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TDP-43 in nuclear condensates: where, how, and why. 核凝聚物中的 TDP-43:在哪里、如何以及为什么。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231447
Ruaridh Lang, Rachel E Hodgson, Tatyana A Shelkovnikova

TDP-43 is an abundant and ubiquitously expressed nuclear protein that becomes dysfunctional in a spectrum of neurodegenerative diseases. TDP-43's ability to phase separate and form/enter biomolecular condensates of varying size and composition is critical for its functionality. Despite the high density of phase-separated assemblies in the nucleus and the nuclear abundance of TDP-43, our understanding of the condensate-TDP-43 relationship in this cellular compartment is only emerging. Recent studies have also suggested that misregulation of nuclear TDP-43 condensation is an early event in the neurodegenerative disease amyotrophic lateral sclerosis. This review aims to draw attention to the nuclear facet of functional and aberrant TDP-43 condensation. We will summarise the current knowledge on how TDP-43 containing nuclear condensates form and function and how their homeostasis is affected in disease.

TDP-43 是一种丰富且普遍表达的核蛋白,在一系列神经退行性疾病中会出现功能障碍。TDP-43 相分离和形成/进入不同大小和组成的生物分子凝聚体的能力对其功能至关重要。尽管细胞核中的相分离集合体密度很高,而且 TDP-43 在细胞核中的丰度也很高,但我们对这一细胞区室中凝聚体与 TDP-43 之间关系的了解却刚刚开始。最近的研究还表明,核 TDP-43 凝聚失调是神经退行性疾病肌萎缩侧索硬化症的早期事件。本综述旨在引起人们对功能性和异常 TDP-43 凝聚的核方面的关注。我们将总结目前关于含有 TDP-43 的核凝聚体如何形成和发挥功能,以及它们在疾病中的稳态如何受到影响的知识。
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引用次数: 0
Early heart development: examining the dynamics of function-form emergence. 早期心脏发育:研究功能形式出现的动态过程。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20230546
Noémie Combémorel, Natasha Cavell, Richard C V Tyser

During early embryonic development, the heart undergoes a remarkable and complex transformation, acquiring its iconic four-chamber structure whilst concomitantly contracting to maintain its essential function. The emergence of cardiac form and function involves intricate interplays between molecular, cellular, and biomechanical events, unfolding with precision in both space and time. The dynamic morphological remodelling of the developing heart renders it particularly vulnerable to congenital defects, with heart malformations being the most common type of congenital birth defect (∼35% of all congenital birth defects). This mini-review aims to give an overview of the morphogenetic processes which govern early heart formation as well as the dynamics and mechanisms of early cardiac function. Moreover, we aim to highlight some of the interplay between these two processes and discuss how recent findings and emerging techniques/models offer promising avenues for future exploration. In summary, the developing heart is an exciting model to gain fundamental insight into the dynamic relationship between form and function, which will augment our understanding of cardiac congenital defects and provide a blueprint for potential therapeutic strategies to treat disease.

在早期胚胎发育过程中,心脏经历了非凡而复杂的转变,获得了标志性的四腔结构,同时收缩以维持其基本功能。心脏形态和功能的形成涉及分子、细胞和生物力学事件之间错综复杂的相互作用,并在空间和时间上精确展开。发育中心脏的动态形态重塑使其特别容易出现先天性缺陷,而心脏畸形是最常见的先天性出生缺陷类型(占所有先天性出生缺陷的 35%)。本微型综述旨在概述支配早期心脏形成的形态发生过程以及早期心脏功能的动态和机制。此外,我们还旨在强调这两个过程之间的一些相互作用,并讨论最新发现和新兴技术/模型如何为未来探索提供了前景广阔的途径。总之,发育中的心脏是一个令人兴奋的模型,它能让我们从根本上了解形态与功能之间的动态关系,这将增强我们对心脏先天缺陷的了解,并为潜在的疾病治疗策略提供蓝图。
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引用次数: 0
Roles for PMP22 in Schwann cell cholesterol homeostasis in health and disease. PMP22 在健康和疾病中的许旺细胞胆固醇稳态中的作用
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231359
Katherine M Stefanski, Mason C Wilkinson, Charles R Sanders

Underexpression, overexpression, and point mutations in peripheral myelin protein 22 (PMP22) cause most cases of Charcot-Marie-Tooth disease (CMTD). While its exact functions remain unclear, PMP22 is clearly essential for formation and maintenance of healthy myelin in the peripheral nervous system. This review explores emerging evidence for roles of PMP22 in cholesterol homeostasis. First, we highlight dysregulation of lipid metabolism in PMP22-based forms of CMTD and recently-discovered interactions between PMP22 and cholesterol biosynthesis machinery. We then examine data that demonstrates PMP22 and cholesterol co-traffic in cells and co-localize in lipid rafts, including how disease-causing PMP22 mutations result in aberrations in cholesterol localization. Finally, we examine roles for interactions between PMP22 and ABCA1 in cholesterol efflux. Together, this emerging body of evidence suggests that PMP22 plays a role in facilitating enhanced cholesterol synthesis and trafficking necessary for production and maintenance of healthy myelin.

外周髓鞘蛋白 22(PMP22)的表达不足、过度表达和点突变导致了大多数夏科-玛丽-牙病(CMTD)病例。虽然 PMP22 的确切功能尚不清楚,但它显然对周围神经系统中健康髓鞘的形成和维持至关重要。本综述探讨了 PMP22 在胆固醇稳态中发挥作用的新证据。首先,我们强调了以 PMP22 为基础的 CMTD 的脂质代谢失调,以及最近发现的 PMP22 与胆固醇生物合成机制之间的相互作用。然后,我们研究了证明 PMP22 和胆固醇在细胞中共同运输并在脂质筏中共同定位的数据,包括致病的 PMP22 基因突变如何导致胆固醇定位异常。最后,我们研究了 PMP22 和 ABCA1 在胆固醇外流中的相互作用。这些新出现的证据共同表明,PMP22 在促进生成和维持健康髓鞘所需的胆固醇合成和运输方面发挥了作用。
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引用次数: 0
Cytokinin and reproductive shoot architecture: bigger and better? 细胞分裂素和生殖芽结构:越大越好?
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231565
Catriona H Walker, Tom Bennett

Cytokinin (CK) is a key plant hormone, but one whose effects are often misunderstood, partly due to reliance on older data from before the molecular genetic age of plant science. In this mini-review, we examine the role of CK in controlling the reproductive shoot architecture of flowering plants. We begin with a long overdue re-examination of the role of CK in shoot branching, and discuss the relatively paucity of genetic evidence that CK does play a major role in this process. We then examine the role of CK in determining the number of inflorescences, flowers, fruit and seed that plants initiate during reproductive development, and how these are arranged in space and time. The genetic evidence for a major role of CK in controlling these processes is much clearer, and CK has profound effects in boosting the size and number of most reproductive structures. Conversely, the attenuation of CK levels during the reproductive phase likely contributes to reduced organ size seen later in flowering, and the ultimate arrest of inflorescence meristems during end-of-flowering. We finish by discussing how this information can potentially be used to improve crop yields.

细胞分裂素(CK)是一种重要的植物激素,但它的作用常常被误解,部分原因是依赖于植物科学分子遗传时代之前的旧数据。在这篇微型综述中,我们将探讨细胞分裂素在控制开花植物生殖枝结构中的作用。首先,我们重新审视了 CK 在嫩枝分枝过程中的作用,并讨论了相对较少的遗传证据表明 CK 在这一过程中确实发挥了重要作用。然后,我们研究了 CK 在决定植物生殖发育过程中的花序、花朵、果实和种子数量方面的作用,以及这些花序、花朵、果实和种子在空间和时间上的排列方式。遗传学证据表明,CK 在控制这些过程中发挥着重要作用。相反,生殖期 CK 水平的降低可能会导致开花后期器官尺寸的缩小,以及花序分生组织在花期结束时的最终停止。最后,我们将讨论如何利用这些信息来提高作物产量。
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引用次数: 0
Nuclear RNA: a transcription-dependent regulator of chromatin structure. 核糖核酸:依赖转录的染色质结构调节器。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20230787
Jon Stocks, Nick Gilbert

Although the majority of RNAs are retained in the nucleus, their significance is often overlooked. However, it is now becoming clear that nuclear RNA forms a dynamic structure through interacting with various proteins that can influence the three-dimensional structure of chromatin. We review the emerging evidence for a nuclear RNA mesh or gel, highlighting the interplay between DNA, RNA and RNA-binding proteins (RBPs), and assessing the critical role of protein and RNA in governing chromatin architecture. We also discuss a proposed role for the formation and regulation of the nuclear gel in transcriptional control. We suggest that it may concentrate the transcriptional machinery either by direct binding or inducing RBPs to form microphase condensates, nanometre sized membraneless structures with distinct properties to the surrounding medium and an enrichment of particular macromolecules.

虽然大多数 RNA 保留在细胞核中,但它们的重要性往往被忽视。然而,现在越来越清楚的是,核 RNA 通过与能影响染色质三维结构的各种蛋白质相互作用,形成了一种动态结构。我们回顾了核 RNA 网状结构或凝胶的新证据,强调了 DNA、RNA 和 RNA 结合蛋白(RBPs)之间的相互作用,并评估了蛋白质和 RNA 在管理染色质结构中的关键作用。我们还讨论了核凝胶的形成和调节在转录控制中的作用。我们认为,核凝胶可通过直接结合或诱导 RBPs 形成微相凝聚物来集中转录机制,这种凝聚物是纳米级的无膜结构,具有与周围介质截然不同的特性,并富含特定的大分子。
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引用次数: 0
Understanding pyrethrin biosynthesis: toward and beyond natural pesticide overproduction. 了解除虫菊酯的生物合成:走向并超越天然杀虫剂的过度生产。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20240213
Kazuhiko Matsuda

Pyrethrins are natural insecticides biosynthesised by Asteraceae plants, such as Tanacetum cinerariifolium and have a long history, dating back to ancient times. Pyrethrins are often used as low-persistence and safe insecticides to control household, horticultural, and agricultural insect pests. Despite its long history of use, pyrethrin biosynthesis remains a mystery, presenting a significant opportunity to improve yields and meet the growing demand for organic agriculture. To achieve this, both genetic modification and non-genetic methods, such as chemical activation and priming, are indispensable. Plants use pyrethrins as a defence against herbivores, but pyrethrin biosynthesis pathways are shared with plant hormones and signal molecules. Hence, the insight that pyrethrins may play broader roles than those traditionally expected is invaluable to advance the basic and applied sciences of pyrethrins.

拟除虫菊酯是由菊科植物(如丹蜱草)生物合成的天然杀虫剂,历史悠久,可追溯到古代。除虫菊素通常被用作低持久性的安全杀虫剂,用于控制家庭、园艺和农业害虫。尽管使用历史悠久,但除虫菊酯的生物合成仍然是一个谜,这为提高产量和满足日益增长的有机农业需求提供了一个重要机会。要实现这一目标,基因改造和非基因方法(如化学激活和引物)都不可或缺。植物利用除虫菊酯来抵御食草动物,但除虫菊酯的生物合成途径与植物激素和信号分子共享。因此,了解到除虫菊酯可能发挥比传统预期更广泛的作用,对于推动除虫菊酯基础科学和应用科学的发展非常有价值。
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引用次数: 0
Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems. X 染色体的非孟德尔传播:机制及其对不同育种系统中性别比例和种群动态的影响。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231411
Sally Adams, Andre Pires-daSilva

The non-Mendelian transmission of sex chromosomes during gametogenesis carries significant implications, influencing sex ratios and shaping evolutionary dynamics. Here we focus on known mechanisms that drive non-Mendelian inheritance of X chromosomes during spermatogenesis and their impact on population dynamics in species with different breeding systems. In Drosophila and mice, X-linked drivers targeting Y-bearing sperm for elimination or limiting their fitness, tend to confer unfavourable effects, prompting the evolution of suppressors to mitigate their impact. This leads to a complex ongoing evolutionary arms race to maintain an equal balance of males and females. However, in certain insects and nematodes with XX/X0 sex determination, the preferential production of X-bearing sperm through atypical meiosis yields wild-type populations with highly skewed sex ratios, suggesting non-Mendelian transmission of the X may offer selective advantages in these species. Indeed, models suggest X-meiotic drivers could bolster population size and persistence under certain conditions, challenging the conventional view of their detrimental effects. Furthering our understanding of the diverse mechanisms and evolutionary consequences of non-Mendelian transmission of X chromosomes will provide insights into genetic inheritance, sex determination, and population dynamics, with implications for fundamental research and practical applications.

配子发生过程中性染色体的非孟德尔遗传具有重要意义,可影响性别比例和进化动态。在此,我们将重点研究在精子发生过程中驱动 X 染色体非孟德尔遗传的已知机制及其对不同繁殖系统物种种群动态的影响。在果蝇和小鼠中,针对含Y精子的X连锁驱动因子往往会产生不利影响,从而导致抑制因子的进化,以减轻其影响。这导致了一场复杂的持续进化军备竞赛,以维持雌雄平衡。然而,在某些性别决定为 XX/X0 的昆虫和线虫中,通过非典型减数分裂优先产生含 X 的精子,从而产生了性别比例高度倾斜的野生型种群。事实上,模型表明,在某些条件下,X-减数分裂的驱动力可以增强种群的规模和持续性,这对传统的有害影响观点提出了挑战。进一步了解 X 染色体非孟德尔传递的各种机制和进化后果,将有助于我们深入了解遗传、性别决定和种群动态,并对基础研究和实际应用产生影响。
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引用次数: 0
Plant supercomplex I + III2 structure and function: implications for the growing field. 植物超级复合体 I + III2 的结构和功能:对不断发展的领域的影响。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20230947
Maria Maldonado

Mitochondrial respiration is major source of chemical energy for all free-living eukaryotes. Nevertheless, the mechanisms of the respiratory complexes and supercomplexes remain poorly understood. Here, I review recent structural and functional investigations of plant supercomplex I + III2 from Arabidopsis thaliana and Vigna radiata. I discuss commonalities, open questions and implications for complex I, complex III2 and supercomplexes in plants and non-plants. Studies across further clades will enhance our understanding of respiration and the potential universal mechanisms of its complexes and supercomplexes.

线粒体呼吸是所有自由生活真核生物的主要化学能量来源。然而,人们对呼吸复合体和超级复合体的机制仍然知之甚少。在此,我回顾了最近对拟南芥和黑叶木槿植物超级复合物 I + III2 的结构和功能研究。我将讨论植物和非植物中复合体 I、复合体 III2 和超级复合体的共性、未决问题和影响。对更多支系的研究将增进我们对呼吸作用及其复合体和超级复合体潜在普遍机制的了解。
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引用次数: 0
Enzymes of sphingolipid metabolism as transducers of metabolic inputs. 鞘脂代谢酶是新陈代谢输入的转换器。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231442
Fabiola N Velazquez, Chiara Luberto, Daniel Canals, Yusuf A Hannun

Sphingolipids (SLs) constitute a discrete subdomain of metabolism, and they display both structural and signaling functions. Accumulating evidence also points to intimate connections between intermediary metabolism and SL metabolism. Given that many SLs exhibit bioactive properties (i.e. transduce signals), these raise the possibility that an important function of SLs is to relay information on metabolic changes into specific cell responses. This could occur at various levels. Some metabolites are incorporated into SLs, whereas others may initiate regulatory or signaling events that, in turn, modulate SL metabolism. In this review, we elaborate on the former as it represents a poorly appreciated aspect of SL metabolism, and we develop the hypothesis that the SL network is highly sensitive to several specific metabolic changes, focusing on amino acids (serine and alanine), various fatty acids, choline (and ethanolamine), and glucose.

鞘磷脂(SL)是新陈代谢的一个独立子域,具有结构和信号功能。不断积累的证据还表明,中间代谢与鞘磷脂代谢之间存在密切联系。鉴于许多可溶性脂质具有生物活性(即传递信号),这就提出了一种可能性,即可溶性脂质的一个重要功能是将新陈代谢变化的信息传递给特定的细胞反应。这可能发生在不同层面。一些代谢物被纳入 SL,而另一些代谢物则可能启动调节或信号事件,进而调节 SL 的代谢。在这篇综述中,我们阐述了前者,因为它代表了 SL 代谢中一个鲜为人知的方面,我们提出了 SL 网络对几种特定代谢变化高度敏感的假设,重点是氨基酸(丝氨酸和丙氨酸)、各种脂肪酸、胆碱(和乙醇胺)和葡萄糖。
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引用次数: 0
Progress in multifactorial single-cell chromatin profiling methods. 多因素单细胞染色质谱分析方法的进展。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1042/BST20231471
Tim Stuart

Chromatin states play a key role in shaping overall cellular states and fates. Building a complete picture of the functional state of chromatin in cells requires the co-detection of several distinct biochemical aspects. These span DNA methylation, chromatin accessibility, chromosomal conformation, histone posttranslational modifications, and more. While this certainly presents a challenging task, over the past few years many new and creative methods have been developed that now enable co-assay of these different aspects of chromatin at single cell resolution. This field is entering an exciting phase, where a confluence of technological improvements, decreased sequencing costs, and computational innovation are presenting new opportunities to dissect the diversity of chromatin states present in tissues, and how these states may influence gene regulation. In this review, I discuss the spectrum of current experimental approaches for multifactorial chromatin profiling, highlight some of the experimental and analytical challenges, as well as some areas for further innovation.

染色质状态在塑造细胞整体状态和命运方面发挥着关键作用。要全面了解细胞中染色质的功能状态,需要同时检测多个不同的生化方面。这些方面包括 DNA 甲基化、染色质可及性、染色体构象、组蛋白翻译后修饰等。虽然这无疑是一项具有挑战性的任务,但在过去几年中,许多新的创造性方法已经开发出来,现在可以在单细胞分辨率下对染色质的这些不同方面进行联合检测。这一领域正进入一个令人兴奋的阶段,技术的改进、测序成本的降低和计算的创新为剖析组织中染色质状态的多样性以及这些状态如何影响基因调控提供了新的机遇。在这篇综述中,我将讨论当前多因素染色质图谱分析的各种实验方法,强调一些实验和分析方面的挑战,以及一些有待进一步创新的领域。
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引用次数: 0
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