Survival of Organic Materials in Hypervelocity Impacts of Ice on Sand, Ice, and Water in the Laboratory

The survival of organic molecules in shock impact events has been investigated in the laboratory. A frozen mixture of anthracene and stearic acid, solvated in dimethylsulfoxide (DMSO), was fired in a two-stage light gas gun at speeds of ?2 and ?4?km s?1 at targets that included water ice, water, and sand. This involved shock pressures in the range of 2–12 GPa. It was found that the projectile materials were present in elevated quantities in the targets after impact and in some cases in the crater ejecta as well. For DMSO impacting water at 1.9?km s?1 and 45° incidence, we quantify the surviving fraction after impact as 0.44±0.05. This demonstrates successful transfer of organic compounds from projectile to target in high-speed impacts. The range of impact speeds used covers that involved in impacts of terrestrial meteorites on the Moon, as well as impacts in the outer Solar System on icy bodies such as Pluto. The results provide laboratory evidence that suggests that exogenous delivery of complex organic molecules from icy impactors is a viable source of such material on target bodies

The Evolving Role of the Oncologic Neurosurgeon: Looking Beyond Extent of Resection in the Modern Era

Neurosurgeons have played an essential role in glioma management and research for over a century. While the past twenty years have played witness to many exciting developments in glioma biology, diagnosis, and classification, relatively few novel, effective treatment strategies have been introduced. The role of neurosurgery in glioma management has been clarified, with a large body of evidence in support of maximal safe resection. However, neurosurgeons have also played a critical role in translational research during this period. The development of new MRI technologies has benefited greatly from validation with stereotactically-targeted human tissue. Careful banking of surgically acquired tissue was key to the development of a new classification scheme for glioma. Similarly, we have garnered a considerably deeper understanding of molecular and genetic properties of glioma through analysis of large surgical specimens. As our classification schemes become more sophisticated, incorporating targeted tissue sampling into the development of novel treatment strategies becomes essential. Such ex vivo analysis could be instrumental in determining mechanisms of treatment failure or success. Modern tumor neurosurgeons should consider themselves surgical neuro-oncologists, with engagement in translational research essential to furthering the field and improving outlooks for our patients

Low-Temperature Fluorocarbonate Mineralization in Lower Devonian Rhynie Chert, UK

Funding: J.G.T.A was partially funded by the Natural Environment Research Council, grant number NE/T003677/1. Acknowledgments: We are grateful to W. Ritchie, J. Johnston, and J. Bowie for skilled technicalsupport. Samples were archived by N.H. Trewin, C.M. Rice and S. Fayers.Peer reviewedPublisher PD

Registration of ‘NE05548’ (Husker Genetics Brand Panhandle) Hard Red Winter Wheat

Western Nebraska wheat producers and those in adjacent areas want taller wheat (Triticum aestivum L.) cultivars that retain their height under drought for better harvestability. ‘NE05548’ (Reg. No. CV-1117, PI 670462) hard red winter wheat was developed cooperatively by the Nebraska Agricultural Experiment Station and the USDA-ARS and released in January 2014 by the developing institutions. NE05548 was released primarily for its superior performance under rainfed conditions in western Nebraska and adjacent areas of the Great Plains and its tall plant stature. NE05548 was selected from the cross NE97426/NE98574 made in 1999 where the pedigree of NE97426 is ‘Brigantina’/2*‘Arapahoe’ and the pedigree of NE98574 is CO850267/‘Rawhide’. The F1 generation was grown in the greenhouse in 2000, and the F2 to F3 generations were advanced using the bulk breeding method in the field at Mead, NE, in 2001 to 2002. In 2003, single F3–derived F4 head rows were grown for selection. There was no further selection thereafter. The F3:5 was evaluated as a single four-row plot at Lincoln, NE, and a single row at Mead, NE, in 2004. In 2005, it was assigned the experimental line number NE05548. NE05548 was evaluated in replicated trials thereafter. It has excellent winter survival, acceptable disease reactions to many of the common diseases in its target area, and acceptable end-use quality for bread making

Registration of ‘NE05548’ (Husker Genetics Brand Panhandle) Hard Red Winter Wheat

Western Nebraska wheat producers and those in adjacent areas want taller wheat (Triticum aestivum L.) cultivars that retain their height under drought for better harvestability. ‘NE05548’ (Reg. No. CV-1117, PI 670462) hard red winter wheat was developed cooperatively by the Nebraska Agricultural Experiment Station and the USDA-ARS and released in January 2014 by the developing institutions. NE05548 was released primarily for its superior performance under rainfed conditions in western Nebraska and adjacent areas of the Great Plains and its tall plant stature. NE05548 was selected from the cross NE97426/NE98574 made in 1999 where the pedigree of NE97426 is ‘Brigantina’/2*‘Arapahoe’ and the pedigree of NE98574 is CO850267/‘Rawhide’. The F1 generation was grown in the greenhouse in 2000, and the F2 to F3 generations were advanced using the bulk breeding method in the field at Mead, NE, in 2001 to 2002. In 2003, single F3–derived F4 head rows were grown for selection. There was no further selection thereafter. The F3:5 was evaluated as a single four-row plot at Lincoln, NE, and a single row at Mead, NE, in 2004. In 2005, it was assigned the experimental line number NE05548. NE05548 was evaluated in replicated trials thereafter. It has excellent winter survival, acceptable disease reactions to many of the common diseases in its target area, and acceptable end-use quality for bread making

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

The EGFR/ErbB inhibitor neratinib modifies the neutrophil phosphoproteome and promotes apoptosis and clearance by airway macrophages

Dysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Therapeutic induction of neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Previous research in our group identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation both in vitro and in vivo. Here, we extend that work using a clinical ErbB inhibitor, neratinib, which has the potential to be repurposed in inflammatory diseases. We show that neratinib reduces neutrophilic migration o an inflammatory site in zebrafish larvae. Neratinib upregulates efferocytosis and reduces the number of persisting neutrophil corpses in mouse models of acute, but not chronic, lung injury, suggesting that the drug may have therapeutic benefits in acute inflammatory settings. Phosphoproteomic analysis of human neutrophils shows that neratinib modifies the phosphorylation of proteins regulating apoptosis, migration, and efferocytosis. This work identifies a potential mechanism for neratinib in treating acute lung inflammation by upregulating the clearance of dead neutrophils and, through examination of the neutrophil phosphoproteome, provides important insights into the mechanisms by which this may be occurring

Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes

BACKGROUND: GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans. METHODS: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM. RESULTS: Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls. CONCLUSION: From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies