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The role of the U1 snRNP complex in the regulation of gene expression: recent reports U1 snRNP 复合物在基因表达调控中的作用:最新报道
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_566
Mikołaj Kiraga, Monika Zakrzewska-Płaczek

U1 snRNP (U1 small nuclear ribonucleoprotein) is a nuclear ribonucleoprotein complex involved mainly in pre-mRNA splicing, which is a key regulatory process in the eukaryotic gene expression pathway, but also in the process of preventing premature transcription termination (telescripting). U1 snRNP interacts directly with RNA polymerase II, thereby influencing the synthesis and maturation of transcripts in the cell nucleus, including the formation of the 3' end of mRNA and polyadenylation. At the level of cell physiology, it regulates the functioning of mitochondria and energy metabolism. The core of the U1 snRNP complex is U1 snRNA, encoded by many copies of genes that differ in sequence and expression level, and the expression of some of them leads to the formation of defective products. According to current reports, U1 snRNA can be used for therapeutic purposes to regulate gene expression and improve mRNA splicing defects, which are the cause of many diseases. Here we present selected recent discoveries and achievements related to U1 snRNP.

U1 snRNP(U1 小核核糖核蛋白)是一种核核糖核蛋白复合物,主要参与真核生物基因表达途径中的关键调控过程--mRNA 前剪接,也参与防止转录过早终止(telescripting)的过程。U1 snRNP 与 RNA 聚合酶 II 直接相互作用,从而影响细胞核中转录本的合成和成熟,包括 mRNA 3' 端的形成和多聚腺苷酸化。在细胞生理层面,它调节线粒体的功能和能量代谢。U1 snRNP 复合物的核心是 U1 snRNA,由许多基因拷贝编码,这些基因的序列和表达水平各不相同,其中一些基因的表达会导致缺陷产物的形成。根据目前的报道,U1 snRNA 可用于治疗目的,以调节基因表达和改善 mRNA 剪接缺陷,而这正是导致许多疾病的原因。在此,我们将介绍与 U1 snRNP 有关的部分最新发现和成果。
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引用次数: 0
Characterization of KPC-type drug resistance in bacteria 细菌的 KPC 型耐药性特征
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_555
Michalina Gniewosz, Sylwia Andrzejczak-Grządko

One of the main problems of modern medicine is the phenomenon of drug resistance. Inappropriate use of antibiotics is considered to be the most important reason for the emergence of new resistance mechanisms in microorganisms. Carbapenems, which belong to the β-lactams, are considered the most effective group of antimicrobial agents. Unfortunately, as a result of prolonged exposure to the aforementioned drugs, bacteria have developed several mechanisms for survival. The most important of these is the production of hydrolytic enzymes (carbapenemases), which cleave the β-lactam ring and inactivate the antibiotics. The mentioned enzymes are encoded by blaKPC genes, which are located in so-called mobile genetic elements (i.e. plasmids and transposons). Such localization is associated with their ease of transfer between different bacterial species in the process of horizontal gene transfer.

现代医学的主要问题之一是抗药性现象。抗生素的不当使用被认为是微生物产生新的抗药性机制的最重要原因。碳青霉烯类属于β-内酰胺类,被认为是最有效的抗菌剂。不幸的是,由于长期接触上述药物,细菌已发展出多种生存机制。其中最重要的是产生水解酶(碳青霉烯酶),它能裂解 β-内酰胺环,使抗生素失活。上述酶由 blaKPC 基因编码,这些基因位于所谓的移动遗传因子(即质粒和转座子)中。这种定位与它们在水平基因转移过程中易于在不同细菌物种之间转移有关。
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引用次数: 0
Heme-based aquareceptors 基于血红素的水生受体
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_551
Savani Anbalagan

How cells sense water is of fundamental importance in biology. Hygrosensation has been demonstrated in specialized sensory cells that sense extracellular moisture. Even in microorganisms, osmosensors do not sense water per se. Water-sensing mechanisms would have been necessary for organisms to migrate and survive in water-poor conditions and to evolve into multicellular organisms. Due to the potential ability of water molecules to bind to gas-binding sites in the heme-based sensing domains of gasoreceptors, I suggest that some of them could have a parallel role as protein aquareceptors. Just as gasoreceptors function in almost every cell, aquareceptors must also function in almost every cell. I think that aquareceptors must be present in the cell membrane, cytoplasm, and every organelle. I also wonder if hemoglobin could also be considered a putative aquareceptor.

细胞如何感知水分在生物学中至关重要。特化的感觉细胞能感知细胞外的水分,这一点已在它们身上得到证实。即使在微生物中,渗透传感器本身也不能感知水分。水感应机制是生物在缺水条件下迁移和生存以及进化成多细胞生物的必要条件。由于水分子有可能与气体感受器基于血红素的感应结构域中的气体结合位点结合,我认为它们中的一些可能具有与蛋白质水感受器平行的作用。正如气体感受器在几乎所有细胞中都起作用一样,水感受器也一定在几乎所有细胞中都起作用。我认为,细胞膜、细胞质和细胞器中一定都有水感受器。我还想知道血红蛋白是否也可以被视为一种潜在的水感受器。
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引用次数: 0
Heavy metal tolerance in crop plants: an in silico comprehensive analysis of Metal- tolerance gene family in barley 作物对重金属的耐受性:对大麦耐金属基因家族的硅学综合分析
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_559
Magda Grabsztunowicz, Ewelina Stolarska, Umesh Kumar Tanwar, Magdalena Arasimowicz-Jelonek, Ewa Sobieszczuk-Nowicka

Heavy metal contamination in soil is a global concern due to its harmful effect to all living organisms. Phytoremediation is an emerging cost- effective technology, which utilizes different types of hyperaccumulator plants for the removal of heavy metal pollutants. Crop plants have been suggested as a good candidate for recultivation of agricultural soil in phytoremediation process, however the molecular mechanisms responsible for the crop tolerance to heavy metals is still unknown. Metal-tolerance proteins (MTPs) are divalent cation transporters that play critical roles in metal tolerance and ion homeostasis in plants. The current study identified 12 HvMTPs in the barley (Hordeum vulgare, Hv) genome; the majority of MTPs were hydrophobic proteins found in the vacuolar membrane. Gene expression profiling suggests that HvMTPs play an active role in maintaining barley nutrient homeostasis throughout its life cycle. The expression of barley HvMTP genes in the presence of heavy metals revealed that these MTPs were induced by at least one metal ion, implying their involvement in metal tolerance.

土壤中的重金属污染对所有生物体都有危害,是全球关注的问题。植物修复是一种新兴的低成本高效益技术,它利用不同类型的高积累植物来清除重金属污染物。在植物修复过程中,农作物植物被认为是农业土壤再耕作的良好候选植物,但农作物耐受重金属的分子机制仍然未知。金属耐受性蛋白(MTPs)是二价阳离子转运体,在植物的金属耐受性和离子平衡中发挥着关键作用。目前的研究在大麦(Hordeum vulgare,Hv)基因组中发现了 12 个 HvMTPs;大多数 MTPs 是存在于液泡膜中的疏水蛋白。基因表达谱分析表明,HvMTPs 在维持大麦整个生命周期的营养平衡方面发挥着积极作用。大麦 HvMTP 基因在重金属存在下的表达表明,这些 MTPs 至少受到一种金属离子的诱导,这意味着它们参与了金属耐受性。
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引用次数: 0
Biosynthesis and metabolic inactivation of auxins 辅酶的生物合成和代谢失活
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_549
Aleksandra Sobiech, Alicja Banasiak

Auxins are a phytohormones that regulates of processes related to plant growth and morphogenesis, therefore their deficiency or excess results in severe developmental disorders. Plants have developed mechanisms aimed at regulating the level of the active form of these hormones, including their: directional transport, local biosynthesis, and degradation, as well as reversible and irreversible inactivation by binding to additional chemical groups. Despite almost a hundred years since the discovery of auxins, the functioning of these mechanisms, especially at the level of metabolism, is still not fully understood. In recent years, thanks to the development of new research methods, significant progress has been made in this field. This applies to both the identification of auxin biosynthetic pathways and the genes involved in them, as well as the detection of new auxin metabolites, their mutual connections and enzymes involved in their biosynthesis, transformation, and degradation. This work focuses on summarizing the current knowledge on this topic, considering the relationship of auxin metabolism with developmental processes and the response to changing environmental conditions.

叶黄素是一种植物激素,调节与植物生长和形态发生有关的过程,因此其缺乏或过量都会导致严重的发育障碍。植物已经形成了旨在调节这些激素活性形式水平的机制,包括:定向运输、局部生物合成和降解,以及通过与其他化学基团结合进行可逆和不可逆失活。尽管从发现植物生长素至今已有近百年的历史,但人们对这些机制的运作,尤其是新陈代谢水平的运作,仍未完全了解。近年来,由于新研究方法的发展,这一领域取得了重大进展。这既体现在对辅助素生物合成途径及其相关基因的鉴定上,也体现在对新的辅助素代谢物、它们之间的相互联系以及参与其生物合成、转化和降解的酶的检测上。这项工作的重点是总结当前有关这一主题的知识,考虑辅助素代谢与发育过程的关系以及对不断变化的环境条件的反应。
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引用次数: 0
Polyploidy as an outcome of anticancer therapies and a contributing cause of their lack of efficacy 多倍体是抗癌疗法的一个结果,也是其缺乏疗效的一个原因
Q3 Medicine Pub Date : 2024-09-17 Print Date: 2024-09-30 DOI: 10.18388/pb.2021_557
Kinga Kołacz, Karolina Gronkowska, Magdalena Strachowska, Agnieszka Robaszkiewicz

In addition to innate and gained resistance poliploidy of cancer cells is described as a mechanism responsible for lack of response or cancer relapses after initial patient recovery. Formation of these cells is induced by cyto- and genotoxic agents, which trigger endoreduplication, cytokinesis failure, cell fusion or canibalism. These processes lead to amplification of DNA, cell cycle arrest and escape from death. Cancer reinitiation results from depolyploidization by neosis, amitotic and meiotic-like divisions. In this paper we review the known mechanisms, which drive cancer cell transition to poliploidy, major features of these cells and their role in cancer progression. We also depict the current approaches, which target metabolic and signaling pathways that are crucial for survival and functioning of polyploid cells. The combination of chemotherapy and radiotherapy with agents capable of inhibiting or eliminating polyploid cells could substantially improve the success rate and efficacy of anticancer therapies.

除了先天和后天的抵抗力外,癌细胞的多倍体化也被描述为导致病人在最初康复后缺乏反应或癌症复发的一种机制。细胞毒素和基因毒性物质会诱导这些细胞的形成,从而引发内复制、细胞分裂失败、细胞融合或同化。这些过程会导致 DNA 扩增、细胞周期停滞和死而复生。新分裂、无性分裂和类似减数分裂的去倍化过程会导致癌症再发。本文回顾了促使癌细胞向多倍体转化的已知机制、这些细胞的主要特征及其在癌症进展中的作用。我们还描绘了目前针对代谢和信号通路的方法,这些通路对多倍体细胞的生存和功能至关重要。将化疗和放疗与能够抑制或消除多倍体细胞的药物相结合,可大大提高抗癌疗法的成功率和疗效。
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引用次数: 0
Can the laws of physics be circumvented? On methods of super-resolution fluorescence microscopy 物理定律可以规避吗?关于超分辨率荧光显微镜的方法
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_527
Adrian Rüfli

Biological sciences are increasingly uncovering the foundations of life in greater detail, made possible by the development of research methods enabling exploration at the nanometer scale. Optical microscopy, a field with a significant contribution to current knowledge, is inherently limited by the Abbe limit, stemming from the fundamental wave properties of light. Through the efforts of scientists, this limit can be circumvented, as evidenced by STED and MINFLUX techniques. STED allows imaging with a resolution down to 40 nm, while MINFLUX enables resolution as fine as 2 nm. Both techniques require labelling of biological molecular targets with fluorescent markers and enable imaging in living cells, facilitating the study of dynamic biological processes. This article provides an introduction to super-resolution techniques STED and MINFLUX, demonstrating their utility through the example of studying kinesin movement along microtubules using the MINFLUX technique.

生物科学正日益深入地揭示生命的基础,这得益于纳米级探索研究方法的发展。光学显微镜是一个对当前知识有重大贡献的领域,但它本身受到源于光的基本波特性的阿贝极限的限制。通过科学家们的努力,这一限制是可以规避的,STED 和 MINFLUX 技术就是证明。STED 的成像分辨率可低至 40 纳米,而 MINFLUX 的分辨率可高达 2 纳米。这两种技术都需要用荧光标记标记生物分子目标,并能在活细胞中成像,从而促进了对动态生物过程的研究。本文介绍了超分辨率技术 STED 和 MINFLUX,并以 MINFLUX 技术研究驱动蛋白沿微管运动为例,展示了这两种技术的实用性。
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引用次数: 0
Advancements in Structural Biology – How to See Molecules of Life? 结构生物学的进步--如何观察生命分子?
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_533
Wojciech Witek, Wiktoria Ragin, Ha Linh Tran, Ewa Połomska, Mikołaj Podlewski, Aleksandra Pawłowicz, Aleksandra Cioch-Biniaś, Amadeusz Woś, Witold Andrałojć, Marta Szachniuk, Miłosz Ruszkowski

Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise – molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.

结构生物学侧重于了解蛋白质和核酸等生物大分子的结构。破译结构有助于在非常精确的分子水平上了解它们在细胞中的功能。这不仅能确定疾病的基础,还能提出治疗策略和工具。结构生物学发展的强大动力促使人们开发了许多方法,从而能够确定生命分子的结构。生物学、化学、物理学和计算机科学的融合推动了结构生物学的不断进步,使其成为一门跨学科的学科。位于波兹南的波兰科学院生物有机化学研究所在其 35 年的历史中,已成为波兰在结构生物学领域开展研究的重要机构之一。一方面,该研究获得了国际认可,另一方面,它也推动了尖端方法的实施和发展。本综述将讨论该研究所在结构生物学领域使用的方法。
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引用次数: 0
Chemical simulations of quantum systems using quantum computers - review of algorithms and their experimental verification 利用量子计算机对量子系统进行化学模拟 - 算法及其实验验证综述
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_536
Konrad Wojciechowski, Krzysztof Kurowski, Cezary Mazurek

Computer simulations using ever-increasing computing power and machine learning techniques allow advanced molecular modelling, molecular dynamics simulations and studies of intermolecular interactions. However, due to the complexity of biological systems and chemical processes at the molecular level, their accurate representation using classical computer models and techniques has faced a number of significant limitations for many years. A new and promising direction for the development of computational science and its potential applications in biochemistry is quantum computing and its integration with classical high-performance supercomputing systems. This article responds to the growing interest in the use of available quantum computers in exemplary applications. In this paper, we aim to provide an overview of the basic notions involved in the development of quantum algorithms and simulations related to issues at the interface of quantum chemistry and biochemistry. In addition, the article introduces the basic principles of performing simulations using the state-of-the-art quantum computers in the era of Noisy Intermediate-Scale Quantum (NISQ). Experimental results of the classical-quantum algorithm Variational Quantum Eigensolver (VQE) for example molecules H2 and CH+ are also presented. Despite the many shortcomings of currently available quantum computers, the analysed VQE algorithm proved to be effective in approximating the ground state of molecules using a minimal functional basis.

利用日益强大的计算能力和机器学习技术进行计算机模拟,可以进行先进的分子建模、分子动力学模拟和分子间相互作用研究。然而,由于生物系统和分子水平化学过程的复杂性,使用经典计算机模型和技术对其进行精确表述多年来一直面临诸多重大限制。量子计算及其与经典高性能超级计算系统的整合是计算科学发展及其在生物化学中潜在应用的一个新的和有前途的方向。本文回应了人们对现有量子计算机在示范应用中的使用日益增长的兴趣。本文旨在概述与量子化学和生物化学界面问题相关的量子算法和模拟开发所涉及的基本概念。此外,文章还介绍了在噪声中量子(NISQ)时代使用最先进的量子计算机进行模拟的基本原理。文章还介绍了经典量子算法变分量子求解器(VQE)对 H2 和 CH+ 分子的实验结果。尽管目前可用的量子计算机存在许多缺陷,但分析的 VQE 算法被证明在使用最小函数基础逼近分子基态方面是有效的。
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引用次数: 0
From Sanger to genome sequencing - an overview of DNA sequencing technologies 从桑格到基因组测序--DNA 测序技术概览
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_534
Małgorzata Marcinkowska-Swojak, Magdalena Rakoczy, Jan Podkowiński, Jurand Handschuh, Paweł Wojciechowski, Luiza Handschuh

There is no technique that would make a greater contribution to the development of genetics, molecular biology and medicine than DNA sequencing. For many years, the method based on enzymatic DNA synthesis developed by Frederic Sanger was the gold standard in this area. At the end of the 20th century, there was a dynamic development of next-generation sequencing (NGS) technologies, which ended the era of single gene analysis and initiated the era of genome sequencing. Despite fierce competition, one NGS technology has practically completely dominated the global market. In the article, we present our own review of DNA sequencing methods, starting from the Sanger method to high-throughput second- and third-generation sequencing technologies, with particular emphasis on those that have achieved commercial success. We present their short history, principles of operation, technical possibilities, applications and limitations. In the summary, we reveal how much human genome sequencing costs at the current stage of the genomic revolution and outline the prospects for further development of genomics.

对遗传学、分子生物学和医学发展贡献最大的技术莫过于 DNA 测序。多年来,弗雷德里克-桑格(Frederic Sanger)开发的基于酶法 DNA 合成的方法一直是这一领域的黄金标准。20 世纪末,新一代测序(NGS)技术蓬勃发展,结束了单基因分析时代,开启了基因组测序时代。尽管竞争激烈,但有一种 NGS 技术几乎完全占据了全球市场。在这篇文章中,我们回顾了从桑格法到高通量第二代和第三代测序技术的 DNA 测序方法,特别强调了已取得商业成功的测序方法。我们介绍了这些技术的简史、工作原理、技术可能性、应用和局限性。在总结中,我们揭示了基因组革命现阶段人类基因组测序的成本,并概述了基因组学进一步发展的前景。
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引用次数: 0
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Postepy biochemii
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