Caroline C. Escoubas, Leah C. Dorman, Phi T. Nguyen, Christian Lagares-Linares, Haruna Nakajo, Sarah R. Anderson, Beatriz Cuevas, Ilia D. Vainchtein, Nicholas J. Silva, Yinghong Xiao, Peter V. Lidsky, Ellen Y. Wang, Sunrae E. Taloma, Hiromi Nakao-Inoue, Bjoern Schwer, Raul Andino, Tomasz J. Nowakowski, Anna V. Molofsky <<<

SummaryMicroglia are brain resident phagocytes that can engulf synaptic components and extracellular matrix as well as whole neurons. However, whether there are unique molecular mechanisms that regulate these distinct phagocytic states is unknown. Here we define a molecularly distinct microglial subset whose function is to engulf neurons in the developing brain. We transcriptomically identified a cluster of Type I interferon (IFN-I) responsive microglia that expanded 20-fold in the postnatal day 5 somatosensory cortex after partial whisker deprivation, a stressor that accelerates neural circuit remodeling.In situ, IFN-I responsive microglia were highly phagocytic and actively engulfed whole neurons. Conditional deletion of IFN-I signaling (Ifnar1fl/fl) in microglia but not neurons resulted in dysmorphic microglia with stalled phagocytosis and an accumulation of neurons with double strand DNA breaks, a marker of cell stress. Conversely, exogenous IFN-I was sufficient to drive neuronal engulfment by microglia and restrict the accumulation of damaged neurons. IFN-I deficient mice had excess excitatory neurons in the developing somatosensory cortex as well as tactile hypersensitivity to whisker stimulation. These data define a molecular mechanism through which microglia engulf neurons during a critical window of brain development. More broadly, they reveal key homeostatic roles of a canonical antiviral signaling pathway in brain development. <<<

Qiming Sun, Timothy C. Berkelbach, Nick S. Blunt, George H. Booth, Sheng Guo, Zhendong Li, Junzi Liu, James McClain, Elvira R. Sayfutyarova, Sandeep Sharma, Sebastian Wouters, Garnet Kin-Lic Chan <<<

PySCF is a general-purpose electronic structure platform designed from theground up to emphasize code simplicity, both to aid new method development, aswell as for flexibility in computational workflow. The package provides a widerange of tools to support simulations of finite size systems, extended systemswith periodic boundary conditions, low dimensional periodic systems, and customHamiltonians, using mean-field and post-mean-field methods with standardGaussian basis functions. To ensure easy of extensibility, PySCF uses thePython language to implement almost all its features, while computationallycritical paths are implemented with heavily optimized C routines. Using thiscombined Python/C implementation, the package is as efficient as the bestexisting C or Fortran based quantum chemistry programs. In this paper wedocument the capabilities and design philosophy of the current version of thePySCF package. <<<

AbstractUnderstanding the structure of a problem, such as the relationships between stimuli, supports fast learning and flexible reasoning. Recent theoretical suggestions have highlighted the usefulness of explicit structural representations that are fully divorced from sensory details for generalisation. Rodent work has suggested that abstraction of structure occurs gradually, over time, in cortex. However, direct evidence of such explicit relational representations in humans is scarce, and its relationship to consolidation mechanisms is underexplored. Here, we use a graph-learning paradigm to find such a relational map in the human medial prefrontal cortex. Importantly, this representation was absent early after learning but emerged on the time scale of days. These results shed new light on neural representations underlying the remarkable human ability to draw accurate inferences from little data. <<<

Chengzhi Jiao, Xiaoming Xie, Chenyang Hao, Liyang Chen, Yuxin Xie, Vanika Garg, Li Zhao, Zihao Wang, Yuqi Zhang, Tian Li, Junjie Fu, Annapurna Chitikineni, Jian Hou, Hongxia Liu, Girish Dwivedi, Xu Liu, Jizeng Jia, Long Mao, Xiue Wang, Rudi Appels, Rajeev K. Varshney, Weilong Guo, Xueyong Zhang <<<

Fuman Jiang, Jinghui Ren, Fang Chen, Yuqiu Zhou, Jiansheng Xie, Shan Dan, Yue Su, Jianhong Xie, Baomin Yin, Wen Su, Huakun Zhang, Wei Wang, Xianghua Chai, Linhua Lin, Hui Guo, Qiyun Li, Peipei Li, Yuying Yuan, Xiaoyu Pan, Yihan Li, Lifu Liu, Huifei Chen, Zhaoling Xuan, Shengpei Chen, Chunlei Zhang, Hongyun Zhang, Zhongming Tian, Zhengyu Zhang, Hui Jiang, Lijian Zhao, Weimou Zheng, Songgang Li, Yingrui Li, Jun Wang, Jian Wang, Xiuqing Zhang <<<

Abstract Background Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy. Methods We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping. Results 16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses. Conclusion Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis. <<<

This letter investigates the optimal hovering altitude of a single UAV toprovide coverage over any convex quadrilateral region on the ground. The UAVemploys a directional antenna with a tiltable beam, producing an ellipticalcoverage pattern. Two scenarios are considered: (1) inscribing the largestellipse within the quadrilateral to cover its interior, and (2) circumscribingthe smallest ellipse about the quadrilateral to ensure full coverage. We derivethe optimal UAV altitude and antenna tilt conditions in both scenarios for asimplified yet widely accepted path loss model and present numerical resultsfor coverage efficiency. The work contributes to the development ofenergy-efficient UAV-based communication systems. <<<

AbstractThe burgeoning interest in in situ multiplexed gene expression profiling technologies has opened new avenues for understanding cellular behavior and interactions. In this study, we present a comparative benchmark analysis of six in situ gene expression profiling methods, including both commercially available and academically developed methods, using publicly accessible mouse brain datasets. We find that standard sensitivity metrics, such as the number of unique molecules detected per cell, are not directly comparable across datasets due to substantial differences in the incidence of off-target molecular artifacts impacting specificity. To address these challenges, we explored various potential sources of molecular artifacts, developed novel metrics to control for them, and utilized these metrics to evaluate and compare different in situ technologies. Finally, we demonstrate how molecular false positives can seriously confound spatially-aware differential expression analysis, requiring caution in the interpretation of downstream results. Our analysis provides guidance for the selection, processing, and interpretation of in situ spatial technologies. <<<

Hua Yang, Yang Xun, Yali Shen, Hongtao Wang, Yu Tao, Huihan Wang, Xinyue Zhang, Rongqiu Liu, Huarong Yu, Li Wei, Jinsong Yan, Xiaoyu Zhu, Hua You <<<

Xinyuan Liang, Lianglong Sun, Xuhong Liao, Tianyuan Lei, Mingrui Xia, Dingna Duan, Zilong Zeng, Qiongling Li, Zhilei Xu, Weiwei Men, Yanpei Wang, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Tengda Zhao, Yong He <<<

AbstractCortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence. <<<

Shuyang Yao, Arvid Harder, Fahimeh Darki, Yu-Wei Chang, Ang Li, Kasra Nikouei, Giovanni Volpe, Johan N Lundström, Jian Zeng, Naomi Wray, Yi Lu, Patrick F Sullivan, Jens Hjerling-Leffler <<<

AbstractUnderstanding the temporal and spatial brain locations etiological for psychiatric disorders is essential for targeted neurobiological research. Integration of genomic insights from genome-wide association studies with single-cell transcriptomics is a powerful approach although past efforts have necessarily relied on mouse atlases. Leveraging a comprehensive atlas of the adult human brain, we prioritized cell types via the enrichment of SNP-heritabilities for brain diseases, disorders, and traits, progressing from individual cell types to brain regions. Our findings highlight specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals important patterns for schizophrenia with distinct subregions in the hippocampus and amygdala exhibiting the highest significance. Cerebral cortical regions display similar enrichments despite the known prefrontal dysfunction in those with schizophrenia highlighting the importance of subcortical connectivity. Using functional MRI connectivity from cases with schizophrenia and neurotypical controls, we identified brain networks that distinguished cases from controls that also confirmed involvement of the central and lateral amygdala, hippocampal body, and prefrontal cortex. Our findings underscore the value of single-cell transcriptomics in decoding the polygenicity of psychiatric disorders and offer a promising convergence of genomic, transcriptomic, and brain imaging modalities toward common biological targets. <<<

Elena Beanato, Hyuk-June Moon, Fabienne Windel, Pierre Vassiliadis, Maximillian J. Wessel, Traian Popa, Menoud Pauline, Esra Neufeld, Emanuela De Falco, Baptiste Gauthier, Melanie Steiner, Olaf Blanke, Friedhelm C. Hummel <<<

Because of the depth of the hippocampal-entorhinal complex (HC-EC) in the brain, understanding of its role in spatial navigation via neuromodulation was limited in humans. Here, we aimed to better elucidate this relationship in healthy volunteers, using transcranial temporal interference electric stimulation (tTIS), a noninvasive technique allowing to selectively neuromodulate deep brain structures. We applied tTIS to the right HC-EC in either continuous or intermittent theta-burst stimulation patterns (cTBS or iTBS), compared to a control condition, during a virtual reality–based spatial navigation task and concomitant functional magnetic resonance imaging. iTBS improved spatial navigation performance, correlated with hippocampal activity modulation, and decreased grid cell–like activity in EC. Collectively, these data provide the evidence that human HC-EC activity can be directly and noninvasively modulated leading to changes of spatial navigation behavior. These findings suggest promising perspectives for patients suffering from cognitive impairment such as following traumatic brain injury or dementia. <<<