An inducible Cre mouse line to sparsely target nervous system cells, including Remak Schwann cells

Nerves of the peripheral nervous system contain two classes of Schwann cells: myelinating Schwann cells that ensheath large caliber axons and generate the myelin sheath, and Remak Schwann cells that surround smaller axons and do not myelinate. While tools exist for genetic targeting of Schwann cell precursors and myelinating Schwann cells, such reagents have been challenging to generate specifically for the Remak population, in part because many of the genes that mark this population in maturity are also robustly expressed in Schwann cell precursors. To circumvent this challenge, we utilized BAC transgenesis to generate a mouse line expressing a tamoxifen-inducible Cre under the control of a Remak-expressed gene promoter (Egr1). However, as Egr1 is also an activity dependent gene expressed by some neurons, we flanked this Cre by flippase (Flpe) recognition sites, and coinjected a BAC expressing Flpe under control of a pan-neuronal Snap25 promoter to excise the Cre transgene from these neuronal cells. Genotyping and inheritance demonstrate that the two BACs co-integrated into a single locus, facilitating maintenance of the line. Anatomical studies following a cross to a reporter line show sparse tamoxifen-dependent recombination in Remak Schwann cells within the mature sciatic nerve. However, depletion of neuronal Cre activity by Flpe is partial, with some neurons and astrocytes also showing evidence of Cre reporter activity in the central nervous system. Thus, this mouse line will be useful in mosaic loss-of-function studies, lineage tracing studies following injury, live cell imaging studies, or other experiments benefiting from sparse labeling

Single-Molecule Analysis of i-motif Within Self-Assembled DNA Duplexes and Nanocircles

The cytosine (C)-rich sequences that can fold into tetraplex structures known as i-motif are prevalent in genomic DNA. Recent studies of i-motif–forming sequences have shown increasing evidence of their roles in gene regulation. However, most of these studies have been performed in short single-stranded oligonucleotides, far from the intracellular environment. In cells, i-motif–forming sequences are flanked by DNA duplexes and packed in the genome. Therefore, exploring the conformational dynamics and kinetics of i-motif under such topologically constrained environments is highly relevant in predicting their biological roles. Using single-molecule fluorescence analysis of self-assembled DNA duplexes and nanocircles, we show that the topological environments play a key role on i-motif stability and dynamics. While the human telomere sequence (C3TAA)3C3 assumes i-motif structure at pH 5.5 regardless of topological constraint, it undergoes conformational dynamics among unfolded, partially folded and fully folded states at pH 6.5. The lifetimes of i-motif and the partially folded state at pH 6.5 were determined to be 6 ± 2 and 31 ± 11 s, respectively. Consistent with the partially folded state observed in fluorescence analysis, interrogation of current versus time traces obtained from nanopore analysis at pH 6.5 shows long-lived shallow blockades with a mean lifetime of 25 ± 6 s. Such lifetimes are sufficient for the i-motif and partially folded states to interact with proteins to modulate cellular processes

BeFaced: A casual game to crowdsource facial expressions in the wild

Creating good quality image databases for affective computing systems is key to most computer vision research, but is unfortunately costly and time-consuming. This paper describes BeFaced, a tile matching casual tablet game that enables massive crowdsourcing of facial expressions to advance facial expression analysis. BeFaced uses state-of-the-art facial expression tracking technology with dynamic difficulty adjustment to keep the player engaged and hence obtain a large and varied face dataset. CHI attendees will be able to experience a novel game interface that uses the iPad's front camera to track and capture facial expressions as the primary player input, and also investigate how the game design in general enables massive crowdsourcing in an extensible manner

Interventions for reducing and/or controlling domestic violence among pregnant women in low- and middle-income countries: A systematic review

© 2019 The Author(s). Background: Domestic violence (DV) during pregnancy is recognized as a global health problem associated with serious health consequences for both the mother and her baby. Several interventions aimed at addressing DV around the time of pregnancy have been developed in the last decade, but they are primarily from developed countries. Low- and middle-income countries (LMICs) are facing both a mounting burden of DV as well as severe resource constraints that keep them from emulating some of the effective interventions implemented in developed settings. A systematic review was conducted to examine the approaches and effects of interventions designed for reducing or controlling DV among pregnant women in LMICs. Methods: Electronic databases were systematically searched, and the search was augmented by bibliographic reviews and expert consultations. Two reviewers assessed eligibility and quality of the studies and extracted data independently. The third reviewer was involved to resolve any discrepancies between the reviewers. Due to the limited number of studies and varied outcomes, a meta-analysis was not possible. Primary outcomes of this review included frequency and/or severity of DV and secondary outcomes included mental health, safety behaviours, and use of community resources. In addition, findings from the critical appraisal of studies were utilised to inform the initial draft of Theory of Change (ToC). Results: Only five studies (two randomized trials and three non-randomized trials) met the eligibility criteria. The interventions consisting of supportive counselling demonstrated a reduction in DV and an improvement in use of safety behaviours. One study has embedded the DV intervention into an existing program on human immunodeficiency virus (HIV). Limited evidence could be drawn for outcomes such as quality of life and the use of community resources. Discussion: This review attempted to address the knowledge gap by collating evidence on interventions aimed at addressing DV among pregnant women in LMICs. The development of a ToC was critical in understanding how certain activities led to the desired outcomes. This ToC can guide the design of future research and development of practice guidelines. The participatory involvement of the stakeholders is recommended to refine the current ToC to support its further development for practice. Systematic review registration: PROSPERO, CRD4201707393

Domestic and Family Violence and its Association with Mental Health Among Pregnant Women Attending Antenatal Care in a Tertiary Hospital of Eastern Nepal.

Background: Pregnancy has been identified as a vulnerable period for both the initiation and escalation in severity of domestic and family violence. There is a significant dearth of scholarly literature documenting the relationship of domestic and family violence with the mental health and quality of life among pregnant women of Nepal. Methods: Baseline data of 140 women enrolled in a trial of a psychosocial intervention for abused pregnant women were analysed. Face-to-face interviews were conducted using standardised scales. Prevalence of domestic and family violence and mental health conditions were estimated and inferential statistics were used to assess the association of domestic and family violence with mental health, quality of life, social support, and use of safety behaviours. Results: The lifetime prevalence of domestic and family violence was found to be 27.7% (n = 173), followed by 17.1% of women (n = 107) fearing someone in their family. Domestic and family violence in the last 12 months was significantly associated with anxiety (p = 0.001), depression (p = 0.005), quality of life (p < 0.05), and perceived social support (p = 0.001). Use of safety behaviours (p = 0.037) was significantly low among women reporting domestic and family violence in the past year as well as during the current pregnancy (p = 0.017). Conclusions: There exists a high psychological morbidity among pregnant women exposed to domestic and family violence. The findings support the need of implementing a screening and support intervention for abused women seeking antenatal services

Quantitative nucleotide level analysis of regulation of translation in response to depolarization of cultured neural cells

Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence—notably upstream open reading frames and secondary structure in the 5′ untranslated region—both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome

Antenatal-Based Pilot Psychosocial Intervention to Enhance Mental Health of Pregnant Women Experiencing Domestic and Family Violence in Nepal.

Survivors of domestic and family violence (DFV) report poorer quality of life and worsening mental health. This study evaluated the effect of a counseling and education intervention on the mental health and help-seeking behaviors among pregnant women living with DFV. A parallel pilot randomized controlled trial was performed among 140 pregnant women attending an antenatal clinic of a tertiary hospital of Nepal. Using computer-generated random numbers, participants were randomized to the intervention group (a counseling session, an information booklet about DFV, and contact details of the counselor) or a control group (usual care plus a booklet containing contact details of local DFV support services). Outcome measures included mental health, quality of life (QOL), self-efficacy, social support, and safety planning behaviors. Analyses followed intention-to-treat, using the generalized estimating equation model. Intervention participants showed significant improvements in anxiety (β = -3.24, p < .001) and depression (β = -3.16, p < .001) at postintervention. Such improvements were also sustained at follow-up assessment (p < .001). Significant group and time interaction for QOL, social support, use of safety behaviors, and self-efficacy (p < .05) revealed a greater increase in these outcome measures among intervention participants at both follow-up assessments compared with the control group. This pilot integrated intervention showed promising outcomes in improving the mental health, social support, and the use of safety behaviors among women with DFV. This intervention could be incorporated into regular antenatal care as a strategy to identify and support victims of DFV. Larger controlled trials with longer follow-up are needed to support and expand on the current findings regarding the effectiveness of a psychosocial intervention targeting victims of DFV in resource-constrained settings

Self-efficacy and social support as mediators of mental health among abused women.

Supportive counseling and facilitated referrals to support organizations have shown positive effects on mental health and coping with domestic and family violence. However, the reasons why and how such effects are significant remain unknown. The current paper used data from a randomized controlled trial of a psychosocial intervention implemented in Nepal among 140 abused pregnant women. The hypothesized mediating effects of self-efficacy and social support on mental health and quality of life of abused pregnant women were tested using serial mediation analyses. Significance of parameter estimates and bias-corrected 95% confidence intervals (CIs) for the indirect effects were generated using bootstrapping. The postintervention changes in self-efficacy and social support were found to have significant mediating effects on the relationship between the intervention and changes in both mental health and quality of life of participants post intervention. The positive effects on outcomes were seen at follow-up as well, though to a lesser extent. Further interventions should focus on enhancing abused women's self-efficacy and social support to ensure their positive mental health and better lives