Search

BackgroundThis paper presents findings from a qualitative effectiveness evaluation of an intervention aimed at improving caregiver-young adolescent sexual and reproductive health (SRH) communication including training modules for caregivers on parent-child SRH communication.MethodsData was collected (October 2021-November 2021) using a narrative interviewing technique with thirty caregivers (8 males and 22 females), who received the parent-child communication intervention in Mbarara district, south-western Uganda. We explored caregivers' experiences with the intervention based on four domains of change: caregiver-young adolescent communication on SRH issues, knowledge and attitudes towards adolescent SRH, parenting skills, and personal life and family. Thematic analysis was used to code and analyse the data, with attention to gender differences.ResultsFindings highlight positive parenting as a key attribute of SRH communication, along with a transformation of knowledge and attitudes towards the SRH of young adolescents leading to an overall improvement in SRH communication. However, communication is still limited to comfortable topics.ConclusionOur findings indicate improved caregiver-adolescent SRH communication practices following a community intervention. Programming for adolescent health on broader sexuality topics, comfortability and attitude change among caregivers could promote behaviour change on a long term. Future studies may focus on the long term impacts of interventions of this nature and test interventions aimed at addressing comfortability with discussingSRH issues.

Abstract Vascular inflammation plays a key role in the development of aortic diseases. A potential novel target for treatment might be CD73, an ecto-5′-nucleotidase that generates anti-inflammatory adenosine in the extracellular space. Here, we investigated whether a lack of CD73 results in enhanced aortic inflammation. To this end, angiotensin II was infused into wildtype and CD73−/− mice over 10 days. Before and after infusion, mice were analyzed using magnetic resonance imaging, ultrasound, flow cytometry, and histology. The impact of age and gender was investigated using female and male mice of three and six months of age, respectively. Angiotensin II infusion led to increased immune cell infiltration in both genotypes’ aortae, but depletion of CD73 had no impact on immune cell recruitment. These findings were not modified by age or sex. No substantial difference in morphological or functional characteristics could be detected between wildtype and CD73−/− mice. Interestingly, the expression of CD73 on neutrophils decreased significantly in wildtype mice during treatment. In summary, we have found no evidence that CD73 deficiency affects the onset of aortic inflammation. However, as CD73 expression decreased during disease induction, an increase in CD73 by pharmaceutical intervention might result in lower vascular inflammation and less vascular disease.

Abstract Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.

Several COVID-19 vaccines have shown good efficacy in clinical trials. Here, the authors provide real world effectiveness data in a group of BNT162b2 vaccinated health care workers and find that breakthrough infections are asymptomatic or mild.

Common Fragile Sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Here the authors use genome-wide and single cell techniques to assess how replication timing and transcriptional activity correlate with genome stability.

Schistosomiasis is a tropical parasitic disease affecting more than 200 million people worldwide, predominantly in Africa. The World Health Organization recently highlighted the importance of targeted control of the freshwater snails acting as intermediate hosts for the parasites causing schistosomiasis. However, because of a shortage of trained experts and resources, detailed information on spatiotemporal snail distributions, which is needed for targeted control measures, is often missing. We explore the potential of citizen science to build these much-needed datasets through fine-grained, frequent snail sampling. We trained a network of 25 citizen scientists to weekly report on snail host abundances in 77 predefined water contact sites in and around Lake Albert (western Uganda). Snail abundance, together with marked GPS locations, water chemistry parameters, and photographs of the identified snails are recorded and submitted using the freely available mobile phone application KoBoToolbox. Trained researchers then engage in remote, semi-automatic validation of the submissions, after which there is an opportunity to provide targeted feedback to the citizen scientists. Five months after the operationalisation of the network, a total of 570 reports were submitted and personalized feedback was given, resulting in lasting improvements in subsequent reporting and snail genus identification. The preliminary results show the possibility of citizen science to independently obtain reliable data on the presence of schistosome snail hosts. We therefore argue that citizen-driven monitoring on a high spatiotemporal resolution could help to generate the much-needed data to support local targeted snail control measures in remote and/or resource-limited environments.

BackgroundCompassion fatigue is associated with negative consequences that undermine workplace performance. However, literature is scarce on compassion fatigue among nurses in the context of Uganda who are at higher risk of compassion fatigue owed to the nature of their occupation and the unfavorable work environment. We aimed to assess the prevalence and predictors of compassion fatigue among nurses in Northern Uganda.MethodsWe conducted a cross-sectional survey among 395 randomly selected nurses from two referral and four general hospitals in Northern Uganda. Data was collected using a self-administered questionnaire. Data analysis consisted of descriptive statistics, cross-tabulations, and logistic regression at a 95% level of significance in SPSS version 25.ResultsOf 395 nurses who took part in the study, 58.2% were female, 39.8% had a diploma, 47.1% were single, and 32.4% had worked for between 11-15 years. Close to 50% of the nurses experienced compassion fatigue. The predictors of compassion fatigue among the participants were; workplace bullying (AOR: 3.83; 95% CI: 1.99-7.36; p = ConclusionMore than 3 in 4 nurses in Northern Uganda experience compassion fatigue. The Ministry of Health together with other stakeholders should strive to increase career enhancement opportunities for nurses, improve nurses' remuneration and improve the overall workplace environment to prevent compassion fatigue among nurses in the country.

The pervasive occurrence of sexual dimorphism demonstrates different adaptive strategies of males and females. While different reproductive strategies of the two sexes are well-characterized, very little is known about differential functional requirements of males and females in their natural habitats. Here, we study the impact environmental change on the selection response in both sexes. Exposing replicated Drosophila populations to a novel temperature regime, we demonstrate sex-specific changes in gene expression, metabolic and behavioral phenotypes in less than 100 generations. This indicates not only different functional requirements of both sexes in the new environment but also rapid sex-specific adaptation. Supported by computer simulations we propose that altered sex-biased gene regulation from standing genetic variation, rather than new mutations, is the driver of rapid sex-specific adaptation. Our discovery of environmentally driven divergent functional requirements of males and females has important implications-possibly even for gender aware medical treatments.

Both nationally and internationally, midwives' practices during the second stage of labour vary. A midwife's practice can be influenced by education and cultural practices but ultimately it should be informed by up-to-date scientific evidence. We conducted a systematic review of the literature to retrieve evidence that supports high quality intrapartum care during the second stage of labour. A systematic literature search was performed to September 2019 in collaboration with a medical information specialist. Bibliographic databases searched included: PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Maternity and Infant Care Database and The Cochrane Library, resulting in 6,382 references to be screened after duplicates were removed. Articles were then assessed for quality by two independent researchers and data extracted. 17 studies focusing on midwives' practices during physiological second stage of labour were included. Two studies surveyed midwives regarding their practice and one study utilising focus groups explored how midwives facilitate women's birthing positions, while another focus group study explored expert midwives' views of their practice of preserving an intact perineum during physiological birth. The remainder of the included studies were primarily intervention studies, highlighting aspects of midwifery practice during the second stage of labour. The empirical findings were synthesised into four main themes namely: birthing positions, non-pharmacological pain relief, pushing techniques and optimising perineal outcomes; the results were outlined and discussed. By implementing this evidence midwives may enable women during the second stage of labour to optimise physiological processes to give birth. There is, however, a dearth of evidence relating to midwives' practice, which provides a positive experience for women during the second stage of labour. Perhaps this is because not all midwives' practices during the second stage of labour are researched and documented. This systematic review provides a valuable insight of the empirical evidence relating to midwifery practice during the physiological second stage of labour, which can also inform education and future research. The majority of the authors were members of the EU COST Action IS1405: Building Intrapartum Research Through Health (BIRTH). The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration CRD42018088300) and is published (Verhoeven, Spence, Nyman, Otten, Healy, 2019).

Intraluminal vesicles are formed by the endosomal sorting complex required for transport (ESCRT) machinery. Here, the authors unravel the timing of vesicle budding, and that endosomal clathrin regulates concerted recruitment of ESCRT subcomplexes, required for efficient membrane remodeling.

Abstract Tissue osmolarity varies among different organs and can be considerably increased under pathologic conditions. Hyperosmolarity has been associated with altered stimulatory properties of immune cells, especially macrophages and dendritic cells. We have recently reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Here, we examined how hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells. Using ovalbumin as model antigen, we showed that exposure of dendritic cells to hyperosmolarity strongly inhibits activation of antigen-specific T cells despite enhancement of antigen uptake, processing and presentation. We identified TRIF as key mediator of this phenomenon. Moreover, we detected a hyperosmolarity-triggered, TRIF-dependent clustering of MHCI loaded with the ovalbumin-derived epitope, but not of overall MHCI molecules, providing a possible explanation for a reduced T cell activation. Our findings identify dendritic cells as important players in hyperosmolarity-mediated immune imbalance and provide evidence for a novel pathway of inhibition of antigen specific CD8+ T cell response in a hypertonic micromilieu.

Extraembryonic tissues contribute to animal development, which often entails spreading over embryo or yolk. Apart from changes in cell shape, the requirements for this tissue spreading are not well understood. Here, we analyze spreading of the extraembryonic serosa in the scuttle fly Megaselia abdita. The serosa forms from a columnar blastoderm anlage, becomes a squamous epithelium, and eventually spreads over the embryo proper. We describe the dynamics of this process in long-term, whole-embryo time-lapse recordings, demonstrating that free serosa spreading is preceded by a prolonged pause in tissue expansion. Closer examination of this pause reveals mechanical coupling to the underlying yolk sac, which is later released. We find mechanical coupling prolonged and serosa spreading impaired after knockdown of M. abdita Matrix metalloprotease 1. We conclude that tissue–tissue interactions provide a critical functional element to constrain spreading epithelia.

It is generally accepted that gene regulation serves an important role in determining the phenotype. To shed light on the evolutionary forces operating on gene regulation, previous studies mainly focused on the expression differences between species and their inter-specific hybrids. Here, we use RNA-Seq to study the intra-specific distribution of cis- and trans-regulatory variation in Drosophila pseudoobscura. Consistent with previous results, we find almost twice as many genes (26%) with significant trans-effects than genes with significant cis-effects (18%). While this result supports the previous suggestion of a larger mutational target of trans-effects, we also show that trans-effects may be subjected to purifying selection. Our results underline the importance of intra-specific analyses for the understanding of the evolution of gene expression.

RNA-Seq is a powerful tool for the annotation of genomes, in particular for the identification of isoforms and UTRs. Nevertheless, several software tools exist and no standard strategy to obtain a reliable annotation is yet established. We tested different combinations of the most commonly used reference-based alignment tools (TopHat, GSNAP) in combination with two frequently used reference-based assemblers (Cufflinks, Scripture) and evaluated the potential of RNA-Seq to improve the annotation of Drosophila pseudoobscura. While GSNAP maps a higher proportion of reads, TopHat resulted in a more accurate annotation when used in combination with Cufflinks. Scripture had the lowest sensitivity. Interestingly, after subsampling to the same coverage for GSNAP and TopHat, we find that both mappers have similar performance, implying that the advantage of TopHat is mainly an artifact of the lower coverage. Overall, we observed a low concordance among the different approaches tested both at junction and isoform levels. Using data from both sexes of two adult strains of D. pseudoobscura we detected alternative splicing for about 30% of the FlyBase multiple-exon genes. Moreover, we extended the boundaries for 6523 genes (about 40%). We annotated 669 new genes, 45% of them with splicing evidence. Most of the new genes are located on unassembled contigs, reflecting their incomplete annotation. Finally, we identified 99 additional new genes that are not represented in the current genome contigs of D. pseudoobscura, probably due to location in genomic regions that are difficult to assemble (e.g. heterochromatic regions).

Recent statistical analyses suggest that sequencing of pooled samples provides a cost effective approach to determine genome-wide population genetic parameters. Here we introduce PoPoolation, a toolbox specifically designed for the population genetic analysis of sequence data from pooled individuals. PoPoolation calculates estimates of θ(Watterson), θ(π), and Tajima's D that account for the bias introduced by pooling and sequencing errors, as well as divergence between species. Results of genome-wide analyses can be graphically displayed in a sliding window plot. PoPoolation is written in Perl and R and it builds on commonly used data formats. Its source code can be downloaded from http://code.google.com/p/popoolation/. Furthermore, we evaluate the influence of mapping algorithms, sequencing errors, and read coverage on the accuracy of population genetic parameter estimates from pooled data.

The expression of BCL11B was reported in T-cells, neurons and keratinocytes. Aberrations of BCL11B locus leading to abnormal gene transcription were identified in human hematological disorders and corresponding animal models. Recently, the elevated levels of Bcl11b protein have been described in a subset of squameous cell carcinoma cases. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open. Here, by employing an overexpression strategy we revealed formerly unidentified features of Bcl11b. Two different T-cell lines were forced to express BCL11B at levels similar to those observed in primary T-cell leukemias. This resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A. The data presented here suggest a potential role of BCL11B in tumor survival and encourage developing Bcl11b-inhibitory approaches as a potential tool to specifically target chemoresistant tumor cells.

The Drosophila C virus (DCV) is a common and well-studied Drosophila pathogen. Although natural infections are known from Drosophila melanogaster and D. simulans, and artificial infections have been reported from several Drosophila species and other insects, it remains unclear to date whether DCV infections also occur naturally in other Drosophila species.Using reverse transcription PCR, we detected natural infections in six Drosophila species, which have not been previously known as natural hosts. By subsequent Sanger sequencing we compared DCV haplotypes among eight Drosophila host species. Our data suggest that cross-infections might be frequent both within and among species within the laboratory environment. Moreover, we find that some lines exhibit multiple infections with distinct DCV haplotypes.Our results suggest that the natural host range of DCV is much broader than previously assumed and that cross-infections might be a common phenomenon in the laboratory, even among different Drosophila hosts.