Structural insight into [Fe–S2–Mo] motif in electrochemical reduction of N2 over Fe1-supported molecular MoS2

The catalytic synthesis of NH3 from the thermodynamically challenging N2 reduction reaction under mild conditions is currently a significant problem for scientists. Accordingly, herein, we report the development of a nitrogenase-inspired inorganic-based chalcogenide system for the efficient electrochemical conversion of N2 to NH3, which is comprised of the basic structure of [Fe–S2–Mo]. This material showed high activity of 8.7 mgNH3 mgFe−1 h−1 (24 μgNH3 cm−2 h−1) with an excellent faradaic efficiency of 27% for the conversion of N2 to NH3 in aqueous medium. It was demonstrated that the Fe1 single atom on [Fe–S2–Mo] under the optimal negative potential favors the reduction of N2 to NH3 over the competitive proton reduction to H2. Operando X-ray absorption and simulations combined with theoretical DFT calculations provided the first and important insights on the particular electron-mediating and catalytic roles of the [Fe–S2–Mo] motifs and Fe1, respectively, on this two-dimensional (2D) molecular layer slab

Characterization of voltage-gated ionic currents in a peripheral sensory neuron in larval Drosophila.

BACKGROUND: The development, morphology and genetics of sensory neurons have been extensively studied in Drosophila. Sensory neurons in the body wall of larval Drosophila in particular have been the subject of numerous anatomical studies, however, little is known about the intrinsic electrical properties of larval sensory cells. FINDINGS: We performed whole cell patch recordings from an identified peripheral sensory cell, the dorsal bipolar sensory neuron (dbd) and measured voltage-gated ionic currents in 1st instar larvae. Voltage clamp analysis revealed that dbds have a TEA sensitive, non-inactivating IK type potassium current as well as a 4-AP sensitive, inactivating IA type potassium current. dbds also show a voltage-gated calcium current (ICa) and a voltage-gated sodium current (INa). CONCLUSIONS: This work provides a first characterization of voltage-activated ionic currents in an identified body-wall sensory neuron in larval Drosophila. Overall, we establish baseline physiology data for future studies aimed at understanding the ionic and genetic basis of sensory neuron function in fruit flies and other model organisms.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia

Human bronchial epithelial (HBE) cells exhibit constitutive anion secretion that is absent in cells from cystic fibrosis (CF) patients. The identity of this conductance is unknown, but SLC26A9, a member of the SLC26 family of CF transmembrane conductance regulator (CFTR)-interacting transporters, is found in the human airway and exhibits chloride channel behavior. We sought differences in the properties of SLC26A9 and CFTR expressed in HEK 293 (HEK) cells as a fingerprint to identify HBE apical anion conductances. HEK cells expressing SLC26A9 displayed a constitutive chloride current that was inhibited by the CFTR blocker GlyH-101 (71 ± 4%, 50 µM) and exhibited a near-linear current–voltage (I-V) relation during block, while GlyH-101–inhibited wild-type (wt)CFTR exhibited a strong inward-rectified (IR) I-V relation. We tested polarized HBE cells endogenously expressing either wt or ΔF508-CFTR for similar activity. After electrical isolation of the apical membrane using basolateral α-toxin permeabilization, wtCFTR monolayers displayed constitutive chloride currents that were inhibited by GlyH-101 (68 ± 6%) while maintaining a near-linear I-V relation. In the absence of blocker, the addition of forskolin stimulated a current increase having a linear I-V; GlyH-101 blocked 69 ± 7% of the current and shifted the I-V relation IR, consistent with CFTR activation. HEK cells coexpressing SLC26A9 and wtCFTR displayed similar properties, as well as forskolin-stimulated currents that exceeded the sum of those in cells separately expressing SLC26A9 or wtCFTR, and an I-V relation during GlyH-101 inhibition that was moderately IR, indicating that SLC26A9 contributed to the stimulated current. HBE cells from CF patients expressed SLC26A9 mRNA, but no constitutive chloride currents. HEK cells coexpressing SLC26A9 with ΔF508-CFTR also failed to exhibit SLC26A9 current. We conclude that SLC26A9 functions as an anion conductance in the apical membranes of HBE cells, it contributes to transepithelial chloride currents under basal and cAMP/protein kinase A–stimulated conditions, and its activity in HBE cells requires functional CFTR

Structural Change and Convergence of Energy Intensity across OECD Countries, 1970-2005

This paper uses new and unique data derived from a consistent framework of national accounts to compute and evaluate energy intensity developments across 18 OECD countries and 50 sectors over the period 1970-2005. We find that across countries energy intensity levels tend to decrease in most Manufacturing sectors. In the Service sector, energy intensity decreases at a relatively slow rate, with diverse trends across sub-sectors. A decomposition analysis reveals that changes in the sectoral composition of the economy explain a considerable and increasing part of aggregate energy intensity dynamics. A convergence analysis reveals that only after 1995 cross-country variation in aggregate energy intensity levels clearly tends to decrease, driven by a strong and robust trend break in Manufacturing and enhanced convergence in Services. Moreover, we find evidence for the hypothesis that across sectors lagging countries are catching-up with leading countries, with rates of convergence that are on average higher in Services than in Manufacturing. Aggregate convergence patterns are almost exclusively caused by convergence of within-sector energy intensity levels, and not by convergence of the sectoral composition of economies. © 2012 Elsevier B.V

The natural history and management of hamstring injuries

Hamstring injuries in sport can be debilitating. The anatomical complexity of this muscle makes uniform assessment of injury epidemiology difficult and insures that post-injury management strategies must be individually focused. This article reviews the anatomy of the hamstring, its role in athletic movement, common mechanisms of injury, and management guidelines with the goal of return into sporting activity in mind

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment