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关键词： biomarkers   extracellular vesicles   leukemia   machine learning   stem cells  

摘要： Many different subpopulations of subcellular extracellular vesicles (EVs) have been described. EVs are released from all cell types and have been shown to regulate normal physiological homeostasis, as well as pathological states by influencing cell proliferation, differentiation. organ homing, injury and recovery, as well as disease progression. In this review, we focus on the bidirectional actions of vesicles from normal and diseased cells on normal or leukemic target cells;and on the leukemic microenvironment as a whole. EVs from human bone marrow mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer, as well as mitigating radiation damage to marrow. The role of EVs in leukemia and their bimodal cross talk with the encompassing microenvironment remains to be fully characterized. This may provide insight for clinical advances via the application of EVs as potential therapy and the employment of statistical and machine learning models to capture the pleiotropic effects EVs endow to a dynamic microenvironment, possibly allowing for precise therapeutic intervention.

关键词： Human physiology lab   physiology   retrospective research   undergraduate physiology   database research  

摘要： Collecting meaningful data in an undergraduate human physiology lab course can be difficult for a variety of reasons. I describe a way of creating an inquiry based, semester-long project that allows students practice in designing retrospective research questions using a large database containing common physiology data. The database generated during this project has the capability of adding new participants each semester the course is taught. This approach can be used with a variety of different physiology acquisition systems and can easily be specialized for the learning outcomes of a given physiology laboratory course.

关键词： Post-translational modification   Methyllysine   Methylarginine   Lysine methyltransferase   Arginine methyltransferase   PRMT   MLL   N(6)-methyladenine   Histone  

摘要： Protein post-translational modifications (PTMs) have long been a topic of intensive investigation. Covalent additions to the 20 genetically encoded amino acids can alter protein interactions and can even change enzymatic function. In eukarya, PTMs can amplify both the complexity and functional paradigms of the cellular environment. Therefore, PTMs have been of substantial research interest, both for understanding fundamental mechanisms and to provide insight into drug design. Indeed, targeting proteins involved in writing, reading, and erasing PTMs important for human pathologies are some of the most fruitful avenues of drug discovery. In this multi-author review, we explore exciting new work on lysine and arginine methylation, molecular and structural understanding of some of the lysine and arginine methyltransferases (KMTs and PRMTs, respectively), novel insights into nucleic acid methylation, and how the enzymes responsible for writing these PTMs and readers responsible for recognizing these PTMs could be drugged. Here, we introduce the background and the topics covered in this issue.

关键词： Cattle   Kidney   Aquaporin   Immunohistochemistry   Western blot  

摘要： To date, 13 aquaporin isoforms (AQPs) have been discovered in mammals, of which as many as 9 are located in epithelial cells lining the individual sections of the nephron and collecting tubules. Detailed analysis of the location and expression of AQPs in the kidneys of laboratory animals and humans allowed to define the key role of these proteins in renal excretion of water and other small molecules. Unfortunately, despite the significant advances in knowledge in this area, still little is known about this subject in livestock, including cattle. Therefore, the aim of the study was to determine the expression and AQPs location in the nephron segment in the bovine kidney by immunohistochemistry and Western blot. The distribution of a total of 8 aquaporins was determined as a result of the conducted experiments. The results obtained in the present study clearly indicate that aquaporins in cattle are involved in the renal regulation of water excretion and maintenance of proper acid-base balance. Undoubtedly, changes in the distribution and expression of AQPs in bovine kidneys may be the cause of water balance disorders and disruption of the normal body fluid composition. Kidney diseases in cattle are poorly described in veterinary medicine. Knowledge of cellular location and expression of all AQPs in the bovine kidney under normal physiological condition allows a deeper understanding of the renal regulation of body homeostasis. It creates new perspective for diagnosis and pharmacotherapy in cattle in the future.

关键词： Microfluidics  

摘要： The investigation of molecular uptake and its kinetics in cells is valuable for understanding the cellular physiological status, the observation of drug interventions, and the development of imaging agents and pharmaceuticals. Microfluidic radiobioassays, or microfluidic radiometric bioassays, constitute a radiometric imaging-on-a-chip technology for the assay of biological samples using radiotracers. From 2006 to date, microfluidic radiobioassays have shown advantages in many applications, including radiotracer characterization, enzyme activity radiobioassays, fast drug evaluation, single-cell imaging, facilitation of dynamic positron emission tomography (PET) imaging, and cellular pharmacokinetics (PK)/pharmacodynamics (PD) studies. These advantages lie in the minimized and integrated detection scheme, allowing real-time tracking of dynamic uptake, high sensitivity radiotracer imaging, and quantitative interpretation of imaging results. In this review, the basics of radiotracers, various radiometric detection methods, and applications of microfluidic radiobioassays will be introduced and summarized, and the potential applications and future directions of microfluidic radiobioassays will be forecasted.

关键词： bacteria   pathogen   secretion   endocytosis   polarity  

摘要： Intracellular trafficking pathways in eukaryotic cells are essential to maintain organelle identity and structure, and to regulate cell communication with its environment. Shigella flexneri invades and subverts the human colonic epithelium by the injection of virulence factors through a type 3 secretion system (T3SS). In this work, we report the multiple effects of two S. flexneri effectors, IpaJ and VirA, which target small GTPases of the Arf and Rab families, consequently inhibiting several intracellular trafficking pathways. IpaJ and VirA induce large-scale impairment of host protein secretion and block the recycling of surface receptors. Moreover, these two effectors decrease clathrin-dependent and -independent endocytosis. Therefore, S. flexneri infection induces a global blockage of host cell intracellular transport, affecting the exchange between cells and their external environment. The combined action of these effectors disorganizes the epithelial cell polarity, disturbs epithelial barrier integrity, promotes multiple invasion events, and enhances the pathogen capacity to penetrate into the colonic tissue in vivo.

关键词： 应用型人才   动物生理学   实验教学  

摘要： 随着当前国家向高等院校提出向技术应用型进行转型的要求,很多高等院校纷纷依照学校的实际情况,结合应用型高等院校的基础要求,结合动物生理学的实验目标、教学方法和教学内容进行相应的改变.在实验的过程中重点培养学生的自主探索的能力,提高学生自主学习的兴趣.