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作者：Patel, Rashmi; Mackem, Susan
作者单位：National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
摘要：Several lines of evidence indicate that posterior (postaxial) digit number in tetrapod vertebrates is constrained to the pentadactyl state by interactions between the two major signaling centers that organize digit pattern and growth, the Sonic hedgehog (Shh)-expressing Zone of Polarizing Activity (ZPA) and the Fgf-expressing Apical Ectodermal Ridge (AER) ectoderm. Negative short-range effects of Shh on the immediately overlying AER limit its posterior extent and function, either by direct Shh...
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作者：Michaowski, Michal A.; Terejko, Katarzyna; Gos, Michalina; Izykowska, Ilona; Czyzewska, Marta M.; Kopotowski, Karol; Kaczor, Przemysaw T.; Brzostowicz, Aleksandra; Puzek, Estera; Migdaek, Monika; Mozrzymas, Jerzy W.
作者单位：Wroclaw Medical University; University of Wroclaw; Wroclaw University of Environmental & Life Sciences; Polish Academy of Sciences; Hirszfeld Institute of Immunology & Experimental Therapy of the Polish Academy of Sciences
摘要：gamma- aminobutyric acid type A receptor (GABAAR) is a pentameric ligand-gated ion channel that plays a crucial role in inhibition in the adult brain. Structural and electrophysiological studies have provided numerous insights into the receptor's functioning but the complete molecular mechanism of GABAAR action remains elusive. Herein, we used high-resolution single-channel recording to analyze point-mutated alpha 1 beta 2 gamma 2 receptors and applied so called Phi value (REFER, rate-equilibr...
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作者：Tapinova, Olga; Finkelman, Tal; Reitich-Stolero, Tamar; Paz, Rony; Tal, Assaf; Gov, Nir S.
作者单位：Weizmann Institute of Science; Weizmann Institute of Science; Tel Aviv University
摘要：Humans and other organisms make decisions choosing between different options, with the aim of maximizing the reward and minimizing the cost. The main theoretical framework for modeling the decision-making process has been based on the highly successful drift-diffusion model, which is a simple tool for explaining many aspects of this process. However, recent observations challenge this model. It was found that inhibitory tone increases during situations of difficult discrimination tasks, but th...
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作者：Willcox, Alexandra C.; Gobillot, Theodore A.; Kikawa, Caroline; Baumgarten, Nell E.; Stoddard, Caitlin I.; Sung, Kevin; Bhattacharya, Tamanash; Freeman, Tiia S.; Marceau, Joshua; Humes, Daryl; Overbaugh, Julie
作者单位：Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; University of Pennsylvania
摘要：Zika virus (ZIKV) has caused multiple human outbreaks, with more recent epidemics associated with severe outcomes in infants. Today, ZIKV is endemic to many countries and presents a persistent threat for future epidemics. The host innate immune proteins that regulate ZIKV replication are incompletely defined. We developed a CRISPR knockout screen to identify host factors that impact ZIKV replication, resulting in the finding of angiomotin-like protein 2 (AMOTL2), a protein that inhibits ZIKV b...
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作者：Horvath, Ferdinand; Jung, Hendrik; Grabmayr, Herwig; Fahrner, Marc; Romanin, Christoph; Hummer, Gerhard
作者单位：Johannes Kepler University Linz; Max Planck Society; Johannes Kepler University Linz; Goethe University Frankfurt; Institute of Science & Technology - Austria
摘要：Stromal interaction molecule 1 (STIM1) is a Ca2+-sensing protein in the endoplasmic reticulum (ER) membrane. The depletion of ER Ca2+ stores induces a large conformational transition of the cytosolic STIM1 C-terminus, initiated by the dimerization of the transmembrane (TM) domain. We use the AI-guided transition path sampling algorithm aimmd to extensively sample the dimerization of STIM1-TM helices in an ER-mimicking lipid bilayer. In nearly 0.5 ms of all-atom molecular dynamics simulations w...
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作者：Keck, Carl H. C.; Schmidt, Elizabeth L.; Roth, Richard H.; Floyd, Brendan M.; Tsai, Andy P.; Garcia, Hassler B.; Cui, Miao; Chen, Xiaoyu; Wang, Chonghe; Park, Andrew; Zhao, Su; Liao, Pinyu A.; Casey, Kerriann M.; Reineking, Wencke; Cai, Sa; Zhang, Ling - Yi; Yang, Qianru; Yuan, Lei; Baghdasaryan, Ani; Lopez, Eduardo R.; Cooper, Lauren; Cui, Han; Esquivel, Daniel; Brinson, Kenneth; Chen, Xiaoke; Wyss-Coray, Tony; Coleman, Todd P.; Brongersma, Mark L.; Bertozzi, Carolyn R.; Wang, Gordon X.; Ding, Jun B.; Hong, Guosong
作者单位：Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
摘要：Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter- wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum...
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作者：Lawton, Ralph
作者单位：Harvard University
摘要：Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the hygiene hypothesis. This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission's deworming c...
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作者：Nuovo, Gerard J.; Tili, Esmerina; Croce, Carlo M.
作者单位：University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute
摘要：Human papillomavirus (HPV)-related lesions contain types with benign outcomes and those with a risk of progression to cancer. We addressed the role of immune surveillance in 76 cervical biopsies (normal = 23, HPV+ benign = 16, HPV+ precancer = 37) by studying the infiltration of cytotoxic T cells and the expression of the immune modulators PDL1, ICOSL, and miR-155 and compared the data to 101 cervical squamous cell carcinomas. In the normal cervix, ICOSL expression was restricted to the endoce...
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作者：Moon, Hyun Seok; Vo, Thanh Tan; Im, Geun Ho; Hong, Seok-Jun; Kim, Seong-Gi
作者单位：Institute for Basic Science - Korea (IBS); Sungkyunkwan University (SKKU)
摘要：Functional connectivity (FC), a statistical correlation of pair-wise brain signals from resting-state (RS) functional MRI (fMRI), is a widely used concept for mapping large-scale functional networks in both humans and animals. However, its underlying causal mechanism remains poorly understood, particularly for strong interhemispheric connectivity (e.g., homotopic connections) consistently observed in FC. In this study, we investigated the neural basis of RS FC in mice using fMRI with anatomica...
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作者：Olivares, Ingrid; Faurby, Soren; Camara-Leret, Rodrigo; Pigot, Alex L.
作者单位：University of Zurich; University of Gothenburg; University of London; University College London
摘要：and parasitic indigobirds provide compelling evidence that it occurs. Still, the frequency of sympatric speciation and its relationship to morphological divergence in plants remains poorly understood, especially in plants. Here, we analyze the geographic distributions, traits, and divergence times of palm and conifer sister species (740 species from 108 genera) to determine the dominant geographic mode and role of morphological divergence in plant speciation. We show that allopatric speciation...
