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681.
颜林林 (2023-03-12 15:29):
#paper doi:10.1016/j.celrep.2023.112230 Cell Reports, 2023, FAM193A is a positive regulator of p53 activity. 这是一篇典型的关于药物敏感机制探索的细胞学研究,通过分子细胞生物学方法和高通量筛选技术,找到一个新调控基因,并确认其功能。癌症研究中最著名的基因当属TP53(其蛋白则称为p53),这是个抑癌基因,在癌组织中常表现出发生突变或被异常调控。针对其抑制型调控蛋白(如MDM2和MDM4),设计的化合物抑制剂,可激活或促进p53功能,进而达到治疗癌症的目的。Nutlin正是这样的候选药物分子。然而Nutlin在不同细胞系或患者中的表现却差异巨大,其作用机制尚待深入研究。这篇论文通过对药物敏感数据库的分析,以及采用CRISPR screening技术,在多个不同细胞系中进行高通量筛选,识别出FAM193A蛋白,其与Nutlin药物敏感性密切相关,并通过一系列证据,证明FAM193A在p53通路中起到正向调节作用,为后续机制研究和药物开发提供了新的方向。
IF:7.500Q1 Cell reports, 2023-03-28. DOI: 10.1016/j.celrep.2023.112230 PMID: 36897777
Abstract:
Inactivation of the p53 tumor suppressor, either by mutations or through hyperactivation of repressors such as MDM2 and MDM4, is a hallmark of cancer. Although many inhibitors of the p53-MDM2/4 … >>>
Inactivation of the p53 tumor suppressor, either by mutations or through hyperactivation of repressors such as MDM2 and MDM4, is a hallmark of cancer. Although many inhibitors of the p53-MDM2/4 interaction have been developed, such as Nutlin, their therapeutic value is limited by highly heterogeneous cellular responses. We report here a multi-omics investigation of the cellular response to MDM2/4 inhibitors, leading to identification of FAM193A as a widespread regulator of p53 function. CRISPR screening identified FAM193A as necessary for the response to Nutlin. FAM193A expression correlates with Nutlin sensitivity across hundreds of cell lines. Furthermore, genetic codependency data highlight FAM193A as a component of the p53 pathway across diverse tumor types. Mechanistically, FAM193A interacts with MDM4, and FAM193A depletion stabilizes MDM4 and inhibits the p53 transcriptional program. Last, FAM193A expression is associated with better prognosis in multiple malignancies. Altogether, these results identify FAM193A as a positive regulator of p53. <<<
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682.
张德祥 (2023-03-12 09:48):
#paper https://doi.org/10.48550/arXiv.1806.08053 Semantic information, autonomous agency, and nonequilibrium statistical physics 论文尝试通过反事实对语义信息进行定义,通过个体跟环境的物理系,热力学的信息交换来实现,但后续工作不多,和自由能框架有些接近,
Abstract:
Shannon information theory provides various measures of so-called "syntactic information", which reflect the amount of statistical correlation between systems. In contrast, the concept of "semantic information" refers to those correlations … >>>
Shannon information theory provides various measures of so-called "syntactic information", which reflect the amount of statistical correlation between systems. In contrast, the concept of "semantic information" refers to those correlations which carry significance or "meaning" for a given system. Semantic information plays an important role in many fields, including biology, cognitive science, and philosophy, and there has been a long-standing interest in formulating a broadly applicable and formal theory of semantic information. In this paper we introduce such a theory. We define semantic information as the syntactic information that a physical system has about its environment which is causally necessary for the system to maintain its own existence. "Causal necessity" is defined in terms of counter-factual interventions which scramble correlations between the system and its environment, while "maintaining existence" is defined in terms of the system's ability to keep itself in a low entropy state. We also use recent results in nonequilibrium statistical physics to analyze semantic information from a thermodynamic point of view. Our framework is grounded in the intrinsic dynamics of a system coupled to an environment, and is applicable to any physical system, living or otherwise. It leads to formal definitions of several concepts that have been intuitively understood to be related to semantic information, including "value of information", "semantic content", and "agency". <<<
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683.
颜林林 (2023-03-02 07:38):
#paper doi:10.1016/j.csbj.2023.02.016 Computational and Structural Biotechnology Journal, 2023, DNAsmart: Multiple attribute ranking tool for DNA data storage systems. 将DNA用作存储介质,已经逐渐成为一个热门的研究方向。由于DNA在读取(测序)和写入(合成)过程中,受到其自身特性和其他环境体系不同因素的影响,存在各类错误。这篇研究提供了一个网站工具DNAsmart,以交互式的方式,可视化地展示核酸片段之间诸如GC含量、汉明距离等不同属性,帮助研究者探索如何有效利用和平衡这些属性的影响,以设计出更合适的DNA存储的编解码方案。
Abstract:
In an ever-growing need for data storage capacity, the Deoxyribonucleic Acid (DNA) molecule gains traction as a new storage medium with a larger capacity, higher density, and a longer lifespan … >>>
In an ever-growing need for data storage capacity, the Deoxyribonucleic Acid (DNA) molecule gains traction as a new storage medium with a larger capacity, higher density, and a longer lifespan over conventional storage media. To effectively use DNA for data storage, it is important to understand the different methods of encoding information in DNA and compare their effectiveness. This requires evaluating which decoded DNA sequences carry the most encoded information based on various attributes. However, navigating the field of coding theory requires years of experience and domain expertise. For instance, domain experts rely on various mathematical functions and attributes to score and evaluate their encodings. To enable such analytical tasks, we provide an interactive and visual analytical framework for multi-attribute ranking in DNA storage systems. Our framework follows a three-step view with user-settable parameters. It enables users to find the optimal en-/de-coding approaches by setting different weights and combining multiple attributes. We assess the validity of our work through a task-specific user study on domain experts by relying on three tasks. Results indicate that all participants completed their tasks successfully under two minutes, then rated the framework for design choices, perceived usefulness, and intuitiveness. In addition, two real-world use cases are shared and analyzed as direct applications of the proposed tool. DNAsmart enables the ranking of decoded sequences based on multiple attributes. In sum, this work unveils the evaluation of en-/de-coding approaches accessible and tractable through visualization and interactivity to solve comparison and ranking tasks. <<<
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684.
小擎子 (2023-02-28 23:59):
#paper  The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota. Cell Rep. 2022 Nov 15;41(7):111625. doi: 10.1016/j.celrep.2022.111625. PMID: 36384132.文章发现结直肠癌里的肿瘤微生物群可以对一线CRC化疗药物5-氟尿嘧啶进行修饰,降低药物的功效。5-氟尿嘧啶既是对结直肠癌上皮细胞有毒性的,也是靶向结肠癌中的核梭杆菌Fn(与癌症进展和复发正相关)的。而肿瘤微生物群修饰5-氟尿嘧啶后,可以减轻对Fn和CRC上皮细胞的毒性。其中结直肠癌肿瘤微生物群里的大肠杆菌在修饰5-氟尿嘧啶的作用得到了证实。文章也用了随机森林对宏基因组数据进行了特征分类,大肠杆菌是5-FU暴露后“修饰者”组的分类,总体而言,具有最高的平均下降精度值,支持大肠杆菌作为模型中分类器的重要性。
IF:7.500Q1 Cell reports, 2022-11-15. DOI: 10.1016/j.celrep.2022.111625 PMID: 36384132
Abstract:
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 … >>>
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 bioactive compounds against a Fn CRC isolate, we find that 15% of inhibitors are antineoplastic agents including fluoropyrimidines. Validation of these findings reveals that 5-fluorouracil (5-FU), a first-line CRC chemotherapeutic, is a potent inhibitor of Fn CRC isolates. We also identify members of the intratumoral microbiota, including Escherichia coli, that are resistant to 5-FU. Further, CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity toward otherwise-sensitive Fn and human CRC epithelial cells. Lastly, we demonstrate that ex vivo patient CRC tumor microbiota undergo community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, reducing local drug efficacy. Together, these observations argue for further investigation into the role of the CRC intratumoral microbiota in patient response to chemotherapy. <<<
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685.
cellsarts (2023-02-28 23:46):
#与海底硫循环有关的新酸杆菌类群Novel taxa of Acidobacteriota implicated in seafloor sulfur cycling The ISME Journal (2021) 15:3159–3180 https://doi.org/10.1038/s41396-021-00992-0 酸杆菌广泛存在于海洋沉积物中,但其代谢和生态特性尚不清楚。在这里,我们通过宏基因组组装基因组(MAGs)的功能预测,16S rRNA和异源亚硫酸盐还原酶(dsrB)基因和转录物的扩增子测序,以及四硫酸盐修饰的基因表达分析,研究了斯瓦尔巴群岛海洋沉积物中酸杆菌的代谢和分布。在斯瓦尔巴群岛沉积物中,酸杆菌属是仅次于脱硫杆菌属的第二大含有亚硫酸盐还原酶dsrB的门(平均13%),平均占亚硫酸盐还原酶dsrB转录物的4%。对亚硫酸盐还原酶dsrAB数据集的荟萃分析还显示,酸杆菌的亚硫酸盐还原酶dsrAB序列在全球海洋沉积物中非常突出,平均占所有分析序列的15%,并代表了海洋沉积物中大部分以前未分类的亚硫酸盐还原酶dsrAB。我们提出了两个新的酸杆菌属,Candidatus sulomarinibacter(类Thermoanaerobaculia,“细分23”)和Ca. Polarisedimenticola(“细分22”),它们具有独特的遗传特性,可以解释它们在生物地球化学特征不同的沉积物中的分布。Ca. sulomarinibacter编码灵活的呼吸途径,具有潜在的氧、氧化亚氮、金属氧化物、四硫酸盐、硫和亚硫酸盐/硫酸盐呼吸,并可能发生硫歧化。潜在的营养物质和能量包括纤维素、蛋白质、蓝藻素、氢和醋酸酯。A Ca. Polarisedimenticola MAG编码各种酶来降解蛋白质,并减少氧气,硝酸盐,硫/多硫化物和金属氧化物。Svalbard沉积物的16S rRNA基因和转录谱分析显示,Ca. sulomarinibacter成员在硫化物峡湾沉积物中相对丰富且具有转录活性,而Ca. Polarisedimenticola成员在富金属峡湾沉积物中相对丰富。总的来说,我们揭示了未经培养的海洋酸杆菌的各种生理特征,以及在海底生物地球化学循环中的基本作用。
Abstract:
Acidobacteriota are widespread and often abundant in marine sediments, yet their metabolic and ecological properties are poorly understood. Here, we examined metabolisms and distributions of Acidobacteriota in marine sediments of … >>>
Acidobacteriota are widespread and often abundant in marine sediments, yet their metabolic and ecological properties are poorly understood. Here, we examined metabolisms and distributions of Acidobacteriota in marine sediments of Svalbard by functional predictions from metagenome-assembled genomes (MAGs), amplicon sequencing of 16S rRNA and dissimilatory sulfite reductase (dsrB) genes and transcripts, and gene expression analyses of tetrathionate-amended microcosms. Acidobacteriota were the second most abundant dsrB-harboring (averaging 13%) phylum after Desulfobacterota in Svalbard sediments, and represented 4% of dsrB transcripts on average. Meta-analysis of dsrAB datasets also showed Acidobacteriota dsrAB sequences are prominent in marine sediments worldwide, averaging 15% of all sequences analysed, and represent most of the previously unclassified dsrAB in marine sediments. We propose two new Acidobacteriota genera, Candidatus Sulfomarinibacter (class Thermoanaerobaculia, "subdivision 23") and Ca. Polarisedimenticola ("subdivision 22"), with distinct genetic properties that may explain their distributions in biogeochemically distinct sediments. Ca. Sulfomarinibacter encode flexible respiratory routes, with potential for oxygen, nitrous oxide, metal-oxide, tetrathionate, sulfur and sulfite/sulfate respiration, and possibly sulfur disproportionation. Potential nutrients and energy include cellulose, proteins, cyanophycin, hydrogen, and acetate. A Ca. Polarisedimenticola MAG encodes various enzymes to degrade proteins, and to reduce oxygen, nitrate, sulfur/polysulfide and metal-oxides. 16S rRNA gene and transcript profiling of Svalbard sediments showed Ca. Sulfomarinibacter members were relatively abundant and transcriptionally active in sulfidic fjord sediments, while Ca. Polarisedimenticola members were more relatively abundant in metal-rich fjord sediments. Overall, we reveal various physiological features of uncultured marine Acidobacteriota that indicate fundamental roles in seafloor biogeochemical cycling. <<<
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686.
大勇 (2023-02-28 23:35):
#paper  CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 2022 Apr 11;40(4):365-378.e6. doi: 10.1016/j.ccell.2022.02.003. Epub 2022 Feb 24. 这篇文献主要讲述了CD8+T细胞通过分泌内源性的IFNγ,可以作用与肿瘤细胞,引起ACSL4的表达升高,与花生四烯酸协同促进肿瘤的脂质代谢并诱导肿瘤细胞铁死亡,在此过程中,可以促进肿瘤对免疫检查点抑制剂的疗效。
IF:48.800Q1 Cancer cell, 2022-04-11. DOI: 10.1016/j.ccell.2022.02.003 PMID: 35216678
Abstract:
Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of … >>>
Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of action for CD8 T cell (CTL)-mediated tumor killing. Mechanistically, IFNγ stimulates ACSL4 and alters tumor cell lipid pattern, thereby increasing incorporations of AA into C16 and C18 acyl chain-containing phospholipids. Palmitoleic acid and oleic acid, two common C16 and C18 fatty acids in blood, promote ACSL4-dependent tumor ferroptosis induced by IFNγ plus AA. Moreover, tumor ACSL4 deficiency accelerates tumor progression. Low-dose AA enhances tumor ferroptosis and elevates spontaneous and immune checkpoint blockade (ICB)-induced anti-tumor immunity. Clinically, tumor ACSL4 correlates with T cell signatures and improved survival in ICB-treated cancer patients. Thus, IFNγ signaling paired with selective fatty acids is a natural tumor ferroptosis-promoting mechanism and a mode of action of CTLs. Targeting the ACSL4 pathway is a potential anti-cancer approach. <<<
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687.
张贝 (2023-02-28 23:21):
#paper Nat Med. 2014 Dec;20(12):1479-84.doi: 10.1038/nm.3729. Anchored multiplex PCR for targeted next-generation sequencing 本文首次报道了锚定多重PCR技术(AMP)在基因融合检测方面的应用。与RACE技术的原理类似,AMP将待检测的DNA片段与半功能通用接头连接,经过两轮巢式PCR扩增富集目标片段。与其他常规PCR技术相比,AMP仅通过一端的信息就可以富集目标区域。目前AMP的应用范围已经扩展检测基因的点突变、插入缺失、拷贝数变异、RNA表达等方面。
IF:58.700Q1 Nature medicine, 2014-Dec. DOI: 10.1038/nm.3729 PMID: 25384085
Abstract:
We describe a rapid target enrichment method for next-generation sequencing, termed anchored multiplex PCR (AMP), that is compatible with low nucleic acid input from formalin-fixed paraffin-embedded (FFPE) specimens. AMP is … >>>
We describe a rapid target enrichment method for next-generation sequencing, termed anchored multiplex PCR (AMP), that is compatible with low nucleic acid input from formalin-fixed paraffin-embedded (FFPE) specimens. AMP is effective in detecting gene rearrangements (without prior knowledge of the fusion partners), single nucleotide variants, insertions, deletions and copy number changes. Validation of a gene rearrangement panel using 319 FFPE samples showed 100% sensitivity (95% confidence limit: 96.5-100%) and 100% specificity (95% confidence limit: 99.3-100%) compared with reference assays. On the basis of our experience with performing AMP on 986 clinical FFPE samples, we show its potential as both a robust clinical assay and a powerful discovery tool, which we used to identify new therapeutically important gene fusions: ARHGEF2-NTRK1 and CHTOP-NTRK1 in glioblastoma, MSN-ROS1, TRIM4-BRAF, VAMP2-NRG1, TPM3-NTRK1 and RUFY2-RET in lung cancer, FGFR2-CREB5 in cholangiocarcinoma and PPL-NTRK1 in thyroid carcinoma. AMP is a scalable and efficient next-generation sequencing target enrichment method for research and clinical applications. <<<
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688.
小小小小小小萌 (2023-02-28 23:18):
#Paper DOI: https://doi.org/10.1016/j.cell.2022.09.010 Proper acquisition of cell class identify in organoids allows definition of fate specification programs of the human cerebral cortex 这篇文章是发布了人脑类器官的发育过程中的单细胞转录组学,染色质开放组学,空间转录组学的数据。其中,选择了类器官自23天至6个月中的8个时间节点,通过对不同阶段皮层细胞类型特征的捕捉,证实了人脑类器官发育过程中的差异表达基因特征反映的是已知的内源性胚胎发育过程中发育阶段细胞类型特异性的标志基因。经过一系列细胞类型调控机制的研究,比较了人脑类器官和胚胎皮层细胞类型的重叠度,并证明了人脑类器官的细胞类型可以很好的代表内源性胚胎皮层的转录及表观状态特征。
IF:45.500Q1 Cell, 2022-09-29. DOI: 10.1016/j.cell.2022.09.010 PMID: 36179669 PMCID:PMC9990683
Abstract:
Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids … >>>
Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development. <<<
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689.
na na na (2023-02-28 23:14):
#paper DOI:10.1038/s41573-021-00387-y. Identification of neoantigens for individualized therapeutic cancer vaccines.目前肿瘤疫苗、CART等通过应用人体自身适应性免疫系统来治疗的方式非常火热,其中有关肿瘤新新抗原识别尤其重要,在20的特斯拉联盟比赛中可以看到,大部分预测出的新抗原,其产生真正免疫原性的数量是很少的,不足30%,继续优化新抗原识别算法非常必要,如果要学习新抗原的识别算法,就必须了解肿瘤新抗原在免疫系统中的作用机制。在这篇综述中,作者比较全面的阐述了T细胞识别新抗原的基本机制,并结合体细胞突变和癌症免疫治疗的新抗原预测的现有方法逻辑之间的关系。并且作者也提出一种新抗原的分类方法,这个分类方法更多考虑了临床关注点,可以了解一下。
Abstract:
Somatic mutations in cancer cells can generate tumour-specific neoepitopes, which are recognized by autologous T cells in the host. As neoepitopes are not subject to central immune tolerance and are … >>>
Somatic mutations in cancer cells can generate tumour-specific neoepitopes, which are recognized by autologous T cells in the host. As neoepitopes are not subject to central immune tolerance and are not expressed in healthy tissues, they are attractive targets for therapeutic cancer vaccines. Because the vast majority of cancer mutations are unique to the individual patient, harnessing the full potential of this rich source of targets requires individualized treatment approaches. Many computational algorithms and machine-learning tools have been developed to identify mutations in sequence data, to prioritize those that are more likely to be recognized by T cells and to design tailored vaccines for every patient. In this Review, we fill the gaps between the understanding of basic mechanisms of T cell recognition of neoantigens and the computational approaches for discovery of somatic mutations and neoantigen prediction for cancer immunotherapy. We present a new classification of neoantigens, distinguishing between guarding, restrained and ignored neoantigens, based on how they confer proficient antitumour immunity in a given clinical context. Such context-based differentiation will contribute to a framework that connects neoantigen biology to the clinical setting and medical peculiarities of cancer, and will enable future neoantigen-based therapies to provide greater clinical benefit. <<<
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690.
(2023-02-28 23:07):
#paper DOI:10.1080/19490976.2021.2022407. Epigenetic regulation by gut microbiota.肠道微生物最近比较火,因为它们可以指导宿主体内健康和疾病的环境刺激。虽然已经在局部肠细胞和外周组织中描述了微生物群敏感的表观遗传机制,但还需要进一步的研究来完全破译宿主和微生物群之间的复杂关系。这篇综述从连接微生物群和哺乳动物细胞的表观遗传调控、微生物代谢物作为表观遗传底物和酶调节因子、微生物群在稳态和炎症过程中指导DNA甲基化模式、宿主-微生物通过组蛋白修饰相互作用、SCFAs对免疫细胞的调节作用、非共价修饰等方面强调了目前对肠道微生物群表观遗传调控的理解,以及这些发现在指导治疗方法以预防或对抗由微生物-宿主相互作用受损引起的疾病方面的重要意义。
IF:12.200Q1 Gut microbes, 2022 Jan-Dec. DOI: 10.1080/19490976.2021.2022407 PMID: 35000562
Abstract:
The gastrointestinal tract is continuously exposed to trillions of commensal microbes, collectively termed the microbiota, which are environmental stimuli that can direct health and disease within the host. In addition … >>>
The gastrointestinal tract is continuously exposed to trillions of commensal microbes, collectively termed the microbiota, which are environmental stimuli that can direct health and disease within the host. In addition to well-established bacterial sensing pathways, microbial signals are also integrated through epigenetic modifications that calibrate the transcriptional program of host cells without altering the underlying genetic code. Microbiota-sensitive epigenetic changes include modifications to the DNA or histones, as well as regulation of non-coding RNAs. While microbiota-sensitive epigenetic mechanisms have been described in both local intestinal cells and as well in peripheral tissues, further research is required to fully decipher the complex relationship between the host and microbiota. This Review highlights current understandings of epigenetic regulation by gut microbiota and important implications of these findings in guiding therapeutic approaches to prevent or combat diseases driven by impaired microbiota-host interactions. <<<
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691.
Ricardo (2023-02-28 22:09):
#paper doi:https://doi.org/10.1016/0730-725X(90)90056-8 Simulation of the influence of magnetic field inhomogeneity and distortion correction in MR imaging. 这篇论文比较老了,1990年发表的。作者在这篇论文中描述了一个用于模拟和校正由静态和梯度磁场中干扰MRI体素位置和信号编码的技术。数学原理其实不复杂,主要思想就是确定映射到目标图像的某个体素左右邻边在源图像上的位置,从而确定在源图像上体素的采样范围,根据线性插值的方法对采样范围内的体素进行加权。本来我想把这个模型用到我自己的工作中,但是思考了好几天发现这个过程貌似无法在模型中传递梯度,遂作罢。
Abstract:
We describe a technique for simulation and correction of the effects of an arbitrary distribution of undesired components of the static and gradient magnetic fields. This technique is applicable to … >>>
We describe a technique for simulation and correction of the effects of an arbitrary distribution of undesired components of the static and gradient magnetic fields. This technique is applicable to direct Fourier NMR imaging. The mathematical basis and details of this technique are fully described. Computer simulation demonstrates the effectiveness of this method. <<<
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692.
muton (2023-02-28 22:04):
#paper DOI: 10.21203/rs.3.rs-2540186/v1 Sleep loss diminishes hippocampal reactivation and replay睡眠有助于记忆,如果学习后立即剥夺睡眠对随后的记忆储存有负面影响。一些著名的假说认为,在睡眠期间发生的离线记忆巩固过程中,海马的尖波涟漪(SWRs)以及清醒时的神经元模式的同时重新激活和记忆重放起着核心作用。然而,当动物被剥夺睡眠时,SWRs、重新激活和重放是如何被影响的,人们对此所知甚少。作者对大鼠海马CA1神经元进行了长时间(约12小时)、高密度的硅探针记录,在这些动物在暴露于一个新的迷宫环境后,一些进入睡眠状态,一些被剥夺睡眠。我们发现,在睡眠剥夺期间,SWRs显示出持续的活动率,类似于或高于自然睡眠,但尖锐波的振幅下降,同时波纹的频率更高。此外,虽然海马锥体细胞在睡眠期间显示出对数正态分布的放电频率,但这些分布是负偏斜的,在睡眠剥夺期间,锥体细胞和中间神经元的平均放电频率都较高。然而,在SWRs期间,两组的放电频率非常相似。尽管两组都有大量的SWRs,并有强烈的放电活动,但我们发现,与睡眠剥夺相比,神经元的重新激活在睡眠剥夺期间要么完全没有,要么明显减少。有趣的是,在恢复睡眠后,重新激活部分又出现,但未能达到自然睡眠的特征水平。同样,与自然睡眠相比,在睡眠剥夺和恢复性睡眠期间,重放的数量明显减少。这些结果为睡眠损失对海马功能的负面影响提供了一个网络层面的解释,并证明睡眠损失通过导致SWRs的数量与这些事件中发生的记忆重放和重新激活之间的分离来影响记忆储存。
Abstract:
Memories benefit from sleep, and sleep loss immediately following learning has a negative impact on subsequent memory storage. Several prominent hypotheses ascribe a central role to hippocampal sharp-wave ripples (SWRs), … >>>
Memories benefit from sleep, and sleep loss immediately following learning has a negative impact on subsequent memory storage. Several prominent hypotheses ascribe a central role to hippocampal sharp-wave ripples (SWRs), and the concurrent reactivation and replay of neuronal patterns from waking experience, in the offline memory consolidation process that occurs during sleep. However, little is known about how SWRs, reactivation, and replay are affected when animals are subjected to sleep deprivation. We performed long duration (~12 h), high-density silicon probe recordings from rat hippocampal CA1 neurons, in animals that were either sleeping or sleep deprived following exposure to a novel maze environment. We found that SWRs showed a sustained rate of activity during sleep deprivation, similar to or higher than in natural sleep, but with decreased amplitudes for the sharp-waves combined with higher frequencies for the ripples. Furthermore, while hippocampal pyramidal cells showed a log-normal distribution of firing rates during sleep, these distributions were negatively skewed with a higher mean firing rate in both pyramidal cells and interneurons during sleep deprivation. During SWRs, however, firing rates were remarkably similar between both groups. Despite the abundant quantity of SWRs and the robust firing activity during these events in both groups, we found that reactivation of neurons was either completely abolished or significantly diminished during sleep deprivation compared to sleep. Interestingly, reactivation partially rebounded upon recovery sleep, but failed to reach the levels characteristic of natural sleep. Similarly, the number of replays were significantly lower during sleep deprivation and recovery sleep compared to natural sleep. These results provide a network-level account for the negative impact of sleep loss on hippocampal function and demonstrate that sleep loss impacts memory storage by causing a dissociation between the amount of SWRs and the replays and reactivations that take place during these events. <<<
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693.
尹志 (2023-02-28 21:51):
#paper https://doi.org/10.48550/arXiv.2203.17003 ICML, 2022, Equivariant Diffusion for Molecule Generation in 3D。扩散模型在各个领域发展极其迅速。除了图形图像,其触角已经扩展到生物制药、材料科学领域。本文就是一篇使用扩散模型进行3D分子生成的文章。作者提出了一种等变扩散模型,其中的等变网络能够很好的同时处理原子坐标这样的连续变量和原子类型这样的离散变量。该工作在QM9和GEOM两个典型的数据集上取得了sota的性能,是将等变性引入扩散模型的开篇工作之一。
Abstract:
This work introduces a diffusion model for molecule generation in 3D that is equivariant to Euclidean transformations. Our E(3) Equivariant Diffusion Model (EDM) learns to denoise a diffusion process with … >>>
This work introduces a diffusion model for molecule generation in 3D that is equivariant to Euclidean transformations. Our E(3) Equivariant Diffusion Model (EDM) learns to denoise a diffusion process with an equivariant network that jointly operates on both continuous (atom coordinates) and categorical features (atom types). In addition, we provide a probabilistic analysis which admits likelihood computation of molecules using our model. Experimentally, the proposed method significantly outperforms previous 3D molecular generative methods regarding the quality of generated samples and efficiency at training time. <<<
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林海onrush (2023-02-28 21:45):
#paper,doi: https://doi.org/10.1038/s41586-023-05859-2,Continuous Symmetry Breaking in a Two-dimensional Rydberg Array,,自发对称性破坏是对物质相位及其相关跃迁进行分类的基础。被打破的潜在对称性的性质决定了相的许多定性特性;离散与连续对称性破坏的情况说明了这一点。与离散情况相反,连续对称性的破坏导致无间隙Goldstone模式的出现,例如控制有序相的热力学稳定性.作者利用可编程的里德伯量子模拟器实现了二维偶极XY模型,展示了XY铁磁体和XY反铁磁体相关低温态的绝热制备。在铁磁情况下,表征了长程XY阶的存在。这项工作对XY相互作用的多体物理学做出了贡献,补充了最近利用里德伯-封锁机制实现表现出离散自旋旋转对称性的Ising型相互作用的工作。该文近期被收录于nature,也证实了工作的严谨和创新。
IF:50.500Q1 Nature, 2023-04. DOI: 10.1038/s41586-023-05859-2 PMID: 36848931
Abstract:
Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions. The nature of the underlying symmetry being broken determines many of the qualitative properties … >>>
Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions. The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase. Here, we realize a two-dimensional dipolar XY model that shows a continuous spin-rotational symmetry using a programmable Rydberg quantum simulator. We demonstrate the adiabatic preparation of correlated low-temperature states of both the XY ferromagnet and the XY antiferromagnet. In the ferromagnetic case, we characterize the presence of a long-range XY order, a feature prohibited in the absence of long-range dipolar interaction. Our exploration of the many-body physics of XY interactions complements recent works using the Rydberg-blockade mechanism to realize Ising-type interactions showing discrete spin rotation symmetry. <<<
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695.
Arwen (2023-02-28 21:39):
#paper https://doi.org/10.1038/s41467-023-36605-x Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis 最近在影像遗传学方面的工作表明,皮层区域内皮层厚度(CT)和表面积(SA)的遗传重叠程度很高。该研究通过应用基因组结构方程模型(Genomic SEM)对这一遗传关系的多变量系统进行建模,并对CT和SA的五个脑部基因组因素以及一个捕捉所有脑区遗传重叠的一般因素进行解析。我们通过证明该模型在独立样本中的普遍性来验证这些因素,并表明这些因素与脑皮层的生物和功能相关分区相一致。我们应用分层基因组SEM来确定特定类别的基因(如神经元细胞类型),这些基因与脑区特定亚群的多态性成正比关系。最后,研究了与精神和认知相关的遗传关系,发现认知功能的广泛与SA的一般因素有关,而与精神方面的关系不明显。这些分析提供了脑皮层两个关键特征的多变量基因组结构的关键见解。
IF:14.700Q1 Nature communications, 2023-02-20. DOI: 10.1038/s41467-023-36605-x PMID: 36806290
Abstract:
Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships … >>>
Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) and parsimoniously define five genomic brain factors underlying both CT and SA along with a general factor capturing genetic overlap across all brain regions. We validate these factors by demonstrating the generalizability of the model to a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex. We apply Stratified Genomic SEM to identify specific categories of genes (e.g., neuronal cell types) that are disproportionately associated with pleiotropy across specific subclusters of brain regions, as indexed by the genomic factors. Finally, we examine genetic associations with psychiatric and cognitive correlates, finding that broad aspects of cognitive function are associated with a general factor for SA and that psychiatric associations are null. These analyses provide key insights into the multivariate genomic architecture of two critical features of the cerebral cortex. <<<
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696.
白鸟 (2023-02-28 21:23):
#paper doi:https://doi.org/10.1038/s41587-021-00895-7, 2021, Nonvolatile Memory Based on Nonlinear Magnetoelectric Effects. 单细胞多模态检测技术:通过各种实验技术进行多模态检测,即在同一个细胞中同时探测不同的分子特征,在高分辨率下,成千上万的细胞拥有越来越多的分子维度,包括基因组、转录组和表观遗传修饰。虽然没有一个单一的“全能”技术可以完全捕捉到复杂的分子机制,但这些数据有可能提供一个基本的生物过程,有机会从描述性的 "快照 "向对基因调控的机械性理解推进。 意义:单细胞多模态检测技术的发展为研究细胞异质性的多个维度提供了强有力的工具,使我们对发育、组织稳态和疾病有了新的认识。通过结合关于分子层之间层次关系的先验知识(即生物学的中心法则),多模式分析将在识别基因调控网络中事件的因果链方面发挥重要作用。 挑战:设计适当的策略,将不同模式的数据联系起来。术语 "数据整合 "(data integration)被用来描述这项工作,这个定义很广泛,从单个组学数据集的批量校正到染色质可及性和遗传变异与转录的关联。 三种类型的数据整合策略:基因组特征作为锚点(水平整合);细胞为锚(垂直整合);高维空间没有锚点(对角线整合); 展望:回顾了数据整合策略的既定原则、局限性,尽管现有的整合策略利用了类似的数学思想,但它们通常有不同的目标,并依赖于不同的原则和假设。因此,需要新的定义和概念,以使单细胞数据整合技术具有本身的背景性,并能开发新的方法。
IF:33.100Q1 Nature biotechnology, 2021-10. DOI: 10.1038/s41587-021-00895-7 PMID: 33941931
Abstract:
The development of single-cell multimodal assays provides a powerful tool for investigating multiple dimensions of cellular heterogeneity, enabling new insights into development, tissue homeostasis and disease. A key challenge in … >>>
The development of single-cell multimodal assays provides a powerful tool for investigating multiple dimensions of cellular heterogeneity, enabling new insights into development, tissue homeostasis and disease. A key challenge in the analysis of single-cell multimodal data is to devise appropriate strategies for tying together data across different modalities. The term 'data integration' has been used to describe this task, encompassing a broad collection of approaches ranging from batch correction of individual omics datasets to association of chromatin accessibility and genetic variation with transcription. Although existing integration strategies exploit similar mathematical ideas, they typically have distinct goals and rely on different principles and assumptions. Consequently, new definitions and concepts are needed to contextualize existing methods and to enable development of new methods. <<<
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697.
LXJ (2023-02-28 21:22):
#paper DOI : 10.3390/vaccines11020408 Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms 2019年冠状病毒(新冠肺炎)大流行是由一种ssRNA严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的。然而,其他人类冠状病毒(hCoV)也存在。历史上的大流行病包括天花和流感,通过有效地针对宿主免疫系统的反应,利用有效的治疗方法来减轻总体疾病负担。免疫系统由初级/次级淋巴结构组成,最初有八种免疫细胞类型,以及许多其他亚型,利用细胞信号级联穿过细胞膜,有助于清除致病蛋白。讨论的其他蛋白质包括分化簇(CD)标记物、主要组织相容性复合物(MHC)、多效性白细胞介素(IL)和趋化因子(CXC)。宿主免疫的历史概念是先天和适应性免疫系统。适应性免疫系统由T细胞、B细胞和抗体代表。先天免疫系统由巨噬细胞、中性粒细胞、树突状细胞和补体系统组成。其他病毒可以影响和调节细胞周期进展,例如,在包括人乳头瘤病毒(HPV:宫颈癌)、EB病毒(EBV:淋巴瘤)、乙型肝炎和丙型肝炎(HB/HC:肝细胞癌)和人T细胞白血病病毒-1(T细胞白血病)的癌症中。细菌感染也会增加患癌症的风险(例如幽门螺杆菌)。病毒和细菌因素可导致发病率和死亡率,并通过影响宿主免疫反应在临床和社区环境中传播。因此,将单细胞测序的进展与其他实验室技术结合起来,有助于深入了解免疫细胞特征。这些发展提供了与自身免疫性疾病重叠的更好的清晰度和理解,这些疾病可能受到先天性B细胞(B1+或边缘区细胞)或对SARS-CoV-2感染和其他病理的适应性T细胞反应的影响。因此,这篇综述首先介绍了宿主呼吸道感染,然后检查了宝贵的细胞信使蛋白和个体免疫细胞标记物。
IF:5.200Q1 Vaccines, 2023-Feb-10. DOI: 10.3390/vaccines11020408 PMID: 36851285
Abstract:
The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include … >>>
The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting a competent host immune system response. The immune system is composed of primary/secondary lymphoid structures with initially eight types of immune cell types, and many other subtypes, traversing cell membranes utilizing cell signaling cascades that contribute towards clearance of pathogenic proteins. Other proteins discussed include cluster of differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), and chemokines (CXC). The historical concepts of host immunity are the innate and adaptive immune systems. The adaptive immune system is represented by T cells, B cells, and antibodies. The innate immune system is represented by macrophages, neutrophils, dendritic cells, and the complement system. Other viruses can affect and regulate cell cycle progression for example, in cancers that include human papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis B and C (HB/HC: hepatocellular carcinoma) and human T cell Leukemia Virus-1 (T cell leukemia). Bacterial infections also increase the risk of developing cancer (e.g., ). Viral and bacterial factors can cause both morbidity and mortality alongside being transmitted within clinical and community settings through affecting a host immune response. Therefore, it is appropriate to contextualize advances in single cell sequencing in conjunction with other laboratory techniques allowing insights into immune cell characterization. These developments offer improved clarity and understanding that overlap with autoimmune conditions that could be affected by innate B cells (B1 or marginal zone cells) or adaptive T cell responses to SARS-CoV-2 infection and other pathologies. Thus, this review starts with an introduction into host respiratory infection before examining invaluable cellular messenger proteins and then individual immune cell markers. <<<
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惊鸿 (2023-02-28 21:15):
#paper DOI : 10.1021/acsnano.2c10477 Floating Seawater Splitting Device Based on NiFeCrMo Metal Hydroxide Electrocatalyst and Perovskite/Silicon Tandem Solar Cells 海水光伏制氢意义重大。太阳能驱动海水电解面临的析氯反应竞争、氯化物腐蚀、催化剂中毒等挑战严重制约了该技术的发展。在本文中,我们报道了一种由 Ni、Fe、Cr 和 Mo 元素组成的二维纳米片季金属氢氧化物催化剂。通过原位电化学活化,部分钼元素在催化剂中被浸出并发生形态转变。获得了更高的金属价态和许多 O 空位,在工业要求的 500 mA cm –2 电流密度下,在整体碱性海水电解中提供了优异的催化活性和耐腐蚀性在室温下 1.82 V 低电压下超过 1000 小时。漂浮的太阳能海水分解装置显示出 20.61 ± 0.77% 的太阳能制氢 (STH) 效率。这项工作展示了高效太阳能海水电解装置的发展,并可能促进清洁能源转换的研究。
IF:15.800Q1 ACS nano, 2023-Mar-14. DOI: 10.1021/acsnano.2c10477 PMID: 36808966
Abstract:
Photovoltaic hydrogen production from seawater is of great significance. Challenges of solar-driven seawater electrolysis, for example, competing among chlorine evolution reactions, chloride corrosion, and catalyst poisoning, seriously restrict the development … >>>
Photovoltaic hydrogen production from seawater is of great significance. Challenges of solar-driven seawater electrolysis, for example, competing among chlorine evolution reactions, chloride corrosion, and catalyst poisoning, seriously restrict the development of this technology. In this paper, we report a two-dimensional nanosheet quaternary metal hydroxide catalyst composed of Ni, Fe, Cr, and Mo elements. By in situ electrochemical activation, a partial Mo element was leached and morphologically transformed in the catalyst. The higher metal valence states and many O vacancies were obtained, providing excellent catalytic activity and corrosion resistance in overall alkaline seawater electrolysis operating at an industrial-required current density of 500 mA cm over 1000 h under 1.82 V low voltages at room temperature. The floating solar seawater splitting device shows a 20.61 ± 0.77% efficiency of solar energy to hydrogen (STH). This work demonstrates the development of efficient solar seawater electrolysis devices and potentially promotes research on clean energy conversion. <<<
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699.
符毓 (2023-02-28 21:08):
#paper https://doi.org/10.1103/PhysRevApplied.6.021001 Physical Review Applied, 2016, Nonvolatile Memory Based on Nonlinear Magnetoelectric Effects。在过去的十年中,已经提出和探索了多种多铁性或磁电存储器的概念。此文提出了一种基于多铁性磁电系数 (α) 的多种状态来实现多级非易失性存储器的新原理。 这种多级磁电存储器保留了铁电随机存取存储器的所有优点,并克服了极化破坏性读取的缺点。
Abstract:
The magnetoelectric effects in multiferroics have a great potential in creating next-generation memory devices. We use an alternative concept of nonvolatile memory based, on a type of nonlinear magnetoelectric effects … >>>
The magnetoelectric effects in multiferroics have a great potential in creating next-generation memory devices. We use an alternative concept of nonvolatile memory based, on a type of nonlinear magnetoelectric effects showing a butterfly-shaped hysteresis loop. The principle is to utilize the states of the magnetoelectric coefficient, instead of magnetization, electric polarization, or resistance, to store binary information. Our experiments in a device made of the PMN-PT/Terfenol- D multiferroic heterostructure clearly demonstrate that the sign of the magnetoelectric coefficient can be repeatedly switched between positive and negative by applying electric fields, confirming the feasibility of this principle. This kind of nonvolatile memory has outstanding practical virtues such as simple structure, easy operation in writing and reading, low power, fast speed, and diverse materials available. <<<
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庞庞 (2023-02-28 21:02):
#paper doi:https://doi.org/10.1038/nn.4164 Parcellating cortical functional networks in individuals 大脑网络的位置、大小等属性具有个体差异。之前的研究忽略了这些差异,运用组水平的分区模板计算功能连接矩阵,导致功能连接个体间差异的混淆。本研究是第一个提出个体化功能网络的研究,基于组水平网络分区模板迭代的思路,获得了具有可重复性、可以捕捉个体间差异、可通过电刺激验证的功能网络个体化分区,为我们进行个体化功能网络的研究提供了新思路。
IF:21.200Q1 Nature neuroscience, 2015-Dec. DOI: 10.1038/nn.4164 PMID: 26551545
Abstract:
The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and … >>>
The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and behavior. Here we developed a cortical parcellation approach to accurately map functional organization at the individual level using resting-state functional magnetic resonance imaging (fMRI). A population-based functional atlas and a map of inter-individual variability were employed to guide the iterative search for functional networks in individual subjects. Functional networks mapped by this approach were highly reproducible within subjects and effectively captured the variability across subjects, including individual differences in brain lateralization. The algorithm performed well across different subject populations and data types, including task fMRI data. The approach was then validated by invasive cortical stimulation mapping in surgical patients, suggesting potential for use in clinical applications. <<<
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