当前共找到 1317 篇文献分享,本页显示第 701 - 720 篇。
701.
AI 5.0.3
(2023-03-31 20:44):
#paper 主要内容:快速伽马震荡精准协调上下神经系统,分别从海马外内侧收集神经元信息传入海马实现在物体识别和方位判断的作用。主要结论:空间导航中快伽马震荡协调齿状回和MEC,慢伽马震荡协调齿状回和LEC,MEC和LEC的信息以伽马周期对任务进行特异性选择。A. Fernández-Ruiz et al., Science 372, eabf3119 (2021). DOI: 10.1126/science.abf3119
Abstract:
Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat …
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Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner. Gamma perturbation disrupted the learning-induced assembly organization of target neurons. Our findings imply that pathway-specific gamma oscillations route task-relevant information between distinct neuronal subpopulations in the entorhinal-hippocampal circuit. We hypothesize that interregional gamma-time-scale spike coordination is a mechanism of neuronal communication.
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702.
cellsarts
(2023-03-31 19:54):
#Paper https://doi.org/10.1038/s41396-022-01195-x 海底热液羽流中硫氧化细菌(SUP05)的生态位分化 Niche differentiation of sulfur-oxidizing bacteria (SUP05) in submarine hydrothermal plumes热液柱将还原态的化学物质和金属输送到开阔的海洋中。尽管它们对生物地球化学循环有广泛及巨大的影响,但对热液柱之中的丰富的微生物演化支的生态位分化知之甚少。在这里,我们分析了在南太平洋的克马德克海内弧上两个热泉的——(兄弟火山;brv锥和西北破火山口;NWC)和中海火山(Macauley火山;McV)絮凝物物微生物生态。通过结合16S rRNA基因、荧光原位杂交和宏基因组分析确定的微生物群落结构与在其他富硫羽流中观察到的群落相似。这包括排硫特征的SUP05分支的优势(在McV中高达22%,在BrV中高达51%)。在分析的三个羽中,群落由不同的尚未培养的化学自养SUP05物种主导,这里暂时命名为Candidatus Thioglobus vadi (McV), Candidatus thiglobus vulcanius (BrV-cone)和Candidatus thiglobus plumae (BrV-NWC)。统计分析、基因组潜能和mRNA表达谱表明,SUP05的生态位划分基于硫化物和铁浓度以及水深。第四种SUP05在整个研究的絮凝状样品中出现频率很低,可能具有异养或混合生长的能力。综上所述,我们认为环境参数和深度的微小变化推动了热液柱中SUP05生态位的划分。
Abstract:
Hydrothermal plumes transport reduced chemical species and metals into the open ocean. Despite their considerable spatial scale and impact on biogeochemical cycles, niche differentiation of abundant microbial clades is poorly …
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Hydrothermal plumes transport reduced chemical species and metals into the open ocean. Despite their considerable spatial scale and impact on biogeochemical cycles, niche differentiation of abundant microbial clades is poorly understood. Here, we analyzed the microbial ecology of two bathy- (Brothers volcano; BrV-cone and northwest caldera; NWC) and a mesopelagic (Macauley volcano; McV) plumes on the Kermadec intra-oceanic arc in the South Pacific Ocean. The microbial community structure, determined by a combination of 16S rRNA gene, fluorescence in situ hybridization and metagenome analysis, was similar to the communities observed in other sulfur-rich plumes. This includes a dominance of the vent characteristic SUP05 clade (up to 22% in McV and 51% in BrV). In each of the three plumes analyzed, the community was dominated by a different yet uncultivated chemoautotrophic SUP05 species, here, provisionally named, Candidatus Thioglobus vadi (McV), Candidatus Thioglobus vulcanius (BrV-cone) and Candidatus Thioglobus plumae (BrV-NWC). Statistical analyses, genomic potential and mRNA expression profiles suggested a SUP05 niche partitioning based on sulfide and iron concentration as well as water depth. A fourth SUP05 species was present at low frequency throughout investigated plume samples and may be capable of heterotrophic or mixotrophic growth. Taken together, we propose that small variations in environmental parameters and depth drive SUP05 niche partitioning in hydrothermal plumes.
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703.
LXJ
(2023-03-31 19:51):
#paper Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection. Cell. 2022 Oct 27;185(22):4170-4189.e20. doi: 10.1016/j.cell.2022.09.008. 伤害性疼痛是许多慢性炎症性疾病的标志,包括炎症性肠病(IBD);然而,痛觉神经元是否会影响肠道炎症仍不清楚。利用化学遗传学沉默、腺病毒介导的结肠特异性沉默和TRPV1+伤害感受器的药理学消融,我们在肠道损伤和炎症的小鼠模型中观察到更严重的炎症和有缺陷的组织保护性修复过程。破坏的伤害感受导致肠道微生物群的显著改变和可传播的微生态失调,而革兰氏+梭菌对无菌小鼠的单定殖。通过伤害感受器依赖性途径促进肠道组织保护。从机制上讲,伤害感受的破坏导致P物质水平下降,而P物质的治疗性递送以微生物群依赖的方式促进了TRPV1+伤害感受器发挥的组织保护作用。最后,在IBD患者的肠道活检中观察到伤害感受器基因表达失调。总之,这些发现表明,伤害感受、肠道微生物群和肠道稳态恢复之间存在进化上保守的功能联系。
Abstract:
Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific …
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Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1 nociceptors, we observed more severe inflammation and defective tissue-protective reparative processes in a murine model of intestinal damage and inflammation. Disrupted nociception led to significant alterations in the intestinal microbiota and a transmissible dysbiosis, while mono-colonization of germ-free mice with GramClostridium spp. promoted intestinal tissue protection through a nociceptor-dependent pathway. Mechanistically, disruption of nociception resulted in decreased levels of substance P, and therapeutic delivery of substance P promoted tissue-protective effects exerted by TRPV1 nociceptors in a microbiota-dependent manner. Finally, dysregulated nociceptor gene expression was observed in intestinal biopsies from IBD patients. Collectively, these findings indicate an evolutionarily conserved functional link between nociception, the intestinal microbiota, and the restoration of intestinal homeostasis.
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704.
半面阳光
(2023-03-31 19:02):
#paper DOI: 10.1016/j.ajhg.2012.12.006, Am J Hum Genet. 2013, Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. 基于NGS的NIPT检测染色体非整倍体技术建立之后,进一步的研究重点和热点之一是将NIPT从检测染色体非整倍体拓展到检测染色体上的微缺失微重复片段。这篇文献可能是首次系统性建立用于检测微缺失和微重复的NIPT方法学文章。
IF:8.100Q1
American journal of human genetics,
2013-Feb-07.
DOI: 10.1016/j.ajhg.2012.12.006
PMID: 23313373
Abstract:
The purpose of this study was to determine the deep sequencing and analytic conditions needed to detect fetal subchromosome abnormalities across the genome from a maternal blood sample. Cell-free (cf) …
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The purpose of this study was to determine the deep sequencing and analytic conditions needed to detect fetal subchromosome abnormalities across the genome from a maternal blood sample. Cell-free (cf) DNA was isolated from the plasma of 11 pregnant women carrying fetuses with subchromosomal duplications and deletions, translocations, mosaicism, and trisomy 20 diagnosed by metaphase karyotype. Massively parallel sequencing (MPS) was performed with 25-mer tags at approximately 10(9) tags per sample and mapped to reference human genome assembly hg19. Tags were counted and normalized to fixed genome bin sizes of 1 Mb or 100 kb to detect statistically distinct copy-number changes compared to the reference. All seven cases of microdeletions, duplications, translocations, and the trisomy 20 were detected blindly by MPS, including a microdeletion as small as 300 kb. In two of these cases in which the metaphase karyotype showed additional material of unknown origin, MPS identified both the translocation breakpoint and the chromosomal origin of the additional material. In the four mosaic cases, the subchromosomal abnormality was not demonstrated by MPS. This work shows that in nonmosaic cases, it is possible to obtain a fetal molecular karyotype by MPS of maternal plasma cfDNA that is equivalent to a chromosome microarray and in some cases is better than a metaphase karyotype. This approach combines the advantage of enhanced fetal genomic resolution with the improved safety of a noninvasive maternal blood test.
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705.
小W
(2023-03-31 16:57):
#paper doi:https://doi.org/10.1038/s41576-022-00511-7 Measuring biological age using omics data.
生物老化是随着实际年龄的增长而发生的系统完整性进行性下降 ,最终导致疾病、残疾和死亡。本文是利用组学数据量化生物衰老方法(衰老时钟)研究的综述文章,介绍了表观遗传、转录组学、蛋白质组学、代谢组学等方面衰老时钟的研究原理、局限性和优化。比较有意思的一点,第一代表观时钟彼此之间只有轻微的相关性,增大样本量的情况下训练第一代甲基化时钟过拟合,又消除了年龄和生物学年龄之间的联系。这里提出对之后开发衰老时钟的展望,定义衰老时钟的应用场景,通过有目的的特征选择或通过开发复合训练指标,将衰老生物学的特定方面纳入其中的建模方法应有助于提高模型的可解释性,并指导它们识别衰老的因果特征。一个大胆的方法是在时钟的训练中排除年龄,从而更接近于测量老化生物学特征。
Abstract:
Age is the key risk factor for diseases and disabilities of the elderly. Efforts to tackle age-related diseases and increase healthspan have suggested targeting the ageing process itself to 'rejuvenate' …
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Age is the key risk factor for diseases and disabilities of the elderly. Efforts to tackle age-related diseases and increase healthspan have suggested targeting the ageing process itself to 'rejuvenate' physiological functioning. However, achieving this aim requires measures of biological age and rates of ageing at the molecular level. Spurred by recent advances in high-throughput omics technologies, a new generation of tools to measure biological ageing now enables the quantitative characterization of ageing at molecular resolution. Epigenomic, transcriptomic, proteomic and metabolomic data can be harnessed with machine learning to build 'ageing clocks' with demonstrated capacity to identify new biomarkers of biological ageing.
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706.
小年
(2023-03-31 15:44):
#paper doi: 10.3389/fonc.2021.641487. Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis. Front Oncol. 2021; 11: 641487.
这篇文章基于88个内质网应激(ERS)相关基因,用Cox回归分析鉴定了肝癌中由5个ERS基因组成的预后生物标志物,并构建预后模型,同时评估模型的性能。其次分析了临床信息与生存预后的关系,识别了独立预后因素并建立预测列线图。还对5个预后基因做了多组学分析(包括mutation、methylation、copy number、post-transcriptional regulation)。
该文值得我们借鉴的是不局限于RNA-seq层面开发预后模型,不仅从多组学维度分析了这些ERS基因在促进肝癌的作用,最后还讨论了关于数据库中一些重要参数和临床资料的局限性,对我们以后的研究有一些启发。
Abstract:
Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding …
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Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.
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707.
Vincent
(2023-03-31 15:34):
#paper https://doi.org/10.48550/arXiv.1904.10098 ICML 2019 DAG-GNN: DAG Structure Learning with Graph Neural Networks. 有向无环图(DAG)的结构学习是一项十分具有挑战性的工作,其搜索空间随着节点数的增多而呈现指数式的增长。常用的研究手段是将结构学习转化为一种score的优化问题。为了让问题可解,传统的方法通常考虑线性结构方程模型(Linear SEM),这篇文章基于线性SEM的框架,发展了一套基于变分自编码器VAE和图神经网络GNN的DAG学习方法,得益于神经网络的非线性拟合,这套方法在保证至少比线性SEM好的情况下还能解决一些非线性的问题。通过数据仿真和真实数据的学习,文章验证了该方法的准确度比线性SEM好,假发现率比线性SEM低。
arXiv,
2019.
DOI: 10.48550/arXiv.1904.10098
Abstract:
Learning a faithful directed acyclic graph (DAG) from samples of a joint distribution is a challenging combinatorial problem, owing to the intractable search space superexponential in the number of graph …
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Learning a faithful directed acyclic graph (DAG) from samples of a joint distribution is a challenging combinatorial problem, owing to the intractable search space superexponential in the number of graph nodes. A recent breakthrough formulates the problem as a continuous optimization with a structural constraint that ensures acyclicity (Zheng et al., 2018). The authors apply the approach to the linear structural equation model (SEM) and the least-squares loss function that are statistically well justified but nevertheless limited. Motivated by the widespread success of deep learning that is capable of capturing complex nonlinear mappings, in this work we propose a deep generative model and apply a variant of the structural constraint to learn the DAG. At the heart of the generative model is a variational autoencoder parameterized by a novel graph neural network architecture, which we coin DAG-GNN. In addition to the richer capacity, an advantage of the proposed model is that it naturally handles discrete variables as well as vector-valued ones. We demonstrate that on synthetic data sets, the proposed method learns more accurate graphs for nonlinearly generated samples; and on benchmark data sets with discrete variables, the learned graphs are reasonably close to the global optima. The code is available at \url{this https URL}.
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708.
庞庞
(2023-03-31 15:06):
#paper https://doi.org/10.1038/s41380-023-01958-8 Individualized fMRI connectivity defines signatures of antidepressant and placebo responses in major depression
由于个体的异质性,不同个体对抗抑郁药物的缓释程度各有不同。因此,理解抗抑郁药物的作用机制对个性化医疗至关重要。本文采用去除组成分的COBE算法,获得个体化的功能连接矩阵,作为特征对抗抑郁药物舍曲林和安慰剂的疗效进行预测。研究发现,个体化的功能连接比起组水平的功能连接显著提高了预测准确率;对预测舍曲林贡献高的脑区主要位于左侧颞中皮层和右侧脑岛;对安慰剂贡献高的主要位于双侧扣带皮层和左侧颞上皮层。这位抗抑郁的疗效预测标志物提供了新视角。
Abstract:
Though sertraline is commonly prescribed in patients with major depressive disorder (MDD), its superiority over placebo is only marginal. This is in part due to the neurobiological heterogeneity of the …
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Though sertraline is commonly prescribed in patients with major depressive disorder (MDD), its superiority over placebo is only marginal. This is in part due to the neurobiological heterogeneity of the individuals. Characterizing individual-unique functional architecture of the brain may help better dissect the heterogeneity, thereby defining treatment-predictive signatures to guide personalized medication. In this study, we investigate whether individualized brain functional connectivity (FC) can define more predictable signatures of antidepressant and placebo treatment in MDD. The data used in the present work were collected by the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study. Patients (N = 296) were randomly assigned to antidepressant sertraline or placebo double-blind treatment for 8 weeks. The whole-brain FC networks were constructed from pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI). Then, FC was individualized by removing the common components extracted from the raw baseline FC to train regression-based connectivity predictive models. With individualized FC features, the established prediction models successfully identified signatures that explained 22% variance for the sertraline group and 31% variance for the placebo group in predicting HAMD change. Compared with the raw FC-based models, the individualized FC-defined signatures significantly improved the prediction performance, as confirmed by cross-validation. For sertraline treatment, predictive FC metrics were predominantly located in the left middle temporal cortex and right insula. For placebo, predictive FC metrics were primarily located in the bilateral cingulate cortex and left superior temporal cortex. Our findings demonstrated that through the removal of common FC components, individualization of FC metrics enhanced the prediction performance compared to raw FC. Associated with previous MDD clinical studies, our identified predictive biomarkers provided new insights into the neuropathology of antidepressant and placebo treatment.
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709.
Spring
(2023-03-31 13:10):
#paper doi: 10.15252/emmm.202317450
EMBO Molecular Medicine[IF:14.26]
① 纳入两个独立的队列人群,比较了早发性卵巢功能不全(POI)女性血清代谢组学,发现其表现为支链氨基酸(BCAA)不足相关的代谢紊乱;② 在小鼠模型中,低BCAA饮食干预使年轻小鼠出现POI样的代谢、内分泌、卵巢和生殖变化;③ 细胞实验表明,BCAA不足会上调神经酰胺,诱导ROS升高,从而使卵巢颗粒细胞功能受损;④ 有趣的是,BCAA膳食补充可以阻止雌性小鼠ROS诱导的POI发展,提示其预防价值。
BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS
Abstract:
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone. Though POI affects many aspects of women's …
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Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch-chain amino acid (BCAA) insufficiency-related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency-induced POI is associated with abnormal activation of the ceramide-reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
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710.
尹志
(2023-03-31 00:12):
#paper https://doi.org/10.1038/s41586-023-05870-7. Nature, 2023, Programmable protein delivery with a
bacterial contractile injection system。这是今年张锋组的一篇新文章。文章介绍了一种叫做外胞质收缩注射系统(eCISs)的纳米机器,它们可以被重新编程以针对人类细胞并传递各种蛋白质负载,包括Cas9、碱基编辑器和毒素。这些系统可以用于基因治疗、癌症治疗和生物控制等领域。还讨论了利用收缩注射系统(CIS)作为蛋白质传递和基因编辑的潜在工具以及它们在生物技术和医学中的应用。基本都是实验,方法部分简直大开眼界,琳琅满目,基本看不懂;但看结论还是觉得挺有前瞻性的工作,而且使用了AF技术作为structure-guided engineering,这个很引起我的兴趣。总之,先浅浅仰慕读一下
Abstract:
Endosymbiotic bacteria have evolved intricate delivery systems that enable these organisms to interface with host biology. One example, the extracellular contractile injection systems (eCISs), are syringe-like macromolecular complexes that inject …
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Endosymbiotic bacteria have evolved intricate delivery systems that enable these organisms to interface with host biology. One example, the extracellular contractile injection systems (eCISs), are syringe-like macromolecular complexes that inject protein payloads into eukaryotic cells by driving a spike through the cellular membrane. Recently, eCISs have been found to target mouse cells, raising the possibility that these systems could be harnessed for therapeutic protein delivery. However, whether eCISs can function in human cells remains unknown, and the mechanism by which these systems recognize target cells is poorly understood. Here we show that target selection by the Photorhabdus virulence cassette (PVC)-an eCIS from the entomopathogenic bacterium Photorhabdus asymbiotica-is mediated by specific recognition of a target receptor by a distal binding element of the PVC tail fibre. Furthermore, using in silico structure-guided engineering of the tail fibre, we show that PVCs can be reprogrammed to target organisms not natively targeted by these systems-including human cells and mice-with efficiencies approaching 100%. Finally, we show that PVCs can load diverse protein payloads, including Cas9, base editors and toxins, and can functionally deliver them into human cells. Our results demonstrate that PVCs are programmable protein delivery devices with possible applications in gene therapy, cancer therapy and biocontrol.
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711.
白鸟
(2023-03-30 17:22):
#paper https://www.cell.com/cell/fulltext/S0092-8674(21)01381-7. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps. 此文是人类肿瘤图谱网络(HTAN)联盟两年多时间在CRC肿瘤领域发的2篇cell文章之一,另一篇文章是构建肿瘤空间3D图谱。该联盟的愿景是构建肿瘤的发生、局部扩张、转移和治疗性耐药的动态3D图谱。该文章的切入点很重要,通过已有文献猜想两条CRC癌变的不同机制,提出了一个整合了单细胞转录组学、基因组学和免疫组织病理学的多组学人类癌前图谱。从功能上验证了建立不同的肿瘤景观的不同起源和分子机制过程。也是该联盟的策略从病变起源来研究,才能对晚期和高度异质性的癌症有更清晰的认识,从而为精准预防、监测和治疗的新策略铺平道路。对于多组学文章,切入点(科学猜想)和策略很重要。
Abstract:
Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell …
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Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC.
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712.
徐炳祥
(2023-03-30 13:13):
#paper doi: 10.1101/gad.333708.119. Genes Dev, 2020, Upon microbial challenge, human neutrophils undergo rapid changes in nuclear architecture and chromatin folding to orchestrate an immediate inflammatory gene program。中性粒细胞免疫应答过程中伴随着核型和染色质构象的剧烈变化,这些变化与免疫应答诱导的转录调控过程之间的关系尚不清楚。本文使用人类中性粒细胞为实验材料,以PMA和大肠杆菌为刺激源诱发免疫反应,以Hi-C测定应答前后的染色质空间构象并进行比较。结果显示,应答之前,炎性基因处于转录抑制的空间构象中,应答后这些基因所在区域发生常染色质化,由核周进入核内部,并与增强子靠近,这些过程与应答过程中转录的快速响应有关。这些染色质构象的重排可能是由cohesin驱动的。本研究处理时长已达3h,但仍未见染色质构象的大范围改变。这些结论提示虽然染色质构象的全基因组重构是罕见事件,其局部的改变依然有研究的价值。
Abstract:
Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior …
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Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior to encounter with bacteria, an armamentarium of inflammatory genes was positioned in a transcriptionally passive environment suppressing premature transcriptional activation. Upon microbial exposure, however, human neutrophils rapidly (<3 h) repositioned the ensemble of proinflammatory genes toward the transcriptionally permissive compartment. We show that the repositioning of genes was closely associated with the swift recruitment of cohesin across the inflammatory enhancer landscape, permitting an immediate transcriptional response upon bacterial exposure. We found that activated enhancers, marked by increased deposition of H3K27Ac, were highly enriched for cistromic elements associated with PU.1, CEBPB, TFE3, JUN, and FOSL2 occupancy. These data reveal how upon microbial challenge the cohesin machinery is recruited to an activated enhancer repertoire to instruct changes in chromatin folding, nuclear architecture, and to activate an inflammatory gene program.
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713.
符毓
(2023-03-30 12:59):
#paper doi:10.1016/j.joule.2020.07.014, Joule, 2020, Ultrasonic Scanning to Observe Wetting and “Unwetting” in Li-Ion Pouch Cells。锂电池的非破坏性检测方式较少见,X射线检测在电极材料结构、尺寸和热机械效应等有应用,但对于电解质和内部气体不敏感;本文主要探讨用超声方式进行检测的可行性
Abstract:
An ultrasonic imaging technique has been developed to investigate the internal changes of pouch cells nondestructively. The local ultrasonic transmittance of pouch cells has been measured and used for imaging …
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An ultrasonic imaging technique has been developed to investigate the internal changes of pouch cells nondestructively. The local ultrasonic transmittance of pouch cells has been measured and used for imaging with a new ultrasonic scanning machine designed and built in-house. The wetting process of the cells is clearly observed via such ultrasonic imaging techniques. Furthermore, ultrasonic transmission images of fresh cells and aged cells with different electrolytes and cycling conditions exhibit very different ultrasonic transmittance, which can be caused by electrolyte dry-out or “unwetting” due to cell swelling. The ultrasonic imaging technique is a very sensitive method to probe failure mechanisms in Li-ion pouch cells.
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714.
李翛然
(2023-03-28 21:41):
#paper A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers doi: 10.1038/s41422-022-00726-7. Cell Research
. 这篇文章是我最近精读的一篇文章,作者我都认识,做的靶点恰恰是我们正在做的。所以聊了很多。 这是很有可能针对未来一个大癌症种类的核心解决方案。 只不过现在rason 的结构还没有解析出来。 我们看看今年怎么处理一下。
Abstract:
Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRAS mutant. Here …
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Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRAS mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo. CRISPR/Cas9-mediated knockout of Rason in mouse embryonic fibroblasts inhibits KRAS-mediated tumor transformation. Genetic deletion of Rason abolishes oncogenic KRAS-driven pancreatic and lung cancer tumorigenesis in LSL-Kras; Trp53 mice. Mechanistically, RASON directly binds to KRAS and inhibits both intrinsic and GTPase activating protein (GAP)-mediated GTP hydrolysis, thus sustaining KRAS in the GTP-bound hyperactive state. Therapeutically, deprivation of RASON sensitizes KRAS mutant pancreatic cancer cells and patient-derived organoids to EGFR inhibitors. Our findings identify RASON as a critical regulator of oncogenic KRAS signaling and a promising therapeutic target for KRAS mutant cancers.
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715.
姗姗来迟
(2023-03-27 15:44):
#paper arXiv:2201.11903
chain of thought Prompting elicits reasoning in large language models
阅读笔记被记录在本人的博文中:https://blog.csdn.net/weixin_44845357/article/details/129566376
主要是了解思维链(通过逐步回答示例来引出复杂的多步推理的技术)
arXiv,
2022.
Abstract:
We explore how generating a chain of thought -- a series of intermediate reasoning steps -- significantly improves the ability of large language models to perform complex reasoning. In particular, …
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We explore how generating a chain of thought -- a series of intermediate reasoning steps -- significantly improves the ability of large language models to perform complex reasoning. In particular, we show how such reasoning abilities emerge naturally in sufficiently large language models via a simple method called chain of thought prompting, where a few chain of thought demonstrations are provided as exemplars in prompting. Experiments on three large language models show that chain of thought prompting improves performance on a range of arithmetic, commonsense, and symbolic reasoning tasks. The empirical gains can be striking. For instance, prompting a 540B-parameter language model with just eight chain of thought exemplars achieves state of the art accuracy on the GSM8K benchmark of math word problems, surpassing even finetuned GPT-3 with a verifier.
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716.
张浩彬
(2023-03-27 15:40):
#paper 10.1109/ijcnn52387.2021.9533426 Self-Supervised Pre-training for Time Series Classification
少有的时间序列迁移学习文章,利用DTW计算距离建立代理任务构建正负样本来做学习,encoder用的transformer,新意少了点。
Abstract:
Recently, significant progress has been made in time series classification with deep learning. However, using deep learning models to solve time series classification generally suffers from expensive calculations and difficulty …
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Recently, significant progress has been made in time series classification with deep learning. However, using deep learning models to solve time series classification generally suffers from expensive calculations and difficulty of data labeling. In this work, we study self-supervised time series pre-training to overcome these challenges. Compared with the existing works, we focus on the universal and unlabeled time series pretraining. To this end, we propose a novel end-to-end neural network architecture based on self-attention, which is suitable for capturing long-term dependencies and extracting features from different time series. Then, we propose two different self-supervised pretext tasks for time series data type: Denoising and Similarity Discrimination based on DTW (Dynamic Time Warping). Finally, we carry out extensive experiments on 85 time series datasets (also known as UCR2015 [2]). Empirical results show that the time series model augmented with our proposed self-supervised pretext tasks achieves state-of-the-art / highly competitive results.
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717.
惊鸿
(2023-03-27 11:42):
#paper doi:https://ma.x-mol.com/paperRedirect/1639426668090503168 Thymidine nucleotide metabolism controls human telomere length
人类的端粒长度与寿命和严重疾病有关,但端粒长度的遗传决定因素仍未完全确定。在这里,我们进行了全基因组 CRISPR-Cas9 功能性端粒长度筛选,并将胸苷 (dT) 核苷酸代谢确定为人类端粒维持的限制因素。使用 CRISPR-Cas9 的靶向基因破坏揭示了胸苷核苷酸代谢途径中的多个端粒长度控制点:通过删除编码核胸苷激酶 ( TK1 ) 的基因减少 dT 核苷酸回收或通过敲除胸苷酸合酶基因 (TYMS )从头产生端粒长度减少,而脱氧核苷三磷酸水解酶编码基因SAMHD1失活延长的端粒。值得注意的是,单独补充 dT 可通过细胞中的端粒酶驱动端粒的稳健延伸,并且三磷酸胸苷在体外以底物非依赖性方式刺激端粒酶活性。在源自遗传性端粒生物学障碍患者的诱导多能干细胞中,补充 dT 或抑制SAMHD1可促进端粒恢复。我们的结果表明胸苷代谢在控制人端粒酶和端粒长度方面的关键作用,这可能对致命的退行性疾病患者具有治疗作用。
Abstract:
Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening …
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Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening and identified thymidine (dT) nucleotide metabolism as a limiting factor in human telomere maintenance. Targeted genetic disruption using CRISPR-Cas9 revealed multiple telomere length control points across the thymidine nucleotide metabolism pathway: decreasing dT nucleotide salvage via deletion of the gene encoding nuclear thymidine kinase (TK1) or de novo production by knockout of the thymidylate synthase gene (TYMS) decreased telomere length, whereas inactivation of the deoxynucleoside triphosphohydrolase-encoding gene SAMHD1 lengthened telomeres. Remarkably, supplementation with dT alone drove robust telomere elongation by telomerase in cells, and thymidine triphosphate stimulated telomerase activity in a substrate-independent manner in vitro. In induced pluripotent stem cells derived from patients with genetic telomere biology disorders, dT supplementation or inhibition of SAMHD1 promoted telomere restoration. Our results demonstrate a critical role of thymidine metabolism in controlling human telomerase and telomere length, which may be therapeutically actionable in patients with fatal degenerative diseases.
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718.
周周复始
(2023-03-27 11:08):
#paper doi:https://doi.org/10.1038/s41596-023-00806-x. iBEAT V2.0: a multisite-applicable, deep learning-based pipeline for infant cerebral cortical surface reconstruction.2023.为了研究正常和异常的早期大脑发育,用不同的扫描仪和成像方案从多个站点收集了许多婴儿大脑磁共振成像(MRI)。但利用这些多站点成像数据精确地处理和量化婴儿的大脑发育是极具挑战性的,因为髓鞘持续形成和成熟而导致的极低和动态的组织对比,以及由于使用不同的成像协议/扫描仪而导致的不同站点间的数据异质性。现有的计算工具和pipeline通常在婴儿MRI数据上表现不佳。为了解决这些挑战,本文提出了一个鲁棒的、多站点适用的、婴儿定制的计算pipeline,它利用强大的深度学习技术。主要功能包括预处理、脑颅骨剥离、组织分割、拓扑校正、皮层表面表面重建和测量。可以很好地处理T1w和大范围(从出生到6岁)的婴儿大脑结构MRI,并且对不同成像协议/扫描仪差异是有效的,尽管只在BCP上训练。在多站点、多模态和多年龄数据集上与现有方法进行了广泛的比较证明ibeat具有优越的有效性、准确性和鲁棒性。
Abstract:
The human cerebral cortex undergoes dramatic and critical development during early postnatal stages. Benefiting from advances in neuroimaging, many infant brain magnetic resonance imaging (MRI) datasets have been collected from …
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The human cerebral cortex undergoes dramatic and critical development during early postnatal stages. Benefiting from advances in neuroimaging, many infant brain magnetic resonance imaging (MRI) datasets have been collected from multiple imaging sites with different scanners and imaging protocols for the investigation of normal and abnormal early brain development. However, it is extremely challenging to precisely process and quantify infant brain development with these multisite imaging data because infant brain MRI scans exhibit (a) extremely low and dynamic tissue contrast caused by ongoing myelination and maturation and (b) inter-site data heterogeneity resulting from the use of diverse imaging protocols/scanners. Consequently, existing computational tools and pipelines typically perform poorly on infant MRI data. To address these challenges, we propose a robust, multisite-applicable, infant-tailored computational pipeline that leverages powerful deep learning techniques. The main functionality of the proposed pipeline includes preprocessing, brain skull stripping, tissue segmentation, topology correction, cortical surface reconstruction and measurement. Our pipeline can handle both T1w and T2w structural infant brain MR images well in a wide age range (from birth to 6 years of age) and is effective for different imaging protocols/scanners, despite being trained only on the data from the Baby Connectome Project. Extensive comparisons with existing methods on multisite, multimodal and multi-age datasets demonstrate superior effectiveness, accuracy and robustness of our pipeline. We have maintained a website, iBEAT Cloud, for users to process their images with our pipeline ( http://www.ibeat.cloud ), which has successfully processed over 16,000 infant MRI scans from more than 100 institutions with various imaging protocols/scanners.
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719.
哪有情可长
(2023-03-24 21:51):
#paper A Gg protein regulates alkaline sensitivity in crops,science,24 march,2023,doi.org/10.1126/science.ade8416. 为了增加粮食产量,利用盐碱地,培养抗盐碱的作物,实现废田利用是现在作物育种的一大趋势。谢旗团队利用高粱这个抗碱性材料来挖掘基因。首先是通过GWAS鉴定到一个跟水稻中同源的基因(GS3)并命名为AT1(Alkaline tolerance 1),对部分高粱品种测序发现该基因能够分成两个单倍型,发现这个基因能够编码非典型G蛋白γ亚基,通过实验证明该基因能够调节环境胁迫下产生的过氧化氢外流,降低碱性敏感性。并且对该基因在小麦,玉米,水稻等作物中都进行大田试验验证,的确能够抗盐碱。
Abstract:
The use of alkaline salt lands for crop production is hindered by a scarcity of knowledge and breeding efforts for plant alkaline tolerance. Through genome association analysis of sorghum, a …
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The use of alkaline salt lands for crop production is hindered by a scarcity of knowledge and breeding efforts for plant alkaline tolerance. Through genome association analysis of sorghum, a naturally high-alkaline-tolerant crop, we detected a major locus, (), specifically related to alkaline-salinity sensitivity. An allele with a carboxyl-terminal truncation increased sensitivity, whereas knockout of increased tolerance to alkalinity in sorghum, millet, rice, and maize. encodes an atypical G protein γ subunit that affects the phosphorylation of aquaporins to modulate the distribution of hydrogen peroxide (HO) These processes appear to protect plants against oxidative stress by alkali. Designing knockouts of homologs or selecting its natural nonfunctional alleles could improve crop productivity in sodic lands.
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720.
DeDe宝
(2023-03-22 11:38):
#paper doi: https://doi.org/10.1111/psyp.14270
Wrinkles in subsecond time perception are synchronized to the heart
心脏在时间知觉中的作用的证据很少,本研究探究了心脏动力学和亚秒级别时间间隔感知之间的相互作用。被试根据与心脏同步的音调做时间二分法任务,结果显示颞叶对时间间隔感知的延长或缩短与心脏动力学同步。较低的刺激前心理与较长的编码偏差相关。本研究开发了心脏漂移模型(cDDM),为心脏在时间感知觉判断中的作用提供了新的方法论。
Abstract:
The role of the heart in the experience of time has been long theorized but empirical evidence is scarce. Here, we examined the interaction between fine-grained cardiac dynamics and the …
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The role of the heart in the experience of time has been long theorized but empirical evidence is scarce. Here, we examined the interaction between fine-grained cardiac dynamics and the momentary experience of subsecond intervals. Participants performed a temporal bisection task for brief tones (80-188 ms) synchronized with the heart. We developed a cardiac Drift-Diffusion Model (cDDM) that embedded contemporaneous heart rate dynamics into the temporal decision model. Results revealed the existence of temporal wrinkles-dilation or contraction of short intervals-in synchrony with cardiac dynamics. A lower prestimulus heart rate was associated with an initial bias in encoding the millisecond-level stimulus duration as longer, consistent with facilitation of sensory intake. Concurrently, a higher prestimulus heart rate aided more consistent and faster temporal judgments through more efficient evidence accumulation. Additionally, a higher speed of poststimulus cardiac deceleration, a bodily marker of attention, was associated with a greater accumulation of sensory temporal evidence in the cDDM. These findings suggest a unique role of cardiac dynamics in the momentary experience of time. Our cDDM framework opens a new methodological avenue for investigating the role of the heart in time perception and perceptual judgment.
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