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FEBS Letters Nov 2014While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to... (Review)
Review
While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to many factors, including maturation during childhood, alterations in our diets, travel, illnesses, and medical treatments. Moreover, there is mounting evidence that our microbiomes change us, by promoting health through their beneficial actions or by increasing our susceptibility to diseases through a process termed dysbiosis. Recent technological advances are enabling unprecedentedly detailed studies of the dynamics of the microbiota in animal models and human populations. This review will highlight key areas of investigation in the field, including establishment of the microbiota during early childhood, temporal variability of the microbiome in healthy adults, responses of the microbiota to intentional perturbations such as antibiotics and dietary changes, and prospective analyses linking changes in the microbiota to host disease status. Given the importance of computational methods in the field, this review will also discuss issues and pitfalls in the analysis of microbiome time-series data, and explore several promising new directions for mathematical model and algorithm development.
Topics: Aging; Animals; Computational Biology; Disease; Environment; Humans; Microbiota; Models, Biological
PubMed: 24583074
DOI: 10.1016/j.febslet.2014.02.037 -
The Biochemical Journal Jul 2009In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response... (Review)
Review
In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response to stressful stimuli, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.
Topics: Acetyltransferases; Animals; Disease; Humans; Oxidoreductases Acting on CH-NH Group Donors; Polyamines; Therapeutics; Polyamine Oxidase
PubMed: 19589128
DOI: 10.1042/BJ20090598 -
Romanian Journal of Morphology and... 2016Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies,... (Review)
Review
Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases. The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease.
Topics: Autoantibodies; Disease; Health; Humans; Neoplasms; Protective Agents
PubMed: 27833954
DOI: No ID Found -
PloS One 2014The objective of this manuscript is to present a systematic review of biosurveillance models that operate on select agents and can forecast the occurrence of a disease... (Meta-Analysis)
Meta-Analysis Review
The objective of this manuscript is to present a systematic review of biosurveillance models that operate on select agents and can forecast the occurrence of a disease event. We define a disease event to be a biological event with focus on the One Health paradigm. These events are characterized by evidence of infection and or disease condition. We reviewed models that attempted to predict a disease event, not merely its transmission dynamics and we considered models involving pathogens of concern as determined by the US National Select Agent Registry (as of June 2011). We searched commercial and government databases and harvested Google search results for eligible models, using terms and phrases provided by public health analysts relating to biosurveillance, remote sensing, risk assessments, spatial epidemiology, and ecological niche modeling. After removal of duplications and extraneous material, a core collection of 6,524 items was established, and these publications along with their abstracts are presented in a semantic wiki at http://BioCat.pnnl.gov. As a result, we systematically reviewed 44 papers, and the results are presented in this analysis. We identified 44 models, classified as one or more of the following: event prediction (4), spatial (26), ecological niche (28), diagnostic or clinical (6), spread or response (9), and reviews (3). The model parameters (e.g., etiology, climatic, spatial, cultural) and data sources (e.g., remote sensing, non-governmental organizations, expert opinion, epidemiological) were recorded and reviewed. A component of this review is the identification of verification and validation (V&V) methods applied to each model, if any V&V method was reported. All models were classified as either having undergone Some Verification or Validation method, or No Verification or Validation. We close by outlining an initial set of operational readiness level guidelines for disease prediction models based upon established Technology Readiness Level definitions.
Topics: Biosurveillance; Decision Support Techniques; Disaster Planning; Disease; Forecasting; Humans; Models, Biological; Reproducibility of Results; Statistics as Topic
PubMed: 24647562
DOI: 10.1371/journal.pone.0091989 -
Current Opinion in Immunology Feb 2020Recognition of invading pathogens and execution of defensive responses are crucial steps in successfully combating infectious diseases. Inflammasomes are a group of... (Review)
Review
Recognition of invading pathogens and execution of defensive responses are crucial steps in successfully combating infectious diseases. Inflammasomes are a group of diverse, signal-transducing complexes with key roles in both processes. While the responses mediated by inflammasomes are vital to host defense, aberrations in inflammasome regulation or activity can lead to the development of autoimmune and sterile inflammatory diseases, including cancer. The field of inflammasome research has rapidly expanded to identify novel regulatory pathways, new inflammasome components, and the mechanistic details of the activation of these complexes. In this review, we discuss recent insights into the regulation of inflammasomes by interferon regulatory factor proteins, newly discovered mechanisms of activation for the NLRP1b and NLRP6 inflammasomes, and recent studies exploring the viability of inflammasome-modulating immunotherapies.
Topics: Animals; Disease; Humans; Inflammasomes
PubMed: 31837596
DOI: 10.1016/j.coi.2019.11.007 -
Revue Medicale de Liege Mar 2020Psychomotor disadaptation syndrome (PDS) was first described by the Geriatrics School of Dijon (France), three decades ago, under the name «psychomotor regression...
Psychomotor disadaptation syndrome (PDS) was first described by the Geriatrics School of Dijon (France), three decades ago, under the name «psychomotor regression syndrome». Over time, the original clinical features remained unchanged. However, progress has been made in its pathophysiology understanding and care, hence the new name, PDS, appeared in the 1990s. The PDS is also called sub-cortico-frontal dysfunction syndrome since the 2000s. It corresponds to a decompensation of posture, gait and psychomotor automatisms, related to an alteration of the postural and motor programming, which is a consequence of sub-cortico-frontal lesions. The clinical features of PDS associate backward disequilibrium, nonspecific gait disorders and neurological signs (akinesia, reactional hypertonia, impaired reactive postural responses and protective reactions, etc.). Psychological disorders of PDS are a fear of standing and walking in its acute form (the post-fall syndrome), or a bradyphrenia and anhedonia in its chronic form. The PDS occurrence results from the combination of three factors implicated in the reduction in functional reserves related to the alteration of the sub-cortico-frontal structures: ageing, chronic afflictions and acute situations, which induce a decrease in cerebral blood flow. The PDS management must be multidisciplinary, including the physician, the physiotherapist, the psychologist, nurses and care assistants.
Topics: Accidental Falls; Adaptation, Physiological; France; Gait; Humans; Postural Balance; Posture; Sensation Disorders; Syndrome
PubMed: 32157844
DOI: No ID Found -
Cold Spring Harbor Perspectives in... Jul 2014Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In... (Review)
Review
Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally.
Topics: Disease; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Precision Medicine
PubMed: 25059740
DOI: 10.1101/cshperspect.a008581 -
Biological & Pharmaceutical Bulletin 2017Secretory and membrane proteins are synthesized in ribosomes, then mature in the endoplasmic reticulum (ER), but if ER function is impaired, immature defective proteins... (Review)
Review
Secretory and membrane proteins are synthesized in ribosomes, then mature in the endoplasmic reticulum (ER), but if ER function is impaired, immature defective proteins accumulate in the ER. This situation is called ER stress: in response, a defensive mechanism called the unfolded protein response (UPR) is activated in cells to reduce the defective proteins. During the UPR, the ER transmembrane sensor molecules inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), and RNA-dependent protein kinase (PKR)-like ER kinase (PERK) are activated, stress signals are transduced to the outside of the ER, and various cell responses, including gene induction, occur. In ER-associated degradation (ERAD), one type of UPR, defective proteins are eventually expelled from the ER and degraded in the cytoplasm through the ubiquitin proteasome system. Since ER stress has been reported to have relationships with neurodegenerative diseases, diabetes, metabolic syndromes, and cancer, it is the focus of increased attention from the perspectives of elucidating pathogenic mechanisms, and in the development of therapeutics.
Topics: Animals; Disease; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Humans; Unfolded Protein Response
PubMed: 28867719
DOI: 10.1248/bpb.b17-00342 -
International Journal of Molecular... Mar 2021Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering...
Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.
Topics: Animals; Biomarkers; Disease; Flavonoids; Humans; Inflammasomes; Inflammation; Mice
PubMed: 33809447
DOI: 10.3390/ijms22063008 -
International Journal of Molecular... Jan 2019In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of... (Review)
Review
In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of transcription, mRNA degradation and protein degradation. Therefore, it is essential to investigate translation in a global scale. Like the other "omics"-methods, translatomics investigates the totality of the components in the translation process, including but not limited to translating mRNAs, ribosomes, tRNAs, regulatory RNAs and nascent polypeptide chains. Technical advances in recent years have brought breakthroughs in the investigation of these components at global scale, both for their composition and dynamics. These methods have been applied in a rapidly increasing number of studies to reveal multifaceted aspects of translation control. The process of translation is not restricted to the conversion of mRNA coding sequences into polypeptide chains, it also controls the composition of the proteome in a delicate and responsive way. Therefore, translatomics has extended its unique and innovative power to many fields including proteomics, cancer research, bacterial stress response, biological rhythmicity and plant biology. Rational design in translation can enhance recombinant protein production for thousands of times. This brief review summarizes the main state-of-the-art methods of translatomics, highlights recent discoveries made in this field and introduces applications of translatomics on basic biological and biomedical research.
Topics: Animals; Disease; Humans; Internet; Protein Biosynthesis; Proteomics; RNA, Messenger; Ribosomes
PubMed: 30626072
DOI: 10.3390/ijms20010212