Physical and functional interaction between DDB and XPA in nucleotide excision repair

Damaged DNA-binding protein (DDB), consisting of DDB1 and DDB2 subunits recognizes a wide spectrum of DNA lesions. DDB is dispensable for in vitro nucleotide excision repair (NER) reaction, but stimulates this reaction especially for cyclobutane pyrimidine dimer (CPD). Here we show that DDB directly interacts with XPA, one of core NER factors, mainly through DDB2 subunit and the amino-acid residues between 185 and 226 in XPA are important for the interaction. Interestingly, the point mutation causing the substitution from Arg-207 to Gly, which was previously identified in a XP-A revertant cell-line XP129, diminished the interaction with DDB in vitro and in vivo. In a defined system containing R207G mutant XPA and other core NER factors, DDB failed to stimulate the excision of CPD, although the mutant XPA was competent for the basal NER reaction. Moreover, in vivo experiments revealed that the mutant XPA is recruited to damaged DNA sites with much less efficiency compared with wild-type XPA and fails to support the enhancement of CPD repair by ectopic expression of DDB2 in SV40-transformed human cells. These results suggest that the physical interaction between DDB and XPA plays an important role in the DDB-mediated NER reaction

Parallel Adaptive Divergence among Geographically Diverse Human Populations

Few genetic differences between human populations conform to the classic model of positive selection, in which a newly arisen mutation rapidly approaches fixation in one lineage, suggesting that adaptation more commonly occurs via moderate changes in standing variation at many loci. Detecting and characterizing this type of complex selection requires integrating individually ambiguous signatures across genomically and geographically extensive data. Here, we develop a novel approach to test the hypothesis that selection has favored modest divergence at particular loci multiple times in independent human populations. We find an excess of SNPs showing non-neutral parallel divergence, enriched for genic and nonsynonymous polymorphisms in genes encompassing diverse and often disease related functions. Repeated parallel evolution in the same direction suggests common selective pressures in disparate habitats. We test our method with extensive coalescent simulations and show that it is robust to a wide range of demographic events. Our results demonstrate phylogenetically orthogonal patterns of local adaptation caused by subtle shifts at many widespread polymorphisms that likely underlie substantial phenotypic diversity

Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer

Effects of Sertraline Treatment for Young Children with Fragile X Syndrome: Family Perspectives

Fragile X syndrome (FXS) is the most common inherited form of intellectual and developmental disability (IDD) and the most common single gene cause of autism spectrum disorder (ASD) (Hess, et al., 2016; NFXF, 2017). FXS is characterized by anxiety, hyperactivity, impulsivity, and sensory processing challenges (Wheeler et al., 2017). Sertraline, trade name Zoloft, a selective serotonin reuptake inhibitor (SSRI) has been used to treat this population. Hess et al., (2016) found benefits from low dose sertraline on social skills, language, visual perception, and fine motor skills for children ages 2-6 years old with FXS. Despite these findings, current FXS literature lacks outcome measures capturing improvements in daily occupations from family perspectives as part of clinical trials. Current research studies on children with FXS have focused on standardized testing rather than occupational performance. This research incorporates family perspectives via semi-structured interviews to promote an in-depth understanding about FXS and its impact on child and family occupations. In our research, we project our qualitative findings to reflect improvements in occupational performance for the child and family living with FXS, beyond what standardized measures can capture. We hope this study propels future occupational therapists to continue research in FXS to explore occupations as an outcome measure in addition to standardized assessment scores. Key words: -Family -Occupations -Sertraline -Behavior -Fragile X Syndrome (FXS) -Standardized assessment scores -Qualitative vs quantitative -Occupational therapists -Occupational performance -Outcome measure

Effects of Sertraline Treatment for Young Children with Fragile X Syndrome: Family Perspectives via Case Studies

Current research on children with Fragile X Syndrome (FXS) lacks inclusion of qualitative outcomes on the child’s daily occupational performance. Standardized measurements are frequently utilized and provide useful information, however, can be less sensitive to change (Berry Kravis et al., 2013) and miss capturing family perspectives and improvements within meaningful occupations. This research incorporates family perspectives via semi-structured interviews to promote an in-depth understanding about FXS and its impact on child and family occupations in addition to standardized assessment scores through in-depth case study analysis. This study used a mixed method research design examining four male participants who were given sertraline in an in-depth case study analysis. Caregivers were interviewed using a semi-structured interview protocol at baseline and at six months post-treatment to discuss their child, occupations, and any potential impacts of sertraline. Baseline and post-testing standardized assessment results were compared to the occupation centered semi-structured interviews. The data was collected from a pre-existing database in a previous study determining the outcome measures of sertraline. Dedoose software was used to code for categories and themes found in the FXS family interviews. Results indicated that standardized assessments have limited sensitivity to fully capture the lived experiences of families with FXS. Standardized assessments test for performance skills that may not necessarily translate to daily occupations as reported by families. While future practitioners should use standardized assessments in their evaluations, they should also include what families report in their daily lives to fully conclude the child’s abilities to participate and engage in their daily occupation

Fragile X Syndrome and Family Occupations: Sertraline Treatment

Current research on children with Fragile X Syndrome (FXS) lacks inclusion of qualitative outcomes on the child’s daily occupational performance. Standardized measurements are frequently utilized and provide useful information, however, can be less sensitive to change (Berry Kravis et al., 2013) and miss capturing family perspectives and improvements within meaningful occupations. This research incorporates family perspectives via semi-structured interviews to promote an in-depth understanding about FXS and its impact on child and family occupations in addition to standardized assessment scores through in-depth case study analysis. This study used a mixed method research design examining four male participants who were given sertraline in an in-depth case study analysis. Caregivers were interviewed using a semi-structured interview protocol at baseline and at six months post-treatment to discuss their child, occupations, and any potential impacts of sertraline. Baseline and post-testing standardized assessment results were compared to the occupation centered semi-structured interviews. The data was collected from a pre-existing database in a previous study determining the outcome measures of sertraline. Dedoose software was used to code for categories and themes found in the FXS family interviews. Results indicated that standardized assessments have limited sensitivity to fully capture the lived experiences of families with FXS. Standardized assessments test for performance skills that may not necessarily translate to daily occupations as reported by families. While future practitioners should use standardized assessments in their evaluations, they should also include what families report in their daily lives to fully conclude the child’s abilities to participate and engage in their daily occupationshttps://scholar.dominican.edu/ug-student-posters/1083/thumbnail.jp

Fragile X Syndrome and Family Occupations: Sertraline Treatment via Case Studies

Current research on children with Fragile X Syndrome (FXS) lacks inclusion of qualitative outcomes on the child’s daily occupational performance. Standardized measurements are frequently utilized and provide useful information, however, can be less sensitive to change (Berry Kravis et al., 2013) and miss capturing family perspectives and improvements within meaningful occupations. This research incorporates family perspectives via semi-structured interviews to promote an in-depth understanding about FXS and its impact on child and family occupations in addition to standardized assessment scores through in-depth case study analysis. This study used a mixed method research design examining four male participants who were given sertraline in an in-depth case study analysis. Caregivers were interviewed using a semi-structured interview protocol at baseline and at six months post-treatment to discuss their child, occupations, and any potential impacts of sertraline. Baseline and post-testing standardized assessment results were compared to the occupation centered semi-structured interviews. The data was collected from a pre-existing database in a previous study determining the outcome measures of sertraline. Dedoose software was used to code for categories and themes found in the FXS family interviews. Results indicated that standardized assessments have limited sensitivity to fully capture the lived experiences of families with FXS. Standardized assessments test for performance skills that may not necessarily translate to daily occupations as reported by families. While future practitioners should use standardized assessments in their evaluations, they should also include what families report in their daily lives to fully conclude the child’s abilities to participate and engage in their daily occupationshttps://scholar.dominican.edu/ug-student-posters/1091/thumbnail.jp

Cell proliferation dynamics in regeneration of the operculum head appendage in the annelid Pomatoceros lamarckii

Regeneration of lost or damaged appendages is a widespread and ecologically important ability in the animal kingdom, and also of great significance to developing regenerative medicine. The operculum of serpulid polychaetes is one among the many diverse appendages found in the lophotrochozoan superphylum, a clade hitherto understudied with respect to the mechanisms of appendage regeneration. In this study, we establish the normal time course of opercular regeneration in the serpulid Pomatoceros lamarckii and describe cell proliferation patterns in the regenerating opercular filament. The P. lamarckii operculum regenerates through a rapid and consistent series of morphogenetic events. Based on 5-bromo-2'-deoxyuridine (BrdU) labelling and anti-phosphohistone H3 immunohistochemistry, opercular regeneration appears to be a mixture of an early morphallactic stage and a later phase characterised by widespread proliferative activity within the opercular filament. Tracking residual pigmentation suggests that the distal part of the stump gives rise to the most distal structures of the operculum via morphallactic remodelling, whereas more proximal structures are derived from the proximal stump. Our work underscores the diversity of regenerative strategies employed by animals and introduces P. lamarckii as an emerging model of appendage regeneration.PostprintPeer reviewe