The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells

MicroRNAs act posttranscriptionally to suppress multiple target genes within a cell population. To what extent this multi-target suppression occurs in individual cells and how it impacts transcriptional heterogeneity and gene co-expression remains unknown. Here we used single-cell sequencing combined with introduction of individual microRNAs. miR-294 and let-7c were introduced into otherwise microRNA-deficient Dgcr8 knockout mouse embryonic stem cells. Both microRNAs induce suppression and correlated expression of their respective gene targets. The two microRNAs had opposing effects on transcriptional heterogeneity within the cell population, with let-7c increasing and miR-294 decreasing the heterogeneity between cells. Furthermore, let-7c promotes, whereas miR-294 suppresses, the phasing of cell cycle genes. These results show at the individual cell level how a microRNA simultaneously has impacts on its many targets and how that in turn can influence a population of cells. The findings have important implications in the understanding of how microRNAs influence the co-expression of genes and pathways, and thus ultimately cell fate

Effect of opiate receptor blockade on the insulin response to oral glucose load in polycystic ovarian disease

In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCO

BATS: a Bayesian user-friendly software for Analyzing Time Series microarray experiments

BATS is a user-friendly software for Bayesian Analysis of Time Series microarray experiments based on the novel, truly functional and fully Bayesian approach proposed in Angelini et at. (2006). The software is specifically designed for time series data. It allows an user to automatically identify and rank differentially expressed genes and to estimate their expression profiles. BATS successfully manages various technical difficulties which arise in microarray time-course experiments, such as a small number of observations, non-uniform sampling intervals, and presence of missing or multiple data. BATS can carry out analysis with both simulated and real experimental data. It also handles data from different platforms. 1 Availability: BATS is written in Matlab and executable in Windows (Macintosh and Linux version are currently under development). It is freely available upon request from the authors.

What About my Privacy, Habibi? Understanding Privacy Concerns and Perceptions of Users From Different Socioeconomic Groups in the Arab World

This paper contributes an in-depth understanding of privacy concerns and perceptions of Arab users. We report on the first comparison of privacy perceptions among (1) users from high socioeconomic groups in Arab countries (HSA), (2) users from medium to low socioeconomic groups in Arab countries (LSA), and (3) as a baseline, users from high socioeconomic groups in Germany (HSG). Our work is motivated by the fact that most research in privacy focused on Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. This excludes a segment of the population whose cultural norms and socioeconomic status influence privacy perception and needs. We report on multiple novel findings and unexpected similarities and differences across the user groups. For example, shoulder surfing is more common across LSA and HSG, and defamation is a major threat in LSA. We discuss the implications of our findings on the design of privacy protection measures for investigated groups

Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments

The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure.Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement.Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders

Voices Raised, Issue 06

Included in this issue: Immaculate Mary; Grants augment women’s research; Mentoring grows; Women’s Studies take root in the neighborhood; Solution-oriented VP to retire; Muslim students strive to educate, support; Don’t let stress ruin your holidays; Dining services dishes up more than you’d expect; Marianist Images Across Campus; Confronting Disrespect: We Owe it to Each Other.https://ecommons.udayton.edu/wc_newsletter/1005/thumbnail.jp

Degree flexibility and university drop-out: the Italian experience

How to reduce university drop-out is a topic of increasing concern. Although several measures have been the subject of numerous debates, little attention has been given to those impacting on the duration, structure and content of the supply of university education. This paper looks at the Italian experience to see what can be learnt about the effectiveness of these measures. In 2001, the Italian university system embarked on a process of reform that introduced greater flexibility in the degree programme structure along with a wider range of services offered to students. Employing a decomposition analysis, we find that this reform is associated with changes in student behaviour leading to a decline in drop-out risk