Drosophila mitoferrin is essential for male fertility: evidence for a role of mitochondrial iron metabolism during spermatogenesis

<p>Abstract</p> <p>Background</p> <p>Mammals and <it>Drosophila melanogaster </it>share some striking similarities in spermatogenesis. Mitochondria in spermatids undergo dramatic morphological changes and syncytial spermatids are stripped from their cytoplasm and then individually wrapped by single membranes in an individualization process. In mammalian and fruit fly testis, components of the mitochondrial iron metabolism are expressed, but so far their function during spermatogenesis is unknown. Here we investigate the role of <it>Drosophila </it>mitoferrin (dmfrn), which is a mitochondrial carrier protein with an established role in the mitochondrial iron metabolism, during spermatogenesis.</p> <p>Results</p> <p>We found that P-element insertions into the 5'-untranslated region of the <it>dmfrn </it>gene cause recessive male sterility, which was rescued by a fluorescently tagged transgenic <it>dmfrn </it>genomic construct (<it>dmfrn^venus</it>). Testes of mutant homozygous <it>dmfrn^SH115</it>flies were either small with unorganized content or contained some partially elongated spermatids, or testes were of normal size but lacked mature sperm. Testis squashes indicated that spermatid elongation was defective and electron micrographs showed mitochondrial defects in elongated spermatids and indicated failed individualization. Using a <it>LacZ </it>reporter and the <it>dmfrn^venus</it>transgene, we found that dmfrn expression in testes was highest in spermatids, coinciding with the stages that showed defects in the mutants. Dmfrn-venus protein accumulated in mitochondrial derivatives of spermatids, where it remained until most of it was stripped off during individualization and disposed of in waste bags. Male sterility in flies with the hypomorph alleles <it>dmfrn^BG00456</it>and <it>dmfrn^EY01302</it>over the deletion <it>Df(3R)ED6277 </it>was increased by dietary iron chelation and suppressed by iron supplementation of the food, while male sterility of <it>dmfrn^SH115/Df(3R)ED6277 </it>flies was not affected by food iron levels.</p> <p>Conclusions</p> <p>In this work, we show that mutations in the <it>Drosophila </it>mitoferrin gene result in male sterility caused by developmental defects. From the sensitivity of the hypomorph mutants to low food iron levels we conclude that mitochondrial iron is essential for spermatogenesis. This is the first time that a link between the mitochondrial iron metabolism and spermatogenesis has been shown. Furthermore, due to the similar expression patterns of some mitochondrial iron metabolism genes in <it>Drosophila </it>and mammals, it is likely that our results are applicable for mammals as well.</p

Green it! Planning more sustainable conferences

Climate change and the COVID-19 pandemic challenge us to re-evaluate the way we live and work. In the academic sector, this includes organising and attending conferences and other scientific meetings. The pandemic has led EAHIL 2020 to be moved online, which is “greener” than physical meetings, but has interactional drawbacks. On the other hand, planning of physical conferences can make use of existing guidance to improve the environmental impact in areas such as venue and travel arrangements, catering, waste reduction as well as communication. In the future, conference organisers can draw upon insights into remote and virtual collaboration gained during the pandemic. Hybrid conferences that allow physical and remote attendance might become an option for increased sustainability of scientific meetings

Neighborhood Experiences and Community Integration: Perspectives from Mental Health Consumers and Providers

This exploratory study examines the social interactional aspect of community integration among persons with psychiatric disabilities. Six focus groups were conducted with 18 mental health consumers in three publicly sponsored community residential programs and 11 staff members providing services to these consumers. Mental health consumers reported both positive and negative experiences in their interactions with community residents. Despite perceived differences between persons with psychiatric disabilities and their neighbors, consumers considered reciprocity and mutual accommodation to be critical for building social relationships in their communities. Mental health providers suggested that social integration can be facilitated by developing independent living and social skills, by overcoming self-stigma and institutional and homeless mindsets, and by having a supportive community of consumers

Anakinra for the treatment of COVID-19 patients: a systematic review and meta-analysis

Background At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin‑1 (IL‑1) receptor antagonist Anakinra for the treatment of COVID‑19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID‑19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS‑CoV‑2 infection. Methods We searched the Cochrane COVID‑19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID‑19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS‑CoV‑2 infection. Results We included five RCTs with 1,627 patients (nAnakinra = 888, ncontrol = 739, mean age 59.63 years, 64% male). Random‑effects meta‑analysis was used to pool data. We found that Anakinra makes little or no difference to all‑cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64–1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I2 = 49%; low certainty of evidence). Conclusions Anakinra has no effect on adult hospitalized patients with SARS‑CoV‑2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone. Trial Registration: PROSPERO Registration Number: CRD42021257552.Peer Reviewe

Medizinbibliotheken in Deutschland: Situation und Entwicklung

Dieser Artikel gibt einen Überblick über den Stand deutscher Medizinbibliotheken und ausgewählte Entwicklungen der Serviceleistungen, mit denen diese Forschung, Ausbildung und klinische Praxis unterstützen. Resultate einer Online-Umfrage und Aspekte des Zugangs zu Information werden mit Bezug zum deutschen Gesundheitswesen diskutiert. Ein wesentliches Hindernis für Fortschritt ist eine Trennung zwischen den Institutionen der Gesundheitsversorgung und der Wissenschaft. Neue Bibliotheksdienste werden zunehmend in Anspruch genommen

Medizinbibliotheken in Deutschland als Unterstützerinnen Evidenzbasierter Medizin: Situation und Entwicklung

Dieser Artikel gibt einen Überblick über den Stand deutscher Medizinbibliotheken und ausgewählte Entwicklungen der Serviceleistungen, mit denen diese die Evidenzbasierte Medizin in Forschung, Ausbildung und klinischer Praxis unterstützen. Resultate einer Online-Umfrage und Aspekte des Zugangs zu medizinischer Evidenz werden mit Bezug zum deutschen Gesundheitswesen diskutiert. Ein wesentliches Hindernis für Fortschritt ist eine Trennung zwischen den Institutionen der Gesundheitsversorgung und der Wissenschaft. Neue Bibliotheksdienste, insbesondere auch solche im Feld der Evidenzbasierten Medizin, werden zunehmend in Anspruch genommen. --- Health sciences libraries in Germany as supporters of evidence-based medicine: current situation and new directions This article gives an overview of the state of medical libraries in Germany and selected developments of their services supporting evidence-based medicine in research, education and clinical practice. Findings from an online survey and issues of access to health information are discussed with reference to the German health care system. A major barrier to progress stems from the separation that exists between institutions of health care practice and research. New library services provided by many German health sciences libraries, especially those supporting evidence-based medicine, are experiencing increasing take-up

Diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years (Review)

Background Child overweight and obesity has increased globally, and can be associated with short‐ and long‐term health consequences. Objectives To assess the effects of diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years. Search methods We performed a systematic literature search in the databases Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS, as well as in the trial registers ClinicalTrials.gov and ICTRP Search Portal. We also checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. Selection criteria We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions for treating overweight or obesity in preschool children aged 0 to 6 years. Data collection and analysis Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Main results We included 7 RCTs with a total of 923 participants: 529 randomised to an intervention and 394 to a comparator. The number of participants per trial ranged from 18 to 475. Six trials were parallel RCTs, and one was a cluster RCT. Two trials were three‐arm trials, each comparing two interventions with a control group. The interventions and comparators in the trials varied. We categorised the comparisons into two groups: multicomponent interventions and dietary interventions. The overall quality of the evidence was low or very low, and six trials had a high risk of bias on individual 'Risk of bias' criteria. The children in the included trials were followed up for between six months and three years. In trials comparing a multicomponent intervention with usual care, enhanced usual care, or information control, we found a greater reduction in body mass index (BMI) z score in the intervention groups at the end of the intervention (6 to 12 months): mean difference (MD) ‐0.3 units (95% confidence interval (CI) ‐0.4 to ‐0.2); P &lt; 0.00001; 210 participants; 4 trials; low‐quality evidence, at 12 to 18 months' follow‐up: MD ‐0.4 units (95% CI ‐0.6 to ‐0.2); P = 0.0001; 202 participants; 4 trials; low‐quality evidence, and at 2 years' follow‐up: MD ‐0.3 units (95% CI ‐0.4 to ‐0.1); 96 participants; 1 trial; low‐quality evidence. One trial stated that no adverse events were reported; the other trials did not report on adverse events. Three trials reported health‐related quality of life and found improvements in some, but not all, aspects. Other outcomes, such as behaviour change and parent‐child relationship, were inconsistently measured. One three‐arm trial of very low‐quality evidence comparing two types of diet with control found that both the dairy‐rich diet (BMI z score change MD ‐0.1 units (95% CI ‐0.11 to ‐0.09); P &lt; 0.0001; 59 participants) and energy‐restricted diet (BMI z score change MD ‐0.1 units (95% CI ‐0.11 to ‐0.09); P &lt; 0.0001; 57 participants) resulted in greater reduction in BMI than the comparator at the end of the intervention period, but only the dairy‐rich diet maintained this at 36 months' follow‐up (BMI z score change in MD ‐0.7 units (95% CI ‐0.71 to ‐0.69); P &lt; 0.0001; 52 participants). The energy‐restricted diet had a worse BMI outcome than control at this follow‐up (BMI z score change MD 0.1 units (95% CI 0.09 to 0.11); P &lt; 0.0001; 47 participants). There was no substantial difference in mean daily energy expenditure between groups. Health‐related quality of life, adverse effects, participant views, and parenting were not measured. No trial reported on all‐cause mortality, morbidity, or socioeconomic effects. All results should be interpreted cautiously due to their low quality and heterogeneous interventions and comparators. Authors' conclusions Muticomponent interventions appear to be an effective treatment option for overweight or obese preschool children up to the age of 6 years. However, the current evidence is limited, and most trials had a high risk of bias. Most trials did not measure adverse events. We have identified four ongoing trials that we will include in future updates of this review. The role of dietary interventions is more equivocal, with one trial suggesting that dairy interventions may be effective in the longer term, but not energy‐restricted diets. This trial also had a high risk of bias