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

An Estimate of Avian Mortality at Communication Towers in the United States and Canada

Avian mortality at communication towers in the continental United States and Canada is an issue of pressing conservation concern. Previous estimates of this mortality have been based on limited data and have not included Canada. We compiled a database of communication towers in the continental United States and Canada and estimated avian mortality by tower with a regression relating avian mortality to tower height. This equation was derived from 38 tower studies for which mortality data were available and corrected for sampling effort, search efficiency, and scavenging where appropriate. Although most studies document mortality at guyed towers with steady-burning lights, we accounted for lower mortality at towers without guy wires or steady-burning lights by adjusting estimates based on published studies. The resulting estimate of mortality at towers is 6.8 million birds per year in the United States and Canada. Bootstrapped subsampling indicated that the regression was robust to the choice of studies included and a comparison of multiple regression models showed that incorporating sampling, scavenging, and search efficiency adjustments improved model fit. Estimating total avian mortality is only a first step in developing an assessment of the biological significance of mortality at communication towers for individual species or groups of species. Nevertheless, our estimate can be used to evaluate this source of mortality, develop subsequent per-species mortality estimates, and motivate policy action

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

Les lysimètres de petite taille : un outil pertinent d'évaluation du transfert des pesticides ?

Small size lysimeters placed under field conditions are compared to field studies for pesticide leaching and fate. Such column apparatus allows easy collection of leachates and use of radiolabeled pesticides. Soil structure can also be preserved as well as when using the usual larger lysimeters. Moreover, the small size permits an increase in the replicate number and to avoid soil sampling variability. Two exemples are provided to evaluate the relevance of those experimental models compared to field monitoring campaigns. / Des lysimètres de petite taille, placés sous conditions naturelles, sont utilisés en parallèle avec des expériences de suivi de transfert d'herbicides au champ. Ce type de dispositif permet une récolte facile des eaux de percolation ainsi que l'utilisation de molécules marquées. Comme pour des lysimètres classiques de grande taille, il est possible de travailler en préservant la structure du sol mais leurs faibles dimensions permettent d'augmenter le nombre de répétitions ainsi que de s'affranchir des problèmes d'échantillonnage. Deux exemples de résultats obtenus sont présentés pour permettre de juger de la validité de ce type de modèle par rapport à des résultats de plein champ

La pollution de l'eau par les produits phytosanitaires : état et origine

Les campagnes d'analyse des eaux de surface ou souterraines utilisées comme ressource en eau potable montrent fréquemment une pollution par les produits phytosanitaires au-delà de la norme UE. Cette situation est en partie due à une agriculture intensive, au non respect des bonnes pratiques agricoles, aux usages non agricoles des pesticides mais également à l'existence de sites particulièrement vulnérables (réseau hydrologique dense et diffus, relief accidenté, sols filtrants ou fissurés, nappes peu profondes). Son évaluation peut être réalisée à différentes échelles. Cependant, seule l'étude régionale apparaît comme satisfaisante. En effet, elle permet de mieux cibler les produits à rechercher, les dates d'échantillonnage et le type d'eau à surveiller en fonction des ressources en eau potable. Les pesticides mis en cause dans la pollution de l'eau en France sont actuellement peu nombreux : atrazine, simazine, lindane, carbofuran, phénylurées. Mais cette liste peut se diversifier en prenant en compte la spécificité de l'agriculture locale par réduction de l'échelle d'investigation ou par la prise en compte des produits de dégradation des pesticides utilisés (dééthylatrazine). Pour les eaux de surface, la pollution peut être très élevée mais de courte durée. Elle est étroitement liée aux possibilités de transport des pesticides par ruissellement et à l'effet de dilution par les eaux provenant de secteurs non traités. En revanche, pour les eaux souterraines, la pollution est plus discrète mais elle peut être permanente. Elle est régulée par le processus de lessivage, lui-même lié à la disponibilité du produit et à la dynamique de l'eau. Dans le cas où le pesticide est à la fois persistant et quelque peu mobile, il peut y avoir un stockage du produit dans le sol, qui entretient la pollution des eaux souterraines.The pollution of water by pesticides: state and origin. In Europe, monitoring campaigns of surface and groundwaters used for drinking water frequently show pollution by pesticides, above the EU specification. This situation is due to intensive agriculture, non-respect of good agricultural practices, non-agricultural uses and the existence of especially vulnerable sites (eg, thick and diffuse hydrological system, broken relief, filtering or cracked soils, water table lying near the surface). The assessment of the pollution can be conducted at different levels. However, local study appears to be the only satisfactory method. Indeed, it allowed us to focus on some pesticides, sampling dates and water supplies, in relation to the local characteristics. In France, few pesticides are involved in water pollution: atrazine, simazine, lindane, carbofuran and phenylureas. However, this list would be different if practices carried out locally or degradation products (deethylatrazine) were taken into account. The pollution of surface water can reach a high level but for a small time. It is closely related to the ability of pesticides to be transported by runoff, and the dilution with water from untreated areas. In contrast, groundwater is weakly but, in some instances, continuously polluted. This depends on the leaching processes, and, hence, on the availability of pesticides and the water dynamics. In the case of pesticides with high persistance and relatively good mobility, the storage of pesticides in soil sustains the groundwater pollution

Direct link between fluoranthene biodegradation and the mobility and sequestration of its residues during aging

International audienceThe aim of this study was to assess the influence of the polycyclic aromatic hydrocarbons (PAH)-degrading activity in the fate of fluoranthene in soils. Three soil samples with different degrading activities (an industrial sod, the same industrial soil after biostimulation, and an agricultural sod) were spiked with C-14-fluoranthene and incubated for 6 mo, with monitoring of biodegradation and mineralization. To follow the distribution C-14-fluoranthene residues (i.e., C-14-fluoranthene and its degradation products) among the soil compartments, we performed successively leaching, centrifiigation (to collect intraaggregate pore water), solvent extraction, and combustion of the soil columns. In the industrial soil, no mineralization of C-14-fluoranthyene was observed, and only 3% of the initial C-14-activity was non-extractable (with acetone:dichloromethane) after 165 d of incubation. The biostimulation (addition of unlabeled polycyclic aromatic hydrocarbons) increased the degrading activity in this soil (59% of 14 C-fluoranthene was mineralized) and increased the residues sequestration (13% of 14 C-activity was non-extractable). The microflora of the agricultural soil mineralized C-14-fluoranthene more slowly and to a lesser extent (25%) than the biostimulated soil, but a higher amount of C-14-activity was sequestered (41 %). Thus, the rate and extent of 14C-fluoranthene mineralization seemed to be related to the C-14-activity sequestration by controlling the accumulation of degradation products in the soil. C-14-Fluoranthene biodegradation enhanced the concentration of C-14-polar compounds in the intra-aggregate pore water. Our results point out the close link between fluoranthene biodegradation and two key aging processes, diffusion and sequestration, in soils. biodegradation controls the mobility and sequestration of residues by transforming fluoranthene into more polar molecules that can diffuse into the intra-aggregate pore water and then might become bound to the matrix or entrapped in the microporosity