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The microbiota's role in flavivirus control: Rosenbergiella_YN46. 微生物群在黄病毒控制中的作用:Rosenbergiella_YN46。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-08 DOI: 10.1016/j.tim.2024.05.009
Biao Hu, Jianping Chen, Zongtao Sun

The transmission of flaviviruses, such as dengue virus (DENV) and Zika virus (ZIKV), poses a significant threat to global public health. Zhang et al. recently showed that Rosenbergiella sp. YN46 (Rosenbergiella_YN46), a bacterium from the mosquito gut, inhibits flavivirus transmission and thus offers a potential biocontrol strategy with broad public health implications.

登革病毒(DENV)和寨卡病毒(ZIKV)等黄病毒的传播对全球公共卫生构成了重大威胁。Zhang 等人最近研究发现,蚊子肠道中的一种细菌 Rosenbergiella sp.
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引用次数: 0
Deciphering Fc-effector functions against SARS-CoV-2. 解密 Fc-效应器对抗 SARS-CoV-2 的功能
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-02-15 DOI: 10.1016/j.tim.2024.01.005
Guillaume Beaudoin-Bussières, Andrés Finzi

Major efforts were deployed to study the antibody response against SARS-CoV-2. Antibodies neutralizing SARS-CoV-2 have been extensively studied in the context of infections, vaccinations, and breakthrough infections. Antibodies, however, are pleiotropic proteins that have many functions in addition to neutralization. These include Fc-effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Although important to combat viral infections, these Fc-effector functions were less studied in the context of SARS-CoV-2 compared with binding and neutralization. This is partly due to the difficulty in developing reliable assays to measure Fc-effector functions compared to antibody binding and neutralization. Multiple assays have now been developed and can be used to measure different Fc-effector functions. Here, we review these assays and what is known regarding anti-SARS-CoV-2 Fc-effector functions. Overall, this review summarizes and updates our current state of knowledge regarding anti-SARS-CoV-2 Fc-effector functions.

研究针对 SARS-CoV-2 的抗体反应是一项重要工作。在感染、疫苗接种和突破性感染方面,对中和 SARS-CoV-2 的抗体进行了广泛的研究。然而,抗体是一种多效蛋白,除了中和作用外,还具有多种功能。这些功能包括 Fc 效应器功能,如抗体依赖性细胞毒性(ADCC)和抗体依赖性细胞吞噬作用(ADCP)。虽然这些 Fc 效应功能对抗病毒感染很重要,但与结合和中和相比,对 SARS-CoV-2 的研究较少。部分原因是,与抗体结合和中和相比,很难开发出可靠的检测方法来测量 Fc-效应器功能。目前已开发出多种检测方法,可用于测量不同的 Fc-效应器功能。在此,我们回顾了这些检测方法以及目前已知的抗 SARS-CoV-2 Fc-效应器功能。总之,本综述总结并更新了我们目前对抗 SARS-CoV-2 Fc-效应器功能的了解。
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引用次数: 0
Broadening the targetable space: engineering and discovery of PAM-flexible Cas proteins. 拓宽靶向空间:PAM 灵活 Cas 蛋白的工程设计与发现。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-29 DOI: 10.1016/j.tim.2024.05.004
Zhenkun Cai, Weiyu Xie, Zehua Bao

The application of CRISPR-Cas systems has been hindered by their requirement for long protospacer-adjacent motifs (PAMs). Recent engineering and discovery of PAM-flexible Cas proteins have substantially broadened the targetable DNA sequence space, thereby facilitating genome editing and improving derivative technologies such as gene regulation, seamless cloning, and large-scale genetic screens.

CRISPR-Cas系统的应用一直受制于对长原位相邻基序(PAM)的要求。最近,PAM 灵活 Cas 蛋白的工程设计和发现大大拓宽了可靶向的 DNA 序列空间,从而促进了基因组编辑,并改善了基因调控、无缝克隆和大规模基因筛选等衍生技术。
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引用次数: 0
Forecasting antimicrobial resistance evolution. 预测抗菌药耐药性的演变。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-01-18 DOI: 10.1016/j.tim.2023.12.009
Jens Rolff, Sebastian Bonhoeffer, Charlotte Kloft, Rasmus Leistner, Roland Regoes, Michael E Hochberg

Antimicrobial resistance (AMR) is a major global health issue. Current measures for tackling it comprise mainly the prudent use of drugs, the development of new drugs, and rapid diagnostics. Relatively little attention has been given to forecasting the evolution of resistance. Here, we argue that forecasting has the potential to be a great asset in our arsenal of measures to tackle AMR. We argue that, if successfully implemented, forecasting resistance will help to resolve the antibiotic crisis in three ways: it will (i) guide a more sustainable use (and therefore lifespan) of antibiotics and incentivize investment in drug development, (ii) reduce the spread of AMR genes and pathogenic microbes in the environment and between patients, and (iii) allow more efficient treatment of persistent infections, reducing the continued evolution of resistance. We identify two important challenges that need to be addressed for the successful establishment of forecasting: (i) the development of bespoke technology that allows stakeholders to empirically assess the risks of resistance evolving during the process of drug development and therapeutic/preventive use, and (ii) the transformative shift in mindset from the current praxis of mostly addressing the problem of antibiotic resistance a posteriori to a concept of a priori estimating, and acting on, the risks of resistance.

抗菌药耐药性(AMR)是一个重大的全球健康问题。目前的应对措施主要包括谨慎用药、开发新药和快速诊断。人们对耐药性演变的预测关注相对较少。在此,我们认为,预测有可能成为我们应对 AMR 的措施库中的一项重要资产。我们认为,如果能够成功实施,抗药性预测将有助于从三个方面解决抗生素危机:(i) 指导更可持续地使用抗生素(从而延长抗生素的寿命),激励对药物开发的投资;(ii) 减少 AMR 基因和病原微生物在环境中和病人之间的传播;(iii) 更有效地治疗顽固性感染,减少抗药性的持续演变。我们发现,要成功建立预测机制,需要应对两个重要挑战:(i) 开发定制技术,使利益相关者能够在药物开发和治疗/预防使用过程中对耐药性演变的风险进行经验评估;(ii) 转变观念,从目前主要在事后解决抗生素耐药性问题的做法转变为事先估计耐药性风险并采取相应行动的理念。
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引用次数: 0
Breaking bad nucleotides: understanding the regulatory mechanisms of bacterial small alarmone hydrolases. 打破不良核苷酸:了解细菌小报警酮水解酶的调控机制。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-01-22 DOI: 10.1016/j.tim.2023.12.011
Adriana Chrenková, Francesco Bisiak, Ditlev E Brodersen

Guanosine tetra- and pentaphosphate nucleotides, (p)ppGpp, function as central secondary messengers and alarmones in bacterial cell biology, signalling a range of stress conditions, including nutrient starvation and exposure to cell-wall-targeting antibiotics, and are critical for survival. While activation of the stringent response and alarmone synthesis on starved ribosomes by members of the RSH (Rel) class of proteins is well understood, much less is known about how single-domain small alarmone synthetases (SASs) and their corresponding alarmone hydrolases, the small alarmone hydrolases (SAHs), are regulated and contribute to (p)ppGpp homeostasis. The substrate spectrum of these enzymes has recently been expanded to include hyperphosphorylated adenosine nucleotides, suggesting that they take part in a highly complex and interconnected signalling network. In this review, we provide an overview of our understanding of the SAHs and discuss their structure, function, regulation, and phylogeny.

四磷酸和五磷酸鸟苷核苷酸((p)ppGpp)是细菌细胞生物学中的核心次级信使和警报素,可发出一系列应激信号,包括营养饥饿和暴露于细胞壁靶向抗生素,对生存至关重要。虽然人们对 RSH(Rel)类蛋白激活严格反应和饥饿核糖体上的报警酮合成已经有了很好的了解,但对单链小报警酮合成酶(SAS)及其相应的报警酮水解酶--小报警酮水解酶(SAH)--如何调节和促进(pp)ppGpp 稳态却知之甚少。这些酶的底物谱最近已扩大到包括过磷酸化腺苷核苷酸,这表明它们参与了一个高度复杂和相互关联的信号网络。在这篇综述中,我们概述了我们对 SAHs 的了解,并讨论了它们的结构、功能、调控和系统发育。
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引用次数: 0
Immunological roads diverged: mapping tuberculosis outcomes in mice. 免疫学道路上的分歧:绘制小鼠结核病结果图。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-20 DOI: 10.1016/j.tim.2024.06.007
Rachel K Meade, Clare M Smith

The journey from phenotypic observation to causal genetic mechanism is a long and challenging road. For pathogens like Mycobacterium tuberculosis (Mtb), which causes tuberculosis (TB), host-pathogen coevolution has spanned millennia, costing millions of human lives. Mammalian models can systematically recapitulate host genetic variation, producing a spectrum of disease outcomes. Leveraging genome sequences and deep phenotyping data from infected mouse genetic reference populations (GRPs), quantitative trait locus (QTL) mapping approaches have successfully identified host genomic regions associated with TB phenotypes. Here, we review the ongoing optimization of QTL mapping study design alongside advances in mouse GRPs. These next-generation resources and approaches have enabled identification of novel host-pathogen interactions governing one of the most prevalent infectious diseases in the world today.

从表型观察到因果遗传机制是一条漫长而充满挑战的道路。对于结核分枝杆菌(Mtb)等导致肺结核(TB)的病原体来说,宿主与病原体的共同进化跨越了数千年,夺走了数百万人的生命。哺乳动物模型可以系统地再现宿主基因变异,产生一系列疾病结果。利用基因组序列和来自受感染小鼠遗传参考群体(GRPs)的深度表型数据,定量性状位点(QTL)绘图方法已成功鉴定出与结核病表型相关的宿主基因组区域。在此,我们回顾了 QTL 图谱研究设计的不断优化以及小鼠 GRPs 的进步。这些下一代资源和方法使我们能够鉴定新的宿主-病原体相互作用,从而控制当今世界上最流行的传染病之一。
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引用次数: 0
Cell-free DNA: a promising biomarker in infectious diseases. 无细胞 DNA:传染性疾病中一种前景广阔的生物标记物。
IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-11 DOI: 10.1016/j.tim.2024.06.005
Yuxuan Hu, Yanping Zhao, Yan Zhang, Weijun Chen, Haiqiang Zhang, Xin Jin

Infectious diseases pose serious threats to public health worldwide. Conventional diagnostic methods for infectious diseases often exhibit low sensitivity, invasiveness, and long turnaround times. User-friendly point-of-care tests are urgently needed for early diagnosis, treatment monitoring, and prognostic prediction of infectious diseases. Cell-free DNA (cfDNA), a promising non-invasive biomarker widely used in oncology and pregnancy, has shown great potential in clinical applications for diagnosing infectious diseases. Here, we discuss the most recent cfDNA research on infectious diseases from both the pathogen and host perspectives. We also discuss the technical challenges in this field and propose solutions to overcome them. Additionally, we provide an outlook on the potential of cfDNA as a diagnostic, treatment, and prognostic marker for infectious diseases.

传染病对全球公共卫生构成严重威胁。传统的传染病诊断方法往往灵敏度低、侵入性大、周转时间长。传染病的早期诊断、治疗监测和预后预测迫切需要方便用户的床旁检测。无细胞 DNA(cfDNA)是一种前景广阔的非侵入性生物标记物,被广泛应用于肿瘤学和妊娠学领域,在传染病诊断的临床应用中也显示出巨大的潜力。在此,我们将从病原体和宿主的角度讨论有关传染性疾病的最新 cfDNA 研究。我们还讨论了这一领域的技术挑战,并提出了克服这些挑战的解决方案。此外,我们还对 cfDNA 作为传染病诊断、治疗和预后标志物的潜力进行了展望。
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引用次数: 0
Addressing challenges associated with nitrification inhibitors 应对与硝化抑制剂有关的挑战
IF 15.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-09 DOI: 10.1016/j.tim.2024.06.004
Yong Zhang, Diego Abalos, Xiaoli Cheng

Despite global yield benefits from the use of nitrification inhibitors (NIs), the uncertainties and limitations surrounding NIs warrant more attention. Understanding the impacts of NIs on the health of organisms, people, and ecosystems is also crucial. Here we present a global budget, current challenges, and future research priorities of NIs.

尽管硝化抑制剂(NIs)的使用给全球产量带来了好处,但围绕硝化抑制剂的不确定性和局限性仍值得更多关注。了解 NIs 对生物、人类和生态系统健康的影响也至关重要。在此,我们将介绍 NIs 的全球预算、当前挑战和未来研究重点。
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引用次数: 0
Melanized root-associated fungi: key players in plant–soil systems 黑色根相关真菌:植物-土壤系统中的关键角色
IF 15.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-09 DOI: 10.1016/j.tim.2024.06.006
Tarquin Netherway, Mohammad Bahram

Melanized root-associated fungi are a group of fungi that produce melanized structures and form root associations, including different mycorrhizal and endophytic symbioses with plants. They are pervasive across terrestrial ecosystems and play an important role in the prevailing soil carbon (C) and nutrient cycling syndromes through direct and indirect mechanisms, where they may strongly modulate plant–microbe interactions and structure root and soil microbiomes. Furthermore, melanized root-associated fungi can confer on plants an enhanced ability to tolerate abiotic and biotic stressors such as drought, extreme temperatures, heavy metals, and pathogen attacks. We propose that melanized root-associated fungi are a cohesive and ecologically relevant grouping that can be an indicator of plant–soil system functioning, and considering them will advance research on plant–soil interactions.

黑色根相关真菌是一类产生黑色结构并与植物形成根缘关系(包括不同的菌根和内生共生关系)的真菌。它们普遍存在于陆地生态系统中,通过直接和间接机制,在当前的土壤碳(C)和养分循环综合体中发挥着重要作用。此外,黑色根相关真菌还能增强植物对干旱、极端温度、重金属和病原体侵袭等非生物和生物胁迫的耐受能力。我们认为,黑色化根相关真菌是一个具有凝聚力和生态相关性的群体,可以作为植物-土壤系统功能的指标,对它们进行研究将推动植物-土壤相互作用的研究。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 15.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-02 DOI: 10.1016/s0966-842x(24)00150-1
No Abstract
无摘要
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引用次数: 0
期刊
Trends in Microbiology
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