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Scientific Reports Nov 2016In the current study, the imprinting control region of the mouse Peg3 domain was deleted to test its functional impact on animal growth and survival. The paternal...
In the current study, the imprinting control region of the mouse Peg3 domain was deleted to test its functional impact on animal growth and survival. The paternal transmission of the deletion resulted in complete abolition of the transcription of two paternally expressed genes, Peg3 and Usp29, causing the reduced body weight of the pups. In contrast, the maternal transmission resulted in the unexpected transcriptional up-regulation of the remaining paternal allele of both Peg3 and Usp29, causing the increased body weight and survival rates. Thus, the imprinted maternal allele of the ICR may be a suppressor antagonistic to the active paternal allele of the ICR, suggesting a potential intralocus allelic conflict. The opposite outcomes between the two transmissions also justify the functional compromise that the maternal allele has become epigenetically repressed rather than genetically deleted during mammalian evolution. The mice homozygous for the deletion develop normally but with a skewed sex ratio, one male per litter, revealing its sex-biased effect. Overall, the Peg3 locus may have evolved to an imprinted domain to cope with both parental and sexual conflicts driven by its growth-stimulating paternal versus growth-suppressing maternal alleles.
Topics: Alleles; Animals; Biological Evolution; Epigenesis, Genetic; Female; Genomic Imprinting; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Protein Domains; Sequence Deletion; Survival Rate; Transcription, Genetic; Ubiquitin-Specific Proteases; Up-Regulation
PubMed: 27901122
DOI: 10.1038/srep38136 -
Molecules (Basel, Switzerland) Oct 2018The eukaryotic genome is packaged into the cell nucleus in the form of chromatin, a complex of genomic DNA and histone proteins. Chromatin structure regulation is... (Review)
Review
The eukaryotic genome is packaged into the cell nucleus in the form of chromatin, a complex of genomic DNA and histone proteins. Chromatin structure regulation is critical for all DNA templated processes and involves, among many things, extensive post-translational modification of the histone proteins. These modifications can be "read out" by histone binding subdomains known as histone reader domains. A large number of reader domains have been identified and found to selectively recognize an array of histone post-translational modifications in order to target, retain, or regulate chromatin-modifying and remodeling complexes at their substrates. Interestingly, an increasing number of these histone reader domains are being identified as also harboring nucleic acid binding activity. In this review, we present a summary of the histone reader domains currently known to bind nucleic acids, with a focus on the molecular mechanisms of binding and the interplay between DNA and histone recognition. Additionally, we highlight the functional implications of nucleic acid binding in chromatin association and regulation. We propose that nucleic acid binding is as functionally important as histone binding, and that a significant portion of the as yet untested reader domains will emerge to have nucleic acid binding capabilities.
Topics: Animals; Binding Sites; DNA; Histones; Humans; Models, Molecular; Prevalence; Protein Binding; Protein Domains
PubMed: 30322003
DOI: 10.3390/molecules23102614 -
International Journal of Molecular... Jul 2021CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in that lead to an... (Review)
Review
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor β (TGFβ) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets.
Topics: CADASIL; Cysteine; Gastrointestinal Microbiome; Gene Frequency; Gene Ontology; Genetic Association Studies; Genome-Wide Association Study; Genomics; Humans; Models, Molecular; Mutation; Nerve Tissue Proteins; Prevalence; Prognosis; Protein Aggregation, Pathological; Protein Conformation; Protein Domains; Proteomics; Receptor, Notch3; Sequence Analysis, DNA; Transcriptome
PubMed: 34298974
DOI: 10.3390/ijms22147357 -
The Journal of Trauma and Acute Care... Jan 2022Patient-reported outcomes are important for understanding recovery after burn injury, benchmarking service delivery and measuring the impact of interventions....
Validation of PROMIS-29 domain scores among adult burn survivors: A National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System Study.
BACKGROUND
Patient-reported outcomes are important for understanding recovery after burn injury, benchmarking service delivery and measuring the impact of interventions. Patient-Reported Outcomes Measurement Information System (PROMIS)-29 domains have been validated for use among diverse populations though not among burn survivors. The purpose of this study was to examine validity and reliability of PROMIS-29 scores in this population.
METHODS
The PROMIS-29 scores of physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, and pain interference were evaluated for validity and reliability in adult burn survivors. Unidimensionality, floor and ceiling effects, internal consistency, and reliability were examined. Differential item functioning was used to examine bias with respect to demographic and injury characteristics. Correlations with measures of related constructs (Community Integration Questionnaire, Satisfaction with Life Scale, Post-Traumatic Stress Checklist-Civilian, and Veteran's Rand-12) and known-group differences were examined.
RESULTS
Eight hundred and seventy-six burn survivors with moderate to severe injury from 6 months to 20 years postburn provided responses on PROMIS-29 domains. Participants' ages ranged from 18 years to 93 years at time of assessment; mean years since injury was 3.4. All PROMIS domain scores showed high internal consistency (Cronbach's α = 0.87-0.97). There was a large ceiling effect on ability to participate in social roles (39.7%) and physical function (43.3%). One-factor confirmatory factor analyses supported unidimensionality (all comparative fit indices >0.95). We found no statistically significant bias (differential item functioning). Reliability was high (>0.9) across trait levels for all domains except sleep, which reached moderate reliability (>0.85). All known-group differences by demographic and clinical characteristics were in the hypothesized direction and magnitude except burn size categories.
CONCLUSION
The results provide strong evidence for reliability and validity of PROMIS-29 domain scores among adult burn survivors. Reliability of the extreme scores could be increased and the ceiling effects reduced by administering PROMIS-43, which includes six items per domain, or by administering by computerized adaptive testing.
LEVEL OF EVIDENCE
Diagnostic Test or Criteria, level III.
Topics: Burns; Disabled Persons; Female; Humans; Independent Living; Male; Middle Aged; Patient Reported Outcome Measures; Physical Functional Performance; Psychometrics; Quality of Life; Rehabilitation Research; Reproducibility of Results; Research Design; Social Interaction; Surveys and Questionnaires; Survivors
PubMed: 34284470
DOI: 10.1097/TA.0000000000003365 -
Journal of Medical Internet Research Aug 2015The rapid spread of Web-based social media in recent years has impacted how patients share health-related information. However, little work has studied the demographics... (Comparative Study)
Comparative Study
BACKGROUND
The rapid spread of Web-based social media in recent years has impacted how patients share health-related information. However, little work has studied the demographics of these users.
OBJECTIVE
Our aim was to study the demographics of users who participate in health-related Web-based social outlets to identify possible links to health care disparities.
METHODS
We analyze and compare three different types of health-related social outlets: (1) general Web-based social networks, Twitter and Google+, (2) drug review websites, and (3) health Web forums. We focus on the following demographic attributes: age, gender, ethnicity, location, and writing level. We build and evaluate domain-specific classifiers to infer missing data where possible. The estimated demographic statistics are compared against various baselines, such as Internet and social networks usage of the population.
RESULTS
We found that (1) drug review websites and health Web forums are dominated by female users, (2) the participants of health-related social outlets are generally older with the exception of the 65+ years bracket, (3) blacks are underrepresented in health-related social networks, (4) users in areas with better access to health care participate more in Web-based health-related social outlets, and (5) the writing level of users in health-related social outlets is significantly lower than the reading level of the population.
CONCLUSIONS
We identified interesting and actionable disparities in the participation of various demographic groups to various types of health-related social outlets. These disparities are significantly distinct from the disparities in Internet usage or general social outlets participation.
Topics: Aged; Demography; Female; Healthcare Disparities; Humans; Male; Middle Aged; Social Media; Social Networking
PubMed: 26250986
DOI: 10.2196/jmir.4308 -
Developmental Cognitive Neuroscience Aug 2018The Adolescent Brain and Cognitive Development (ABCD) Study incorporates a comprehensive range of measures assessing predictors and outcomes related to both mental and... (Review)
Review
The Adolescent Brain and Cognitive Development (ABCD) Study incorporates a comprehensive range of measures assessing predictors and outcomes related to both mental and physical health across childhood and adolescence. The workgroup developed a battery that would assess a comprehensive range of domains that address study aims while minimizing participant and family burden. We review the major considerations that went into deciding what constructs to cover in the demographics, physical health and mental health domains, as well as the process of selecting measures, piloting and refining the originally proposed battery. We present a description of the baseline battery, as well as the six-month interim assessments and the one-year follow-up assessments. This battery includes assessments from the perspectives of both the parent and the target youth, as well as teacher reports. This battery will provide a foundational baseline assessment of the youth's current function so as to permit characterization of stability and change in key domains over time. The findings from this battery will also be utilized to identify both resilience markers that predict healthy development and risk factors for later adverse outcomes in physical health, mental health, and substance use and abuse.
Topics: Adolescent; Brain; Child; Cognition; Demography; Female; Humans; Male; Mental Health
PubMed: 29113758
DOI: 10.1016/j.dcn.2017.10.010 -
American Journal of Health Promotion :... Nov 2018To propose collective well-being as a holistic measure of the overall "health" of a community. To define collective well-being as a group-level construct measured across... (Review)
Review
OBJECTIVES
To propose collective well-being as a holistic measure of the overall "health" of a community. To define collective well-being as a group-level construct measured across 5 domains (vitality, opportunity, connectedness, contribution, and inspiration) and introduce an actionable model that demonstrates how community characteristics affect collective well-being. To review the literature describing each domain's association with health outcomes and community characteristics' associations with collective well-being.
METHODS
We came to consensus on topics describing each component of our conceptual model. Because "well-being" is not indexed in MEDLINE, we performed topic-specific database searches and examined bibliographies of papers retrieved. We excluded articles that were limited to narrow subtopics or studies within small subpopulations. Preference was given to quasi-experimental or randomized studies, systematic reviews, or meta-analyses. Consensus was reached on inclusion or exclusion of all articles.
RESULTS
Reviewed literature supported each of the proposed domains as important aspects of collective well-being and as determinants of individual or community health. Evidence suggests a broad range of community characteristics support collective well-being.
CONCLUSIONS
The health and quality of life of a community may be improved by focusing efforts on community characteristics that support key aspects of well-being. Future work should develop a unified measure of collective well-being to evaluate the relative impact of specific efforts on the collective well-being of communities.
Topics: Environment; Humans; Mental Health; Population Health; Quality of Life; Residence Characteristics; Social Capital; Socioeconomic Factors
PubMed: 30079743
DOI: 10.1177/0890117118791993 -
Epidemiology (Cambridge, Mass.) Mar 2013Between 1600 and 1700, sudden, profound, and multifarious changes occurred in philosophy, science, medicine, politics, and society. In an extremely convulsed century,...
Between 1600 and 1700, sudden, profound, and multifarious changes occurred in philosophy, science, medicine, politics, and society. In an extremely convulsed century, these profound and convergent upheavals produced the equivalent of a cultural big bang, which opened a new domain of knowledge acquisition based on population thinking and group comparisons. In 1662, when John Graunt applied-for the first time-the new approach to the analysis of causes of death in London, he gave epidemiology a singular date of birth. This was exactly 350 years ago.
Topics: Demography; Epidemiology; History, 17th Century; Humans; Mortality; Plague
PubMed: 23377087
DOI: 10.1097/EDE.0b013e31827b5359 -
PloS One 2011Autoantibodies to the catalytic domain of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) have been recently identified as a new family of autoantibodies...
BACKGROUND
Autoantibodies to the catalytic domain of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) have been recently identified as a new family of autoantibodies involved in rheumatoid arthritis (RA). The objective of this study was to determine antibody responses to the catalytic domain of BRAF in RA and other autoimmune diseases. The association between RA-related clinical indices and these antibodies was also assessed.
METHODOLOGY/PRINCIPAL FINDINGS
The presence of autoantibodies to the catalytic domain of BRAF (anti-BRAF) or to peptide P25 (amino acids 656-675 of the catalytic domain of BRAF; anti-P25) was determined in serum samples from patients with RA, primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), and healthy controls by using indirect enzyme-linked immunosorbent assays (ELISAs) based on the recombinant catalytic domain of BRAF or a synthesized peptide, respectively. Associations of anti-BRAF or anti-P25 with disease variables of RA patients were also evaluated. Our results show that the BRAF-specific antibodies anti-BRAF and anti-P25 are equally present in RA, pSS, and SLE patients. However, the erythrocyte sedimentation rate (ESR) used to detect inflammation was significantly different between patients with and without BRAF-specific antibodies. The anti-BRAF-positive patients were found to have prolonged disease, and active disease occurred more frequently in anti-P25-positive patients than in anti-P25-negative patients. A weak but significant correlation between anti-P25 levels and ESRs was observed (r = 0.319, p = 0.004).
CONCLUSIONS/SIGNIFICANCE
The antibody response against the catalytic domain of BRAF is not specific for RA, but the higher titers of BRAF-specific antibodies may be associated with increased inflammation in RA.
Topics: Antibody Formation; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Blood Sedimentation; Case-Control Studies; Catalytic Domain; Demography; Electrophoresis, Polyacrylamide Gel; Female; Humans; Middle Aged; Proto-Oncogene Proteins B-raf; Recombinant Proteins
PubMed: 22174938
DOI: 10.1371/journal.pone.0028975 -
International Journal of Environmental... Aug 2020The aim of this study was to identify socio-demographic correlates of total and domain-specific sedentary behavior (SB).
PURPOSE
The aim of this study was to identify socio-demographic correlates of total and domain-specific sedentary behavior (SB).
METHODS
Cross-sectional findings are based on 9218 participants (15-65 years) from the Latin American Study of Nutrition and Health. Data were collected between September 2014 and February 2015. Participants reported time spent in SB across specific domains. Sex, age, ethnicity, socioeconomic (SEL), and education level were used as sociodemographic indicators.
RESULTS
Participants spent a total of 373.3 min/day engaged in total SB. Men, younger adults, other ethnicities, higher SEL and educational level presented higher total SB when compared with women, older adults, white/Caucasian, and low SEL and educational level. Men spent more time on the playing videogames (: 32.8: 95% CI: 14.6;51.1) and riding in an automobile (40.5: 31.3; 49.8). Computer time, reading, socializing or listening to music was higher in younger participants (<30 years) compared with those ≥50 years in the total sample. Compared to the low SEL and educational level groups, middle (11.7: 5.7; 17.6) and higher (15.1: 5.3; 24.9) SEL groups as well as middle (9.8: 3.6; 15.9) and higher (16.6: 6.5; 26.8) education level groups reported more time spent reading.
CONCLUSION
Socio-demographic characteristics are associated with SB patterns (total and specific) across Latin American countries.
Topics: Aged; Cross-Sectional Studies; Demography; Female; Humans; Latin America; Male; Middle Aged; Sedentary Behavior; Time Factors
PubMed: 32756330
DOI: 10.3390/ijerph17155587