Chandra's first decade of discovery.
Ontology highlight
ABSTRACT:
SUBMITTER: Swartz DA
PROVIDER: S-EPMC2867717 | biostudies-other | 2010 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:GATA2 deficiency syndrome (G2DS) is a rare autosomal dominant genetic disease predisposing to a range of symptoms, of which myeloid malignancy and immunodeficiency including recurrent infections are most common. In the last decade since it was first reported, there have been over 480 individuals identified carrying a pathogenic or likely pathogenic germline GATA2 variant with symptoms of G2DS, with 240 of these confirmed to be familial and 24 de novo. For those that develop myeloid malignancy (75% of all carriers with G2DS disease symptoms), the median age of onset is 17 years (range 0-78 years) and myelodysplastic syndrome is the first diagnosis in 75% of these cases with acute myeloid leukemia in a further 9%. All variant types appear to predispose to myeloid malignancy and immunodeficiency. Apart from lymphedema in which haploinsufficiency seems necessary, the mutational requirements of the other less common G2DS phenotypes is still unclear. These predominantly loss-of-function variants impact GATA2 expression and function in numerous ways including perturbations to DNA binding, protein structure, protein:protein interactions, and gene transcription, splicing, and expression. In this review, we provide the first expert-curated ACMG/AMP classification with codes of published variants compatible for use in clinical or diagnostic settings.
| S-EPMC9291163 | biostudies-literature
Project description:It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.
| S-EPMC3194831 | biostudies-literature
Project description:In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study sites, OPPERA recruited and examined 3,258 community-based TMD-free adults assessing genetic and phenotypic measures of biological, psychosocial, clinical, and health status characteristics. During follow-up, 4% of participants per annum developed clinically verified TMD, although that was a "symptom iceberg" when compared with the 19% annual rate of facial pain symptoms. The most influential predictors of clinical TMD were simple checklists of comorbid health conditions and nonpainful orofacial symptoms. Self-reports of jaw parafunction were markedly stronger predictors than corresponding examiner assessments. The strongest psychosocial predictor was frequency of somatic symptoms, although not somatic reactivity. Pressure pain thresholds measured at cranial sites only weakly predicted incident TMD yet were strongly associated with chronic TMD, cross-sectionally, in OPPERA's separate case-control study. The puzzle was resolved in OPPERA's nested case-control study where repeated measures of pressure pain thresholds revealed fluctuation that coincided with TMD's onset, persistence, and recovery but did not predict its incidence. The nested case-control study likewise furnished novel evidence that deteriorating sleep quality predicted TMD incidence. Three hundred genes were investigated, implicating 6 single-nucleotide polymorphisms (SNPs) as risk factors for chronic TMD, while another 6 SNPs were associated with intermediate phenotypes for TMD. One study identified a serotonergic pathway in which multiple SNPs influenced risk of chronic TMD. Two other studies investigating gene-environment interactions found that effects of stress on pain were modified by variation in the gene encoding catechol O-methyltransferase. Lessons learned from OPPERA have verified some implicated risk factors for TMD and refuted others, redirecting our thinking. Now it is time to apply those lessons to studies investigating treatment and prevention of TMD.
| S-EPMC5004239 | biostudies-literature
Project description:The protein methyltransferases (PMTs) represent a large class of enzymes that catalyse the methylation of side chain nitrogen atoms of the amino acids lysine or arginine at specific locations along the primary sequence of target proteins. These enzymes play a key role in the spatio-temporal control of gene transcription by performing site-specific methylation of lysine or arginine residues within the histone proteins of chromatin, thus effecting chromatin conformational changes that activate or repress gene transcription. Over the past decade, it has become clear that the dysregulated activity of some PMTs plays an oncogenic role in a number of human cancers. Here we review research of the past decade that has identified specific PMTs as oncogenic drivers of cancers and progress toward the discovery and development of selective, small molecule inhibitors of these enzymes as precision cancer therapeutics.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.
| S-EPMC5915721 | biostudies-literature
Project description:More than two decades have elapsed since the publication of the first genome sequence of Mycobacterium tuberculosis (Mtb) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of mechanism of action has to date been the most fruitful approach to progressing inhibitors into the tuberculosis drug discovery pipeline although target-based approaches are gaining momentum. This review discusses scaffolds that have been identified over the last decade from screens of small molecule libraries against Mtb or defined targets where mechanism of action investigation has defined target-hit couples and structure-activity relationship studies have described the pharmacophore.
| S-EPMC8005628 | biostudies-literature
Project description:Helping B cells and antibody responses is a major function of CD4+ T cells. It has been 10 years since the publication of Bcl6 as the lineage-defining transcription factor for T follicular helper (Tfh) differentiation and the requirement of Tfh cells as the specialized subset of CD4+ T cells needed for germinal centers (the microanatomical sites of B cell mutation and antibody affinity maturation) and related B cell responses. A great deal has been learned about Tfh cells in the past 10 years, particularly regarding their roles in a surprising range of diseases. Advances in the understanding of Tfh cell differentiation and function are discussed, as are the understanding of Tfh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer. This includes discussion of Tfh cells in the human immune system. Based on the discoveries to date, the next decade of Tfh research surely holds many more surprises. VIDEO ABSTRACT.
| S-EPMC6532429 | biostudies-literature
Project description:Diagnostic shifts have been prospectively examined in the short term, but the long-term stability of diagnoses has rarely been evaluated. The authors examined diagnostic shifts over a 10-year follow-up period.A cohort of 470 first-admission patients with psychotic disorders was systematically assessed at baseline and at 6-month, 2-year, and 10-year follow-ups. Longitudinal best-estimate consensus diagnoses were formulated after each assessment.At baseline, the diagnostic distribution was 29.6% schizophrenia spectrum disorders, 21.1% bipolar disorder with psychotic features, 17.0% major depression with psychotic features, 2.4% substance-induced psychosis, and 27.9% other psychoses. At year 10, the distribution changed to 49.8%, 24.0%, 11.1%, 7.0%, and 8.1%, respectively. Overall, diagnoses were changed for 50.7% of study participants at some point during the study. Most participants who were initially diagnosed with schizophrenia or bipolar disorder retained the diagnosis at year 10 (89.2% and 77.8%, respectively). However, 32.0% of participants (N=98) originally given a non-schizophrenia diagnosis had gradually shifted to a schizophrenia diagnosis by year 10. The second largest shift was to bipolar disorder (10.7% of those not given this diagnosis at baseline). Changes in the clinical picture explained many diagnostic shifts. In particular, poorer functioning and greater negative and psychotic symptom ratings predicted a subsequent shift to schizophrenia. Better functioning and lower negative and depressive symptom ratings predicted the shift to bipolar disorder.First-admission patients with psychotic disorders run the risk of being misclassified at early stages in the illness course, including more than 2 years after first hospitalization. Diagnosis should be reassessed at all follow-up points.
| S-EPMC3589618 | biostudies-literature
Project description:ObjectiveTo examine the prevalence of maternal and paternal spanking of children at 3 and 5 years of age and the associations between spanking and children's externalizing behavior and receptive vocabulary through age 9.MethodsThe Fragile Families and Child Well-Being Study, a longitudinal birth cohort study of children in 20 medium to large US cities, was used. Parental reports of spanking were assessed at age 3 and 5, along with child externalizing behavior and receptive vocabulary at age 9 (N = 1933). The data set also included an extensive set of child and family controls (including earlier measures of the child outcomes).ResultsOverall, 57% of mothers and 40% of fathers engaged in spanking when children were age 3, and 52% of mothers and 33% of fathers engaged in spanking at age 5. Maternal spanking at age 5, even at low levels, was associated with higher levels of child externalizing behavior at age 9, even after an array of risks and earlier child behavior were controlled for. Father's high-frequency spanking at age 5 was associated with lower child receptive vocabulary scores at age 9.ConclusionsSpanking remains a typical rearing experience for American children. These results demonstrate negative effects of spanking on child behavioral and cognitive development in a longitudinal sample from birth through 9 years of age.
| S-EPMC3813398 | biostudies-literature
Project description:Significant progress has been made in the 21st century towards a comprehensive understanding of the mechanisms of action of general anesthetics, coincident with progress in structural biology and molecular, cellular, and systems neuroscience. This review summarizes important new findings that include target identification through structural determination of anesthetic binding sites, details of receptors and ion channels involved in neurotransmission, and the critical roles of neuronal networks in anesthetic effects on memory and consciousness. These recent developments provide a comprehensive basis for conceptualizing pharmacological control of amnesia, unconsciousness, and immobility.
| S-EPMC6830308 | biostudies-literature
Project description:The number of Parkinson's disease (PD) patients increases with aging, which brings heavy burden to families and society. The emergence of patient-derived induced pluripotent stem cells (iPSCs) has brought hope to the current situation of lacking new breakthroughs in diagnosis and treatment of PD. In this article, we reviewed and analyzed the current researches related to PD patient-derived iPSCs, in order to provide solid theoretical basis for future study of PD. In 2008, successful iPSCs derived from PD patients were reported. The current iPSCs research in PD mostly focused on the establishment of specific iPSCs models of PD patients carrying susceptible genes. The main source of PD patient-derived iPSCs is skin fibroblasts and the mainstream reprogramming methodology is the mature "four-factor" method, which introduces four totipotent correlation factors Oct4, Sox2, Klf4 and c-Myc into somatic cells. The main sources of iPSCs are patients with non-pedigrees and there have been no studies involving both PD patients and unaffected carriers within the same family. Most of the existing studies of PD patient-derived iPSCs started with the induction method for obtaining dopaminergic neurons in the first instance, but therapeutic applications are being increased. Although it is not the ultimate panacea, and there are still some unsolved problems (e.g., whether the mutated genes should be corrected or not), a better understanding of iPSCs may be a good gift for both PD patients and doctors due to their advantages in diagnosis and treatment of PD.
| S-EPMC6944564 | biostudies-literature