of chronic traumatic encephalopathy (CTE), codeposition of tau and amyloid-beta (A beta) leads to worsening of clinical outcomes and disease progression. Despite the importance of such heterotypic interactions, the underlying molecular mechanisms have proven challenging to be established. Here, we investigated the direct interact...
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作者：Liang, Yingke; Bueler, Stephanie A.; Rubinstein, John L.
作者单位：University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto
摘要：The presence of mycolic acid is a defining feature of the mycobacterial cell wall, which provides a highly impermeable barrier to many antibiotics. Biosynthesis of this fatty acid, as well as tuberculostearic acid, requires precursor molecules produced by the essential long-chain acyl-coenzyme A (CoA) carboxylase (LCC) complex. The LCC complex catalyzes carboxylation of the alpha- carbon of long-chain acyl-CoA, but also short-chain acetyl-CoA and propionyl-CoA. The complex includes the subunit...
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作者：Wang, Kou; Tian, Zhong; King-Jones, Kirst; Zhu, Fen; Wang, Xiao-Ping; Liu, Wen
作者单位：Huazhong Agricultural University; University of Alberta
摘要：Many animals rely on diapause to survive unfavorable seasons, but how environmental cues are transduced into endocrine changes remains poorly understood. In insects, reproductive diapause is triggered when juvenile hormone (JH) production from the corpora allata (CA) is suppressed, yet the regulatory basis of this suppression is unclear. Here, we show in the cabbage beetle (Colaphellus bowringi) that seasonal photoperiod controls CA growth, which in turn sets the gland's capacity for JH biosyn...
