Functional consequences of seven novel mutations in the CYP11B1 Gene: four mutations associated with nonclassic and three mutations causing classic 11 -Hydroxylase Deficiency

Context: Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases of nonclassic 11OHD are rare compared with the incidence of nonclassic 21-hydroxylase deficiency. Objective: The aim of the study was to analyze the functional consequences of seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients with classic 11OHD, two patients with nonclassic 11OHD, and three heterozygous carriers for CYP11B1 mutations. Methods: We conducted functional studies employing a COS7 cell in vitro expression system comparing wild-type (WT) and mutant CYP11B1 activity. Mutants were examined in a computational three-dimensional model of the CYP11B1 protein. Results: All mutations (p.W116G, p.A165D, p.K254_A259del) found in patients with classic 11OHD have absent or very little 11β-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively. Conclusion: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling i

Ellinaite, CaCr2O4, a New Natural Post-Spinel Oxide from Hatrurim Basin, Israel, and Juína Kimberlite Field, Brazil

Ellinaite, a natural analog of the post-spinel phase β-CaCr2O4, was discovered at the Hatrurim Basin, Hatrurim pyrometamorphic formation (the Mottled Zone), Israel, and in an inclusion within the super-deep diamond collected at the placer of the Sorriso River, Juína kimberlite field, Brazil. Ellinaite at the Hatrurim Basin is confined to a reduced rankinite-gehlenite paralava, where it occurs as subhedral grains up to 30μm in association with gehlenite, rankinite and pyrrhotite or forms the rims overgrowing zoned chromite-magnesiochromite. The empirical formula of the Hatrurim sample is (Ca0.960Fe0.0162+Na0.012Mg0.003)0.992(Cr1.731V0.1833+Ti0.0683+Al0.023Ti0.0034+)2.008O4. The mineral crystallizes in the orthorhombic system, space group Pnma, unit-cell parameters refined from X-ray single-crystal data: A 8.868(9), b 2.885(3), c 10.355(11)Å, V 264.9(5)Å3 and ZCombining double low line4. The crystal structure of ellinaite from the Hatrurim Basin has been solved and refined to R1Combining double low line0.0588 based on 388 independent observed reflections. Ellinaite in the Juína diamond occurs within the micron-sized polyphase inclusion in association with ferropericlase, magnesioferrite, orthorhombic MgCr2O4, unidentified iron carbide and graphite. Its empirical formula is Ca1.07(Cr1.71Fe0.063+V0.06Ti0.03Al0.03Mg0.02Mn0.02)ς1.93O4. The unit-cell parameters obtained from HRTEM data are as follows: Space group Pnma, a 9.017, b 2.874Å, c 10.170Å, V 263.55Å3, ZCombining double low line4. Ellinaite belongs to a group of natural tunnel-structured oxides of the general formula AB2O4, the so-called post-spinel minerals: Marokite CaMn2O4, xieite FeCr2O4, harmunite CaFe2O4, wernerkrauseite CaFe23+Mn4+O6, chenmingite FeCr2O4, maohokite MgFe2O4 and tschaunerite Fe(FeTi)O4. The mineral from both occurrences seems to be crystallized under highly reduced conditions at high temperatures (>1000°C), but under different pressure: Near-surface (Hatrurim Basin) and lower mantle (Juína diamond). © 2021 Victor V. Sharygin et al.Raman spectroscopy and EBSD investigations for the Hatrurim ellinaite were done on state assignment of IGM SB RAS (IX.125.2) and the Initiative Project of Ministry of Science and Higher Education of the Russian Federation (Act 211 of the Government of the Russian Federation (grant agreement no. 02.A03.21.0006)). SEM and microprobe studies for the Hatrurim ellinaite were supported by the Russian Science Foundation (grant no. 17-17-01056p). Crystallographic studies of the Hatrurim ellinaite were provided by the Russian Science Foundation (grant no. 18-17-00079)

Pseudogap behavior of nuclear spin relaxation in high Tc superconductors in terms of phase separation

We analyze anew experiments on the NMR in cuprates and find an important information on their phase separation and its stripe character hidden in the dependence of $1/^{63}T_{1}$ on degree of doping. In a broad class of materials $1/^{63}T_{1}$ is the sum of two terms: the temperature independent one attributed to ``incommensurate'' stripes that occur at external doping, and an ``universal'' temperature dependent term ascribed to moving metallic and AF sub-phases. We argue that the frustrated first order phase transition in a broad temperature interval bears a dynamical character.Comment: 5 pages, 3 figures; some comments and references added; accepted for publication in JETP Letter

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

Search for Two-Neutrino Double Electron Capture of 124^{124}Xe with XENON100

Two-neutrino double electron capture is a rare nuclear decay where two electrons are simultaneously captured from the atomic shell. For $^{124}$Xe this process has not yet been observed and its detection would provide a new reference for nuclear matrix element calculations. We have conducted a search for two-neutrino double electron capture from the K-shell of $^{124}$Xe using 7636 kg$\cdot$d of data from the XENON100 dark matter detector. Using a Bayesian analysis we observed no significant excess above background, leading to a lower 90 % credibility limit on the half-life $T_{1/2}>6.5\times10^{20}$ yr. We also evaluated the sensitivity of the XENON1T experiment, which is currently being commissioned, and find a sensitivity of $T_{1/2}>6.1\times10^{22}$ yr after an exposure of 2 t$\cdot$yr.Comment: 6 pages, 4 figure

Search for Event Rate Modulation in XENON100 Electronic Recoil Data

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an un-binned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1 sigma for all periods suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure

Infrared Absorption Investigations Confirm the Extraterrestrial Origin of Carbonado-Diamonds

The first complete infrared FTIR absorption spectra for carbonado-diamond confirm the interstellar origin for the most enigmatic diamonds known as carbonado. All previous attempts failed to measure the absorption of carbonado-diamond in the most important IR-range of 1000-1300 cm-1 (10.00-7.69 micro-m.) because of silica inclusions. In our investigation, KBr pellets were made from crushed silica-free carbonado-diamond and thin sections were also prepared. The 100 to 1000 times brighter synchrotron infrared radiation permits a greater spatial resolution. Inclusions and pore spaces were avoided and/or sources of chemical contamination were removed. The FTIR spectra of carbonado-diamond mostly depict the presence of single nitrogen impurities, and hydrogen. The lack of identifiable nitrogen aggregates in the infrared spectra, the presence of features related to hydrocarbon stretch bonds, and the resemblance of the spectra to CVD and presolar diamonds indicate that carbonado-diamonds formed in a hydrogen-rich interstellar environment. This is consistent with carbonado-diamond being sintered and porous, with extremely reduced metals, metal alloys, carbides and nitrides, light carbon isotopes, surfaces with glassy melt-like patinas, deformation lamellae, and a complete absence of primary, terrestrial mineral inclusions. The 2.6-3.8 billion year old fragmented body was of asteroidal proportions