CYBRD1 as a modifier gene that modulates iron phenotype in HFE p.C282Y homozygous patients

Background. Most patients with Hereditary Hemochromatosis are homozygous for the p.C282Y mutation in the HFE gene in Caucasian population. Penetrance and expression of Hemochromatosis largely differ in p.C282Y homozygous cases. Besides environmental factors, genetic factors might be implicated. Design and Methods. In the present study, we analysed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 Italian p.C282Y homozygous cases. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. Results. We found a series of 17 genetic variants located in different genes with possible additive effect on the studied outcomes. In order to evaluate if the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction can be achieved adding genetic information to clinical data. Among the selected polymorphisms, a significant association between rs3806562, located in the 5\u2019UTR of CYBRD1, and transferrin saturation was observed. This variant belongs to the same haplotype block which contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. Luciferase assay indicates that rs3806562 has not a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. Conclusions. While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-HH, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of HH phenotype

Understanding The Correlation Of Libs And Acoustic Measurements Of Rocks And Soils Found In The Traverse Of The Perseverance Rover Across The Jezero Crater, Mars

The SuperCam instrument of the NASA MARS 2020 Perseverance rover combines a suite of atomic and molecular spectroscopies intended for an extensive description of rocks, soils and minerals in the surroundings of the landing site of the mission – the Jezero crater. The microphone installed on the SuperCam instrument allows the acquisition of acoustic signals resulting from the expansion of laser-induced plasmas towards the atmosphere. Apart from being affected by the propagation characteristics of the Mars atmosphere, the acoustic signal has an additional component related to the properties of the target including surface morphology, hardness, deformation parameters, and elasticity, among others. This information is currently being investigated as a complementary resource for characterization of the ablated material and may well supplement the LIBS data gathered from coincident laser shots. This talk will present SuperCam acoustic data of rocks and minerals found in the traverse of the Perseverance rover and will discuss its correlation with LIBS spectra.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

The sound of geological targets on Mars from the absolute intensity of laser-induced sparks shock waves

Inspection of geological material is one of the main goals of the Perseverance rover during its journey across the landscape of the Jezero crater in Mars. NASA's rover integrates SuperCam, an instrument capable of performing standoff characterization of samples using a variety of techniques. Among those tools, SuperCam can perform laser-induced breakdown spectroscopy (LIBS) studies to elucidate the chemical composition of the targets of interest. Data from optical spectroscopy can be supplemented by simultaneously-produced laser-produced plasma acoustics in order to expand the information acquired from the probed rocks thanks to the SuperCam's microphone (MIC) as it can be synchronized with the LIBS laser. Herein, we report cover results from LIBS and MIC during Perseverance's first 380 sols on the Martian surface. We study the correlation between both recorded signals, considering the main intrasample and environmental sources of variation for each technique, to understand their behavior and how they can be interpreted together towards complimenting LIBS with acoustics. We find that louder and more stable acoustic signals are recorded from rock with compact surfaces, i.e., low presence loose particulate material, and harder mineral phases in their composition. Reported results constitute the first description of the evolution of the intensity in the time domain of shockwaves from laser-produced plasmas on geological targets recorded in Mars. These signals are expected contain physicochemical signatures pertaining to the inspected sampling positions. As the dependence of the acoustic signal recorded on the sample composition, provided by LIBS, is unveiled, the sound from sparks become a powerful tool for the identification of mineral phases with similar optical emission spectra.Many people helped with this project in addition to the co-authors, including hardware and operation teams, and we are most grateful for their support. This project was supported in the USA by NASA’s Mars Exploration Program and in France is conducted under the authority of CNES. Research funded by projects UMA18-FEDERJA-272 from Junta de Andalucía and PID2020-119185GB-I00 from Ministerio de Ciencia e Innovacion, of Spain. P.P. is grateful to the European Union’s Next Generation EU (NGEU) plan and the Spanish Ministerio de Universidades for his Margarita Salas fellowship under the program ′′Ayudas para la Recualificacion del Sistema Universitario Español′′. RCW was funded by JPL contract 1681089. A.U was funded by NASA Mars 2020 Participating Scientist program 80NSSC21K0330. Funding for open access charge: Universidad de Málaga / CBU

Sudden death associated with group A streptococcal infection in an 8-year-old girl with undiagnosed hypertrophic cardiomyopathy.

An 8-year-old girl died suddenly without prior symptoms. Post-mortem examination identified both systemic group A streptococcal infection and hypertrophic cardiomyopathy. She had no history of cardiac symptoms and was not in a high-risk group for sudden death due to hypertrophic cardiomyopathy. We believe the disseminated but asymptomatic group A streptococcal infection precipitated her early death from hypertrophic cardiomyopathy. Sudden unexpected death during systemic infection should be followed by post-mortem examination to look for evidence of hypertrophic cardiomyopathy, as this diagnosis has genetic implications for other family members