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Biomedical subjects

Barbara Davis

Publications and source records attributed to Barbara Davis.

8 recordsLinked to original sources
PubMed2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Humans↗
PubMed2006

Use of environmental supports among patients with schizophrenia.

OBJECTIVE: Cognitive adaptation training is a psychosocial treatment that uses individually tailored environmental supports, such as signs, calendars, hygiene supplies, and pill containers, to cue and sequence adaptive behavior in the client's home environment. Generic environmental supports offer a less costly treatment that provides a predetermined package of helpful supports to clients at the time of their routine clinic visit. Previous studies have demonstrated the efficacy of cognitive adaptation training. The study reported here examined the extent to which environmental supports are used by clients. METHODS: As part of an ongoing study, persons with schizophrenia were randomly assigned to one of three conditions: cognitive adaptation training, generic environmental supports, or assessment only. Rates of use of supports for the first three months of treatment were examined for the first 64 patients assigned to the first two groups. RESULTS: Rates of overall use averaged approximately 80 percent for cognitive adaptation training and 44 percent for generic environmental supports. Specific categories of supports were also significantly more likely to be used by patients who were receiving cognitive adaptation training. More than 66 percent of patients in cognitive adaptation training were classified as high users of supports (used more than 75 percent of supports provided appropriately), compared with only 13 percent of those who were receiving generic environmental supports. CONCLUSIONS: Environmental supports have been found to improve functional behaviors for patients with schizophrenia. However, supports are not likely to be used unless they are customized for individual clients and set up in the home environment.

Adaptation, Psychological↗
PubMed2005

Mono(2-ethylhexyl)phthalate and mono-n-butyl phthalate activation of peroxisome proliferator activated-receptors alpha and gamma in breast.

The phthalates di(2-ethylhexyl)phthalate (DEHP) and di-n-butyl phthalate (DBP) are environmental contaminants with significant human exposures. Both compounds are known reproductive toxins in rodents and DEHP also induces rodent hepatocarcinogenesis in a process believed to be mediated via the peroxisome proliferator-activated receptor alpha (PPARalpha). DEHP and DBP are metabolised to their respective monoesters, mono-(2-ethylhexyl)phthalate (MEHP) and mono-n-butyl phthalate (MBP), which are the active metabolites. MEHP also activates another member of the PPAR subfamily, PPARgamma. The effects of PPARalpha and PPARgamma activation in human breast cells appears to be opposing; PPARalpha activators in breast cells cause an increase in proliferation, while PPARgamma activation in breast cells is associated with differentiation and an inhibition of cell proliferation. Further to this the activation of the PPARs is cell and ligand specific, suggesting the importance of examining the effect of MEHP and MBP on the activation of PPARalpha, PPARbeta and PPARgamma in human breast. We used the common model of human breast cancer MCF-7 and examined the ability of MEHP and MBP to activate human PPARs in this system. The ability of MBP and MEHP to block PPAR responses was also assessed. We found that both human PPARalpha and PPARgamma were activated by MEHP whereas MEHP could not activate PPARbeta. MBP was unable to activate any PPAR isoforms in this breast model, despite being a weak peroxisome proliferator in liver, although MBP was an antagonist for both PPARgamma and PPARbeta. Our results suggest that the toxicological consequences of MEHP in the breast could be complex given the opposing effects of PPARalpha and PPARgamma in human breast cells.

Breast Neoplasms↗
PubMed2005

Chromatin remodeling by DNA bending, not twisting.

Single-stranded regions (gaps) in nucleosomal DNA interfere with action of the RSC chromatin-remodeling complex, monitored by exposure of restriction endonuclease cutting sites. Single-strand breaks (nicks) in the DNA, by contrast, have no effect. Gaps on one side of the cutting site are inhibitory, but gaps on the other side are not. A gap >100 bp from the cutting site is as effective as a gap <20 bp from the site. These findings suggest a remodeling process involving bending, but not twisting, of the DNA and further point to the propagation of a bent region (loop or bulge) from one end of the nucleosome to the other.

Alu Elements↗
PubMed2003

Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus.

Perinatal exposure to diethylstilbestrol (DES) induces reproductive tract cancers later in life in both humans and animals. Because there is no clear evidence that perinatal DES exposure induces gene mutation, we proposed that perinatal DES exposure causes epigenetic methylation changes that result in persistent alterations in gene expression, leading to tumorigenesis. The proto-oncogene c-fos is one of the immediately induced genes in uterine epithelium after estrogen simulation and a key player in uterine carcinogenesis. Here, we investigated c-fos expression in mice neonatally exposed to DES (2 microg/pup/day on postnatal days 1-5). The mRNA levels of c-fos in uteri of neonatal DES-treated mice were persistently 1.4-1.9-fold higher than that in the control mice from day 5 to day 60. Overall, the uterine c-fos expression level in the neonatal DES-exposed group was significantly higher than that in the control group. After examination of the methylation status of the c-fos gene, we found that the CpGs in promoter and intron-1 regions were completely unmethylated. In exon-4, from day 17 to day 60, the percentage of unmethylated CpGs was higher in neonatal DES-exposed mice uteri than that in control (42%, 51%, 47%, and 42% in DES-exposed mice vs 33%, 34%, 33%, and 21% in control mice at day 17, 21, 30, and 60, respectively). These results suggest that perinatal DES exposure may permanently alter gene expression and methylation, and the methylation modification may occur in either the promoter regions or other regulatory sites in the gene.

Animals↗
PubMedDate not supplied

The affordability of a nutritious diet for households on welfare in Toronto.

OBJECTIVES: This study assesses the affordability of a nutritious diet for households in Toronto that are supported by welfare. METHODS: For three hypothetical households, welfare incomes were compared to the monthly costs for food, shelter, and other essential expenditures in Toronto. RESULTS: If households lived in market rental accommodation, average monthly incomes were insufficient to cover expenses for the single-person household and two-parent family, and barely adequate for the single-parent family considered in this study. However, the single-parent family's actual income fell below expenses for six months of the year. For households with children, the relative inadequacy of welfare increased as children grew older. Living in rent-geared-to-income housing afforded substantial financial advantage, but the welfare income of single-person households was still insufficient to meet basic needs. INTERPRETATION: These findings indicate discrepancies between welfare incomes and costs of basic needs, which may explain the vulnerability of welfare recipients to food insecurity.

Budgets↗