Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling.

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control

RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1

Ribonucleases are critically important in many cellular and developmental processes and defects in their expression are associated with human disease. Pacman/XRN1 is a highly conserved cytoplasmic exoribonuclease which degrades RNAs in a 5' - 3' direction. In Drosophila, null mutations in pacman result in small imaginal discs, a delay in onset of pupariation and lethality during the early pupal stage. In this paper, we have used RNA-seq in a genome-wide search for mRNAs misregulated in pacman null wing imaginal discs. Only 4.2% of genes are misregulated ±>2-fold in pacman null mutants compared to controls, in line with previous work showing that Pacman has specificity for particular mRNAs. Further analysis of the most upregulated mRNAs showed that Pacman post-transcriptionally regulates the expression of the secreted insulin-like peptide Dilp8. Dilp8 is related to human IGF-1, and has been shown to co-ordinate tissue growth with developmental timing in Drosophila. The increased expression of Dilp8 is consistent with the developmental delay seen in pacman null mutants. Our analysis, together with our previous results, show that the normal role of this exoribonuclease in imaginal discs is to suppress the expression of transcripts that are crucial in apoptosis and growth control during normal development

Meta-analysis of honey bee neurogenomic response links deformed wing virus type A to precocious behavioral maturation

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and North America. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in individuals that were much younger than typical foragers. In addition, brain transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of infected bees from one colony mistakenly entering another colony, especially under crowded modern apiary conditions. These findings provide new insights into the mechanisms by which DWV-A affects honey bee health and colony survival

Experiences and Attitudes of Genome Investigators Regarding Return of Individual Genetic Test Results

Purpose Whether and how to return individual genetic results to study participants is among the most contentious policy issues in contemporary genomic research. Methods: We surveyed corresponding authors of genome-wide association studies (GWAS), identified through the National Human Genome Research Institute's Catalog of Published GWAS, to describe the experiences and attitudes of these stakeholders. Results: Of 357 corresponding authors, 200 (56%) responded. One hundred twenty-six (63%) had been responsible for primary data and sample collection, whereas 74 (37%) had performed secondary analyses. Only 7 (4%) had returned individual results within their index GWAS. Most (69%) believed that return of results to individual participants was warranted under at least some circumstances. Most respondents identified a desire to benefit participants's health (63%) and respect for participants's; desires for information (57%) as major motivations for returning results. Most also identified uncertain clinical utility (76%), the possibility that participants will misunderstand results (74%), the potential for emotional harm (61%), the need to ensure access to trained clinicians (59%), and the potential for loss of confidentiality (51%) as major barriers to return. Conclusion: Investigators have limited experience returning individual results from genome-scale research, yet most are motivated to do so in at least some circumstances

Measures of sun exposure and sun protection practices for behavioural and epidemiological research

Objective: To develop, in a collaborative project, core measures of sun exposure and sun protection habits, since the lack of standard outcome measures hampers comparison of population surveys and interventions used in skin cancer prevention research. Design: A work group of investigators evaluated available questionnaire measures of sun exposure and protection. Their deliberations led to a proposed set of core questionnaire items for adults, adolescents aged 11 to 17 years, and children 10 years or younger. These core items were used in cognitive testing by the investigators. Cross-site summaries of methods, response samples, and descriptive data were prepared. Setting: Nine locations across the United States. Participants: The study population comprised 81 individuals. Results: No unusual response patterns were detected in any of the respondent groups or for any specific question. Some revisions to the survey items resulted from the need for clarification or emphasis of frames of reference such as adding or underlining key phrases in a question. Conclusions: The combination of expert review followed by cognitive interviewing yielded standardized core survey items with good clarity and applicability for measuring sun exposure and sun protection behaviors across a broad range of populations. They are appropriate for studies tracking morbidity and/or mortality and evaluating prevention program effects

Sodium bicarbonate ingestion and individual variability in time to peak pH

The aim of this study was to determine the individual variability in time to peak pH after the consumption of a 300mg.kg-1 dose of sodium bicarbonate (NaHCO3). Seventeen active males volunteered to participate in the study (mean ± SD: age 21.38 ± 1.5y; mass 75.8 ± 5.8kg; height 176.8 ± 7.6cm). Participants reported to the laboratory where a resting capillary blood sample was taken aseptically from the fingertip. After this, 300 mg.kg-1 of NaHCO3 in 400ml of water with 50ml of flavoured cordial was ingested. Participants then rested for 90 min during which repeated blood samples were procured at 10 minute intervals for 60 mins and then every 5 min until 90 min. Blood pH concentrations were measured using a blood gas analyser. Results suggested that time to peak pH (64.41±18.78 min) was highly variable with a range of 10-85 min and a coefficient of variation of 29.16%. A bi-modal distribution occurred, at 65 and 75 min. In conclusion, researchers and athletes, when using NaHCO3 as an ergogenic aid, should determine, in advance their time to peak pH to best utilise the added buffering capacity this substance allows

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

Bidirectional Modulation of Alcohol-Associated Memory Reconsolidation through Manipulation of Adrenergic Signaling.

Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive Pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self-administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a Pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive Pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The β-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories.This work was supported by a UK Medical Research Council Programme Grant (G1002231) to BJE and ALM and was conducted in the Behavioural and Clinical Neuroscience Institute (BCNI), an initiative jointly funded by the MRC and the Wellcome Trust. MJWS was supported by an MRC Doctoral Training Grant and the James Baird Fund at the Medical School of the University of Cambridge. ALM was partly supported by a BCNI lectureship and the Ferreras-Willetts Fellowship from Downing College, Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.24