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A linamarase transgene controlled by heatshock creates a pro-toxin activation system in Drosophila melanogaster .
No full textLinamarase is a plant β-glucosidase enzyme involved in the activation of plant protoxins. It thereby plays a key role in plant defense mechanisms against herbivory. We have taken the linamarase gene sequence from cassava and placed it into the genome of Drosophila melanogaster under the control of non-leaky heat-shock promoter. We show that Drosophila larvae carrying the transgene become sensitive to the pro-toxin linamarin after heat-shock. Furthermore, the sensitivity is elevated in sealed containers and control-larvae sharing such containers with linamarase-larvae are also sensitive, suggesting that the larvae are dying from poisoning with gaseous hydrogen cyanide
Longitudinal Assessment of Structural and Functional Changes in Rod-cone Dystrophy: A 10-year Follow-up Study
No full textPurpose: Emerging clinical trials for inherited retinal disease (IRD) require an understanding of long-term progression. This longitudinal study investigated the genetic diagnosis and change in retinal structure and function over 10 years in rod-cone dystrophies (RCDs). Design: Longitudinal observational follow-up study. Participants: Individuals initially diagnosed with retinitis pigmentosa who underwent baseline assessment between 2010 and 2013. Methods: Baseline and follow-up assessments included best-corrected visual acuity (VA), Goldmann visual field (GVF) perimetry, spectral-domain OCT imaging, electroretinogram, and panel-based genetic testing. Linear mixed models were used to investigate disease progression and interaction between progression rate and baseline measurement. Interocular symmetry in disease progression was assessed using intraclass correlation coefficients (ICCs). Main Outcome Measures: Change in VA, GVF area, and ellipsoid zone (EZ) width over 10 years in RCD. Results: A total of 23 participants attended follow-up (mean age 63 ± 15 years at follow-up; 48% female), with 20 classified as having RCD and 3 reclassified as having cone-rod dystrophy based on genetic diagnosis. At 10-year follow-up, only 60% of RCD participants showed progression of ≥15 letters in either or both eyes, and 40% did not meet the criteria in either eye. Between the eye with poorer versus better VA at baseline, high symmetry in disease progression was observed for GVF area (ICC = 0.87; 95% confidence interval [CI]: 0.68–0.95), and moderate interocular symmetry in disease progression was observed for VA (ICC = 0.50 [95% CI: 0.07–0.77]) and EZ width (ICC = 0.64 [95% CI: 0.25–0.85]). Baseline values influenced progression for VA and percentage change in GVF area, whereas total percentage change in EZ width did not differ across baseline values. Conclusions: Many individuals with RCD did not have a significant 15-letter decline in VA over a 10-year follow-up, highlighting the challenges of relying on VA as a measure of disease progression. Symmetry between eyes varies, emphasizing a key consideration for selection of outcome measures in IRD clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article
Suppression of Aedes aegypti may not affect sympatric Aedes albopictus populations: findings from two years of entomological surveillance in Singapore
No full textGlobally, multiple trials have successfully demonstrated the effectiveness of novel tools, such as the sterile and incompatible insect techniques, in suppressing Aedes aegypti populations. However, there is concern that Aedes albopictus, another arbovirus-competent vector, may occupy the niches vacated by Ae. aegypti in areas where these species occur in sympatry. Here we investigate these concerns within the context of a Wolbachia-based Ae. aegypti suppression programme in highly urban Singapore, where general mosquito management is sustained through environmental management. Using nationally representative and longitudinal Aedes surveillance data, we show (1) no consistent association of increase in Ae. albopictus abundance with Ae. aegypti population suppression within Wolbachia-Aedes release sites, and (2) no significant change in the vertical spatial distribution of Ae. albopictus in high-rise residential apartment blocks even after two years of Ae. aegypti suppression. Finally, we report that dengue viruses were less prevalent in field Ae. albopictus than in Ae. aegypti, which is consistent with previous findings that Ae. albopictus is a lesser vector than Ae. aegypti in Singapore. Together, these results indicate that suppression of Ae. aegypti in the community may not be directly associated with any increase of Ae. albopictus population or capacity. Nonetheless, the risk of increase in Ae. albopictus population is anticipated if the reduction in disease transmission leads to less aggressive source reduction efforts and environmental management for mosquito control
Genetic structure and common ancestry expose the dingo-dog hybrid myth
No full textThe evolutionary history of canids has been shown to be complex, with hybridization and domestication confounding our understanding of speciation among various canid lineages. The dingo is a recent canid lineage that was completely isolated from other canids for over 5000 years on the Australian mainland, but the introduction of domestic dogs in 1788 has placed doubt on its independence, with recent studies highlighting hybridization between dingoes and domestic dogs. Using genomic single nucleotide polymorphism data from 434 Australian canid samples, we explicitly test for introgression between closely related canid groups and dingoes. We found no evidence of introgression between dingoes and domestic dogs and show that previous work has likely mischaracterized shared ancestral genetic variation as evidence for hybridization. Further, New Guinea Singing Dogs are the only canid group that significantly shared genetic variation with dingoes, which fits with our understanding of previous phylogenetic analyses. Despite more recent sympatric distributions with dogs, dingoes have likely maintained their independence since their arrival in Australia, even in areas with high lethal control, indicating that their evolutionary trajectory is currently being conserved. The future conservation of the dingo lineage will require policies that promote coexistence pathways between humans and dingoes that protect rangeland systems and the dingoes' evolutionary future
A paradoxical population structure of var DBLα types in Africa
No full textThe var multigene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), central to host-parasite interactions. Genome structure studies have identified three major groups of var genes by specific upstream sequences (upsA, B, or C). Var with these ups groups have different chromosomal locations, transcriptional directions, and associations with disease severity. Here we explore temporal and spatial diversity of a region of var genes encoding the DBLα domain of PfEMP1 in Africa. By applying a novel ups classification algorithm (cUps) to publicly-available DBLα sequence datasets, we categorised DBLα according to association with the three ups groups, thereby avoiding the need to sequence complete genes. Data from deep sequencing of DBLα types in a local population in northern Ghana surveyed seven times from 2012 to 2017 found variants with rare-to-moderate-to-extreme frequencies, and the common variants were temporally stable in this local endemic area. Furthermore, we observed that every isolate repertoire, whether mono- or multiclonal, comprised DBLα types occurring with these frequency ranges implying a common genome structure. When comparing African countries of Ghana, Gabon, Malawi, and Uganda, we report that some DBLα types were consistently found at high frequencies in multiple African countries while others were common only at the country level. The implication of these local and pan-Africa population patterns is discussed in terms of advantage to the parasite with regards to within-host adaptation and resilience to malaria control
Factors influencing community engagement approaches used in Aedes aegypti management in Cairns, Australia
No full textISSUE ADDRESSED: An important part of preventing and managing Aedes-borne mosquito disease outbreak risk is engaging the community. Research shows that high-income countries tend to use top-down measures for Aedes mosquito management, favouring educational approaches to engage the community over participatory approaches that actively involve and empower the community in addressing disease risk. Little is known about the reasons behind the use of these approaches and how they could be strengthened. This research explores the community engagement approaches used in Aedes mosquito management in Cairns, Queensland, Australia and the factors influencing the choice of these approaches. METHODS: A case study design was used, drawing on two qualitative methods-key informant, semi-structured interviews (n = 25), and a document review (n = 20). Thematic analysis was used to identify, analyse and attribute meaning from the data. RESULTS: Various approaches were used to engage the community, including direct interaction through door-to-door inspections, broad outreach via mass media campaigns, and community participation in a novel mosquito replacement strategy. Factors influencing the choice of these approaches included government legislative responsibilities, research-related ethical obligations, work norms within local government and public health units, the perceived importance of gaining community trust, constraints on workforce capacity, time and funding. CONCLUSIONS: There were multiple factors influencing the community engagement approaches used in this study. Resource constraints, institutional norms and prevailing attitudes and beliefs were identified as hindering the use of more empowering approaches to engaging the community. These barriers should be considered and addressed in the planning of Aedes mosquito management to better support community engagement in this setting. SO WHAT?: Community engagement is an important aspect of managing the Aedes mosquito disease threat. With the global increase in Aedes mosquito-borne disease risk, these findings can help other at-risk settings understand potential organisational impediments to engaging the community. This is particularly important when advocating for the inclusion of bottom-up approaches in policy, and to ensure sufficient resources are allocated to strengthen community engagement in Aedes mosquito management
Childhood Influenza Vaccination Is Not a Priority for Parents: A National, Cross-Sectional Survey of Barriers to Childhood Influenza Vaccination in Australia
No full textBackground/objectives: Influenza vaccines are recommended and free in Australia for children aged <5 years, but uptake remains low at 25.8% compared to the targets of 40% and 50%. National data on barriers hindering paediatric influenza vaccination can inform strategies to improve uptake. The aim of this study was to measure barriers to influenza vaccination in Australian children aged <5 years. Methods: A national, cross-sectional survey of parents of children aged <5 years was conducted in March/April 2024. Parents were recruited using an online panel and asked about their intention to get an influenza vaccine for their youngest child in the upcoming influenza season. An adapted version of the validated Vaccine Barriers Assessment Tool measured 14 influenza vaccination barriers. Analysis assessed the prevalence of barriers and differences between parents intending to and those unsure or not intending to vaccinate by calculating the prevalence difference and 95% confidence interval. Results: A total of 2000 parents were recruited nationally. The most common barrier was parents feeling distressed when thinking about vaccinating their child against influenza (66.1% of intending parents, 65.6% of unsure/not intending parents). The barrier with the largest difference between intending and not intending/unsure parents was not prioritising their child's influenza vaccination (47.2% vs. 6.1%, PD = 41.1 ppts, 95% CI: 35.9%, 46.3%). Other barriers with large differences were parents not feeling guilty if their unvaccinated child got influenza (41.5% vs. 7.5%, PD = 34.0 ppts, 95% CI: 28.8%, 39.1%) and parents not believing that influenza vaccines are effective (31.3% vs. 3.0%, PD = 28.2 ppts, 95% CI: 23.6%, 32.9%). Conclusions: Parents should be encouraged and supported to prioritise influenza vaccination alongside routine childhood vaccines in campaigns that emphasise disease risk and the importance, safety and effectiveness of influenza vaccination, and by optimising access to influenza vaccination. We recommend conducting similar surveys regularly to monitor trends in parental barriers to childhood influenza vaccination
Heterogeneity in the management of diabetic ketoacidosis in Australia: a national survey
No full textBACKGROUND: Diabetic ketoacidosis (DKA) is a hyperglycaemic emergency, and insulin administration is highly protocolised with either variable- or fixed-rate intravenous infusions. There are limited data supporting superiority of one regimen over another; however, international guidelines recommend fixed-rate infusions. AIM: To characterise DKA management protocols used in Australian hospitals. METHODS: An online survey of Australian endocrinologists and intensive care physicians between May and July 2024. The main outcome measure was the proportion of respondents using a fixed or variable rate, or combination, for the management of DKA. Secondary outcomes were the location of management, definition of resolution and intravenous fluid specification. RESULTS: There were 31 respondents from individual hospitals around Australia, with 84% of endocrinologists and 84% from metropolitan hospitals. There was wide variation in insulin regimens including fixed (n = 12), variable (n = 14) and combination (n = 5) infusion protocols. Most (23/30, 77%) respondents had worked at another hospital that had a different DKA management protocol. There was a 50% split (n = 14 each) in personal preference for fixed- or variable-rate infusion, with three respondents having no preference. Most (21/31, 68%) protocols defined resolution of DKA. Blood pH (15/21, 71%) and/or ketone level (18/21, 86%) were the most frequently used end points to define resolution. CONCLUSIONS: There are substantial variations in insulin regimens and resolution criteria in DKA management protocols across Australian hospitals. Clinician preference was diverse. This likely reflects the lack of high-quality evidence to guide practice
Rapid Resolution of Anabolic Androgenic Steroid-Induced Refractory Pruritus and Bile Cast Nephropathy With Therapeutic Plasma Exchange
No full textThe proportion of non-paracetamol drug-induced liver injury (DILI) is increasing in Australia and other Western countries. Androgenic anabolic steroids (AAS) commonly cause a bland cholestasis that can persist for months despite withdrawal. A 35-year-old male presented with progressive painless jaundice associated with pruritus, nausea, loss of weight, dark urine, and pale stools. He had recently commenced AAS; DILI was suspected and confirmed on biopsy. His pruritus was refractory to medical therapy, and PLEX was commenced. He also developed renal failure from bile cast nephropathy (BCN) and required hemodialysis. At 10 weeks post-discharge, his pruritus and jaundice were significantly improved, and his renal function had completely recovered. The case adds to the growing evidence that PLEX can be used safely and effectively to treat cholestatic pruritus and BCN
Холодное лето 1943-го: побеги советских военно-пленных из офицерского лагеря XIII D = Kholodnoe leto 1943-go: pobegi sovetskikh voennoplennykh iz ofitserskogo lageria XIII D = The Cold Summer of 1943: Escapes of Soviet Prisoners of War from the Officers' Camp XIII D
No full textThis article investigates a hitherto untapped topic — an examination of Soviet runaways and prison breaks from the German POW officer camp Hammelburg. It draws on unique Russian, Ukrainian and German materials and traces the cinema-worthy fates of Red Army officers who absconded from Germany and walked or hitchhiked back to the Soviet Union