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Physiological Research May 2018Immunity plays an important role in the reactivity of the organism and, in this context, is an essential factor in the pathogenesis of many diseases. Basically, there is... (Review)
Review
Immunity plays an important role in the reactivity of the organism and, in this context, is an essential factor in the pathogenesis of many diseases. Basically, there is no system or organ in the body, whose dysfunction is not related to immunity consequences. In addition, there are also multisystem diseases simultaneously involving multiple body systems. They are not always caused by weak immunity, but also often by modified immune reactions known as overshooting. The essence of all these diseases is a change in the reactivity of the organism where immunity plays an important role. The immunity as such is then part of the systems of neuroendocrine-immune regulation, which have common mediators and receptors. The establishment of psychoneuroimmunology, a relatively new discipline in neuroscience, contributed to a detailed understanding of these mechanisms between central and peripheral nervous system, the endocrine system and the immune system. This research enabled the uncovering of the nature of stress-diseases and impact of other regulatory disturbances on the function of various body organs and systems of the organism as a whole. The aim of this short review is to show complex interconnections of these relationships to better understand the human health and disease.
Topics: Animals; Gene Expression Regulation; Humans; Immunity; Immunologic Factors; Neurosecretory Systems; Psychoneuroimmunology; Stress, Psychological
PubMed: 29303607
DOI: 10.33549/physiolres.933656 -
Yeast (Chichester, England) May 2018Genome editing is a form of highly precise genetic engineering which produces alterations to an organism's genome as small as a single base pair with no incidental or... (Review)
Review
Genome editing is a form of highly precise genetic engineering which produces alterations to an organism's genome as small as a single base pair with no incidental or auxiliary modifications; this technique is crucial to the field of synthetic biology, which requires such precision in the installation of novel genetic circuits into host genomes. While a new methodology for most organisms, genome editing capabilities have been used in the budding yeast Saccharomyces cerevisiae for decades. In this review, I will present a brief history of genome editing in S. cerevisiae, discuss the current gold standard method of Cas9-mediated genome editing, and speculate on future directions of the field.
Topics: CRISPR-Cas Systems; Gene Editing; Genome, Fungal; History, 20th Century; History, 21st Century; Saccharomyces cerevisiae
PubMed: 29247562
DOI: 10.1002/yea.3300 -
The Biochemical Journal Aug 2013The modern synthesis of evolutionary theory and genetics has enabled us to discover underlying molecular mechanisms of organismal evolution. We know that in order to... (Review)
Review
The modern synthesis of evolutionary theory and genetics has enabled us to discover underlying molecular mechanisms of organismal evolution. We know that in order to maximize an organism's fitness in a particular environment, individual interactions among components of protein and nucleic acid networks need to be optimized by natural selection, or sometimes through random processes, as the organism responds to changes and/or challenges in the environment. Despite the significant role of molecular networks in determining an organism's adaptation to its environment, we still do not know how such inter- and intra-molecular interactions within networks change over time and contribute to an organism's evolvability while maintaining overall network functions. One way to address this challenge is to identify connections between molecular networks and their host organisms, to manipulate these connections, and then attempt to understand how such perturbations influence molecular dynamics of the network and thus influence evolutionary paths and organismal fitness. In the present review, we discuss how integrating evolutionary history with experimental systems that combine tools drawn from molecular evolution, synthetic biology and biochemistry allow us to identify the underlying mechanisms of organismal evolution, particularly from the perspective of protein interaction networks.
Topics: Biochemistry; Biological Evolution; Evolution, Molecular; Protein Interaction Maps; Synthetic Biology
PubMed: 23849056
DOI: 10.1042/BJ20130205 -
Experimental Biology and Medicine... Sep 2014The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical... (Review)
Review
The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ's biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different "organoids" to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology.
Topics: Animals; Brain; Drug Evaluation, Preclinical; Humans; Lab-On-A-Chip Devices; Neurogenesis; Neuronal Plasticity; Organ Culture Techniques; Rats
PubMed: 24912505
DOI: 10.1177/1535370214537738 -
Hellenic Journal of Nuclear Medicine 2023Personalized dosimetry is tending to become the "gold standard" in Molecular Radiotherapy (MRT). Setting up carefully all the procedures involved in the workflow is...
INTRODUCTION
Personalized dosimetry is tending to become the "gold standard" in Molecular Radiotherapy (MRT). Setting up carefully all the procedures involved in the workflow is crucial for the final clinical result.
AIM
Individualized MRT dosimetry using a recently installed commercial system, comprising of a dual SPECT/CT camera, a treatment planning software (TPS) and a dose calibrator was implemented on patients undergoing Lu-DOTATATE and Lu-PSMA therapies. The clinical workflow implemented in our department is presented in detail. Measurement and calculation of the Calibration Factor (CF) to translate the count rate into activity concentration (quantitative data), and system's commissioning, was discussed.
MATERIALS AND METHODS
Calibration of the dose calibrator, the SPECT/CT system and the TPS, measured using the clinical acquisition protocol, were analyzed along with potential errors introduced by the procedure and means of future optimization. In addition, image acquisition parameters, image reconstruction and image registration were discussed. Anatomical contouring of the organs at risk (OARs) and functional contouring of the lesions, followed by the dose calculation of the aforementioned structures, with the use of different calculation algorithms, were presented, compared and evaluated.
RESULTS AND DISCUSSION
According to our experience, different fitting of each organ's activity curve, results in differences in the final calculated dose. Use of bi-exponential fitting seems to better approach physical and metabolic decay. Calculated absorbed doses for the OARs were found similar to those expected from literature. Finally, department's future work was discussed, including reproducible patient setup for image acquisition, high dose CT for finer contouring and comparison of the calculated doses with other TPSs.
Topics: Humans; Radiometry; Single Photon Emission Computed Tomography Computed Tomography; Image Processing, Computer-Assisted; Radiotherapy Dosage; Algorithms
PubMed: 37658554
DOI: No ID Found -
Biochimica Et Biophysica Acta Nov 2013Over recent years, analyses of secretomes (complete sets of secreted proteins) have been reported in various organisms, cell types, and pathologies and such studies are... (Review)
Review
Over recent years, analyses of secretomes (complete sets of secreted proteins) have been reported in various organisms, cell types, and pathologies and such studies are quickly gaining popularity. Fungi secrete enzymes can break down potential food sources; plant secreted proteins are primarily parts of the cell wall proteome; and human secreted proteins are involved in cellular immunity and communication, and provide useful information for the discovery of novel biomarkers, such as for cancer diagnosis. Continuous development of methodologies supports the wide identification and quantification of secreted proteins in a given cellular state. The role of secreted factors is also investigated in the context of the regulation of major signaling events, and connectivity maps are built to describe the differential expression and dynamic changes of secretomes. Bioinformatics has become the bridge between secretome data and computational tasks for managing, mining, and retrieving information. Predictions can be made based on this information, contributing to the elucidation of a given organism's physiological state and the determination of the specific malfunction in disease states. Here we provide an overview of the available bioinformatics databases and software that are used to analyze the biological meaning of secretome data, including descriptions of the main functions and limitations of these tools. The important challenges of data analysis are mainly related to the integration of biological information from dissimilar sources. Improvements in databases and developments in software will likely substantially contribute to the usefulness and reliability of secretome studies. This article is part of a Special Issue entitled: An Updated Secretome.
Topics: Animals; Databases, Protein; Humans; Proteome; Proteomics; Software; Systems Biology
PubMed: 23395702
DOI: 10.1016/j.bbapap.2013.01.039 -
Chemical Society Reviews Mar 2011Membrane fusion has an overarching influence on living organisms. The fusion of sperm and egg membranes initiates the life of a sexually reproducing organism.... (Review)
Review
Membrane fusion has an overarching influence on living organisms. The fusion of sperm and egg membranes initiates the life of a sexually reproducing organism. Intracellular membrane fusion facilitates molecular trafficking within every cell of the organism during its entire lifetime, and virus-cell membrane fusion may signal the end of the organism's life. Considering its importance, surprisingly little is known about the molecular-level mechanism of membrane fusion. Due to the complexity of a living cell, observations often leave room for ambiguity in interpretation. Therefore artificial model systems composed of only a few components are being used to further our understanding of controlled fusion processes. In this critical review we first give an overview of the hypothesized mechanism of membrane fusion and the techniques that are used to investigate it, and then present a selection of non-targeted and targeted model systems, finishing with current applications and predictions on future developments (85 references).
Topics: Lipid Bilayers; Liposomes; Membrane Fusion; Models, Molecular; Nanotechnology; SNARE Proteins
PubMed: 21152599
DOI: 10.1039/c0cs00115e -
Bone Feb 2019Hematopoiesis in land dwelling vertebrates and marine mammals occurs within the bone marrow, continually providing mature progeny over the course of an organism's... (Review)
Review
Hematopoiesis in land dwelling vertebrates and marine mammals occurs within the bone marrow, continually providing mature progeny over the course of an organism's lifetime. This conserved dependency highlights the critical relationship between these two organs, yet the skeletal and hematopoietic systems are often thought of as separate. In fact, data are beginning to show that skeletal disease pathogenesis influences hematopoiesis and viceversa, offering novel opportunities to approach disease affecting bone and blood. With a growing global population of aged individuals, interest has focused on cell autonomous changes in hematopoietic and skeletal systems that result in dysfunction. The purpose of this review is to summarize the literature on aging effects in both fields, and provide critical examples of organ cross-talk in the aging process.
Topics: Aging; Animals; Bone Marrow; Bone and Bones; Hematopoiesis; Hematopoietic Stem Cells; Humans; Signal Transduction
PubMed: 30010082
DOI: 10.1016/j.bone.2018.07.012 -
Frontiers in Neuroanatomy 2015The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing... (Review)
Review
The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism's development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors (TF), secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.
PubMed: 25954163
DOI: 10.3389/fnana.2015.00047 -
Aging and Disease Jul 2022Ovarian aging leads to menopause, loss of fertility and other disorders in multiple organs, which brings great distress to women. For ethical reasons, it is impossible... (Review)
Review
Ovarian aging leads to menopause, loss of fertility and other disorders in multiple organs, which brings great distress to women. For ethical reasons, it is impossible to use humans as direct study subjects for aging research. Therefore, biomedical researchers have employed different non-human organisms to study ovarian aging, including worms, fruit flies, fishes, amphibians, birds, mice, rats, cavies, rabbits, pigs, sheep, cows, horses, monkeys, and apes. Because each of these model organisms has its own features, multiple factors, such as size, anatomical structure, cost, ease of operation, fertility, generation time, lifespan, and gene heredity, should be carefully considered when selecting a model system to study ovarian aging. An appropriate model organism would help researchers explore the risk factors and elucidate molecular mechanisms underlying declined ovarian functions, which might be conducive to preventing or delaying the ovarian aging process. This article will offer an overview on several currently available and commonly used model organisms for ovarian aging research by comparing their pros and cons. In doing so, we hope to provide useful information for ovarian aging researchers.
PubMed: 35855343
DOI: 10.14336/AD.2021.1209