Combinatorial clustering of distinct DNA motifs directs synergistic binding of Caenorhabditis elegans dosage compensation complex to X chromosomes.

Organisms that count X-chromosome number to determine sex utilize dosage compensation mechanisms to balance X-gene expression between sexes. Typically, a regulatory complex is recruited to X chromosomes of one sex to modulate gene expression. A major challenge is to determine the mechanisms that target regulatory complexes specifically to X. Here, we identify critical X-sequence motifs in Caenorhabditis elegans that act synergistically in hermaphrodites to direct X-specific recruitment of the dosage compensation complex (DCC), a condensin complex. We find two DNA motifs that collaborate with a previously defined 12-bp motif called MEX (motif enriched on X) to mediate binding: MEX II, a 26-bp X-enriched motif and Motif C, a 9-bp motif that lacks X enrichment. Inserting both MEX and MEX II into a new location on X creates a DCC binding site equivalent to an endogenous recruitment site, but inserting only MEX or MEX II alone does not. Moreover, mutating MEX, MEX II, or Motif C in endogenous recruitment sites with multiple different motifs dramatically reduces DCC binding in vivo to nearly the same extent as mutating all motifs. Changing the orientation or spacing of motifs also reduces DCC binding. Hence, synergy in DCC binding via combinatorial clustering of motifs triggers DCC assembly specifically on X chromosomes. Using an in vitro DNA binding assay, we refine the features of motifs and flanking sequences that are critical for DCC binding. Our work reveals general principles by which regulatory complexes can be recruited across an entire chromosome to control its gene expression.

Evidence-Based Practice and Associated Factors Among Health Care Providers Working in Public Hospitals in Northwest Ethiopia During 2017.

BACKGROUND: Despite the fact that evidence-based practice (EBP) is believed to be associated with improved health, safety, and cost outcomes, most medical practice in low- and middle-income countries such as Ethiopia is not evidence-based. Understanding the extent of and barriers to EBP in Ethiopia is important for learning how to best to improve quality of care. Few studies have assessed EBP in Ethiopia. OBJECTIVE: This study aimed to assess reported level of EBP and associated factors among health care providers working in public hospitals in northwest Ethiopia. METHODS: A cross-sectional study was conducted with 415 randomly selected nurses, midwives, and physicians using stratified sampling (97.6% response rate). Data were collected using a structured, self-administered questionnaire that was developed by reviewing the literature and adapting the Melnyk and Fineout-Overholt EBP Implementation Scale. After validating scales, bivariate and multivariate linear regression models were used to identify factors associated with EBP implementation. RESULTS: The mean EBP implementation score was 10.3 points out of a possible 32 points and 60% of respondents scored below average. Most (60.2%) respondents reported poor confidence in their ability to judge the quality of research and half (50.1%) said that they were unable to find resources for implementing EBP. The most frequently mentioned barriers to EBP were lack of training (81.2%), poor health facility infrastructure (79.3%), and lack of formal EBP/patient education units in facilities (78.0%). The factors found to be significantly and independently associated with EBP implementation were years of work experience (ß = -0.10; P < 0.05); having been trained as a bachelor's degree-level nurse (ß = 3.45; P < 0.001) or a bachelor's degree-level midwife (ß = 2.96; P < 0.001), a general practitioner (ß = 7.86; P < 0.001), or a specialist physician (ß = 15.04; P < 0.001) rather than a diploma-level nurse; working in a pediatrics ward (ß = -1.74; P < 0.05); and reporting as barriers either a lack of clarity on the importance of EBP (ß = -0.93; P < 0.05) or a lack of orientation sessions on new health priorities (ß = -0.91; P < 0.05). CONCLUSIONS: Health professionals had low levels of EBP implementation and poor EBP skills. These problems were particularly acute for providers with lower levels of training. A large number of respondents reported structural and institutional barriers to EBP. These results suggest that clear leadership and ongoing, cross-disciplinary, skill-building approaches are needed to increase EBP implementation in Ethiopia. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Factors associated with reintegration trajectory following female genital fistula surgery in Uganda.

BACKGROUND: A female genital fistula, primarily caused by prolonged obstructed labor or after cesarean delivery in resource-limited countries, affects 500,000 to 2,000,000 women worldwide. Fistula is preventable with timely access to high-quality obstetrical care. Access to surgical repair of a female genital fistula has greatly increased over time. However, research surrounding postrepair reintegration, the process of returning to an individual's normal life, remains limited, and further efforts are needed to understand the factors shaping women's ability to rebuild their relationships and lives following repair. OBJECTIVE: This study aimed to characterize the 12-month reintegration trajectory after female genital fistula repair by participant sociodemographic and clinical characteristics. STUDY DESIGN: This study analyzed quantitative survey and medical record data of women (N=60) participating in a longitudinal cohort study assessing recovery after genital fistula repair in Uganda, with baseline and 4 quarterly follow-up assessments in 12 months. The primary outcome of reintegration was assessed using a 19-item postfistula repair reintegration instrument (range, 0-100) where a higher score represents better reintegration. Predictors of interest included parity and living children, quality of life, depressive symptoms at baseline, self-esteem, stigma, trauma, physical symptoms, and social support. We described participant baseline characteristics using means and proportions and estimated a series of mixed-effects linear regression models, including interactions of characteristics with time to understand how these characteristics influence reintegration trajectory in the 12 months after repair. RESULTS: The participants' physical and psychosocial morbidities at baseline were high; more than 80% of participants reported fistula-related physical symptoms, 82% of participants described their general health as poor, and measures of self-esteem, overall social support, and overall quality of life were low. The mean reintegration score at baseline was 33 (standard deviation, 20), which increased to 78 (standard deviation, 19) at 12 months after fistula repair. The participant sociodemographic characteristics statistically associated with reintegration included any living children (ß, 1.08; 95% confidence interval, -0.08 to 2.23). Moreover, psychosocial factors significantly affected reintegration with steeper trajectories for women with depressive symptoms (ß, 0.89; 95% confidence interval, 0.02-1.75) or women experiencing internalized stigma (ß, 0.05; 95% confidence interval, -0.00 to 0.11) and less steep for those with higher self-esteem (ß, -0.11; 95% confidence interval, -0.24 to 0.01), overall social support (ß, -0.06; 95% confidence interval, -0.12 to -0.01), and partner support (ß, -0.21; 95% confidence interval, -0.35 to -0.07). CONCLUSION: Understanding the prominent factors associated with differences in reintegration trajectories across the year after genital fistula surgery has the potential to inform interventions that mitigate challenges and improve women's postrepair recovery experiences.

Evidence for hormonal control of heart regenerative capacity during endothermy acquisition.

Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the ¾-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.

Insights into nuclear dynamics using live-cell imaging approaches.

The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems. Live-cell imaging approaches are capable of providing quantitative assessment of the dynamics of gene regulatory interactions within the nucleus. We survey recent insights into what live-cell imaging approaches have provided the field of nuclear dynamics. In this review, we focus on interactions of DNA with other DNA loci, proteins, RNA, and the nuclear envelope. WIREs Syst Biol Med 2017, 9:e1372. doi: 10.1002/wsbm.1372 For further resources related to this article, please visit the WIREs website.