首页 > 最新文献

Biochemical Society transactions最新文献

英文 中文
Mechanoimmunology in the solid tumor microenvironment. 实体肿瘤微环境中的机制免疫学。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231427
Matteo Golo, Peter L H Newman, Daryan Kempe, Maté Biro

The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.

肿瘤微环境(TME)是一个复杂而动态的生态系统,它与实体瘤内的癌细胞相邻,由细胞外基质、基质和免疫细胞、血管以及大量信号分子等不同成分组成。近年来,TME 的机械特性已成为肿瘤进展和治疗反应的关键决定因素。异常的机械线索,包括组织结构和硬度的改变,会导致肿瘤的进展、转移和抗药性。此外,蓬勃发展的免疫疗法为利用免疫系统靶向消除实体恶性肿瘤带来了巨大希望;然而,它们的成功却受阻于 TME 充满敌意的机械结构,这可能会阻碍免疫细胞的浸润、功能和持久性。因此,了解TME机械免疫学--机械力与免疫细胞行为之间的相互作用--对于开发有效的实体肿瘤疗法至关重要。在此,我们回顾了TME力学在肿瘤免疫学中的作用,重点介绍了近期旨在调节TME力学特性以增强T细胞免疫疗法的治疗干预措施,以及为评估其临床疗效而量身定制的创新检测方法。
{"title":"Mechanoimmunology in the solid tumor microenvironment.","authors":"Matteo Golo, Peter L H Newman, Daryan Kempe, Maté Biro","doi":"10.1042/BST20231427","DOIUrl":"10.1042/BST20231427","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1489-1502"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nano-organization of synaptic calcium signaling. 突触钙信号的纳米组织
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231385
Clara I McCarthy, Ege T Kavalali

Recent studies suggest an exquisite structural nano-organization within single synapses, where sites of evoked fusion - marked by clustering of synaptic vesicles, active zone proteins and voltage-gated calcium channels - are directly juxtaposed to postsynaptic receptor clusters within nanocolumns. This direct nanometer scale alignment between presynaptic fusion apparatus and postsynaptic receptors is thought to ensure the fidelity of synaptic signaling and possibly allow multiple distinct signals to occur without interference from each other within a single active zone. The functional specificity of this organization is made possible by the inherent nano-organization of calcium signals, where all the different calcium sources such as voltage-gated calcium channels, intracellular stores and store-operated calcium entry have dedicated local targets within their nanodomain to ensure precision of action. Here, we discuss synaptic nano-organization from the perspective of calcium signals, where some of the principal findings from early work in the 1980s continue to inspire current studies that exploit new genetic tools and super-resolution imaging technologies.

最近的研究表明,在单个突触内存在一种精致的纳米结构组织,其中诱发融合的部位(以突触小泡、活性区蛋白和电压门控钙通道的聚集为标志)与纳米柱内的突触后受体群直接并列。突触前融合器和突触后受体之间这种直接的纳米级排列被认为是为了确保突触信号的保真度,并有可能使多个不同的信号在单个活跃区内不受干扰地发生。这种组织的功能特异性得益于钙信号固有的纳米组织,其中所有不同的钙源(如电压门控钙通道、细胞内贮存和贮存操作钙离子进入)在其纳米域内都有专门的局部目标,以确保作用的精确性。在这里,我们从钙信号的角度讨论突触纳米组织,20 世纪 80 年代早期工作中的一些主要发现继续启发着当前的研究,这些研究利用了新的遗传工具和超分辨率成像技术。
{"title":"Nano-organization of synaptic calcium signaling.","authors":"Clara I McCarthy, Ege T Kavalali","doi":"10.1042/BST20231385","DOIUrl":"10.1042/BST20231385","url":null,"abstract":"<p><p>Recent studies suggest an exquisite structural nano-organization within single synapses, where sites of evoked fusion - marked by clustering of synaptic vesicles, active zone proteins and voltage-gated calcium channels - are directly juxtaposed to postsynaptic receptor clusters within nanocolumns. This direct nanometer scale alignment between presynaptic fusion apparatus and postsynaptic receptors is thought to ensure the fidelity of synaptic signaling and possibly allow multiple distinct signals to occur without interference from each other within a single active zone. The functional specificity of this organization is made possible by the inherent nano-organization of calcium signals, where all the different calcium sources such as voltage-gated calcium channels, intracellular stores and store-operated calcium entry have dedicated local targets within their nanodomain to ensure precision of action. Here, we discuss synaptic nano-organization from the perspective of calcium signals, where some of the principal findings from early work in the 1980s continue to inspire current studies that exploit new genetic tools and super-resolution imaging technologies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1459-1471"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the role non-coding RNAs during myocardial cell fate. 探索非编码 RNA 在心肌细胞命运中的作用
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231216
Diego Franco, Cristina Sánchez-Fernández, Carlos García-Padilla, Estefania Lozano-Velasco

Myocardial cell fate specification takes place during the early stages of heart development as the precardiac mesoderm is configured into two symmetrical sets of bilateral precursor cells. Molecular cues of the surrounding tissues specify and subsequently determine the early cardiomyocytes, that finally matured as the heart is completed at early postnatal stages. Over the last decade, we have greatly enhanced our understanding of the transcriptional regulation of cardiac development and thus of myocardial cell fate. The recent discovery of a novel layer of gene regulation by non-coding RNAs has flourished their implication in epigenetic, transcriptional and post-transcriptional regulation of cardiac development. In this review, we revised the current state-of-the-art knowledge on the functional role of non-coding RNAs during myocardial cell fate.

心肌细胞命运的指定发生在心脏发育的早期阶段,因为心肌前中胚层被配置成两组对称的双侧前体细胞。周围组织的分子线索指定并随后决定了早期心肌细胞,这些细胞最终在出生后早期心脏发育完成时成熟。在过去的十年中,我们对心脏发育的转录调控以及心肌细胞命运的了解有了很大的提高。最近,我们发现了非编码 RNA 对基因调控的一个新的层次,这使得非编码 RNA 在心脏发育的表观遗传、转录和转录后调控中的作用更加突出。在这篇综述中,我们回顾了目前关于非编码 RNA 在心肌细胞命运过程中的功能作用的最新知识。
{"title":"Exploring the role non-coding RNAs during myocardial cell fate.","authors":"Diego Franco, Cristina Sánchez-Fernández, Carlos García-Padilla, Estefania Lozano-Velasco","doi":"10.1042/BST20231216","DOIUrl":"10.1042/BST20231216","url":null,"abstract":"<p><p>Myocardial cell fate specification takes place during the early stages of heart development as the precardiac mesoderm is configured into two symmetrical sets of bilateral precursor cells. Molecular cues of the surrounding tissues specify and subsequently determine the early cardiomyocytes, that finally matured as the heart is completed at early postnatal stages. Over the last decade, we have greatly enhanced our understanding of the transcriptional regulation of cardiac development and thus of myocardial cell fate. The recent discovery of a novel layer of gene regulation by non-coding RNAs has flourished their implication in epigenetic, transcriptional and post-transcriptional regulation of cardiac development. In this review, we revised the current state-of-the-art knowledge on the functional role of non-coding RNAs during myocardial cell fate.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1339-1348"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease. 让我们胖起来:S-酰化成为亨廷顿病的治疗靶点。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231290
Dale D O Martin, Shaun S Sanders

Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene. The protein that is mutated in HD, huntingtin, is less S-acylated which is associated with mutant HTT aggregation and cytotoxicity. Recent exciting findings indicate that restoring S-acylation in HD models using small molecule inhibitors of the deacylation enzymes is protective. Herein, we set out to describe the known roles of S-acylation in HD and how it can be targeted for therapeutic design.

无论病因如何,蛋白质错位都是神经变性的关键第一步,它与蛋白质中饱和脂肪酸的动态添加变化有关,这一过程被称为 S-酰化。随着研究 S-酰化的新技术的出现,以及最近发现促进蛋白质脱酰化的新酶,新型小分子药物正在成为潜在的新疗法。亨廷顿病(Huntington disease,HD)是一种毁灭性的致命神经退行性疾病,其特征是由 HTT 基因中的 CAG 重复扩增引起的运动、认知和精神障碍。在 HD 中发生突变的亨廷蛋白的 S-酰化程度较低,这与突变 HTT 的聚集和细胞毒性有关。最近令人兴奋的研究结果表明,使用脱乙酰化酶的小分子抑制剂恢复 HD 模型中的 S-乙酰化具有保护作用。在此,我们将介绍S-酰化在HD中的已知作用,以及如何将其作为治疗设计的靶点。
{"title":"Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease.","authors":"Dale D O Martin, Shaun S Sanders","doi":"10.1042/BST20231290","DOIUrl":"10.1042/BST20231290","url":null,"abstract":"<p><p>Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene. The protein that is mutated in HD, huntingtin, is less S-acylated which is associated with mutant HTT aggregation and cytotoxicity. Recent exciting findings indicate that restoring S-acylation in HD models using small molecule inhibitors of the deacylation enzymes is protective. Herein, we set out to describe the known roles of S-acylation in HD and how it can be targeted for therapeutic design.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1385-1392"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PROPPINs and membrane fission in the endo-lysosomal system. 内溶酶体系统中的 PROPPINs 和膜裂变。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20230897
Navin Gopaldass, Andreas Mayer

PROPPINs constitute a conserved protein family with multiple members being expressed in many eukaryotes. PROPPINs have mainly been investigated for their role in autophagy, where they co-operate with several core factors for autophagosome formation. Recently, novel functions of these proteins on endo-lysosomal compartments have emerged. PROPPINs support the division of these organelles and the formation of tubulo-vesicular cargo carriers that mediate protein exit from them, such as those generated by the Retromer coat. In both cases, PROPPINs provide membrane fission activity. Integrating information from yeast and human cells this review summarizes the most important molecular features that allow these proteins to facilitate membrane fission and thus provide a critical element to endo-lysosomal protein traffic.

PROPPINs 是一个保守的蛋白质家族,其多个成员在许多真核生物中都有表达。人们主要研究了 PROPPINs 在自噬过程中的作用,它们与自噬体形成过程中的几个核心因子合作。最近,人们发现了这些蛋白在内含溶酶体区室中的新功能。PROPPINs 支持这些细胞器的分裂,并支持形成管泡货物载体,从而介导蛋白质从这些细胞器中排出,例如由 Retromer 衣壳产生的载体。在这两种情况下,PROPPINs 都具有膜分裂活性。本综述综合了酵母和人类细胞的信息,总结了这些蛋白质促进膜裂解的最重要的分子特征,从而为内溶酶体蛋白质的运输提供了一个关键因素。
{"title":"PROPPINs and membrane fission in the endo-lysosomal system.","authors":"Navin Gopaldass, Andreas Mayer","doi":"10.1042/BST20230897","DOIUrl":"10.1042/BST20230897","url":null,"abstract":"<p><p>PROPPINs constitute a conserved protein family with multiple members being expressed in many eukaryotes. PROPPINs have mainly been investigated for their role in autophagy, where they co-operate with several core factors for autophagosome formation. Recently, novel functions of these proteins on endo-lysosomal compartments have emerged. PROPPINs support the division of these organelles and the formation of tubulo-vesicular cargo carriers that mediate protein exit from them, such as those generated by the Retromer coat. In both cases, PROPPINs provide membrane fission activity. Integrating information from yeast and human cells this review summarizes the most important molecular features that allow these proteins to facilitate membrane fission and thus provide a critical element to endo-lysosomal protein traffic.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1233-1241"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission. 超乎年龄的成熟:尽管生活在疟疾高度传播的环境中,但仍有幼儿未能被检测出寄生虫血症。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20230401
Prasida Holla, Jyoti Bhardwaj, Tuan M Tran

Despite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child's own immune system may contribute to control of malarial symptoms early in life and prior to the development of more effective adaptive immunity. Prospective studies of active and passive detection of Plasmodium falciparum blood-stage infections have identified young children (<5 years old) who remain uninfected through a defined surveillance period despite living in settings of highly intense malaria transmission. Yet, little is known about the potential immunological basis for this 'aparasitemic' phenotype. In this review, we summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. We discuss the challenges of distinguishing malaria protection from lack of malaria exposure in field studies. We also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.

尽管由于缺乏获得性免疫而发展成严重疾病的风险最高,但长期以来,人们一直观察到,生活在疟疾传播高度密集地区的最年幼儿童的感染率低于年龄较大的儿童。这一观察结果究竟是由于行为和生物因素、母体转移的免疫力、遗传因素,还是幼儿先天免疫力的增强导致接触传染性蚊虫叮咬的机会减少,半个多世纪以来一直困扰着疟疾研究人员。最近的证据表明,母体转移的免疫力可能仅限于婴儿早期,而幼儿自身的免疫系统可能有助于在生命早期和更有效的适应性免疫力发展之前控制疟疾症状。对恶性疟原虫血期感染进行主动和被动检测的前瞻性研究发现,幼儿 (
{"title":"Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.","authors":"Prasida Holla, Jyoti Bhardwaj, Tuan M Tran","doi":"10.1042/BST20230401","DOIUrl":"10.1042/BST20230401","url":null,"abstract":"<p><p>Despite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child's own immune system may contribute to control of malarial symptoms early in life and prior to the development of more effective adaptive immunity. Prospective studies of active and passive detection of Plasmodium falciparum blood-stage infections have identified young children (<5 years old) who remain uninfected through a defined surveillance period despite living in settings of highly intense malaria transmission. Yet, little is known about the potential immunological basis for this 'aparasitemic' phenotype. In this review, we summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. We discuss the challenges of distinguishing malaria protection from lack of malaria exposure in field studies. We also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1025-1034"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Technology to the rescue: how to uncover the role of transposable elements in preimplantation development. 技术拯救:如何揭示转座元件在植入前发育中的作用。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231262
Lauryn A Deaville, Rebecca V Berrens

Transposable elements (TEs) are highly expressed in preimplantation development. Preimplantation development is the phase when the cells of the early embryo undergo the first cell fate choice and change from being totipotent to pluripotent. A range of studies have advanced our understanding of TEs in preimplantation, as well as their epigenetic regulation and functional roles. However, many questions remain about the implications of TE expression during early development. Challenges originate first due to the abundance of TEs in the genome, and second because of the limited cell numbers in preimplantation. Here we review the most recent technological advancements promising to shed light onto the role of TEs in preimplantation development. We explore novel avenues to identify genomic TE insertions and improve our understanding of the regulatory mechanisms and roles of TEs and their RNA and protein products during early development.

可转座元件(TE)在胚胎植入前的发育过程中高度表达。胚胎植入前发育是早期胚胎细胞进行第一次细胞命运选择并从全能细胞转变为多能细胞的阶段。一系列研究加深了我们对植入前发育过程中 TEs 及其表观遗传调控和功能作用的了解。然而,关于 TE 表达在早期发育过程中的影响仍存在许多问题。首先,基因组中存在大量 TE,其次,胚胎植入前的细胞数量有限,这些都是面临挑战的原因。在此,我们回顾了有望揭示 TE 在植入前发育中作用的最新技术进展。我们将探索识别基因组 TE 插入的新途径,加深我们对 TE 及其 RNA 和蛋白质产物在早期发育过程中的调控机制和作用的理解。
{"title":"Technology to the rescue: how to uncover the role of transposable elements in preimplantation development.","authors":"Lauryn A Deaville, Rebecca V Berrens","doi":"10.1042/BST20231262","DOIUrl":"10.1042/BST20231262","url":null,"abstract":"<p><p>Transposable elements (TEs) are highly expressed in preimplantation development. Preimplantation development is the phase when the cells of the early embryo undergo the first cell fate choice and change from being totipotent to pluripotent. A range of studies have advanced our understanding of TEs in preimplantation, as well as their epigenetic regulation and functional roles. However, many questions remain about the implications of TE expression during early development. Challenges originate first due to the abundance of TEs in the genome, and second because of the limited cell numbers in preimplantation. Here we review the most recent technological advancements promising to shed light onto the role of TEs in preimplantation development. We explore novel avenues to identify genomic TE insertions and improve our understanding of the regulatory mechanisms and roles of TEs and their RNA and protein products during early development.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1349-1362"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nucleosomal asymmetry: a novel mechanism to regulate nucleosome function. 核小体不对称:调节核小体功能的新机制
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20230877
Devisree Valsakumar, Philipp Voigt

Nucleosomes constitute the fundamental building blocks of chromatin. They are comprised of DNA wrapped around a histone octamer formed of two copies each of the four core histones H2A, H2B, H3, and H4. Nucleosomal histones undergo a plethora of posttranslational modifications that regulate gene expression and other chromatin-templated processes by altering chromatin structure or by recruiting effector proteins. Given their symmetric arrangement, the sister histones within a nucleosome have commonly been considered to be equivalent and to carry the same modifications. However, it is now clear that nucleosomes can exhibit asymmetry, combining differentially modified sister histones or different variants of the same histone within a single nucleosome. Enabled by the development of novel tools that allow generating asymmetrically modified nucleosomes, recent biochemical and cell-based studies have begun to shed light on the origins and functional consequences of nucleosomal asymmetry. These studies indicate that nucleosomal asymmetry represents a novel regulatory mechanism in the establishment and functional readout of chromatin states. Asymmetry expands the combinatorial space available for setting up complex sets of histone marks at individual nucleosomes, regulating multivalent interactions with histone modifiers and readers. The resulting functional consequences of asymmetry regulate transcription, poising of developmental gene expression by bivalent chromatin, and the mechanisms by which oncohistones deregulate chromatin states in cancer. Here, we review recent progress and current challenges in uncovering the mechanisms and biological functions of nucleosomal asymmetry.

核小体是染色质的基本组成部分。核小体由 DNA 组成,外面包着组蛋白八聚体,组蛋白八聚体由四种核心组蛋白 H2A、H2B、H3 和 H4 各两份组成。核糖体组蛋白经过大量的翻译后修饰,通过改变染色质结构或招募效应蛋白来调节基因表达和其他染色质引发的过程。鉴于核小体的对称排列,核小体内的姐妹组蛋白通常被认为是等同的,并携带相同的修饰。然而,现在已经很清楚,核小体可以表现出不对称性,在单个核小体内结合了不同修饰的姐妹组蛋白或同一组蛋白的不同变体。由于开发出了可生成不对称修饰核小体的新型工具,最近的生化研究和基于细胞的研究已开始揭示核小体不对称的起源和功能性后果。这些研究表明,核小体不对称是染色质状态建立和功能读出的一种新型调控机制。不对称性扩大了可用于在单个核小体上建立复杂组蛋白标记集的组合空间,调节了与组蛋白修饰物和阅读器的多价相互作用。由此产生的不对称功能性后果可调节转录、二价染色质对发育基因表达的调控,以及共价组蛋白对癌症染色质状态的失调机制。在此,我们回顾了在揭示核小体不对称的机制和生物学功能方面的最新进展和当前挑战。
{"title":"Nucleosomal asymmetry: a novel mechanism to regulate nucleosome function.","authors":"Devisree Valsakumar, Philipp Voigt","doi":"10.1042/BST20230877","DOIUrl":"10.1042/BST20230877","url":null,"abstract":"<p><p>Nucleosomes constitute the fundamental building blocks of chromatin. They are comprised of DNA wrapped around a histone octamer formed of two copies each of the four core histones H2A, H2B, H3, and H4. Nucleosomal histones undergo a plethora of posttranslational modifications that regulate gene expression and other chromatin-templated processes by altering chromatin structure or by recruiting effector proteins. Given their symmetric arrangement, the sister histones within a nucleosome have commonly been considered to be equivalent and to carry the same modifications. However, it is now clear that nucleosomes can exhibit asymmetry, combining differentially modified sister histones or different variants of the same histone within a single nucleosome. Enabled by the development of novel tools that allow generating asymmetrically modified nucleosomes, recent biochemical and cell-based studies have begun to shed light on the origins and functional consequences of nucleosomal asymmetry. These studies indicate that nucleosomal asymmetry represents a novel regulatory mechanism in the establishment and functional readout of chromatin states. Asymmetry expands the combinatorial space available for setting up complex sets of histone marks at individual nucleosomes, regulating multivalent interactions with histone modifiers and readers. The resulting functional consequences of asymmetry regulate transcription, poising of developmental gene expression by bivalent chromatin, and the mechanisms by which oncohistones deregulate chromatin states in cancer. Here, we review recent progress and current challenges in uncovering the mechanisms and biological functions of nucleosomal asymmetry.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1219-1232"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Making the leap from technique to treatment - genetic engineering is paving the way for more efficient phage therapy. 从技术到治疗的飞跃--基因工程正在为更有效的噬菌体疗法铺平道路。
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20231289
Jessica M Lewis, Joshua Williams, Antonia P Sagona

Bacteriophages (phages) are viruses specific to bacteria that target them with great efficiency and specificity. Phages were first studied for their antibacterial potential in the early twentieth century; however, their use was largely eclipsed by the popularity of antibiotics. Given the surge of antimicrobial-resistant strains worldwide, there has been a renaissance in harnessing phages as therapeutics once more. One of the key advantages of phages is their amenability to modification, allowing the generation of numerous derivatives optimised for specific functions depending on the modification. These enhanced derivatives could display higher infectivity, expanded host range or greater affinity to human tissues, where some bacterial species exert their pathogenesis. Despite this, there has been a noticeable discrepancy between the generation of derivatives in vitro and their clinical application in vivo. In most instances, phage therapy is only used on a compassionate-use basis, where all other treatment options have been exhausted. A lack of clinical trials and numerous regulatory hurdles hamper the progress of phage therapy and in turn, the engineered variants, in becoming widely used in the clinic. In this review, we outline the various types of modifications enacted upon phages and how these modifications contribute to their enhanced bactericidal function compared with wild-type phages. We also discuss the nascent progress of genetically modified phages in clinical trials along with the current issues these are confronted with, to validate it as a therapy in the clinic.

噬菌体(噬菌体)是针对细菌的特异性病毒,能高效、特异地攻击细菌。早在二十世纪初,人们就开始研究噬菌体的抗菌潜力;然而,随着抗生素的普及,噬菌体的应用在很大程度上黯然失色。随着全球抗生素耐药菌株的激增,利用噬菌体进行治疗的热潮再次兴起。噬菌体的主要优势之一是易于改造,可以根据改造情况生成许多具有特定功能的优化衍生物。这些增强型衍生物可以显示出更高的感染性、更广的宿主范围或对人体组织更强的亲和力,而某些细菌物种正是在人体组织中发挥致病作用的。尽管如此,体外衍生物的产生与体内的临床应用之间仍存在明显差异。在大多数情况下,噬菌体疗法只是在所有其他治疗方法都已用尽的情况下,出于同情才使用。缺乏临床试验和众多监管障碍阻碍了噬菌体疗法的发展,进而阻碍了工程变体在临床上的广泛应用。在这篇综述中,我们概述了噬菌体的各种修饰类型,以及这些修饰如何使噬菌体的杀菌功能比野生型噬菌体更强。我们还讨论了转基因噬菌体在临床试验中取得的新进展,以及目前面临的问题,以便将其作为一种疗法应用于临床。
{"title":"Making the leap from technique to treatment - genetic engineering is paving the way for more efficient phage therapy.","authors":"Jessica M Lewis, Joshua Williams, Antonia P Sagona","doi":"10.1042/BST20231289","DOIUrl":"10.1042/BST20231289","url":null,"abstract":"<p><p>Bacteriophages (phages) are viruses specific to bacteria that target them with great efficiency and specificity. Phages were first studied for their antibacterial potential in the early twentieth century; however, their use was largely eclipsed by the popularity of antibiotics. Given the surge of antimicrobial-resistant strains worldwide, there has been a renaissance in harnessing phages as therapeutics once more. One of the key advantages of phages is their amenability to modification, allowing the generation of numerous derivatives optimised for specific functions depending on the modification. These enhanced derivatives could display higher infectivity, expanded host range or greater affinity to human tissues, where some bacterial species exert their pathogenesis. Despite this, there has been a noticeable discrepancy between the generation of derivatives in vitro and their clinical application in vivo. In most instances, phage therapy is only used on a compassionate-use basis, where all other treatment options have been exhausted. A lack of clinical trials and numerous regulatory hurdles hamper the progress of phage therapy and in turn, the engineered variants, in becoming widely used in the clinic. In this review, we outline the various types of modifications enacted upon phages and how these modifications contribute to their enhanced bactericidal function compared with wild-type phages. We also discuss the nascent progress of genetically modified phages in clinical trials along with the current issues these are confronted with, to validate it as a therapy in the clinic.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1373-1384"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retrotransposons in embryogenesis and neurodevelopment. 胚胎发生和神经发育中的逆转录载体
IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-26 DOI: 10.1042/BST20230757
Mary Jo Talley, Michelle S Longworth

Retrotransposable elements (RTEs) are genetic elements that can replicate and insert new copies into different genomic locations. RTEs have long been identified as 'parasitic genes', as their mobilization can cause mutations, DNA damage, and inflammation. Interestingly, high levels of retrotransposon activation are observed in early embryogenesis and neurodevelopment, suggesting that RTEs may possess functional roles during these stages of development. Recent studies demonstrate that RTEs can function as transcriptional regulatory elements through mechanisms such as chromatin organization and noncoding RNAs. It is clear, however, that RTE expression and activity must be restrained at some level during development, since overactivation of RTEs during neurodevelopment is associated with several developmental disorders. Further investigation is needed to understand the importance of RTE expression and activity during neurodevelopment and the balance between RTE-regulated development and RTE-mediated pathogenesis.

逆转录可逆元件(RTE)是一种可复制并在不同基因组位置插入新拷贝的遗传元件。RTE 长期以来一直被认为是 "寄生基因",因为它们的移动会导致突变、DNA 损伤和炎症。有趣的是,在早期胚胎发育和神经发育过程中观察到高水平的逆转录转座子活化,这表明 RTE 在这些发育阶段可能具有功能性作用。最近的研究表明,RTE 可通过染色质组织和非编码 RNA 等机制发挥转录调控元件的功能。然而,很明显,RTE 的表达和活性在发育过程中必须受到一定程度的抑制,因为神经发育过程中 RTE 的过度激活与多种发育障碍有关。要了解神经发育过程中 RTE 表达和活性的重要性,以及 RTE 调节的发育和 RTE 介导的发病机制之间的平衡,还需要进一步的研究。
{"title":"Retrotransposons in embryogenesis and neurodevelopment.","authors":"Mary Jo Talley, Michelle S Longworth","doi":"10.1042/BST20230757","DOIUrl":"10.1042/BST20230757","url":null,"abstract":"<p><p>Retrotransposable elements (RTEs) are genetic elements that can replicate and insert new copies into different genomic locations. RTEs have long been identified as 'parasitic genes', as their mobilization can cause mutations, DNA damage, and inflammation. Interestingly, high levels of retrotransposon activation are observed in early embryogenesis and neurodevelopment, suggesting that RTEs may possess functional roles during these stages of development. Recent studies demonstrate that RTEs can function as transcriptional regulatory elements through mechanisms such as chromatin organization and noncoding RNAs. It is clear, however, that RTE expression and activity must be restrained at some level during development, since overactivation of RTEs during neurodevelopment is associated with several developmental disorders. Further investigation is needed to understand the importance of RTE expression and activity during neurodevelopment and the balance between RTE-regulated development and RTE-mediated pathogenesis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1159-1171"},"PeriodicalIF":3.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biochemical Society transactions
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1