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Single-cell transcriptome in the identification of disease biomarkers: opportunities and challenges.Journal of Translational Medicine Aug 2014Single cell transcriptome defined as the entire RNA or polyadenylated products of RNA polymerase II on a cell can describe the gene regulation networks responsible for...
Single cell transcriptome defined as the entire RNA or polyadenylated products of RNA polymerase II on a cell can describe the gene regulation networks responsible for physiological functions, behaviours, and phenotypes in response to signals and microenvironmental changes. Single cell transcriptome/sequencing has the special power to investigate small groups of differentiating cells, circulating tumour cells, or tissue stem cells. A large number of factors may influence the extent of single-cell heterogeneity within a system. It is the opportunity that the single-cell sequencing can be used for the identification of genetic changes in rare cells, e.g. cancer and tissue stem cells, in clinical samples. The methodologies of single-cell sequencing have been improved and developed with the increase of the understanding and attention. The clinical research and application of the single cell sequencing analysis are expected to identify and validate disease-specific biomarkers, network biomarkers, dynamic network biomarkers. The single cell research and value will be also dependent upon the understanding of genomic heterogeneity, planning and design of study protocol, representative of selected and targeted cells, and sensitivity and repeatability of the methodology. The single cell sequencing can be used to develop new diagnostics, monitor disease progresses, measure responses to therapies, and predict the prognosis of patients, although there are still a large number of challenges and difficulties to be faced. It would be more values and specificities of the single cell sequencing to integrate with the function of cells, organs, and systems of the body, the clinical phenotypes of patients, and the description of clinical bioinformatics.
Topics: Disease; Gene Expression Profiling; Genetic Heterogeneity; Genetic Markers; Humans; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 25113546
DOI: 10.1186/s12967-014-0212-3 -
Human Molecular Genetics Oct 2011The populations of Africa harbour the greatest human genetic diversity following an evolutionary history tracing its beginnings on the continent to time before the... (Review)
Review
The populations of Africa harbour the greatest human genetic diversity following an evolutionary history tracing its beginnings on the continent to time before the emergence of Homo sapiens. Signatures of selection are detectable as responses to ancient environments and cultural practices, modulated by more recent events including infectious epidemics, migrations, admixture and, of course, chance. The age of high-throughput biology is not passing Africa by. African-based cohort studies and networks with an African footprint are ideal springboards for disease-related genetic and genomic studies. Initiatives like HapMap, the 1000 Genomes Project, MalariaGEN, the INDEPTH network and Human Heredity and Health in Africa are catalysts to exploring African genetic diversity and its role in the spectrum from health to disease. The challenges are abundant in dissecting biological questions in the light of linguistic, cultural, geographic and political boundaries and their respective roles in shaping health-related profiles. Will studies based on African populations lead to a new wave of discovery of genetic contributors to disease?
Topics: Africa; Black People; Disease; Genetic Variation; Genetics, Medical; Humans
PubMed: 21908518
DOI: 10.1093/hmg/ddr401 -
Methods in Molecular Biology (Clifton,... 2014The physiological role of the mast cell and basophil has for many years remained enigmatic. In this chapter we briefly summarize some of the more recent studies that... (Review)
Review
The physiological role of the mast cell and basophil has for many years remained enigmatic. In this chapter we briefly summarize some of the more recent studies that shed new light on the role of mast cells and basophils in health and disease. What we gain from these studies is a new appreciation for mast cells and basophils as sentinels in host defense and a further understanding that dysregulation of mast cell and basophil function can be a component of various diseases other than allergies. Perhaps, the most important insight reaped from this work is the increasing awareness that mast cells and basophils can function as immunoregulatory cells that modulate the immune response in health and disease. Collectively, the recent knowledge provides new challenges and opportunities towards the development of novel therapeutic strategies to augment host protection and modify disease through manipulation of mast cell and basophil function.
Topics: Animals; Basophils; Dermatitis, Atopic; Disease; Health; Humans; Immune System; Mast Cells; Obesity; Peptide Hydrolases
PubMed: 25149480
DOI: 10.1007/978-1-4939-1173-8_1 -
FEBS Letters Nov 2014The regulation of gene expression in response to stress is an essential cellular protection mechanism. Recent advances in tRNA modification analysis and genome-based... (Review)
Review
The regulation of gene expression in response to stress is an essential cellular protection mechanism. Recent advances in tRNA modification analysis and genome-based codon bias analytics have facilitated studies that lead to a novel model for translational control, with translation elongation dynamically regulated during stress responses. Stress-induced increases in specific anticodon wobble bases are required for the optimal translation of stress response transcripts that are significantly biased in the use of degenerate codons keyed to these modified tRNA bases. These findings led us to introduce the notion of tRNA modification tunable transcripts (MoTTs - transcripts whose translation is regulated by tRNA modifications), which are identifiable using genome-wide codon counting algorithms. In support of this general model of translational control of stress response, studies making use of detailed measures of translation, tRNA methyltransferase mutants, and computational and mass spectrometry approaches reveal that stress reprograms tRNA modifications to translationally regulate MoTTs linked to arginine and leucine codons, which helps cells survive insults by damaging agents. These studies highlight how tRNA methyltransferase activities and MoTTs are key components of the cellular stress response.
Topics: Animals; Cells; Disease; Humans; Protein Biosynthesis; RNA, Transfer; Stress, Physiological
PubMed: 25304425
DOI: 10.1016/j.febslet.2014.09.038 -
Food & Function Jan 2012Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death... (Review)
Review
Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.
Topics: Animals; Chronic Disease; Dietary Fats; Disease; Fatty Acids; Humans; Metabolism; Postprandial Period
PubMed: 22020286
DOI: 10.1039/c1fo10085h -
Transactions of the Association of... 1947
Topics: Adrenal Cortex; Adrenal Gland Diseases; Adrenal Glands; Disease; Humans
PubMed: 18917236
DOI: No ID Found -
Pathologie-biologie Feb 2012It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various... (Review)
Review
It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.
Topics: Adaptive Immunity; Aging; Animals; Disease; Elastin; Humans; Immunity, Innate; Inflammation; Models, Biological; Peptides
PubMed: 22099332
DOI: 10.1016/j.patbio.2011.10.006 -
Advances in Experimental Medicine and... 2012Receptor-activity modifying proteins (RAMPs) belong to a single family of transmembrane proteins. RAMPs determine ligand specificity of G-protein coupled receptors;... (Review)
Review
Receptor-activity modifying proteins (RAMPs) belong to a single family of transmembrane proteins. RAMPs determine ligand specificity of G-protein coupled receptors; calcitonin receptor and the calcitonin-receptor like receptor (CLR). To date, three members of RAMP family (RAMP-1, -2, -3) have been identified. The co-expression of RAMP-1 with CLR constitutes the calcitonin gene related peptide receptor whereas the association of the RAMP-2 or RAMP-3 with CLR forms the adrenomedullin (AM) receptor. Alterations in signaling and subcellular distribution of G-protein coupled receptors can be responsible for the regulation of many disease conditions. These changes may be mediated by the different isoforms of RAMPs associated with such receptors. In this chapter, we describe the differential responses associated with upregulation of RAMPs in disease conditions. For instance, the upregulation of all three RAMP isoforms contributes to the cardioprotective effects of the CLR/RAMP ligands. On the other hand, strong evidence exists for the involvement of AM in various cancers and that its action is mediated by the upregulation of RAMP isoforms, RAMP-2 and -3. Though limited, a few studies have been reported on the differential response associated with the upregulation of RAMP in other disease conditions such as sepsis, liver cirrhosis, glomerulonephritis, Type 1 diabetes and Parkinson's disease. Thus, the regulation of RAMP expression is involved in the pathophysiology associated with various diseases.
Topics: Animals; Disease; Humans; Receptor Activity-Modifying Proteins
PubMed: 22434110
DOI: 10.1007/978-1-4614-2364-5_8 -
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 -
Journal of Investigative Medicine : the... Jun 2021
Topics: Cannabinoids; Cannabis; Humans; Syndrome; Vomiting
PubMed: 34074708
DOI: 10.1136/jim-2021-001982