Chronic Hypoxia Induces Epigenetic Modifications in the Fetal Rat Heart

Heart disease remains the leading cause of death worldwide. As a result of studies done by Barker and associates, our awareness of the significance of stress during gestation as a risk factor for heart diseases has expanded. We now know that events in utero can significantly alter gene expression patterns in heart tissue leading to increase susceptibility to ischemia reperfusion injury in adulthood. The focus of this project was to elucidate the role of chronic hypoxia in the programming of the cardio-protective gene, Protein Kinase C epsilon (PKCε) in fetal rat heart. We used an animal, organ base, and cell culturing with the rat embryonic cell line H9c2 to determine the molecular events underpinning the heightened sensitivity to ischemia reperfusion injury of adult offspring exposed to chronic hypoxia in utero. We determined that chronic hypoxia directly represses PKCε expression through increase methylation of CpG dinucleotides for two SP1 binding sites located at proximal region of the PKCε promoter. Previous studies using reporter gene assays concluded the region encompassing both SP1 binding sites played a significant role in the activity of PKCε promoter. Chromatin immunoprecipitation (ChIP) assays further verified the functional significance of methylation for both Sp1 sites in reducing SP1 protein binding. In the presence of the DNA methylation inhibitor, 5-aza-2-deoxycytidine, binding of SP1 to PKCε promoter, promoter methylation, and PKCε protein and mRNA were restored to control levels. Connecting epigenetics to chronic hypoxia in utero led us to further investigate the underlining mechanism of hypoxia-induced methylation of PKCε promoter. The dominant pathway of cellular adaptation to hypoxic stress involves the stabilization of the Hypoxia-Inducible-Factor 1 alpha (HIF-1α). We found blockade of nuclear accumulation of HIF-1α did not restore PKCε mRNA to control values. Next, we found the ROS Scavengers N-acetylcysteine and 4-hydroxy Tempo protect against hypoxia-induced repression of PKCε gene activity, which linked oxidative stress to PKCε repression in fetal hearts. This project has demonstrated that chronic hypoxia directly regulates PKCε gene expression through ROS mediated epigenetic repression of PKCε promoter, which leads to long term programming of the fetal heart

Reading, Writing, \u27 Rithmetic and Relationships: Advisories, the Fourth R in Enhancing Student Achievement?

Urban communities are challenged by increasing numbers of young people dropping out of school. The small school movement\u27s focus on personalization represents a response to social, economic, and political forces that require new approaches to educating students. Small size may nurture relationships; however, it cannot guarantee academic achievement. This exploratory quantitative study examined the predictive capacity for AVID (Advancement Via Individual Determination) Elective (advisory) students\u27 sense of membership, coupled with academic press, to influence academic achievement. A survey and scores on English Language Arts and Math assessments were used to determine what impact the two variables had on students\u27 achievement. Findings indicated minimal evidence of the predictive capacity for AVID Elective (advisory) students\u27 sense of membership to impact students\u27 academic achievement. There was evidence of the predictive capacity for AVID Elective (advisory) students\u27 sense of academic press to impact academic achievement. A significant difference was found between Math benchmark scores for stratified matched samples of AVID students versus Non-AVID. AVID students scored higher on Math assessments than did Non-AVID students. There was not a significant difference between English Language Arts assessment scores for stratified matched samples of AVID versus Non-AVID students. Among stratified matched samples of AVID students (large and small schools) and Non-AVID students (large and small schools), AVID students jn large schools scored the highest on Math benchmarks. AVID students in small schools scored the highest in English Language Arts among the four groups. The author proposes a new model for an ethic of care for urban students where social interactions between students and teachers, and among groups of students engender an ethos where academic achievement is possible

Space Station Freedom data management system growth and evolution report

The Information Sciences Division at the NASA Ames Research Center has completed a 6-month study of portions of the Space Station Freedom Data Management System (DMS). This study looked at the present capabilities and future growth potential of the DMS, and the results are documented in this report. Issues have been raised that were discussed with the appropriate Johnson Space Center (JSC) management and Work Package-2 contractor organizations. Areas requiring additional study have been identified and suggestions for long-term upgrades have been proposed. This activity has allowed the Ames personnel to develop a rapport with the JSC civil service and contractor teams that does permit an independent check and balance technique for the DMS

Inactivation of SARS-CoV-2 on surfaces and in solution with Virusend (TX-10), a novel disinfectant

Until an effective vaccine against SARS-CoV-2 is available on a widespread scale, the control of the COVID-19 pandemic is reliant upon effective pandemic control measures. The ability of SARS-CoV-2 to remain viable on surfaces and in aerosols, means indirect contact transmission can occur and there is an opportunity to reduce transmission using effective disinfectants in public and communal spaces. Virusend (TX-10), a novel disinfectant, has been developed as a highly effective disinfectant against a range of microbial agents. Here we investigate the ability of Virusend to inactivate SARS-CoV-2. Using surface and solution inactivation assays, we show that Virusend is able to reduce SARS-CoV-2 viral titre by 4 log10 p.f.u. ml−1 within 1min of contact. Ensuring disinfectants are highly effective against SARS-CoV-2 is important in eliminating environmental sources of the virus to control the COVID-19 pandemi

Knockdown resistance allele L1014F introduced by CRISPR/Cas9 is not associated with altered vector competence of Anopheles gambiae for o’nyong nyong virus

Knockdown resistance (kdr) alleles conferring resistance to pyrethroid insecticides are widespread amongst vector populations. Previous research has suggested that these alleles are associated with changes in the vector competence of mosquitoes for arboviruses and Plasmodium, however non-target genetic differences between mosquito strains may have had a confounding effect. Here, to minimise genetic differences, the laboratory Anopheles gambiae Kisumu strain was compared to a CRISPR/Cas9 homozygous kdr L1014F mutant Kisumu-kdr line in order to examine associations with vector competence for o’nyong nyong virus (ONNV). Mosquitoes were infected using either blood feeds or intrathoracic microinjections. There were no significant differences in the prevalence of virus in mosquito body parts between kdr mutant and wildtype lines from either oral or intrathoracic injection routes. The ONNV titre was significantly higher in the legs of the wildtype strain at 7dpi following intrathoracic microinjection, but no other significant differences in viral titre were detected. ONNV was not detected in the saliva of mosquitoes from either strain. Our findings from per os infections suggest that the kdr L1014F allele is not associated with altered infection prevalence for ONNV, a key component of vector competence

Safety of dietary camelina oil supplementation in healthy, adult dogs

This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls, as they are similar and generally regarded as safe (GRAS) for canine diets. A total of thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and a body weight (BW) of 27.4 ± 14.0 kg were used. After a 4-week wash-in period using sunflower oil and kibble, the dogs were blocked by breed, age, and size and were randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100 g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All of the data were analyzed with ANOVA using the PROC GLIMMIX of SAS. No biologically significant differences were seen between the treatment groups in terms of BW, BCS, FI, and hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and were due to normal biological variation. These results support the conclusion that camelina oil is safe for use in canine nutrition

Effect of Alzheimer Caregiving Stress and Age on Frailty Markers Interleukin-6, C-Reactive Protein, and D-Dimer

Background. Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome,” defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. Methods. Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 ± 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. Results. Caregivers had higher mean levels of IL-6 (1.38 ± 1.42 vs 1.00 ± 0.92 pg/mL, p =.032) and of D-dimer (723 ± 530 vs 471 ± 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (β =.20, p =.029) and of borderline significance for IL-6 (β =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (β =.50, p <.001) and IL-6 (β =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. Conclusions. The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular disease