Neutrophil gelatinase-associated lipocalin (NGAL) is related with the proteinuria degree and the microscopic kidney findings in leishmania-infected dogs

Early diagnosis of renal damage in Leishmania infected dogs may allow appropriate treatments and prevent some deaths. This study investigates neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney disease in dogs experimentally infected with Leishmania infantum. Serum, urine, and kidney samples were collected from 30 infected beagle dogs and six uninfected control dogs. Based on proteinuria and azotemia values, dogs were initially classified. NGAL was measured in urine and serum samples. Then, the urinary NGAL to creatinine ratio (uNGAL/C) was calculated. Kidney samples were taken for histopathological studies, and the dogs were classified according to the severity of glomerular and tubulointerstitial lesions. In Leishmania-infected dogs, the uNGAL/C was significantly higher in proteinuric non-azotemic dogs compared with non-proteinuric non-azotemic dogs (p = 0.038). Serum NGAL (sNGAL) concentration did not differ between groups. Microscopic studies revealed several degrees of glomerulonephritis and slight focal lymphoplasmacytic interstitial nephritis in 89% and 55% of infected dogs, respectively. Urinary protein to creatinine ratio (UPC) and uNGAL/C were significantly higher in dogs with affected glomeruli compared to infected dogs without renal lesions (p = 0.045 and p = 0.043, respectively). The results show that uNGAL/C correlates with proteinuria and the presence of moderate glomerular lesions in non-azotemic dogs experimentally infected with L. infantum

Few-layer antimonene electrical properties

Antimonene -a single layer of antimony atoms- and its few layer forms are among the latest additions to the 2D mono-elemental materials family. Numerous predictions and experimental evidence of its remarkable properties including (opto)electronic, energetic or biomedical, among others, together with its robustness under ambient conditions, have attracted the attention of the scientific community. However, experimental evidence of its electrical properties is still lacking. Here, we characterized the electronic properties of mechanically exfoliated flakes of few-layer (FL) antimonene of different thicknesses (∼ 2–40 nm) through photoemission electron microscopy, kelvin probe force microscopy and transport measurements, which allows us to estimate a sheet resistance of ∼ 1200 Ω sq−1 and a mobility of ∼ 150 cm2V−1s−1 in ambient conditions, independent of the flake thickness. Alternatively, our theoretical calculations indicate that topologically protected surface states (TPSS) should play a key role in the electronic properties of FL antimonene, which supports our experimental findings. We anticipate our work will trigger further experimental studies on TPSS in FL antimonene thanks to its simple structure and significant stability in ambient environmentsWe acknowledge financial support through the “Maríade Maeztu” Programme for Units of Excellence in R&D (CEX2018-000805-M), the Spanish MINECO through projects PCI2018-093081, FIS2016-80434-P, PID2019-109539GB-C43, PID2019- 106268GB-C31 and -C32, MAT2016-77608-C3-1-P and -3-P, MAT2013-46753-C2-2-P and MAT2017-85089-C2-1R, the EU Graphene Flagship funding (Graphene Flagship Core3 881603 and JTC2017/2D-Sb&Ge), the EU via the ERC-Synergy Program (GrantERC-2013-SYG-610256 NANOCOSMOS), the Comunidad Autónoma de Madrid through MAD2D-CM, S2018/NMT-4321 (NanomagCOST-CM) and the European StructuralFunds via FotoArt CM project (S2018/NMT-4367), and the Fundación Ramón Areces. S.P. acknowledges financial support by the VILLUM FONDEN via the Centre of Excellence for Dirac Materials (Grant No. 11744

Exfoliation of Alpha-Germanium: A Covalent Diamond-Like Structure

2D materials have opened a new field in materials science with outstanding scientific and technological impact. A largely explored route for the preparation of 2D materials is the exfoliation of layered crystals with weak forces between their layers. However, its application to covalent crystals remains elusive. Herein, a further step is taken by introducing the exfoliation of germanium, a narrow-bandgap semiconductor presenting a 3D diamond-like structure with strong covalent bonds. Pure α-germanium is exfoliated following a simple one-step procedure assisted by wet ball-milling, allowing gram-scale fabrication of high-quality layers with large lateral dimensions and nanometer thicknesses. The generated flakes are thoroughly characterized by different techniques, giving evidence that the new 2D material exhibits bandgaps that depend on both the crystallographic direction and the number of layers. Besides potential technological applications, this work is also of interest for the search of 2D materials with new properties

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe