Core Levels, Band Alignments, and Valence-Band States in CuSbS2 for Solar Cell Applications

The earth-abundant material CuSbS2 (CAS) has shown good optical properties as a photovoltaic solar absorber material, but has seen relatively poor solar cell performance. To investigate the reason for this anomaly, the core levels of the constituent elements, surface contaminants, ionization potential, and valence-band spectra are studied by X-ray photoemission spectroscopy. The ionization potential and electron affinity for this material (4.98 and 3.43 eV) are lower than those for other common absorbers, including CuInxGa(1–x)Se2 (CIGS). Experimentally corroborated density functional theory (DFT) calculations show that the valence band maximum is raised by the lone pair electrons from the antimony cations contributing additional states when compared with indium or gallium cations in CIGS. The resulting conduction band misalignment with CdS is a reason for the poor performance of cells incorporating a CAS/CdS heterojunction, supporting the idea that using a cell design analogous to CIGS is unhelpful. These findings underline the critical importance of considering the electronic structure when selecting cell architectures that optimize open-circuit voltages and cell efficiencies

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Epistasis between FLG and IL4R genes on the risk of allergic sensitization: results from two population-based birth cohort studies

Immune-specifc genes as well as genes responsible for the formation and integrity of the epidermal barrier have been implicated in the pathogeneses of allergic sensitization. This study sought to determine whether an epistatic efect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) and flaggrin (FLG) genes predispose to the development of allergic sensitization. Data from two birth cohort studies were analyzed, namely the Isle of Wight (IOW; n=1,456) and the Manchester Asthma and Allergy Study (MAAS; n=1,058). In the IOW study, one interaction term (IL4R rs3024676×FLG variants) showed statistical signifcance (interaction term: P=0.003). To illustrate the observed epistasis, stratifed analyses were performed, which showed that FLG variants were associated with allergic sensitization only among IL4R rs3024676 homozygotes (OR, 1.97; 95% CI, 1.27–3.05; P=0.003). In contrast, FLG variants efect was masked among IL4R rs3024676 heterozygotes (OR, 0.53; 95% CI, 0.22–1.32; P=0.175). Similar results were demonstrated in the MAAS study. Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the pathogenesis of allergic sensitization. Hence, genetic susceptibility towards defective epidermal barrier and deviated immune responses could work together in the development of allergic sensitization

Uptake in cancer screening programmes:a priority in cancer control

Achieving adequate levels of uptake in cancer screening requires a variety of approaches that need to be shaped by the characteristics of both the screening programme and the target population. Strategies to improve uptake typically produce only incremental increases. Accordingly, approaches that combine behavioural, organisational and other strategies are most likely to succeed. In conjunction with a focus on uptake, providers of screening services need to promote informed decision making among invitees. Addressing inequalities in uptake must remain a priority for screening programmes. Evidence informing strategies targeting low-uptake groups is scarce, and more research is needed in this area. Cancer screening has the potential to make a major contribution to early diagnosis initiatives in the United Kingdom, and will best be achieved through uptake strategies that emphasise wide coverage, informed choice and equitable distribution of cancer screening services

progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve

Multiorgan Metastasis of Human HER-2+ Breast Cancer in Rag2−/−;Il2rg−/− Mice and Treatment with PI3K Inhibitor

In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors fail to consistently metastasize in immunodeficient mice like nude mice. We describe a model system based on a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity. In this model human metastatic HER-2+ breast cancer cells displayed their full multiorgan metastatic potential, without the need for selections or additional manipulations of the system. Human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 injected into Rag2−/−;Il2rg−/− mice faithfully reproduced human cancer dissemination, with multiple metastatic sites that included lungs, bones, brain, liver, ovaries, and others. Multiorgan metastatic spread was obtained both from local tumors, growing orthotopically or subcutaneously, and from cells injected intravenously. The problem of brain recurrencies is acutely felt in HER-2+ breast cancer, because monoclonal antibodies against HER-2 penetrate poorly the blood-brain barrier. We studied whether a novel oral small molecule inhibitor of downstream PI3K, selected for its penetration of the blood-brain barrier, could affect multiorgan metastatic spread in Rag2−/−; Il2rg−/− mice. NVP-BKM120 effectively controlled metastatic growth in multiple organs, and resulted in a significant proportion of mice free from brain and bone metastases. Human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduced the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents

High-Resolution X-Ray Structure of the Trimeric Scar/WAVE-Complex Precursor Brk1

The Scar/WAVE-complex links upstream Rho-GTPase signaling to the activation of the conserved Arp2/3-complex. Scar/WAVE-induced and Arp2/3-complex-mediated actin nucleation is crucial for actin assembly in protruding lamellipodia to drive cell migration. The heteropentameric Scar/WAVE-complex is composed of Scar/WAVE, Abi, Nap, Pir and a small polypeptide Brk1/HSPC300, and recent work suggested that free Brk1 serves as a homooligomeric precursor in the assembly of this complex. Here we characterized the Brk1 trimer from Dictyostelium by analytical ultracentrifugation and gelfiltration. We show for the first time its dissociation at concentrations in the nanomolar range as well as an exchange of subunits within different DdBrk1 containing complexes. Moreover, we determined the three-dimensional structure of DdBrk1 at 1.5 Å resolution by X-ray crystallography. Three chains of DdBrk1 are associated with each other forming a parallel triple coiled-coil bundle. Notably, this structure is highly similar to the heterotrimeric α-helical bundle of HSPC300/WAVE1/Abi2 within the human Scar/WAVE-complex. This finding, together with the fact that Brk1 is collectively sandwiched by the remaining subunits and also constitutes the main subunit connecting the triple-coil domain of the HSPC300/WAVE1/Abi2/ heterotrimer to Sra1(Pir1), implies a critical function of this subunit in the assembly process of the entire Scar/WAVE-complex

Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility

Background Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine. Methods We have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding variant of the GABRQ gene. Results Our study did not show any association between the examined SNPs in our test population (P > 0.05). Conclusion Although these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility

Host Iron Binding Proteins Acting as Niche Indicators for Neisseria meningitidis

Neisseria meningitidis requires iron, and in the absence of iron alters its gene expression to increase iron acquisition and to make the best use of the iron it has. During different stages of colonization and infection available iron sources differ, particularly the host iron-binding proteins haemoglobin, transferrin, and lactoferrin. This study compared the transcriptional responses of N. meningitidis, when grown in the presence of these iron donors and ferric iron, using microarrays