Progress in Biophysics & Molecular Biology最新文献

DNA is the macromolecule responsible for storing the genetic information of a cell and it has intrinsic properties such as deformability, stability and curvature. DNA Curvature plays an important role in gene transcription and, consequently, in the subsequent production of proteins, a fundamental process of cells. With recent advances in bioinformatics and theoretical biology, it became possible to analyze and understand the involvement of DNA Curvature as a discriminatory characteristic of gene-promoting regions. These regions act as sites where RNAp (ribonucleic acid-polymerase) binds to initiate transcription. This review aims to describe the formation of Curvature, as well as highlight its importance in predicting promoters. Furthermore, this article provides the potential of DNA Curvature as a distinguishing feature for promoter prediction tools, as well as outlining the calculation procedures that have been described by other researchers. This work may support further studies directed towards the enhancement of promoter prediction software.

Superfamily of cytochromes P450 (CYPs) is composed of heme-thiolate-containing monooxygenase enzymes, which play crucial roles in the biosynthesis, bioactivation, and detoxification of a variety of organic compounds, both endogenic and exogenic. Majority of CYP monooxygenase systems are multi-component and contain various redox partners, cofactors and auxiliary proteins, which contribute to their diversity in both prokaryotes and eukaryotes. Recent progress in bioinformatics and computational biology approaches make it possible to undertake whole-genome and phylogenetic analyses of CYPomes of a variety of organisms. Considerable variations in sequences within and between CYP families and high similarity in secondary and tertiary structures between all CYPs along with dramatic conformational changes in secondary structure elements of a substrate binding site during catalysis have been reported. This provides structural plasticity and substrate promiscuity, which underlie functional diversity of CYPs. Gene duplication and mutation events underlie CYP evolutionary diversity and emergence of novel selectable functions, which provide the involvement of CYPs in high adaptability to changing environmental conditions and dietary restrictions. In our review, we discuss the recent advancements and challenges in the elucidating the evolutionary origin and mechanisms underlying the CYP monooxygenase system diversity and plasticity. Our review is in the view of hypothesis that diversity of CYP monooxygenase systems is translated into the broad metabolic profiles, and this has been acquired during the long evolutionary time to provide structural plasticity leading to high adaptative capabilities to environmental stress conditions.

Animal diseases are a major concern to animal welfare, human health and the global economy. Early detection, prevention and control of these animal diseases are crucial to ensure sustainability of livestock sector, to reduce farm losses and protecting public health. Points of care (POC) devices are small, portable instruments that provide rapid results thus reduce the risk of disease transmission and enable early intervention. CRISPR based diagnostics offer more accurate and efficient solution for monitoring animal health due to their quick response, can detect very low level of pathogenic organism or disease markers and specificity. These diagnostics are particularly useful in the in area with limited resources or access to common diagnostic methods, especially in developing countries. The ability of electrochemical sensors to detect accurately very low analyte concentration makes them suitable for POC diagnostics and field application. CRISPR base electrochemical biosensors show great potential in revolutionizing disease detection and diagnosis including animal health. However, challenges, such as achieving selectivity and sensitivity, need to be addressed to enhance the competitiveness of these biosensors. Currently, most CRISPR based bioassay research focuses on nucleic acid target detection, but researchers exploring to monitor small organic/inorganic non-nucleic acid molecules like toxins and proteins. Emerging diagnostics would be centered on CRISPR-Cas system will offer great potential as an accurate, specific and effective means to identify microorganism, virus, toxins, small molecules, peptides and nucleic acid related to various animal health disorders particularly when integrated into electrochemical biosensing platform.

In the bloodstream or other physiological fluids, "circulating cells and sub-cellular bio-particles" include many microscopic biological elements such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, microRNAs, platelets, immune cells, and proteins are the most well-known and investigated. These structures are crucial biomarkers in healthcare and medical research for the early detection of cancer and other disorders, enabling treatment to commence before the onset of clinical symptoms and enhancing the efficacy of treatments. As the size of these biomarkers to be detected decreases and their numbers in body fluids diminishes, the detection materials, ranging from visual inspection to advanced microscopy techniques, begin to become smaller, more sensitive, faster, and more effective, thanks to developing nanotechnology. This review first defines the circulating cells and subcellular bio-particles with their biological, physical, and mechanical properties and second focuses on their diagnostic importance, including their most recent applications as biomarkers, the biosensors that are utilized to detect them, the present obstacles that must be surmounted, and prospective developments in the domain. As technology advances and biomolecular pathways are deepens, diagnostic tests will become more sensitive, specific, and thorough. Finally, integrating recent advances in the diagnostic use of circulating cells and bioparticles into clinical practice is promising for precision medicine and patient outcomes.

The origin of life and its evolution are generally taught as occurring by abiogenesis and gene-centric neo-Darwinism. Significant biological evolutionary changes are preserved and given direction (descent with modification) by Darwin's (Spencer's) natural selection by survival of the fittest. Only survival of the fittest (adapted/broadened) is available to provide a ‘naturalistic’ direction to prefer one outcome/reaction over another for abiogenesis. Thus, assembly of first life must reach some threshold (the first minimal cell) before ‘survival of the fittest’ (the only naturalistic explanation available) can function as Darwin proposed for biological change. We propose the novel concept that the requirement for co-origination of vitamins with enzymes is a fundamental, but overlooked, problem that survival of the fittest (even broadly redefined beyond Darwin) cannot reasonably overcome. We support this conclusion with probability calculations. We focus on the stage of evolution involving the transition from non-life to the first, minimal living cell. We show that co-origination of required biochemical processes makes the origin of life probabilistically absurdly improbable even when all assumptions are chosen to unreasonably favor evolutionary theories.

Sugar serves as the primary energy source for mammals, with glucose metabolism facilitating energy acquisition in human cells. The proper functioning of intracellular glucose metabolism is essential for the maintenance of orderly and healthy physiological activities. Tumor cells, characterized by uncontrolled growth, exhibit dysregulated proliferation and apoptosis processes, leading to abnormal alterations in glucose metabolism. Specifically, tumor cells exhibit a shift towards aerobic glycolysis, resulting in the production of lactic acid that can be utilized as a metabolic intermediate for sustained tumor cell growth. This article provides a comprehensive overview of the enzymes involved in glucose metabolism and the alterations in gene expression that occur during tumor progression. It also examines the current research on targeting abnormal glucose metabolism processes for tumor treatment and discusses potential future directions for utilizing glucose metabolism as a therapeutic target.

Diabetic foot ulcers, as one of the chronic wounds, are a serious challenge in the global healthcare system which have shown notable growth in recent years. DFU is associated with impairment in various stages of wound healing, including angiogenesis. Aberrant expression of microRNAs (miRNAs) involved in the disruption of the balance between angiogenic and anti-angiogenic factors, plays a crucial role in angiogenesis dysfunction. Alteration in the expression of angiomiRNAs (angiomiRs) have the potential to function as biomarkers in chronic wounds. Additionally, considering the rising importance of therapeutic RNAs, there is potential for utilizing angiomiRs in wound healing to induce angiogenesis. This review aims to explore angiogenesis in chronic wounds and investigate the mechanisms mediated by pro- and anti-angiomiRs in the context of diabetic foot ulcers.

Symbiogenesis has been systematically exploited to understand consciousness as the aggregate of our physiology. The Symbiogenic mechanism for assimilation of factors in the environment formulates the continuum from inside the cell to the Cosmos, both consciousness and cosmology complying with the Laws of Nature. Since Symbiogenesis is ‘constructive’, whereas eliminating what threatens us is ‘destructive’, why do we largely practice Symbiogenesis? Hypothetically, Symbiogenesis recursively simulates the monism of our origin, recognizing ‘something bigger than ourselves’. That perspective explains many heretofore unexplained aspects of consciousness, such as mind, epigenetic inheritance, physiology, behaviors, social systems, mathematics, the Arts, from an a priori perspective. Moreover, there is an energetic continuum from Newtonian to Quantum Mechanics, opening up to a novel way of understanding the ‘true nature of our being’, not as ‘materialism’, but instead being the serial homeostatic control of energy. The latter is consistent with the spirit of Claude Bernard and Walter B. Cannon's perspectives on physiology. Such a paradigm shift is overdue, given that materialism is causing the destruction of the Earth and ourselves.

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels. The roles of ion channels in cancer are consistent with the importance of bioelectrical parameters in cell regulation and with the functions of bioelectric signaling in morphogenetic signals that act as cancer suppressors. We find that compounds that are well-known for having targets in the nervous system, such as voltage-gated ion channels, ligand-gated ion channels, proton pumps, and gap junctions are especially relevant to cancer. Our review suggests further opportunities for the repurposing of numerous promising candidates in the field of cancer electroceuticals.

Basing on logical assumptions and necessary steps of complexification along biological evolution, we propose here an evolutionary path from molecules to cells presenting four ages and three major transitions. At the first age, the basic biomolecules were formed and become abundant. The first transition happened with the event of a chemical symbiosis between nucleic acids and peptides worlds, which marked the emergence of both life and the process of organic encoding. FUCA, the first living process, was composed of self-replicating RNAs linked to amino acids and capable to catalyze their binding. The second transition, from the age of FUCA to the age of progenotes, involved the duplication and recombination of proto-genomes, leading to specialization in protein production and the exploration of protein to metabolite interactions in the prebiotic soup. Enzymes and metabolic pathways were incorporated into biology from protobiotic reactions that occurred without chemical catalysts, step by step. Then, the fourth age brought origin of organisms and lineages, occurring when specific proteins capable to stackle together facilitated the formation of peptidic capsids. LUCA was constituted as a progenote capable to operate the basic metabolic functions of a cell, but still unable to interact with lipid molecules. We present evidence that the evolution of lipid interaction pathways occurred at least twice, with the development of bacterial-like and archaeal-like membranes. Also, data in literature suggest at least two paths for the emergence of DNA biosynthesis, allowing the stabilization of early life strategies in viruses, archaeas and bacterias. Two billion years later, the eukaryotes arouse, and after 1,5 billion years of evolution, they finally learn how to evolve multicellularity via tissue specialization.