Expression of PEG11 and PEG11AS transcripts in normal and callipyge sheep

BACKGROUND: The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18. The callipyge trait exhibits polar overdominant inheritance due to the fact that only heterozygotes inheriting a mutant paternal allele (paternal heterozygotes) have a phenotype of muscle hypertrophy, reduced fat and a more compact skeleton. The mutation is a single A to G transition in an intergenic region that results in the increased expression of several genes within the imprinted cluster without changing their parent-of-origin allele-specific expression. RESULTS: There was a significant effect of genotype (p < 0.0001) on the transcript abundance of DLK1, PEG11, and MEG8 in the muscles of lambs with the callipyge allele. DLK1 and PEG11 transcript levels were elevated in the hypertrophied muscles of paternal heterozygous animals relative to animals of the other three genotypes. The PEG11 locus produces a single 6.5 kb transcript and two smaller antisense strand transcripts, referred to as PEG11AS, in skeletal muscle. PEG11AS transcripts were detectable over a 5.5 kb region beginning 1.2 kb upstream of the PEG11 start codon and spanning the entire open reading frame. Analysis of PEG11 expression by quantitative PCR shows a 200-fold induction in the hypertrophied muscles of paternal heterozygous animals and a 13-fold induction in homozygous callipyge animals. PEG11 transcripts were 14-fold more abundant than PEG11AS transcripts in the gluteus medius of paternal heterozygous animals. PEG11AS transcripts were expressed at higher levels than PEG11 transcripts in the gluteus medius of animals of the other three genotypes. CONCLUSIONS: The effect of the callipyge mutation has been to alter the expression of DLK1, GTL2, PEG11 and MEG8 in the hypertrophied skeletal muscles. Transcript abundance of DLK1 and PEG11 was highest in paternal heterozygous animals and exhibited polar overdominant gene expression patterns; therefore, both genes are candidates for causing skeletal muscle hypertrophy. There was unique relationship of PEG11 and PEG11AS transcript abundance in the paternal heterozygous animals that suggests a RNA interference mechanism may have a role in PEG11 gene regulation and polar overdominance in callipyge sheep

Impact of age and race on outcomes of a program to prevent excess weight gain and disordered eating in adolescent girls

Interpersonal psychotherapy (IPT) prevents weight gain and reduces loss-of-control (LOC)-eating in adults. However, IPT was not superior to health-education (HE) for preventing excess weight gain and reducing LOC-eating over 1-year in adolescent girls at risk for excess weight gain and eating disorders. Limited data suggest that older and non-White youth may be especially responsive to IPT. In secondary analyses, we examined if age or race moderated weight and LOC-eating outcomes. The 113 participants (12–17 years; 56.6% White) from the original trial were re-contacted 3 years later for assessment. At baseline and follow-up visits through 3 years, we assessed BMI, adiposity by dual energy X-ray absorptiometry, and LOC-eating presence. In linear mixed models, baseline age moderated 3-year BMI outcome; older girls in IPT had the lowest 3-year BMI gain compared to younger girls in IPT and all girls in HE, p = 0.04. A similar pattern was observed for adiposity. Race moderated 3-year LOC-eating; non-White girls in IPT were most likely to abstain from LOC-eating at 3 years compared to all other girls, p = 0.04. This hypothesis-generating analysis suggests future studies should determine if IPT is especially efficacious at reducing LOC-eating in older, non-White adolescents

E,E-farnesol Inhibits Swarming Motility in \u3cem\u3eBurkholderia cepacia\u3c/em\u3e Through Rhamnolipid Production

Burkholderia cepacia and Candida albicans both exhibit cell-to-cell communication through the use of quorum-sensing molecules (QSM) known as autoinducers. E,E-farnesol is a QSM produced by C. albicans which regulates its conversion from yeast to mycelium. Because there is a positive correlation between the presence of B. cepacia and C. albicans in the lungs of individuals with cystic fibrosis (CF), we examined whether E,E-farnesol had an effect on swarming motility in B. cepacia. Swarming motility was inhibited when B. cepacia was exposed to 250 µM of E,E-farnesol. In addition, there was a 26.8% decrease in rhamnolipid production when cells were grown in the presence of E,E-farnesol. These biosurfactants are known to regulate swarming motility. Changes in the rhamnoplipid concentrations could account for the inhibition of swarming motility observed in the presence of E,E-farnesol. The effect of E,E-farnesol on B. cepacia biofilms was also examined because these complex-community structures are detrimental to the lungs of CF patients and are quorum-sensing regulated. Crystal violet staining showed that E,E-farnesol did not significantly affect biofilm formation in B. cepacia. Further studies are needed to determine the effects of E,E-farnesol on established B. cepacia biofilms and whether it can be combined with traditional antibiotics to disrupt these structures

Evaluation of a school-based physical activity intervention in Alexandra Township

Objectives. Non-communicable diseases and limited participation in school physical education have become increasing concerns in South Africa. In response to these concerns, a schoolbased physical activity intervention, Healthnutz, was implemented in three primary schools in Alexandra Township, Johannesburg. Evaluation of Healthnutz included assessing its feasibility and acceptability, and short-term changes in learners’ physical fitness, knowledge and attitudes. Methods. To assess feasibility and acceptability, a situational analysis and focus groups with teachers and programme monitors were conducted. Pre-post fitness testing (3-month interval) was conducted with learners, and a questionnaire assessed changes in learners’ knowledge, attitudes, self-efficacy, and perceived barriers to physical activity, in control and intervention schools. Results. At implementation, teachers identified the need for more physical activity in the school environment and were positive about Healthnutz. Follow-up focus group discussions suggested that it was positively impacting teachers, learners and the school in general. Scores for sit and reach (p<0.001), sit ups (p<0.02) and shuttle run (p<0.0001) improved significantly in intervention but not control schools. A significant decrease was observed in learners’ perceived external barriers to physical activity (p<0.0001) along with a positive change in learners’ self-efficacy for physical activity (p<0.05). Conclusions. Healthnutz raised awareness of the importance of physical activity in intervention schools. Findings indicate that even limited exposure to a physical activity intervention can lead to a significant improvement in aspects of learners’ fitness, knowledge, attitudes and perceptions regarding physical activity. Furthermore, training and support of teachers needs to be nonjudgemental and empowering

Leveraging Public-Private Partnerships During COVID-19: Providing Virtual Field Opportunities for Student Learners and Addressing Social Isolation in Older Adults

While preventive and management measures are important to mitigate the spread of COVID-19, strategies like social distancing can have devastating effects on older adults who are already at risk for social isolation and loneliness. In response, two Colleges of Health Professions (Social Work and Nursing) at a large public University leveraged a partnership with a national health and wellbeing company to address social isolation and loneliness in Houston area older adults during the COVID-19 pandemic. This intergenerational linkage initiative involved 707 older adults and 177 graduate social work and nursing students. This study describes the process of developing a virtual educational opportunity for students while also meeting the needs of vulnerable older adults in Houston, the third largest, and one of the most diverse cities in the U.S. Findings include student/learner outcomes, as well as self-reported improvements in loneliness scores, and unhealthy physical and mental health days among enrolled older adults

Change in longitudinal trends in sleep quality and duration following breast cancer diagnosis: results from the Women's Health Initiative

Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women's Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis. To examine sleep duration, we fit a logistic regression model with random effects for both short (<6 h) and long (≥9 h) sleep. In addition, we studied the association between depressive symptoms and changes in WHIIRS and sleep duration. There was a significantly slower increase in the trend of WHIIRS after diagnosis (β = 0.06; p = 0.03), but there were non-significant increases in the trend of the probability of short or long sleep after diagnosis. The probability of depressive symptoms significantly decreased, though the decrease was more pronounced after diagnosis (p < 0.01). Trends in WHIIRS worsened at a relatively slower rate following diagnosis and lower depression rates may explain the slower worsening in WHIIRS. Our findings suggest that over a long period of time, breast cancer diagnosis does not adversely affect sleep quality and duration in postmenopausal women compared to sleep pre-diagnosis, yet both sleep quality and duration continue to worsen over time.WHI - National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C]; Ohio State University Susan G Komen Graduate Trainee Program [GTDR15334082]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Study of lone working magnetic resonance technologists in Western Australia

Objectives: It is recommended that magnetic resonance (MR) technologists should not work alone due to potential occupational health risks although lone working is legally acceptable. The objective of this study was to investigate the current situation of lone working of MR technologists in Western Australia (WA) and any issue against the regulations. Materials and Methods: A questionnaire regarding the issues of occupational health of lone MR technologists was developed based on relevant literature and distributed to WA MR technologists. Descriptive (percentage of frequency, mean and standard deviation) and inferential statistics (Fisher’s exact, chi-square and t tests, and analysis of variance) were used to analyse the responses of the yes/no, multiple choice and 5 point scale questions from the returned questionnaires.Results: The questionnaire response rate was 65.6% (59/90). It was found that about half of the MR technologists (45.8%, 27/59) experienced lone working. The private magnetic resonance imaging (MRI) centres were more likely to arrange technologists to work alone (p <0.05). The respondents expressed positive views on issues of adequacy of training and arrangement, confidence and comfort towards lone working except immediate assistance for emergency (mean: 3). Factors of existence of MRI safety officer (p < 0.05) and nature of lone working (p < 0.001-0.05) affected MR technologists’ concerns. Conclusions: Lone working of MR technologists is common in WA especially private centres. The training and arrangement provided seem to be adequate for meeting the legal requirements. However, several areas should be improved by the workplaces including enhancement on immediate assistance for emergency and concern relief

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and threematernally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins.We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such asmRNAexport, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in human