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1.
Public Health Nurs ; 40(5): 603-611, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37166791

RESUMO

OBJECTIVES: To evaluate the outcomes of increasing mobile market service from mostly biweekly in 2019 to weekly in 2021. DESIGN: Repeated, cross-sectional customer intercept surveys. SAMPLE: Mobile market customers in Summers 2019 (N = 302) and 2021 (N = 72). INTERVENTION: Mobile food markets bring affordable, high-quality foods to communities that lack such access. MEASURES/ANALYSIS: Outcomes included food security, fruit/vegetable intake, and food-related characteristics and behaviors. General linear and logistic regression models were used to assess associations between outcomes and survey year and length of mobile market shopping. Models were adjusted for economic assistance use, race, and ethnicity. RESULTS: No outcomes were significantly different between 2019 (with mostly biweekly service) and 2021 (with weekly service). Length of mobile market shopping (e.g., >2 years, 1-2 years, etc.) was positively associated with affordable, quality food access (ß = 0.20, SE = 0.10, p = .03) and fruit/vegetable intake (ß = 0.28, SE = 0.08, p < .001) as well as lower odds of food insecurity in the last 12 months (aOR = 0.79, 95% CI = 0.64, 0.99). CONCLUSIONS: Despite COVID-19 interrupting scheduled market service, the length of time that a survey respondent identified as a full-service mobile market customer was associated with higher food access and fruit/vegetable intake and reduced food insecurity odds. These findings suggest promise and encourage further evaluation.


Assuntos
Dieta , Assistência Alimentar , Humanos , Frutas , Verduras , Estudos Transversais , Abastecimento de Alimentos , Inquéritos e Questionários
2.
Appetite ; 166: 105466, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34139297

RESUMO

Mobile markets (MM) bring affordable, quality, healthy foods to high-need, low-food access communities. However, little is known about food insecurity of MM customers. This manuscript evaluates food insecurity prevalence in MM customers and assesses associations between food insecurity and MM use, food-related characteristics and behaviors, and fruit and vegetable (FV) intake. Customers (N = 302) completed cross-sectional surveys in summer 2019 that assessed: food security, food availability, cooking attitude, self-efficacy for healthy cooking, self-efficacy for cooking and eating FV, social connectedness, and FV intake. Descriptive and multivariate analyses were used to describe and assess associations with food insecurity and FV intake. Results show most MM customers were food insecure (85%). In logistic regression models adjusted for sociodemographic characteristics, long-term MM use (OR = 0.77, CI = 0.60-0.997), access to affordable, quality foods (OR = 0.81, CI = 0.71-0.93), and self-efficacy for both cooking healthy foods (OR = 0.88, CI = 0.80-0.97) and cooking and eating FV (OR = 0.90, CI = 0.82-0.98) were associated with lower odds of food insecurity; negative cooking attitudes (OR = 1.12, CI = 1.02-1.24) were associated with higher odds of food insecurity. Being food insecure (ß = -1.37, SE=0.43, p < 0.01) was associated with poorer FV intake; this association attenuated slightly (ß = -1.22, SE=0.43, p < 0.01) when length of MM use was added to the general linear model, which was also associated with higher fruit and vegetable intake (ß = 0.26, SE=0.10, p = 0.01). Results suggest the MM reaches customers experiencing high levels of food insecurity and long-term MM use is associated with lower food insecurity and higher FV intake. Relationships between food insecurity and several food characteristics/behaviors provide insight for potential targets for wrap-around interventions to address food insecurity among customers. Findings suggest longitudinal evaluation of the MM's impact on food security and other food-related characteristics/behaviors is warranted.


Assuntos
Frutas , Verduras , Estudos Transversais , Dieta , Insegurança Alimentar , Abastecimento de Alimentos , Humanos
3.
Nat Commun ; 12(1): 2901, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006870

RESUMO

Proliferative chronic myelomonocytic leukemia (pCMML), an aggressive CMML subtype, is associated with dismal outcomes. RAS pathway mutations, mainly NRASG12D, define the pCMML phenotype as demonstrated by our exome sequencing, progenitor colony assays and a Vav-Cre-NrasG12D mouse model. Further, these mutations promote CMML transformation to acute myeloid leukemia. Using a multiomics platform and biochemical and molecular studies we show that in pCMML RAS pathway mutations are associated with a unique gene expression profile enriched in mitotic kinases such as polo-like kinase 1 (PLK1). PLK1 transcript levels are shown to be regulated by an unmutated lysine methyl-transferase (KMT2A) resulting in increased promoter monomethylation of lysine 4 of histone 3. Pharmacologic inhibition of PLK1 in RAS mutant patient-derived xenografts, demonstrates the utility of personalized biomarker-driven therapeutics in pCMML.


Assuntos
Proteínas de Ciclo Celular/genética , GTP Fosfo-Hidrolases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Mielomonocítica Crônica/genética , Proteínas de Membrana/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Animais , Proteínas de Ciclo Celular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Estimativa de Kaplan-Meier , Leucemia Mielomonocítica Crônica/metabolismo , Leucemia Mielomonocítica Crônica/terapia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/genética , Transplante de Células-Tronco/métodos , Transplante Homólogo , Sequenciamento do Exoma/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Quinase 1 Polo-Like
4.
Nature ; 582(7810): 119-123, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494069

RESUMO

The three-dimensional architecture of the genome governs its maintenance, expression and transmission. The cohesin protein complex organizes the genome by topologically linking distant loci, and is highly enriched in specialized chromosomal domains surrounding centromeres, called pericentromeres1-6. Here we report the three-dimensional structure of pericentromeres in budding yeast (Saccharomyces cerevisiae) and establish the relationship between genome organization and function. We find that convergent genes mark pericentromere borders and, together with core centromeres, define their structure and function by positioning cohesin. Centromeres load cohesin, and convergent genes at pericentromere borders trap it. Each side of the pericentromere is organized into a looped conformation, with border convergent genes at the base. Microtubule attachment extends a single pericentromere loop, size-limited by convergent genes at its borders. Reorienting genes at borders into a tandem configuration repositions cohesin, enlarges the pericentromere and impairs chromosome biorientation during mitosis. Thus, the linear arrangement of transcriptional units together with targeted cohesin loading shapes pericentromeres into a structure that is competent for chromosome segregation. Our results reveal the architecture of the chromosomal region within which kinetochores are embedded, as well as the restructuring caused by microtubule attachment. Furthermore, we establish a direct, causal relationship between the three-dimensional genome organization of a specific chromosomal domain and cellular function.


Assuntos
Centrômero/genética , Centrômero/metabolismo , Genes Fúngicos , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/metabolismo , Centrômero/química , Proteínas Cromossômicas não Histona/metabolismo , Segregação de Cromossomos , Genoma Fúngico/genética , Viabilidade Microbiana/genética , Mitose/genética , Conformação Molecular , Coesinas
5.
Hepatol Commun ; 2(12): 1493-1512, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30556038

RESUMO

With the epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common pediatric liver disease. The influence of a perinatal obesity-inducing diet (OID) on the development and progression of NAFLD in offspring is important but incompletely studied. Hence, we fed breeding pairs of C57BL/6J mice during gestation and lactation (perinatally) either chow or an OID rich in fat, fructose, and cholesterol (FFC). The offspring were weaned to either chow or an FFC diet, generating four groups: perinatal (p)Chow-Chow, pChow-FFC, pFFC-Chow, and pFFC-FFC. Mice were sacrificed at 10 weeks of age. We examined the whole-liver transcriptome by RNA sequencing (RNA-seq) and whole-liver genome methylation by reduced representation bisulfite sequencing (RRBS). Our results indicated that the pFFC-FFC mice had a significant increase in hepatic steatosis, injury, inflammation, and fibrosis, as assessed histologically and biochemically. We identified 189 genes that were differentially expressed and methylated in the pFFC-FFC mice versus the pChow-FFC mice. Gene set enrichment analysis identified hepatic fibrosis/hepatic stellate cell activation as the top canonical pathway, suggesting that the differential DNA methylation events in the mice exposed to the FFC diet perinatally were associated with a profibrogenic transcriptome. To verify that this finding was consistent with perinatal nutritional reprogramming of the methylome, we exposed pFFC-Chow mice to an FFC diet in adulthood. These mice developed significant hepatic steatosis, injury, inflammation, and more importantly fibrosis when compared to the appropriate controls. Conclusion: Perinatal exposure to an OID primes the immature liver for an accentuated fibrosing nonalcoholic steatohepatitis (NASH) phenotype, likely through nutritional reprogramming of the offspring methylome. These data have potential clinical implications for monitoring children of obese mothers and risk stratification of children with NAFLD.

6.
Genome Biol ; 19(1): 43, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587824

RESUMO

BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of stem-like cells that contribute to glioblastoma (GBM) aggressiveness, recurrence, and resistance to radiation and chemotherapy. Therapeutically targeting the GSC population may improve patient survival, but unique vulnerabilities need to be identified. RESULTS: We isolate GSCs from well-characterized GBM patient-derived xenografts (PDX), characterize their stemness properties using immunofluorescence staining, profile their epigenome including 5mC, 5hmC, 5fC/5caC, and two enhancer marks, and define their transcriptome. Fetal brain-derived neural stem/progenitor cells are used as a comparison to define potential unique and common molecular features between these different brain-derived cells with stem properties. Our integrative study reveals that abnormal expression of ten-eleven-translocation (TET) family members correlates with global levels of 5mC and 5fC/5caC and may be responsible for the distinct levels of these marks between glioma and neural stem cells. Heterogenous transcriptome and epigenome signatures among GSCs converge on several genes and pathways, including DNA damage response and cell proliferation, which are highly correlated with TET expression. Distinct enhancer landscapes are also strongly associated with differential gene regulation between glioma and neural stem cells; they exhibit unique co-localization patterns with DNA epigenetic mark switching events. Upon differentiation, glioma and neural stem cells exhibit distinct responses with regard to TET expression and DNA mark changes in the genome and GSCs fail to properly remodel their epigenome. CONCLUSIONS: Our integrative epigenomic and transcriptomic characterization reveals fundamentally distinct yet potentially targetable biologic features of GSCs that result from their distinct epigenomic landscapes.


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Células-Tronco Neoplásicas/metabolismo , Animais , Diferenciação Celular , Metilação de DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Glioma/metabolismo , Código das Histonas , Humanos , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Regiões Promotoras Genéticas
7.
Science ; 355(6329)2017 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-28280153

RESUMO

Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain.


Assuntos
Cromossomos Artificiais de Levedura/fisiologia , Genoma Fúngico , Saccharomyces cerevisiae/genética , Segregação de Cromossomos , Cromossomos Artificiais de Levedura/química , Cromossomos Artificiais de Levedura/genética , Meios de Cultura/química , Replicação do DNA , Glicerol , Proteômica , Saccharomyces cerevisiae/crescimento & desenvolvimento , Análise de Sequência de DNA , Biologia Sintética , Transcriptoma
8.
G3 (Bethesda) ; 3(4): 741-756, 2013 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-23550123

RESUMO

Repetitive elements comprise a significant portion of most eukaryotic genomes. Minisatellites, a type of repetitive element composed of repeat units 15-100 bp in length, are stable in actively dividing cells but change in composition during meiosis and in stationary-phase cells. Alterations within minisatellite tracts have been correlated with the onset of a variety of diseases, including diabetes mellitus, myoclonus epilepsy, and several types of cancer. However, little is known about the factors preventing minisatellite alterations. Previously, our laboratory developed a color segregation assay in which a minisatellite was inserted into the ADE2 gene in the yeast Saccharomyces cerevisiae to monitor alteration events. We demonstrated that minisatellite alterations that occur in stationary-phase cells give rise to a specific colony morphology phenotype known as blebbing. Here, we performed a modified version of the synthetic genetic array analysis to screen for mutants that produce a blebbing phenotype. Screens were conducted using two distinctly different minisatellite tracts: the ade2-min3 construct consisting of three identical 20-bp repeats, and the ade2-h7.5 construct, consisting of seven-and-a-half 28-bp variable repeats. Mutations in 102 and 157 genes affect the stability of the ade2-min3 and ade2-h7.5 alleles, respectively. Only seven hits overlapped both screens, indicating that different factors regulate repeat stability depending upon minisatellite size and composition. Importantly, we demonstrate that mismatch repair influences the stability of the ade2-h7.5 allele, indicating that this type of DNA repair stabilizes complex minisatellites in stationary phase cells. Our work provides insight into the factors regulating minisatellite stability.

9.
Mol Cell Biol ; 33(2): 457-72, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23149941

RESUMO

Most DNA alterations occur during DNA replication in the S phase of the cell cycle. However, the majority of eukaryotic cells exist in a nondividing, quiescent state. Little is known about the factors involved in preventing DNA instability within this stationary-phase cell population. Previously, we utilized a unique assay system to identify mutations that increased minisatellite alterations specifically in quiescent cells in Saccharomyces cerevisiae. Here we conducted a modified version of synthetic genetic array analysis to determine if checkpoint signaling components play a role in stabilizing minisatellites in stationary-phase yeast cells. Our results revealed that a subset of checkpoint components, specifically MRC1, CSM3, TOF1, DDC1, RAD17, MEC3, TEL1, MEC1, and RAD53, prevent stationary-phase minisatellite alterations within the quiescent cell subpopulation of stationary-phase cells. Pathway analysis revealed at least three pathways, with MRC1, CSM3, and TOF1 acting in a pathway independent of MEC1 and RAD53. Overall, our data indicate that some well-characterized checkpoint components maintain minisatellite stability in stationary-phase cells but are regulated differently in those cells than in actively growing cells. For the MRC1-dependent pathway, the checkpoint itself may not be the important element; rather, it may be loss of the checkpoint proteins' other functions that contributes to DNA instability.


Assuntos
Pontos de Checagem do Ciclo Celular , Proteínas Fúngicas/metabolismo , Instabilidade Genômica , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Ciclo Celular , Replicação do DNA , DNA Fúngico/genética , DNA Fúngico/metabolismo , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Repetições Minissatélites , Mutação , Transdução de Sinais
10.
DNA Repair (Amst) ; 10(6): 556-66, 2011 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-21515092

RESUMO

Alterations in minisatellite DNA repeat tracts are associated with a variety of human diseases including Type 1 diabetes, progressive myoclonus epilepsy, and some types of cancer. However, in spite of their role in human health, the factors required for minisatellite alterations are not well understood. We previously identified a stationary phase specific increase in minisatellite instability caused by mutations in the high affinity zinc transporter ZRT1, using a minisatellite inserted into the ADE2 locus in Saccharomyces cerevisiae. Here, we examined ZRT1-mediated minisatellite instability in yeast strains lacking key recombination genes to determine the mechanisms by which these alterations occur. Our analysis revealed that minisatellite alterations in a Δzrt1 mutant occur by a combination of RAD52-dependent and RAD52-independent mechanisms. In this study, plasmid-based experiments demonstrate that ZRT1-mediated minisatellite alterations occur independently of chromosomal context or adenine auxotrophy, and confirmed the stationary phase timing of the events. To further examine the stationary phase specificity of ZRT1-mediated minisatellite alterations, we deleted ETR1 and POR1, genes that were previously shown to differentially affect the viability of quiescent or nonquiescent cells in stationary phase populations. These experiments revealed that minisatellite alterations in Δzrt1 mutants occur exclusively in quiescent stationary phase cells. Finally, we show that loss of ZRT1 stimulates alterations in a derivative of the human HRAS1 minisatellite. We propose that the mechanism of ZRT1-mediated minisatellite instability during quiescence is relevant to human cells, and thus, human disease.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Repetições Minissatélites , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte de Cátions/genética , Cromossomos Fúngicos , Humanos , Mutação , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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