Three masses of the Chelyabinsk meteorite have been studied with a wide range of analytical techniques to understand the mineralogical variation and thermal history of the Chelyabinsk parent body. ...The samples exhibit little to no postentry oxidation via Mössbauer and Raman spectroscopy indicating their fresh character, but despite the rapid collection and care of handling some low levels of terrestrial contamination did nonetheless result. Detailed studies show three distinct lithologies, indicative of a genomict breccia. A light‐colored lithology is LL5 material that has experienced thermal metamorphism and subsequent shock at levels near S4. The second lithology is a shock‐darkened LL5 material in which the darkening is caused by melt and metal‐troilite veins along grain boundaries. The third lithology is an impact melt breccia that formed at high temperatures (~1600 °C), and it experienced rapid cooling and degassing of S2 gas. Portions of light and dark lithologies from Chel‐101, and the impact melt breccias (Chel‐102 and Chel‐103) were prepared and analyzed for Rb‐Sr, Sm‐Nd, and Ar‐Ar dating. When combined with results from other studies and chronometers, at least eight impact events (e.g., ~4.53 Ga, ~4.45 Ga, ~3.73 Ga, ~2.81 Ga, ~1.46 Ga, ~852 Ma, ~312 Ma, and ~27 Ma) are clearly identified for Chelyabinsk, indicating a complex history of impacts and heating events. Finally, noble gases yield young cosmic ray exposure ages, near 1 Ma. These young ages, together with the absence of measurable cosmogenic derived Sm and Cr, indicate that Chelyabinsk may have been derived from a recent breakup event on an NEO of LL chondrite composition.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Serial studies have demonstrated that induction therapy with FLAM flavopiridol (alvocidib) 50 mg/m(2) days 1-3, cytarabine 667 mg/m(2)/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 ...mg/m(2) day 9 yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011-July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m(2)/day continuous infusion days 1-7 and daunorubicin 90 mg/m(2) days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m(2)/day continuous infusion days 1-5 and daunorubicin 45 mg/m(2) days 1-2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development. This study is registered with clinicaltrials.gov identifier: 01349972.
The linkage between phylogenetic and functional processes may provide profound insights into the effects of hydrocarbon contamination and biodegradation processes in high-diversity environments. ...Here, the impacts of petroleum contamination and the bioremediation potential of compost amendment, as enhancer of the microbial activity in semiarid soils, were evaluated in a model experiment. The analysis of phospholipid fatty-acids (PLFAs) and metaproteomics allowed the study of biomass, phylogenetic and physiological responses of the microbial community in polluted semiarid soils. Petroleum pollution induced an increase of proteobacterial proteins during the contamination, while the relative abundance of Rhizobiales lowered in comparison to the non-contaminated soil. Despite only 0.55% of the metaproteome of the compost-treated soil was involved in biodegradation processes, the addition of compost promoted the removal of polycyclic aromatic hydrocarbons (PAHs) and alkanes up to 88% after 50days. However, natural biodegradation of hydrocarbons was not significant in soils without compost. Compost-assisted bioremediation was mainly driven by Sphingomonadales and uncultured bacteria that showed an increased abundance of catabolic enzymes such as catechol 2,3-dioxygenases, cis-dihydrodiol dehydrogenase and 2-hydroxymuconic semialdehyde. For the first time, metaproteomics revealed the functional and phylogenetic relationships of petroleum contamination in soil and the microbial key players involved in the compost-assisted bioremediation.
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•The impact of hydrocarbon pollution in the soil microbial community was evaluated.•Functional and phylogenetic insights were retrieved by metaproteomics.•Fatty acid analysis and proteomics tracked the variations in microbial biomass.•Compost amendment stimulated the biodegradation of hydrocarbons in semiarid soils.•Sphingomonadales bacteria were involved in the biodegradation of hydrocarbons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable ...genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Desulfatibacillum alkenivorans AK‐01 serves as a model organism for anaerobic alkane biodegradation because of its distinctive biochemistry and metabolic versatility. The D. alkenivorans ...genome provides a blueprint for understanding the genetic systems involved in alkane metabolism including substrate activation, CoA ligation, carbon‐skeleton rearrangement and decarboxylation. Genomic analysis suggested a route to regenerate the fumarate needed for alkane activation via methylmalonyl‐CoA and predicted the capability for syntrophic alkane metabolism, which was experimentally verified. Pathways involved in the oxidation of alkanes, alcohols, organic acids and n‐saturated fatty acids coupled to sulfate reduction and the ability to grow chemolithoautotrophically were predicted. A complement of genes for motility and oxygen detoxification suggests that D. alkenivorans may be physiologically adapted to a wide range of environmental conditions. The D. alkenivorans genome serves as a platform for further study of anaerobic, hydrocarbon‐oxidizing microorganisms and their roles in bioremediation, energy recovery and global carbon cycling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity ...(waist-to-hip ratio adjusted for body mass index WHRadjBMI) and general adiposity (body mass index BMI) with cardiometabolic disease.
METHODS:Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis CARDIoGRAM plus The Coronary Artery Disease C4D Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.
RESULTS:Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio OR for CHD, 1.48; 95% confidence interval CI, 1.28–1.71), similar to findings for BMI (1 SD≈4.6 kg/m; OR for CHD, 1.36; 95% CI, 1.22–1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03–1.70). For type 2 diabetes mellitus, both measures had large effectsOR, 1.82 (95% CI, 1.38–2.42) and OR, 1.98 (95% CI, 1.41–2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%–77% per 1 SD).
CONCLUSIONS:Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
Ground-penetrating radar (GPR) is an established geophysical technique used extensively for the accurate reconstruction of the shallow (<10 m) subsurface. Reconstructions have largely been completed ...and presented as 2D vertical and horizontal planes, leaving limited visualization of subsurface 3D shapes and their spatial relationships. With technological advancements, particularly the availability and integration of various software platforms, 3D modelling of GPR data is now emerging as the new standard. However, despite these developments, there remains an inadequate examination and testing of these techniques, particularly in determining if their application is beneficial and warranted. In this study we conducted a GPR grid survey on a churchyard cemetery to generate and evaluate 2D and 3D-modelled reconstructions of the cemetery burial sites. Data collection and processing was completed using a Sensors and Software Incorporated pulseEKKO™ Pro SmartCart GPR system and EKKO_Project™ software, respectively. The modelling component was achieved using Schlumberger’s Petrel™ E & P software platform, which is tailored to the petroleum industry. The subsurface patterns present in the 2D and 3D models closely matched the cemetery plot plan, validating our data collection, processing, and modelling methods. Both models were adequate for 2D horizontal visualization of reflection patterns at any specific depth. The 3D model was used to identify the presence of a companion burial plot (stacked caskets) and possible leachate plumes below and encircling burial sites, both of which were not evident in the 2D model, highlighting the benefits of 3D modelling when discerning subsurface objects. We expect our findings to be of value to similar GPR studies, with particular significance to geoforensic studies and criminal investigations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study ...aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients.
The study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals.
One known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria.
These findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome.
Continental shelf sediments are globally important for biogeochemical activity. Quantification of shelf-scale stocks and fluxes of carbon and nutrients requires the extrapolation of observations made ...at limited points in space and time. The procedure for selecting exemplar sites to form the basis of this upscaling is discussed in relation to a UK-funded research programme investigating biogeochemistry in shelf seas. A three-step selection process is proposed in which (1) a target area representative of UK shelf sediment heterogeneity is selected, (2) the target area is assessed for spatial heterogeneity in sediment and habitat type, bed and water column structure and hydrodynamic forcing, and (3) study sites are selected within this target area encompassing the range of spatial heterogeneity required to address key scientific questions regarding shelf scale biogeochemistry, and minimise confounding variables. This led to the selection of four sites within the Celtic Sea that are significantly different in terms of their sediment, bed structure, and macrofaunal, meiofaunal and microbial community structures and diversity, but have minimal variations in water depth, tidal and wave magnitudes and directions, temperature and salinity. They form the basis of a research cruise programme of observation, sampling and experimentation encompassing the spring bloom cycle. Typical variation in key biogeochemical, sediment, biological and hydrodynamic parameters over a pre to post bloom period are presented, with a discussion of anthropogenic influences in the region. This methodology ensures the best likelihood of site-specific work being useful for up-scaling activities, increasing our understanding of benthic biogeochemistry at the UK-shelf scale.
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BFBNIB, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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