当前共找到 1276 篇文献分享,本页显示第 721 - 740 篇。
721.
Ricardo (2023-01-31 23:52):
#paper doi:https://doi.org/10.1038/s41592-022-01703-z Multifaceted atlases of the human brain in its infancy 脑图谱是整合、处理和分析从不同个体、来源和尺度收集的大脑特征的空间参考。这篇发表于nature methods的文章介绍了一组关于脑皮层-脑体积的联合脑图谱,以时空密集的方式绘制了从两周到两岁的人脑产后发育轨迹。这套特异性图谱捕捉了早期大脑发育的关键特征,因此有助于识别正常发育轨迹的异常。这些图谱将促进绘制婴儿大脑的不同特征,从而为精确量化皮层和皮层下变化提供一个共同的参考框架,从而增强我们对早期结构和功能发展的理解。
IF:36.100Q1 Nature methods, 2023-01. DOI: 10.1038/s41592-022-01703-z PMID: 36585454 PMCID:PMC9834057
Abstract:
Brain atlases are spatial references for integrating, processing, and analyzing brain features gathered from different individuals, sources, and scales. Here we introduce a collection of joint surface-volume atlases that chart … >>>
Brain atlases are spatial references for integrating, processing, and analyzing brain features gathered from different individuals, sources, and scales. Here we introduce a collection of joint surface-volume atlases that chart postnatal development of the human brain in a spatiotemporally dense manner from two weeks to two years of age. Our month-specific atlases chart normative patterns and capture key traits of early brain development and are therefore conducive to identifying aberrations from normal developmental trajectories. These atlases will enhance our understanding of early structural and functional development by facilitating the mapping of diverse features of the infant brain to a common reference frame for precise multifaceted quantification of cortical and subcortical changes. <<<
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722.
笑对人生 (2023-01-31 23:51):
#paper Tan J, et al. Cell-type-specific prediction of 3D chromatin organization enables high-throughput in silico genetic screening. Nat Biotechnol. 2023 Jan 9. doi: 10.1038/s41587-022-01612-8.  在过去,三维基因组学的发展已经极大地拓宽了人们对染色质空间结构和相关构象变化对基因表达的影响。然而,受限于时间和技术成本的原因,针对特定细胞类型类型的染色质重塑事件的研究仍存在巨大挑战。本研究利用7份公开的小鼠和人的Hi-C数据,基于Transformer的多模态深度学习框架,以DNA序列信息、CTCF结合状态和ATAC-seq密度特征(非peak特征)作为输入,二维的Hi-C矩阵作为输出,构建了一个名为C.Origami,具有细胞类型特异性的三维基因组构象变化预测模型。该模型不仅de novo预测特定细胞类型的不同层次的基因组结构,而且还可以预测可能影响染色质构象的DNA元件,以及发现导致疾病发生的染色质重塑调控事件。
IF:33.100Q1 Nature biotechnology, 2023-08. DOI: 10.1038/s41587-022-01612-8 PMID: 36624151
Abstract:
Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application … >>>
Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of cell-type-specific chromatin organization using DNA sequence and two cell-type-specific genomic features-CTCF binding and chromatin accessibility. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. We further developed an in silico genetic screening approach to assess how individual DNA elements may contribute to chromatin organization and to identify putative cell-type-specific trans-acting regulators that collectively determine chromatin architecture. Applying this approach to leukemia cells and normal T cells, we demonstrate that cell-type-specific in silico genetic screening, enabled by C.Origami, can be used to systematically discover novel chromatin regulation circuits in both normal and disease-related biological systems. <<<
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723.
(2023-01-31 23:40):
#paper Dachs N, Upadhyay M, Hannemann E. Quantitative trait locus for calving traits on Bos taurus autosome 18 in Holstein cattle is embedded in a complex genomic region. J Dairy Sci. 2023 Jan 27:S0022-0302(23)00025-5. doi: 10.3168/jds.2021-21625. 已有研究显示荷斯坦-里弗斯牛及其杂交牛18号染色体上的数量性状与其产犊质量有关,但还未确定具体的相关基因。该研究通过分析大样本的群体基因分型数据、全基因组测序数据、荷斯坦-里弗斯牛动物样本的基因组组装,确定了与畅读质量相关的数量性状位点95%置信区间在18号染色体58.34 至 59.43 Mbp之间。其中有4个SNP与QTL单倍型为连锁不平衡。接下来的工作可能就是分析相关基因或与繁殖性状进行关联分析等等。该研究提供的数据全面描述了基因组特征,这些特征也可能与其他各种牛品种和家畜物种中的其他此类难以捉摸的QTL相关。
IF:3.700Q2 Journal of dairy science, 2023-Mar. DOI: 10.3168/jds.2021-21625 PMID: 36710189
Abstract:
Although the quantitative trait locus (QTL) on chromosome 18 (BTA18) associated with paternal calving ease and stillbirth in Holstein Friesian cattle and its cross has been known for over 20 … >>>
Although the quantitative trait locus (QTL) on chromosome 18 (BTA18) associated with paternal calving ease and stillbirth in Holstein Friesian cattle and its cross has been known for over 20 years, to our knowledge, the exact causal genetic sequence has yet escaped identification. The aim of this study was to re-examine the region of the published QTL on BTA18 and to investigate the possible reasons behind this elusiveness. For this purpose, we carried out a combined linkage disequilibrium and linkage analysis using genotyping data of 2,697 German Holstein Friesian (HF) animals and subsequent whole-genome sequencing (WGS) data analyses and genome assembly of HF samples. We confirmed the known QTL in the 95% confidence interval of 1.089 Mbp between 58.34 and 59.43 Mbp on BTA18. Additionally, these 4 SNPs in the near-perfect linkage disequilibrium with the QTL haplotype were identified: rs381577268 (on 57,816,137 bp, C/T), rs381878735 (on 59,574,329 bp, A/T), rs464221818 (on 59,329,176 bp, C/T), and rs472502785 (on 59,345,689 bp, T/C). Search for the causal mutation using short and long-read sequences, and methylation data of the BTA18 QTL region did not reveal any candidates though. The assembly showed problems in the region, as well as an abundance of segmental duplications within and around the region. Taking the QTL of BTA18 in Holstein cattle as an example, the data presented in this study comprehensively characterize the genomic features that could also be relevant for other such elusive QTL in various other cattle breeds and livestock species as well. <<<
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724.
半面阳光 (2023-01-31 23:38):
#paper doi: 10.1016/j.pcl.2015.03.004. Pediatr Clin North Am, 2015, Prader-Willi, Angelman, and 15q11-q13 Duplication Syndromes, 15号染色体区段15q11-q13上的缺失或者重复会导致三种综合征,Prader-Willi 综合征, Angelman 综合征和 15q11-q13 duplication 综合征。这篇综述文章总结了这三种综合征的临床背景信息、遗传机制、诊断策略以及治疗方案。通过这篇文章能够清楚地了解这三种综合征之间的异同。
Abstract:
Three distinct neurodevelopmental disorders arise primarily from deletions or duplications that occur at the 15q11-q13 locus: Prader-Willi syndrome, Angelman syndrome, and 15q11-q13 duplication syndrome. Each of these disorders results from … >>>
Three distinct neurodevelopmental disorders arise primarily from deletions or duplications that occur at the 15q11-q13 locus: Prader-Willi syndrome, Angelman syndrome, and 15q11-q13 duplication syndrome. Each of these disorders results from the loss of function or overexpression of at least 1 imprinted gene. This article discusses the clinical background, genetic cause, diagnostic strategy, and management of each of these 3 disorders. <<<
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725.
cellsarts (2023-01-31 23:31):
#paper Comparison of Different Packing Materials for the Biofiltration of Air Toxics DOI 10.1023/A:1021240500817 比较了四种不同的生物过滤器生物除臭滤塔的填料(两种多孔陶瓷、珍珠岩和开孔聚氨酯泡沫)去除废气中甲苯蒸汽的效果。重点是评估各填料在相对较短的气体保留时间(13.5秒和27秒)下的性能。反应器最初是作为生物滴滤器运行的,连续进料和滴入营养液。在观察到生物质生物滴滤床明显堵塞后,操作模式切换为仅定期供应矿物营养物质的生物过滤。这利于废气处理系统的稳定的运行,调查的过程持续超过6个月。牛骨瓷(CBP)是一种含有微量元素和宏量元素的陶瓷材料,其填充反应器表现出最高的性能。临界负荷(即发生95%去除率的负荷)为29克/m3/小时1,气体保留时间为13.5秒;66克/m3/小时,气体保留时间为27秒。在长期实验后,从反应器中取出填料并进行检查。将反应器分为顶部、中间和底部三个部分,以确定生物质是否存在空间分异。测定包括双染色技术,以计数总微生物和活微生物,并测定水分,蛋白质和干重含量。采用变性梯度凝胶电泳进行微生物群落分析。结果表明,大多数反应器都有相当比例的非活性生物质。相比之下,牛骨瓷CBP填料生物滤池的活性生物量密度明显较高,这可能是其去除甲苯性能较高的原因。分析表明,良好的物质条件和CBP缓慢释放的养分为工艺培养提供了较好的环境条件。
Abstract:
Modern CNNs are learning the weights of vast numbers of convolutional operators. In this paper, we raise the fundamental question if this is actually necessary. We show that even in … >>>
Modern CNNs are learning the weights of vast numbers of convolutional operators. In this paper, we raise the fundamental question if this is actually necessary. We show that even in the extreme case of only randomly initializing and never updating spatial filters, certain CNN architectures can be trained to surpass the accuracy of standard training. By reinterpreting the notion of pointwise (1×1) convolutions as an operator to learn linear combinations (LC) of frozen (random) spatial filters, we are able to analyze these effects and propose a generic LC convolution block that allows tuning of the linear combination rate. Empirically, we show that this approach not only allows us to reach high test accuracies on CIFAR and ImageNet but also has favorable properties regarding model robustness, generalization, sparsity, and the total number of necessary weights. Additionally, we propose a novel weight sharing mechanism, which allows sharing of a single weight tensor between all spatial convolution layers to massively reduce the number of weights. <<<
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726.
前进 (2023-01-31 23:30):
#paper Rethinking 1x1 Convolutions: Can we train CNNs with Frozen Random Filters? arXiv:2301.11360 本文引入了一种新的卷积块,计算(冻结随机)滤波器的可学习线性组合(LC),并由此提出 LCResNets,还提出一种新的权重共享机制,可大幅减少权重的数量。在本文中,即使在仅随机初始化且从不更新空间滤波器的极端情况下,某些CNN架构也可以被训练以超过标准训练的精度。通过将逐点(1x1)卷积的概念重新解释为学习冻结(随机)空间滤波器的线性组合(LC)的算子,这种方法不仅可以在CIFAR和ImageNet上达到较高的测试精度,而且在模型鲁棒性、泛化、稀疏 性和所需权重的总数方面具有良好。此外本文提出了一种新的权重共享机制,该机制允许在所有空间卷积层之间共享单个权重张量,以大幅减少权重的数量。
arXiv, 2023.
Abstract:
Modern CNNs are learning the weights of vast numbers of convolutional operators. In this paper, we raise the fundamental question if this is actually necessary. We show that even in … >>>
Modern CNNs are learning the weights of vast numbers of convolutional operators. In this paper, we raise the fundamental question if this is actually necessary. We show that even in the extreme case of only randomly initializing and never updating spatial filters, certain CNN architectures can be trained to surpass the accuracy of standard training. By reinterpreting the notion of pointwise (1×1) convolutions as an operator to learn linear combinations (LC) of frozen (random) spatial filters, we are able to analyze these effects and propose a generic LC convolution block that allows tuning of the linear combination rate. Empirically, we show that this approach not only allows us to reach high test accuracies on CIFAR and ImageNet but also has favorable properties regarding model robustness, generalization, sparsity, and the total number of necessary weights. Additionally, we propose a novel weight sharing mechanism, which allows sharing of a single weight tensor between all spatial convolution layers to massively reduce the number of weights. <<<
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727.
姗姗来迟 (2023-01-31 23:24):
#paper PageNet: Towards End-to-End Weakly Supervised Page-Level Handwritten Chinese Text Recognition https://link.springer.com/article/10.1007/s11263-022-01654-0?utm_source=xmol&utm_content=meta 该工作针对篇幅级手写中文文本识别问题,提出了端到端弱监督的方法PageNet。该方法的主要优势在于:(1)从一个新的角度解决篇幅级中文文本识别问题——检测识别单字并预测单字间的阅读顺序。(2)模型可以弱监督地训练。对于真实数据仅需要标注文本,不需要任何边界框标注,极大地降低了数据的标注成本。(3)尽管只需要文本标注信息,模型却可以预测出单字级和文本行级的检测和识别结果。(4)该方法深入研究篇幅级文本识别中的阅读顺序问题,所提出的阅读顺序模块可以处理多方向文本、弯曲文本等复杂的阅读顺序。
Abstract:
Handwritten Chinese text recognition (HCTR) has been an active research topic for decades. However, most previous studies solely focus on the recognition of cropped text line images, ignoring the error … >>>
Handwritten Chinese text recognition (HCTR) has been an active research topic for decades. However, most previous studies solely focus on the recognition of cropped text line images, ignoring the error caused by text line detection in real-world applications. Although some approaches aimed at page-level text recognition have been proposed in recent years, they either are limited to simple layouts or require very detailed annotations including expensive line-level and even character-level bounding boxes. To this end, we propose PageNet for end-to-end weakly supervised page-level HCTR. PageNet detects and recognizes characters and predicts the reading order between them, which is more robust and flexible when dealing with complex layouts including multi-directional and curved text lines. Utilizing the proposed weakly supervised learning framework, PageNet requires only transcripts to be annotated for real data; however, it can still output detection and recognition results at both the character and line levels, avoiding the labor and cost of labeling bounding boxes of characters and text lines. Extensive experiments conducted on five datasets demonstrate the superiority of PageNet over existing weakly supervised and fully supervised page-level methods. These experimental results may spark further research beyond the realms of existing methods based on connectionist temporal classification or attention. The source code is available at https://github.com/shannanyinxiang/PageNet. <<<
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728.
钟鸣 (2023-01-31 23:18):
#paper Sex Matters: Male Hamsters Are More Susceptible to Lethal Infection with Lower Doses of Pathogenic Leptospira than Female Hamsters https://doi.org/10.1128/IAI.00369-18 过去的研究中发现女性比男性更容易感染钩端螺旋体,但现实生活中男性感染钩端螺旋体的发病率和重症率却高于女性,为解释这个矛盾的现象,作者使用仓鼠做了动物实验。使用人工攻毒的方式建立动物模型,他们发现不同性别动物感染钩端螺旋体后确实存在差异,但是这种差异仅在感染低剂量时才能够体现出来,即在感染低剂量病原时雄性具有更严重的症状,包括存活率和病理评分以及病原负荷(载毒量)。进一步调查发现,病理评分的差异主要存在于肾脏,并且伴随着更高的炎症因子水平。新冠病毒引起的症状在不同性别间也有差异,而且我们也早就知道男女性之间的抗炎能力存在差异。但是为什么一些病原体的致病性在不同性别间有差异但是有些没有,虽然感染病原后都会引发炎症。以及为什么钩端螺旋体引起的炎症反应差异仅存在于肾脏中?研究没有继续深入,至此戛然而止。
IF:2.900Q2 Infection and immunity, 2018-10. DOI: 10.1128/IAI.00369-18 PMID: 30012637
Abstract:
A somewhat contradictory published body of evidence suggests that sex impacts severity outcomes of human leptospirosis. In this study, we used an acute animal model of disease to analyze leptospirosis … >>>
A somewhat contradictory published body of evidence suggests that sex impacts severity outcomes of human leptospirosis. In this study, we used an acute animal model of disease to analyze leptospirosis in male and female hamsters infected side by side with low but increasing doses of serovar Copenhageni. We found that male hamsters were considerably more susceptible to leptospirosis, given that only 6.3% survived infection, whereas 68.7% of the females survived the same infection doses. In contrast to the females, male hamsters had high burdens of in kidney and high histopathological scores after exposure to low infection doses (∼10 bacteria). In hamsters infected with higher doses of (∼10 bacteria), differences in pathogen burdens as well as cytokine and fibrosis transcript levels in kidney were not distinct between sexes. Our results indicate that male hamsters infected with are more susceptible to severe leptospirosis after exposure to lower infectious doses than females. <<<
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729.
小W (2023-01-31 23:13):
#paper doi:https://doi.org/10.1038/s41467-022-35320-3 Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis. Nat Commun 13, 7694 (2022) 本文是清华大学团队开发的使用 cfDNA 甲基化特征来构建SRFD-Bayes诊断模型,通过去卷积混合甲基化特征来估计cfDNA的肿瘤的起源组织 (TOO),用于预测原发性肿瘤的位置和对癌症早期诊断。本文分为三个部分,使用肿瘤和正常样本甲基化数据模拟 cfdna 数据;甲基化标记物选择,使用半参考反卷积(SRFD)从血浆cfDNA甲基化谱中学习的参考数据库, 构建SRFD-Bayes 模型;在早期患者和健康个体上验证时,该模型对癌症早期检测的敏感性为86.1%,对肿瘤定位的平均准确性为76.9%,特异性为94.7%。
IF:14.700Q1 Nature communications, 2022-12-13. DOI: 10.1038/s41467-022-35320-3 PMID: 36509772
Abstract:
Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions … >>>
Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring. <<<
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730.
小擎子 (2023-01-31 23:12):
#paper doi:10.1038/s41467-022-35237-x Nat Commun., 2022, Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity。将HMM方法与机器学习相结合,以鉴定PET水解酶,根据序列预测酶的最佳活性温度。从公开数据库获得序列和环境最佳生长温度(OGT),只保留OGT大于50℃的序列,对于没有OGT信息的序列,使用计算氨基酸特征的支持向量机方法训练机器学习模型(ThermoProt)来区分来自嗜热菌大于50℃的8000种蛋白和来自非嗜热菌的小于50℃的8000种蛋白。ThremProt表现出86.6%的准确率。选择了74种假定的耐热PET水解酶进行实验筛选。实验筛选出了23种热稳定酶,均未被报道,并且超过先前报道的36种酶的PET水解酶活性。
IF:14.700Q1 Nature communications, 2022-12-21. DOI: 10.1038/s41467-022-35237-x PMID: 36543766
Abstract:
Enzymatic deconstruction of poly(ethylene terephthalate) (PET) is under intense investigation, given the ability of hydrolase enzymes to depolymerize PET to its constituent monomers near the polymer glass transition temperature. To … >>>
Enzymatic deconstruction of poly(ethylene terephthalate) (PET) is under intense investigation, given the ability of hydrolase enzymes to depolymerize PET to its constituent monomers near the polymer glass transition temperature. To date, reported PET hydrolases have been sourced from a relatively narrow sequence space. Here, we identify additional PET-active biocatalysts from natural diversity by using bioinformatics and machine learning to mine 74 putative thermotolerant PET hydrolases. We successfully express, purify, and assay 51 enzymes from seven distinct phylogenetic groups; observing PET hydrolysis activity on amorphous PET film from 37 enzymes in reactions spanning pH from 4.5-9.0 and temperatures from 30-70 °C. We conduct PET hydrolysis time-course reactions with the best-performing enzymes, where we observe differences in substrate selectivity as function of PET morphology. We employed X-ray crystallography and AlphaFold to examine the enzyme architectures of all 74 candidates, revealing protein folds and accessory domains not previously associated with PET deconstruction. Overall, this study expands the number and diversity of thermotolerant scaffolds for enzymatic PET deconstruction. <<<
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731.
muton (2023-01-31 23:03):
#paper # Yu, W., Zadbood, A., Chanales, A. J., & Davachi, L. (2022). Repetition accelerates neural markers of memory consolidation. bioRxiv, 2022-12.https://doi.org/10.1101/2022.12.14.520481; 认知加工过程中一旦体验结束,神经记忆表征就开始通过记忆回放的过程得到加强和转化。使用功能磁共振成像技术,作者研究了编码过程中通过重复操纵而改变的记忆强度如何调节人类的编码后回放。结果显示,重复不能增强海马的回放频率,但是皮层区域的回放以及皮层海马共同协调的回放在重复事件中被显著增强,表明重复加速了记忆巩固的过程,另外在海马和皮层的回放频率可以调节即时联想辨认测试中编码较弱的信息的行为成功率,这表明了编码后回放在帮助回忆曾经出现过事件的重要作用。总的来说这篇文章突出了回放在巩固较弱记忆和加速皮层记忆巩固来增强记忆过程中的作用。
Abstract:
AbstractNo sooner is an experience over than its neural memory representation begins to be strengthened and transformed through the process of memory replay. Using fMRI, we examined how memory strength … >>>
AbstractNo sooner is an experience over than its neural memory representation begins to be strengthened and transformed through the process of memory replay. Using fMRI, we examined how memory strength manipulated through repetition during encoding modulates post-encoding replay in humans. Results revealed that repetition did not increase replay frequency in the hippocampus. However, replay in cortical regions and hippocampal-cortical coordinated replay were significantly enhanced for repeated events, suggesting that repetition accelerates the consolidation process. Interestingly, we found that replay frequency in both hippocampus and cortex modulated behavioral success on an immediate associative recognition test for the weakly encoded information, indicating a significant role for post-encoding replay in rescuing once-presented events. Together, our findings highlight the relationships of replay to stabilizing weak memories and accelerating cortical consolidation for strong memories. <<<
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732.
Spring (2023-01-31 23:02):
#paper An epithelial cell-derived metabolite tunes immunoglobulin A secretion by gut-resident plasma cells 01-19, doi: 10.1038/s41590-022-01413-w Nature子刊:膳食胆固醇如何影响肠道驻留浆细胞介导的体液免疫 Nature Immunology[IF:31.25] ① 十二指肠的肠上皮细胞(IEC)依赖代谢酶CH25H将胆固醇代谢为氧化甾醇7α,25-OHC;② Myd88依赖的模式识别受体检测肠道菌群以及NPC1L1介导的膳食胆固醇吸收是IEC产生7α,25-OHC的必要条件;③ 7α,25-OHC可被十二指肠固有层驻留的浆细胞(PC)通过趋化受体GPR183感知,促进其迁移到小肠绒毛中心靠近淋巴管的周围,并抑制抗原特异性的IgA分泌;④ 抑制肠道胆固醇吸收或抑制GPR183信号可使PC分泌更多的IgA,增强肠道对沙门氏菌的免疫反应。
IF:27.700Q1 Nature immunology, 2023-03. DOI: 10.1038/s41590-022-01413-w PMID: 36658240
Abstract:
Immunoglobulin A (IgA) secretion by plasma cells, terminally differentiated B cells residing in the intestinal lamina propria, assures microbiome homeostasis and protects the host against enteric infections. Exposure to diet-derived … >>>
Immunoglobulin A (IgA) secretion by plasma cells, terminally differentiated B cells residing in the intestinal lamina propria, assures microbiome homeostasis and protects the host against enteric infections. Exposure to diet-derived and commensal-derived signals provides immune cells with organizing cues that instruct their effector function and dynamically shape intestinal immune responses at the mucosal barrier. Recent data have described metabolic and microbial inputs controlling T cell and innate lymphoid cell activation in the gut; however, whether IgA-secreting lamina propria plasma cells are tuned by local stimuli is completely unknown. Although antibody secretion is considered to be imprinted during B cell differentiation and therefore largely unaffected by environmental changes, a rapid modulation of IgA levels in response to intestinal fluctuations might be beneficial to the host. In the present study, we showed that dietary cholesterol absorption and commensal recognition by duodenal intestinal epithelial cells lead to the production of oxysterols, evolutionarily conserved lipids with immunomodulatory functions. Using conditional cholesterol 25-hydroxylase deleter mouse line we demonstrated that 7α,25-dihydroxycholesterol from epithelial cells is critical to restrain IgA secretion against commensal- and pathogen-derived antigens in the gut. Intestinal plasma cells sense oxysterols via the chemoattractant receptor GPR183 and couple their tissue positioning with IgA secretion. Our findings revealed a new mechanism linking dietary cholesterol and humoral immune responses centered around plasma cell localization for efficient mucosal protection. <<<
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733.
张贝 (2023-01-31 22:54):
#paper Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics,Nat Biomed Eng. 2022 Mar;6(3):232-245.doi:10.1038/s41551-021-00837-3. 本文是2022年发表在Nature Biomedical Engineering上的一篇关于cfDNA的综述,血浆中的游离DNA(cfDNA)来源于细胞裂解后(包括主动裂解和被动裂解)释放的DNA,经核酸酶裂解成长度约为160bp的片段,半衰期约为5~150分钟,这种“全局快照”能力使cfDNA成为许多疾病的理想生物标志物。本文讨论了现阶段肿瘤cfDNA检测领域面临的机遇与挑战,从cfDNA检测在癌症管理中的角色、分析前的限制因素、cfDNA的低重分析方法、cfDNA的NGS分析方法、唯一分子标签技术、等位基因富集技术、cfDNA的非突变标志物和肿瘤早筛对精度的要求这8个方面分别进行介绍。
Abstract:
Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, … >>>
Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, and for the early detection of cancers. However, the analysis of cfDNA for clinical diagnostic applications remains challenging because of the low concentrations of cfDNA, and because cfDNA is fragmented into short lengths and is susceptible to chemical damage. Barcodes of unique molecular identifiers have been implemented to overcome the intrinsic errors of next-generation sequencing, which is the prevailing method for highly multiplexed cfDNA analysis. However, a number of methodological and pre-analytical factors limit the clinical sensitivity of the cfDNA-based detection of cancers from liquid biopsies. In this Review, we describe the state-of-the-art technologies for cfDNA analysis, with emphasis on multiplexing strategies, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve cancer diagnostics and patient care. <<<
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734.
na na na (2023-01-31 22:49):
#paper,dentification of neoantigens for individualized therapeutic cancer vaccines. Nat Rev Drug Discov. https://www.nature.com/articles/s41573-021-00387-y. PMID: 35105974; PMCID: PMC7612664. 近几年肿瘤疫苗是一个非常热门的领域,我们知道肿瘤细胞的体细胞突变可以产生肿瘤特异性的肿瘤表位,被宿主体内的自体T细胞识别,从而产生相应的杀伤;而肿瘤的异质性和个体化程度高,因此个体化治疗性癌症疫苗肿瘤抗原的鉴定就显得十分重要。目前已经开发了许多计算算法和机器学习工具,以识别序列数据中的突变,并优先筛选可能被T细胞识别的突变,为下游每个患者的个体化疫苗设计提供靶点。本篇综述结合T细胞识别肿瘤抗原的基本机制和发现体细胞突变和癌症免疫治疗预测肿瘤抗原的计算方法,比较完整的提供了新抗原算法开发目前成果和待解决问题。是一篇比较好的学习指南,推荐一下
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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735.
Arwen (2023-01-31 22:38):
#paper, Inflammation and cognition in severe mental illness: patterns of covariation and subgroups, https://doi.org/10.1038/s41380-022-01924-w 严重精神疾病(SMI)如精神分裂症(SZ)和双相情感障碍(BD)中免疫/炎症通路失调和认知障碍之间的潜在关系已被提出。然而,外周炎症/免疫相关标记物与认知领域之间的多变量关系尚不清楚,许多研究没有解释认知功能和炎症/免疫状态的个体间差异。本研究旨在研究炎症/免疫相关标记物与认知域之间的协方差模式,并进一步阐明大型SMI和健康对照(HC)队列(SZ=343, BD=289, HC=770)的异质性。应用典型相关分析(CCA)来确定综合选择的认知域和炎症/免疫标记之间的最大共变模式。发现较差的语言学习和精神运动处理速度与较高水平的白细胞介素-18系统细胞因子和β防御素2有关,反映了先天免疫的增强激活,与HC相比,SMI的这种模式有所增强。对CCA确定的协方差模式进行分层聚类,发现以HC为主的高认知-低免疫失调亚组(24% SZ, 45% BD, 74% HC)和以SMI患者为主的低认知-高免疫失调亚组(76% SZ, 55% BD, 26% HC)。这些亚组在智商、受教育年限、年龄、CRP、BMI(所有组)、功能水平、症状和抗精神病药物的限定日剂量(DDD) (SMI队列)方面存在差异。
Abstract:
AbstractA potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate … >>>
AbstractA potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness. <<<
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736.
林海onrush (2023-01-31 22:08):
#paper https://www.nature.com/articles/s42256-022-00569-2,Deep transfer operator learning for partial differential equations under conditional shift,“迁移学习「求解」偏微分方程,条件偏移下PDE的深度迁移算子学习",来自美国布朗大学和约翰斯·霍普金斯大学(JHU)的研究人员提出了一种新的迁移学习框架,用于基于深度算子网络 (DeepONet) 的条件转移下的任务特定学习(偏微分方程中的函数回归)。由于几何域和模型动力学的变化,研究人员展示了该方法在不同条件下涉及非线性偏微分方程的各种迁移学习场景的优势。尽管源域和目标域之间存在相当大的差异,但提出的迁移学习框架能够快速高效地学习异构任务。该研究发布在《Nature Machine Intelligence》上。深度学习已经成功地应用于模拟偏微分方程(PDE)描述的计算成本很高的复杂物理过程,并实现了卓越的性能,从而加速了不确定性量化、风险建模和设计优化等众多任务。但此类模型的预测性能通常受到用于训练的标记数据的可用性的限制。在许多情况下,收集大量且足够的标记数据集在计算上可能很棘手。此外,孤立学习(即为独特但相关的任务训练单个预测模型)可能非常昂贵。为了解决这个瓶颈,可以在称为迁移学习的框架中利用相关领域之间的知识。在这种情况下,来自在具有足够标记数据的特定域(源)上训练的模型的信息可以转移到只有少量训练数据可用的不同但密切相关的域(目标)。由于缺乏针对特定任务的算子(operator)学习和不确定性量化的 TL 方法,在这项工作中,研究人员提出了一个使用神经算子在条件转换下高效 TL 的新框架。 在这项工作中,研究人员采用了更通用的深度神经算子 (DeepONet),它使我们能够充分学习算子,从而对任意新输入和复杂域执行实时预测。重要的是,所提出的迁移学习框架能够在标记数据非常有限的领域中识别 PDE 算子。这项工作的主要贡献可归纳如下: 提出了一种新的框架,用于在深度神经算子的条件转移下迁移学习问题。 所提出的框架可用于快速高效的特定于任务的 PDE 学习和不确定性量化。 利用 RKHS 和条件嵌入算子理论的原理来构建新的混合损失函数并对目标模型进行微调。 所提出框架的优点和局限性通过各种迁移学习问题得到证明,包括由于域几何、模型动力学、材料特性、非线性等变化引起的分布变化。
Abstract:
Transfer learning enables the transfer of knowledge gained while learning to perform one task (source) to a related but different task (target), hence addressing the expense of data acquisition and … >>>
Transfer learning enables the transfer of knowledge gained while learning to perform one task (source) to a related but different task (target), hence addressing the expense of data acquisition and labelling, potential computational power limitations and dataset distribution mismatches. We propose a new transfer learning framework for task-specific learning (functional regression in partial differential equations) under conditional shift based on the deep operator network (DeepONet). Task-specific operator learning is accomplished by fine-tuning task-specific layers of the target DeepONet using a hybrid loss function that allows for the matching of individual target samples while also preserving the global properties of the conditional distribution of the target data. Inspired by conditional embedding operator theory, we minimize the statistical distance between labelled target data and the surrogate prediction on unlabelled target data by embedding conditional distributions onto a reproducing kernel Hilbert space. We demonstrate the advantages of our approach for various transfer learning scenarios involving nonlinear partial differential equations under diverse conditions due to shifts in the geometric domain and model dynamics. Our transfer learning framework enables fast and efficient learning of heterogeneous tasks despite considerable differences between the source and target domains. <<<
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737.
大勇 (2023-01-31 21:58):
#paper # Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. Gut. 2022 Jul 8:gutjnl-2022-326928. doi: 10.1136/gutjnl-2022-326928. 这篇文献主要讲述了甲硫氨酸(蛋氨酸)的缺乏饮食可以抑制肿瘤的增殖,而这个过程依赖于PDL1和VISTA的m6A甲基化水平的改变,甲硫氨酸缺乏所引起的甲基代谢的异常,会使得YDHDF1对PDL1和VISTA mRNA的m6A甲基化水平下降,从而增强了它们的翻译和表达,最终促进了T细胞的浸润和PDL1抑制剂治疗的疗效。
IF:23.000Q1 Gut, 2023-03. DOI: 10.1136/gutjnl-2022-326928 PMID: 35803704
Abstract:
OBJECTIVE: Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are … >>>
OBJECTIVE: Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are molecularly intertwined.DESIGN: The antitumour immunity effect of methionine-restricted diet (MRD) feeding was assessed in murine models. The mechanisms of methionine and YTH domain-containing family protein 1 (YTHDF1) in tumour immune escape were determined in vitro and in vivo. The synergistic effects of MRD or YTHDF1 depletion with PD-1 blockade were also investigated.RESULTS: We found that dietary methionine restriction reduced tumour growth and enhanced antitumour immunity by increasing the number and cytotoxicity of tumour-infiltrating CD8+ T cells in different mouse models. Mechanistically, the S-adenosylmethionine derived from methionine metabolism promoted the N6-methyladenosine (m6A) methylation and translation of immune checkpoints, including PD-L1 and V-domain Ig suppressor of T cell activation (VISTA), in tumour cells. Furthermore, MRD or m6A-specific binding protein YTHDF1 depletion inhibited tumour growth by restoring the infiltration of CD8+ T cells, and synergised with PD-1 blockade for better tumour control. Clinically, YTHDF1 expression correlated with poor prognosis and immunotherapy outcomes for cancer patients.CONCLUSIONS: Methionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T cells. Targeting methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy. <<<
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738.
尹志 (2023-01-31 20:59):
#paper Diffusion Models: A Comprehensive Survey of Methods and Applications, https://doi.org/10.48550/arXiv.2209.00796. 这篇综述对当前非常热门的扩散模型进行了详细的介绍与梳理。文章将当前的扩散模型总结为三类主要模型:DDPMs、SGMs、score SDEs,三类模型逐级一般化,可处理更广泛的问题。除了对三类主流扩散模型进行了详细的讲解,对比,对其相关改进工作进行了梳理,文章还探讨了扩散模型与其它主流的生成模型的联系与区别。文章在最后列举了扩散模型目前在各个领域的应用。考虑到扩散模型受物理概念启发,非常看好其后续结合数学物理的更多推广和应用,比如最近顾险峰老师就在文章中指出基于最优传输的可能改进,这确实是非常有意思的想法和主题。
Abstract:
Diffusion models have emerged as a powerful new family of deep generative models with record-breaking performance in many applications, including image synthesis, video generation, and molecule design. In this survey, … >>>
Diffusion models have emerged as a powerful new family of deep generative models with record-breaking performance in many applications, including image synthesis, video generation, and molecule design. In this survey, we provide an overview of the rapidly expanding body of work on diffusion models, categorizing the research into three key areas: efficient sampling, improved likelihood estimation, and handling data with special structures. We also discuss the potential for combining diffusion models with other generative models for enhanced results. We further review the wide-ranging applications of diffusion models in fields spanning from computer vision, natural language processing, temporal data modeling, to interdisciplinary applications in other scientific disciplines. This survey aims to provide a contextualized, in-depth look at the state of diffusion models, identifying the key areas of focus and pointing to potential areas for further exploration. Github: this https URL. <<<
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739.
周周复始 (2023-01-31 20:41):
#paper 《Unsupervised Learning for Fast Probabilistic Diffeomorphic Registration》,MICCAI,2018,https://doi.org/10.1007/978-3-030-00928-1_82 传统的可形变配准方法虽然有很好的效果和严格的理论证明,但由于是对每个图像对进行优化,计算量很大。而基于学习的方法虽然通过学习空间形变函数提高了配准速度,但限制了形变模型:需要监督标签,可能不保证微分同胚。因此本文提出一种使用微分图像配准的概率生成模型,推导出使用CNN和直观损失函数的学习算法,还引入了缩放和平方层。实现了快速有效的运算,保证了微分同胚并提供了不确定性估计。
Abstract:
Traditional deformable registration techniques achieve impressive results and offer a rigorous theoretical treatment, but are computationally intensive since they solve an optimization problem for each image pair. Recently, learning-based methods … >>>
Traditional deformable registration techniques achieve impressive results and offer a rigorous theoretical treatment, but are computationally intensive since they solve an optimization problem for each image pair. Recently, learning-based methods have facilitated fast registration by learning spatial deformation functions. However, these approaches use restricted deformation models, require supervised labels, or do not guarantee a diffeomorphic (topology-preserving) registration. Furthermore, learning-based registration tools have not been derived from a probabilistic framework that can offer uncertainty estimates. In this paper, we present a probabilistic generative model and derive an unsupervised learning-based inference algorithm that makes use of recent developments in convolutional neural networks (CNNs). We demonstrate our method on a 3D brain registration task, and provide an empirical analysis of the algorithm. Our approach results in state of the art accuracy and very fast runtimes, while providing diffeomorphic guarantees and uncertainty estimates. Our implementation is available online at http://voxelmorph.csail.mit.edu. <<<
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740.
哪有情可长 (2023-01-31 19:16):
#paper # De novo genome assembly and analyses of 12 founder inbred lines provide insights into maize heterosis, Nature Genetics,16 January 2023,doi.org/10.1038/s41588-022-01283-w.玉米是三大粮食作物中杂种优势研究最多的物种,只是证明玉米存在杂种优势,但是关于对不同的育种目标对父母本的选择还没有文章说明,所以作者想对现在的骨干亲本组装想鉴定发现前人杂种优势形成的缘由。作者首先通过进化树分析对现在玉米常用的350自交系进行分析,对进化树每个分支上选取目前世界范围内广泛使用的12个骨干自交系,通过三代测序组装高质量基因组,同时结合玉米中之前已经发表的B73和Mo17基因组,构建了温带玉米核心育种种质泛基因组。作者对14个材料之间进行基因组比较分析发现存在广泛的遗传变异,通过对对玉米中现在 常用的自交系350份对花期、穗行数、穗粒数等表型进行鉴定和关键基因的单倍型分析,发现结构变异对杂种有事的形成和表型分化具有重要的贡献。通过对131份自交系雌穗的转录组数据分析,鉴定到306,868个调控基因表达的顺式eQTL,并挖掘到了一批调控玉米雄穗分枝数、穗位高及穗腐病抗性相关的候选基因及其关键结构变异;进一步结合14 个自交系的双列杂交群体 (91个F1)及3个环境的表型数据分析发现,玉米杂种优势与双亲基因组间结构变异的数量呈显著正相关,而与双亲基因组间共线性程度呈显著负相关,说明玉米杂种优势与双亲在全基因组水平的遗传互补性密切相关,为杂种优势的遗传互补模型提供了强有力的支持。同时结合遗传和分子生物学证据,挖掘到了ZmACO2 (编码一个乙烯合成酶)和ARGOS1 (ZAR1, 编码一个乙烯信号传导相关蛋白) 2个关键产量杂种优势位点,证明了其以超显性效应发挥作用。
IF:31.700Q1 Nature genetics, 2023-02. DOI: 10.1038/s41588-022-01283-w PMID: 36646891
Abstract:
Hybrid maize displays superior heterosis and contributes over 30% of total worldwide cereal production. However, the molecular mechanisms of heterosis remain obscure. Here we show that structural variants (SVs) between … >>>
Hybrid maize displays superior heterosis and contributes over 30% of total worldwide cereal production. However, the molecular mechanisms of heterosis remain obscure. Here we show that structural variants (SVs) between the parental lines have a predominant role underpinning maize heterosis. De novo assembly and analyses of 12 maize founder inbred lines (FILs) reveal abundant genetic variations among these FILs and, through expression quantitative trait loci and association analyses, we identify several SVs contributing to genomic and phenotypic differentiations of various heterotic groups. Using a set of 91 diallel-cross F hybrids, we found strong positive correlations between better-parent heterosis of the F hybrids and the numbers of SVs between the parental lines, providing concrete genomic support for a prevalent role of genetic complementation underlying heterosis. Further, we document evidence that SVs in both ZAR1 and ZmACO2 contribute to yield heterosis in an overdominance fashion. Our results should promote genomics-based breeding of hybrid maize. <<<
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