Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
Genes Dev ; 36(3-4): 225-240, 2022 02 01.
Article in English | MEDLINE | ID: mdl-35144965

ABSTRACT

The BEN domain is a recently recognized DNA binding module that is present in diverse metazoans and certain viruses. Several BEN domain factors are known as transcriptional repressors, but, overall, relatively little is known of how BEN factors identify their targets in humans. In particular, X-ray structures of BEN domain:DNA complexes are only known for Drosophila factors bearing a single BEN domain, which lack direct vertebrate orthologs. Here, we characterize several mammalian BEN domain (BD) factors, including from two NACC family BTB-BEN proteins and from BEND3, which has four BDs. In vitro selection data revealed sequence-specific binding activities of isolated BEN domains from all of these factors. We conducted detailed functional, genomic, and structural studies of BEND3. We show that BD4 is a major determinant for in vivo association and repression of endogenous BEND3 targets. We obtained a high-resolution structure of BEND3-BD4 bound to its preferred binding site, which reveals how BEND3 identifies cognate DNA targets and shows differences with one of its non-DNA-binding BEN domains (BD1). Finally, comparison with our previous invertebrate BEN structures, along with additional structural predictions using AlphaFold2 and RoseTTAFold, reveal distinct strategies for target DNA recognition by different types of BEN domain proteins. Together, these studies expand the DNA recognition activities of BEN factors and provide structural insights into sequence-specific DNA binding by mammalian BEN proteins.


Subject(s)
Repressor Proteins , Transcription Factors , Animals , Binding Sites , Drosophila/metabolism , Mammals , Protein Binding , Protein Domains , Repressor Proteins/genetics , Transcription Factors/metabolism
2.
Ethn Health ; 28(6): 809-821, 2023 08.
Article in English | MEDLINE | ID: mdl-36803178

ABSTRACT

AIMS: This study examines: (a) the prevalence rate of type 2 diabetes mellitus (T2DM) in Chinese Americans (CAs); (b) the influence of acculturative status (i.e. generational status and linguistic fluency) on T2DM prevalence; (c) and differences in diabetes management between CAs and Non-Hispanic Whites (NHWs). METHODS: We used 2011-2018 data from the California Health Interview Survey (CHIS) to analyze the prevalence rate and management of diabetes among the CAs. Chi-squares, linear regressions, and logistic regressions were used to analyze the data. RESULTS: After controlling for demographic, socioeconomic, and health behaviors, there were no significant differences in the T2DM prevalence rate between CAs overall or of varying acculturative statuses compared with NHWs. However, there were differences in diabetes management, with first-generation CAs being less likely to exam glucose daily, have medical care plans developed by medical providers, or have confidence in controlling diabetes compared to NHWs. CAs with limited English proficiency (LEP) were less likely to perform self-monitoring of blood glucose or have confidence in managing their diabetes care compared to NHWs. Finally, non-first generation CAs were also more likely to take diabetes medication compared to NHWs. CONCLUSIONS: Although the prevalence rate of T2DM was found to be similar between CAs and NHWs, significant differences were found in diabetes care and management. Specifically, those who were less acculturated (e.g. first generation and those with LEP) were less likely to actively manage and have confidence in managing their T2DM. These results highlight the importance of targeting immigrants with LEP in prevention and intervention efforts.


Subject(s)
Asian , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , East Asian People , Ethnicity , Prevalence , White , United States/epidemiology , Asian/statistics & numerical data
3.
Children (Basel) ; 11(4)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38671658

ABSTRACT

OBJECTIVES: This study investigated the correlation between early exposure to maternal depression (from 1 month to Grade 3) and the body mass index (BMI) and potential for overweight in adolescents at age 15. It further examined if the pathway of this correlation was influenced by psychosocial adjustment during mid-childhood (Grade 3 to Grade 6), specifically through internalizing and externalizing behaviors. METHODS: Our study utilized data from 844 participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) to assess the effects of maternal depression, observed from when the children were one month old to Grade 3, on BMI and the likelihood of overweight or obesity in adolescents aged 15. We also explored whether the average scores of internalizing and externalizing behaviors between Grades 3 and 6 mediated the impact of early maternal depressive symptoms on subsequent health outcomes. The analysis was adjusted for demographic and socioeconomic factors. RESULTS: Findings revealed that internalizing and externalizing behavioral issues significantly mediated the relationship between prolonged maternal depression exposure and subsequent BMI, as well as the risk of overweight or obesity, in adolescents at age 15. Notably, this mediating effect was predominantly evident in girls. CONCLUSIONS: Our research demonstrated that the correlation between prolonged exposure to maternal depressive symptoms in childhood and increased BMI and overweight risk in adolescence was significantly mediated through psychosocial adjustment behaviors. We advocate for further exploration of additional mediating factors in future studies.

4.
Food Chem Toxicol ; 49(9): 2336-42, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21722698

ABSTRACT

Seafood is an important source of nutrients for many populations worldwide. Unfortunately the contamination of seafood with methylmercury (MeHg) has raised health concerns, particularly for developing infants. The modification of MeHg toxicity by nutrients, including antioxidants, has been reported in both epidemiological and animal exposure studies. We used a rat perinatal exposure model to investigate the modulation of developmental MeHg toxicity by an extract of Rhododendron tomentosum ssp. subarcticum, a plant rich in antioxidants traditionally consumed by Inuit. Sprague-Dawley rat dams were exposed daily to 2 mg MeHg/kg bw and 100 mg R. tomemtosum extract/kg bw administered either separately or jointly, from the first day of gestation until weaning. MeHg exposure was associated with impaired pup growth and survival, decreased grip strength, hyperactivity and altered exploratory behaviour, delayed acoustic startle response, elevated brain N-methyl-D-aspartate receptor (NMDA-R) levels, and increased serum lipid peroxidation. R. tomemtosum extract co-exposure modulated MeHg's effects on oxidative stress and brain NMDA-R levels and may have affected MeHg pharmacokinetic. However, modulation of these molecular endpoints did not lead to significant alterations of MeHg's effects on rat neurobehaviour.


Subject(s)
Methylmercury Compounds/toxicity , Nervous System/drug effects , Rhododendron/chemistry , Animals , Behavior, Animal/drug effects , Cytochrome P-450 Enzyme System/metabolism , Enzyme Activation , Female , Liver/enzymology , Male , Nervous System/embryology , Nervous System/growth & development , Nervous System/metabolism , Oxidative Stress , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL