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pH and buffering capacity: Fundamental yet underappreciated drivers of algal-bacterial interactions pH 值和缓冲能力:藻类与细菌相互作用的基本驱动力,但却未得到充分重视
IF 9.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.cels.2024.08.003
Understanding microbial interactions in native habitats has been difficult given the complexity of such environments. Using state-of-the-art microflui…
鉴于原生栖息地环境的复杂性,要了解这种环境中微生物之间的相互作用一直很困难。利用最先进的微流控技术,我们可以...
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引用次数: 0
What’s driving rhythmic gene expression: Sleep or the clock? 是什么在驱动有节奏的基因表达?睡眠还是时钟?
IF 9.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-17 DOI: 10.1016/j.cels.2024.06.006

Rhythmic gene expression can originate not only from the autonomous rhythm of clock genes but likely also from sleep-wake cycles. Jan and colleagues used a novel model-based approach to dissect these individual effects and found that both factors contribute to gene expression rhythms, varying in degree within and across tissues.

有节律的基因表达不仅源于时钟基因的自主节律,也可能源于睡眠-觉醒周期。杨及其同事使用了一种基于模型的新方法来剖析这些个体效应,发现这两种因素都有助于基因表达节律,而且在组织内部和组织之间的程度各不相同。
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引用次数: 0
Model integration of circadian- and sleep-wake-driven contributions to rhythmic gene expression reveals distinct regulatory principles 昼夜节律和睡眠-觉醒对节律性基因表达贡献的模型整合揭示了不同的调控原理
IF 9.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-09 DOI: 10.1016/j.cels.2024.06.005
Maxime Jan, Sonia Jimenez, Charlotte N. Hor, Derk-Jan Dijk, Anne C. Skeldon, Paul Franken

Analyses of gene-expression dynamics in research on circadian rhythms and sleep homeostasis often describe these two processes using separate models. Rhythmically expressed genes are, however, likely to be influenced by both processes. We implemented a driven, damped harmonic oscillator model to estimate the contribution of circadian- and sleep-wake-driven influences on gene expression. The model reliably captured a wide range of dynamics in cortex, liver, and blood transcriptomes taken from mice and humans under various experimental conditions. Sleep-wake-driven factors outweighed circadian factors in driving gene expression in the cortex, whereas the opposite was observed in the liver and blood. Because of tissue- and gene-specific responses, sleep deprivation led to a long-lasting intra- and inter-tissue desynchronization. The model showed that recovery sleep contributed to these long-lasting changes. The results demonstrate that the analyses of the daily rhythms in gene expression must take the complex interactions between circadian and sleep-wake influences into account. A record of this paper’s transparent peer review process is included in the supplemental information.

在有关昼夜节律和睡眠平衡的研究中,对基因表达动态的分析通常使用不同的模型来描述这两个过程。然而,有节律表达的基因很可能同时受到这两个过程的影响。我们采用了一个驱动型阻尼谐振子模型来估计昼夜节律和睡眠-觉醒驱动对基因表达的影响。该模型可靠地捕捉到了小鼠和人类在各种实验条件下大脑皮层、肝脏和血液转录组的各种动态变化。在大脑皮层中,睡眠-觉醒因素对基因表达的影响超过了昼夜节律因素,而在肝脏和血液中则相反。由于组织和基因的特异性反应,睡眠剥夺导致了组织内和组织间的长期不同步。该模型显示,恢复性睡眠促成了这些持久的变化。研究结果表明,对基因表达日节律的分析必须考虑到昼夜节律和睡眠-觉醒之间复杂的相互作用。本文的同行评审过程透明,其记录见补充信息。
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引用次数: 0
On knowing a gene: A distributional hypothesis of gene function 认识基因基因功能分布假说
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-05-28 DOI: 10.1016/j.cels.2024.04.008
Jason J. Kwon, Joshua Pan, Guadalupe Gonzalez, William C. Hahn, Marinka Zitnik

As words can have multiple meanings that depend on sentence context, genes can have various functions that depend on the surrounding biological system. This pleiotropic nature of gene function is limited by ontologies, which annotate gene functions without considering biological contexts. We contend that the gene function problem in genetics may be informed by recent technological leaps in natural language processing, in which representations of word semantics can be automatically learned from diverse language contexts. In contrast to efforts to model semantics as “is-a” relationships in the 1990s, modern distributional semantics represents words as vectors in a learned semantic space and fuels current advances in transformer-based models such as large language models and generative pre-trained transformers. A similar shift in thinking of gene functions as distributions over cellular contexts may enable a similar breakthrough in data-driven learning from large biological datasets to inform gene function.

单词可以有多种含义,取决于句子的上下文,基因也可以有多种功能,取决于周围的生物系统。基因功能的这种多义性受到本体论的限制,本体论只注释基因功能,而不考虑生物背景。我们认为,遗传学中的基因功能问题可以借鉴自然语言处理领域最近的技术飞跃,在自然语言处理领域,单词语义的表征可以从不同的语言上下文中自动学习。与 20 世纪 90 年代将语义建模为 "is-a "关系的努力不同,现代分布语义学将单词表示为学习语义空间中的向量,并推动了目前基于转换器的模型(如大型语言模型和生成预训练转换器)的进步。将基因功能视为细胞上下文分布的类似思维转变,可能会在从大型生物数据集进行数据驱动学习以了解基因功能方面带来类似的突破。
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引用次数: 0
Acute response to pathogens in the early human placenta at single-cell resolution 以单细胞分辨率观察早期人类胎盘对病原体的急性反应
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-05-03 DOI: 10.1016/j.cels.2024.04.002
Regina Hoo, Elias R. Ruiz-Morales, Iva Kelava, Mukul Rawat, Cecilia Icoresi Mazzeo, Elizabeth Tuck, Carmen Sancho-Serra, Sara Chelaghma, Alexander V. Predeus, Simon Murray, David Fernandez-Antoran, Ross F. Waller, Damiana Álvarez-Errico, Marcus C.S. Lee, Roser Vento-Tormo

The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child’s health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications—Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications.

胎盘是母体和胎儿之间的一道选择性屏障,为母体和胎儿提供营养和免受感染的保护。然而,某些病原体会附着在胎盘上,甚至穿过胎盘,引起妊娠并发症,对胎儿的健康造成潜在的终生影响。在这里,我们在单细胞水平上分析了胎盘对三种与宫内并发症有关的病原体--恶性疟原虫、单核细胞增生李斯特菌和弓形虫的反应。我们发现,在接触病原体后,所有胎盘细胞系都会引发炎症反应,从而可能损害胎盘功能。此外,我们还描述了被称为霍夫鲍尔细胞(HBCs)的胎儿巨噬细胞对每种病原体的反应,并提出它们可能是弓形虫的栖息地。最后,我们揭示了恶性疟原虫如何通过调节蛋白质输出到宿主红细胞和营养摄取途径来适应胎盘微环境。总之,我们已经确定了介导可能导致妊娠并发症的急性胎盘炎症反应的细胞网络和信号通路。
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引用次数: 0
Combinatorial interpretation of BMP and WNT controls the decision between primitive streak and extraembryonic fates BMP和WNT的组合解释控制着原始条纹和胚外命运之间的抉择
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-04-30 DOI: 10.1016/j.cels.2024.04.001
Elena Camacho-Aguilar, Sumin T. Yoon, Miguel A. Ortiz-Salazar, Siqi Du, M. Cecilia Guerra, Aryeh Warmflash

BMP signaling is essential for mammalian gastrulation, as it initiates a cascade of signals that control self-organized patterning. As development is highly dynamic, it is crucial to understand how time-dependent combinatorial signaling affects cellular differentiation. Here, we show that BMP signaling duration is a crucial control parameter that determines cell fates upon the exit from pluripotency through its interplay with the induced secondary signal WNT. BMP signaling directly converts cells from pluripotent to extraembryonic fates while simultaneously upregulating Wnt signaling, which promotes primitive streak and mesodermal specification. Using live-cell imaging of signaling and cell fate reporters together with a simple mathematical model, we show that this circuit produces a temporal morphogen effect where, once BMP signal duration is above a threshold for differentiation, intermediate and long pulses of BMP signaling produce specification of mesoderm and extraembryonic fates, respectively. Our results provide a systems-level picture of how these signaling pathways control the landscape of early human development.

BMP 信号对哺乳动物的胃形成至关重要,因为它启动了一连串控制自组织形态的信号。由于发育是高度动态的,因此了解随时间变化的组合信号如何影响细胞分化至关重要。在这里,我们展示了 BMP 信号持续时间是一个关键的控制参数,它通过与诱导次级信号 WNT 的相互作用,决定了细胞从多能状态退出时的命运。BMP信号直接将细胞从多能性转化为胚外型,同时上调Wnt信号,促进原始条纹和中胚层的规范化。通过对信号传导和细胞命运报告的活细胞成像以及一个简单的数学模型,我们发现这一回路产生了一种时间形态发生器效应,一旦 BMP 信号持续时间超过分化阈值,BMP 信号的中脉冲和长脉冲就会分别产生中胚层和胚外命运的规格化。我们的研究结果提供了一幅系统水平的图景,展示了这些信号通路是如何控制人类早期发育的。
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引用次数: 0
The resilience of Ukrainian scientists 乌克兰科学家的复原力
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-04-17 DOI: 10.1016/j.cels.2024.03.006
Oksana Piven, Valerii Pokrytiuk, Nadiia Kasianchuk, Bohdan Ostash, Svitlana Dekina, Rostyslav Panchuk, Oleksiy Boldyriev, Vitalina Bashynska, Andrii Zaremba, Yuliia Faidiuk, Maria Yu Obolenskaya, Anastasiia Polishchuk, Oleksandr Petrenko

We have asked Ukrainian scientists how they have been able to persist in pursuing their research since the beginning of the full-scale invasion of Ukraine by the Russian Federation in February of 2022. We thank the scientists who were willing to share their thoughts and experiences; the views expressed are those of the contributors alone.

我们询问了乌克兰科学家,自 2022 年 2 月俄罗斯联邦开始全面入侵乌克兰以来,他们是如何坚持开展研究的。我们对愿意分享其想法和经验的科学家表示感谢;所表达的观点仅代表撰稿人本人。
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引用次数: 0
Integrating multiplexed imaging and multiscale modeling identifies tumor phenotype conversion as a critical component of therapeutic T cell efficacy 整合多重成像和多尺度建模,确定肿瘤表型转换是治疗性 T 细胞疗效的关键组成部分
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-04-17 DOI: 10.1016/j.cels.2024.03.004
Abstract not available
无摘要
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引用次数: 0
Context matters: DNA virus infection reshapes DNA damage response pathways 背景很重要:DNA病毒感染重塑DNA损伤应答途径
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-04-17 DOI: 10.1016/j.cels.2024.03.008
Jeffrey R. Johnson

The cellular DNA damage response pathway can have vastly different outcomes depending on the source of its activation. Justice and colleagues apply phosphoproteomics to uncover a divergence in DNA-PK and ATM kinase activities in the contexts of DNA damage and DNA virus infection.

细胞 DNA 损伤反应途径会因激活源的不同而产生截然不同的结果。贾斯特及其同事应用磷蛋白组学发现了DNA-PK和ATM激酶在DNA损伤和DNA病毒感染情况下的活性差异。
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引用次数: 0
Evaluation of McCauley et al.: A framework for systematic evaluation of tissue signaling responses by single-cell RNA-seq 对 McCauley 等人的评价通过单细胞 RNA-seq 系统评估组织信号反应的框架
IF 9.3 1区 生物学 Q1 Medicine Pub Date : 2024-04-17 DOI: 10.1016/j.cels.2024.03.007
Laure-Emmanuelle Zaragosi

One snapshot of the peer review process for “A map of signaling responses in the human airway epithelium” (McCauley et al., 2024).1

人类气道上皮细胞信号反应图"(McCauley 等人,2024 年)1 同行评审过程的一个缩影。
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Cell Systems
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