Clinical characterization of a family with a mutation in the uromodulin (Tamm-Horsfall glycoprotein) gene

Clinical characterization of a family with a mutation in the uromodulin (Tamm-Horsfall glycoprotein) gene.BackgroundWe have recently identified a mutation in the uromodulin gene in a large family affected with hyperuricemia, gout, and renal failure. The purpose of this investigation is to provide a comprehensive characterization of the clinical findings of this syndrome in family members who had a mutation in the uromodulin gene.MethodsAn extended family suffering from hyperuricemia and gout was identified by a local practitioner. After consent was obtained, patients provided a directed clinical history and blood and urine specimens for chemical and genetic testing. All family members were tested for the presence of uromodulin gene mutations by direct DNA sequence analysis. The clinical and biochemical characteristics of family members carrying the affected mutation were then investigated.ResultsThirty-nine family members were found to have an exon 5 uromodulin gene mutation (g.1966 1922 del), and 29 unaffected family members were identified. The cardinal clinical features in individuals with the uromodulin mutation included hyperuricemia, decreased fractional excretion of uric acid, and chronic interstitial renal disease leading to end-stage renal disease (ESRD) in the fifth through seventh decade. Women did not always develop hyperuricemia or gout, but still developed progressive chronic renal failure.ConclusionMutation of the uromodulin gene resulted in hyperuricemia, reduced fractional excretion of uric acid, and renal failure. Genetic testing will be required to definitively identify individuals suffering from this condition. We are interested in studying other families that may suffer from this condition and would appreciate any such referrals

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community

Citizen science versus professional data collection: Comparison of approaches to mosquito monitoring in Germany

Due to the recent emergence of invasive mosquito species and the outbreaks of mosquito-borne diseases in Europe, research on the ecology and diversity of the mosquito fauna has returned to scientific agendas. Through a nationwide surveillance programme in Germany, mosquitoes have been monitored actively by systematically operated traps since 2011, and passively by the 'Mückenatlas' (mosquito atlas) citizen science project launched in 2012. To assess the performance of both monitoring methods we compared the two respective datasets with regard to habitat coverage, species composition and the ability to detect invasive mosquitoes. The datasets include observations from the beginning of the project until the end of 2017. We found significant differences in species composition caused by land use types and the participants' recording activity. Active monitoring performed better in mapping mosquito diversity, whereas passive monitoring better detected invasive species, thereby using data from private premises scientists usually cannot access. Synthesis and applications. Active and passive monitoring is complementary. Combining them allows for the determination of mosquito diversity, efficient detection of emerging invasive species and the initiation of rapid-response actions against such invaders. The 'Mückenatlas' sets an example for the usefulness of citizen science when included in a national monitoring programme, an approach that may be worth copying for tackling the global spread of arthropod vectors of disease agents

Vision Impairs the Abilities of Bats to Avoid Colliding with Stationary Obstacles

Background: Free-flying insectivorous bats occasionally collide with stationary objects they should easily detect by echolocation and avoid. Collisions often occur with lighted objects, suggesting ambient light may deleteriously affect obstacle avoidance capabilities. We tested the hypothesis that free-flying bats may orient by vision when they collide with some obstacles. We additionally tested whether acoustic distractions, such as ‘‘distress calls’ ’ of other bats, contributed to probabilities of collision. Methodology/Principal Findings: To investigate the role of visual cues in the collisions of free-flying little brown bats (Myotis lucifugus) with stationary objects, we set up obstacles in an area of high bat traffic during swarming. We used combinations of light intensities and visually dissimilar obstacles to verify that bats orient by vision. In early August, bats collided more often in the light than the dark, and probabilities of collision varied with the visibility of obstacles. However, the probabilities of collisions altered in mid to late August, coincident with the start of behavioural, hormonal, and physiological changes occurring during swarming and mating. Distress calls did not distract bats and increase the incidence of collisions. Conclusions/Significance: Our findings indicate that visual cues are more important for free-flying bats than previously recognized, suggesting integration of multi-sensory modalities during orientation. Furthermore, our study highlight

Recommendations for accelerating open preprint peer review to improve the culture of science

Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints