Physiology, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of the Drosophila Genetics Reference Panel to assess the phenotypic variation of six physiological and fitness traits, namely, female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. We found continuous variation in the approximately 150 strains tested for each trait, with extreme values differing by more than four standard deviations for all traits. In addition, we assessed the effects of commonly used DrosophilaUAS-RNAi transgenic strains and their backcrossed isogenized counterparts, in the same traits plus baseline intestinal mitosis and tracheal branching in normoxia, in heterozygous conditions, when only half of the genetic background was different among strains. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenized counterparts without Gal4 induction. Survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other traits were affected in only 10-25% of the cases. When 11 isogenic and their corresponding non-isogenic UAS-RNAi lines were expressed ubiquitously with Gal4, 4 isogenic vs. non-isogenic pairs exhibited differences in survival to infection. Furthermore, when a single UAS-RNAi line was crossed with the same Gal4 transgene inserted in different genetic backgrounds, the quantitative variations observed were unpredictable on the basis of pure line performance. Thus, irrespective of the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ_1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.

Hemoglobinopathies comprise the most common monogenic diseases worldwide. In Europe, formerly low-prevalence regions have seen increasing numbers of carriers and patients, with important public health implications. Implementation of policies and laboratory methodologies varies across countries, affecting equitable care. This study aimed to provide a snapshot of current screening and diagnostic practices and to identify gaps and priorities. A cross-sectional online survey was conducted from May to October 2024 across the COST (European Cooperation in Science and Technology) Action Haemoglobinopathies in European Liaison of Medicine and Science network participants. The survey, including 21 questions, covered hematological methods, molecular diagnostics, and laboratory practices and policies. Responses were provided directly by centers and summarized descriptively in tables and maps. Responses were received from 38 centers in 20 countries. Hematology remains the diagnostic backbone for hemoglobinopathies, DNA-based testing is widely adopted although advanced genomics are limited, newborn screening is implemented widely for sickle cell disease and thalassemia, carrier reporting practices vary, and genetic modifier testing is emerging. The findings highlight opportunities for cross-country collaboration and targeted capacity building, identifying centers that could benefit from shared expertise and resources. These findings can guide strategies to harmonize protocols, strengthen diagnostic capabilities, and support broader implementation of best practices across Europe.

Haemoglobinopathies remain a major public health challenge, predominantly in endemic regions. Increasing migration has extended their prevalence in previously non-endemic areas, complicating early detection and prevention. As part of the HELIOS CA22119 COST Action Working Group 1, this narrative review critically examines established and emerging laboratory techniques for haemoglobinopathy carrier detection. It also explores diagnostic limitations, regional disparities, and opportunities for global harmonisation to support early detection, prevention, and equitable care. A literature search of MEDLINE, PubMed, Scopus, and EMBASE (2014–2024) identified studies on the screening, diagnosis, and prevention of haemoglobinopathies. Findings were synthesised across three domains: (1) preventive strategies, (2) carrier screening methods, and (3) prenatal diagnostic approaches. Advances in molecular technologies have improved diagnostic sensitivity and specificity. However, conventional haematological approaches, particularly complete blood count and haemoglobin typing, remain essential and cost-effective first-line tools. Key challenges include unequal access to advanced diagnostics and the lack of standardised protocols across regions. Strengthening prevention requires coordinated global efforts to promote accessible, accurate, and standardised diagnostic approaches tailored to regional genomic, economic, and healthcare contexts. Early and equitable carrier detection, combined with effective prenatal diagnosis, is critical to reducing the global burden and improving health outcomes in both endemic and emerging regions.