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作者：Zoefel, Benedikt; Abbasi, Omid; Gross, Joachim; Kotz, Sonja A.
作者单位：Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of Munster; University of Munster; Maastricht University; Max Planck Society
摘要：Evidence accumulates that the cerebellum's role in the brain is not restricted to motor functions. Rather, cerebellar activity seems to be crucial for a variety of tasks that rely on precise event timing and prediction. Due to its complex structure and importance in communication, human speech requires a particularly precise and predictive coordination of neural processes to be successfully comprehended. Recent studies proposed that the cerebellum is indeed a major contributor to speech proces...
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作者：Chen, Tony; Zhang, Haoyu; Mazumder, Rahul; Lin, Xihong
作者单位：Harvard University; Harvard T.H. Chan School of Public Health; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Massachusetts Institute of Technology (MIT); Harvard University
摘要：Polygenic risk scores (PRS) enhance population risk stratification and advance personalized medicine, but existing methods face several limitations, encompassing issues related to computational burden, predictive accuracy, and adaptability to a wide range of genetic architectures. To address these issues, we propose Aggregated L0Learn using Summary- level data (ALL- Sum), a fast and scalable ensemble learning method for computing PRS using summary statistics from genome-wide association studie...
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作者：Kocher, Charles D.; Dill, Ken A.
作者单位：State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
摘要：How did specific useful protein sequences arise from simpler molecules at the origin of life? This seemingly needle-in-a-haystack problem has remarkably close resemblance to the old Protein Folding Problem, for which the solution is now known from statistical physics. Based on the logic that Origins must have come only after there was an operative evolution mechanism-which selects on phenotype, not genotype-we give a perspective that proteins and their folding processes are likely to have been...
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作者：Rath, Sneha P.; Gupta, Rahul; Todres, Ellen; Wang, Hong; Jourdain, Alexis A.; Ardlie, Kristin G.; Calvo, Sarah E.; Mootha, Vamsi K.
作者单位：Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Lausanne
摘要：The mammalian mitochondrial genome (mtDNA) is multicopy and its copy number (mtCN) varies widely across tissues, in development and in disease. Here, we systematically catalog this variation by assaying mtCN in 52 human tissues across 952 donors (10,499 samples from the Genotype- Tissue Expression project) and 20 murine tissues using qPCR, capturing 50- and 200- fold variation, respectively. We also estimate per cell mtCN across 173 human cell lines from the Cancer Cell Line Encyclopedia using...
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作者：Shang, Jinhui; Ma, Yuan; Liu, Xixuan; Sun, Shijie; Pang, Xiayun; Zhou, Rui; Huan, Shuangyan; He, Yan; Xiong, Bin; Zhang, Xiao-Bing
作者单位：Hunan University; Shaanxi University of Chinese Medicine; Tsinghua University
摘要：The formation of macrophage-derived foam cells has been recognized as the pathological hallmark of atherosclerotic diseases. However, the pathological evolution dynamics and underlying regulatory mechanisms remain largely unknown. Herein, we introduce a single-particle rotational microrheology method for pathological staging of macrophage foaming and antiatherosclerotic explorations by probing the dynamic changes of lysosomal viscous feature over the pathological evolution progression. The pri...
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作者：Watson, Matthew; Sabirova, Dilyara; Hardy, Megan C.; Pan, Yuming; Carpentier, David C. J.; Yates, Henry; Wright, Charlotte J.; Chan, W. H.; Destan, Ebru; Stott, Katherine
作者单位：University of Cambridge; University of Cambridge
摘要：Linker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fiber of nucleosomal beads on a string. The result is a heterogeneous condensed state with local properties that range from dynamic, irregular, and liquid- like to stable and regular structures (the 30-nm fiber), which in turn impact chromatin- dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly dis...
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作者：Johnston, Kadina E.; Almhjell, Patrick J.; Watkins-Dulaney, Ella J.; Liu, Grace; Porter, Nicholas J.; Yang, Jason; Arnold, Frances H.
作者单位：Merck & Company; Merck & Company USA; Stanford University; Harvard University; Harvard Medical School; California Institute of Technology; California Institute of Technology
摘要：Protein engineering often targets binding pockets or active sites which are enriched in epistasis-nonadditive interactions between amino acid substitutions-and where the combined effects of multiple single substitutions are difficult to predict. Few existing sequence- fitness datasets capture epistasis at large scale, especially for enzyme catalysis, limiting the development and assessment of model- guided enzyme engineering approaches. We present here a combinatorially complete, 160,000- vari...
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作者：Teng, Xiao-Yu; Hu, Ping; Zhang, Cai-Ming; Zhang, Qin-Xin; Yang, Guolin; Zang, Yan-Yu; Liu, Zhi-Xiong; Chen, Guiquan; Shi, Yun Stone
作者单位：Nanjing University; Nanjing Medical University; Southern Medical University - China
摘要：a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding followed by mass spectrometry. An OL- specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional k...
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作者：Pecheva, Diliana; Smith, Diana M.; Casey, B. J.; Woodward, Lianne J.; Dale, Anders M.; Filippi, Christopher G.; Watts, Richard
作者单位：University of California System; University of California San Diego; University of California System; University of California San Diego; Columbia University; University of Canterbury; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids)
摘要：Some mental health problems such as depression and anxiety are more common in females, while others such as autism and attention deficit/hyperactivity (AD/H) are more common in males. However, the neurobiological origins of these sex differences are poorly understood. Animal studies have shown substantial sex differences in neuronal and glial cell structure, while human brain imaging studies have shown only small differences, which largely reflect overall body and brain size. Advanced diffusio...
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作者：He, Jinfeng; Tong, Yun; Wang, Zhe; Zhou, Guorong; Ren, Xuhui; Zhu, Jiaye; Zhang, Nan; Chen, Lu; Chen, Pengzuo
作者单位：Zhejiang Sci-Tech University; University of Cambridge
摘要：High- entropy compounds have been emerging as promising candidates for electrolysis, yet their controllable electrosynthesis strategy remains a formidable challenge because of the ambiguous ionic interaction and codeposition mechanism. Herein, we report a oxygenates directionally induced electrodeposition strategy to construct high- entropy materials with amorphous features, on which the structural evolution from high- entropy phosphide to oxide is confirmed by introducing vanadate, thus reali...
