Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE) and the U.S. National Institutes of Health (HD045784). None of the authors had any financial or personal conflicts of interest.Peer reviewedPostprin

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

MOLES3: implementing an ISO standards driven data catalogue

ISO19156 Observations and Measurements (O&M) provides a standardised framework for organising information about the collection of information about the environment. Here we describe the implementation of a specialisation of O&M for environmental data, the Metadata Objects for Linking Environmental Sciences (MOLES3). MOLES3 provides support for organising information about data, and for user navigation around data holdings. The implementation described here, “CEDA-MOLES”, also supports data management functions for the Centre for Environmental Data Archival, CEDA. The previous iteration of MOLES (MOLES2) saw active use over five years, being replaced by CEDA-MOLES in late 2014. During that period important lessons were learnt both about the information needed, as well as how to design and maintain the necessary information systems. In this paper we review the problems encountered in MOLES2; how and why CEDA-MOLES was developed and engineered; the migration of information holdings from MOLES2 to CEDA-MOLES; and, finally, provide an early assessment of MOLES3 (as implemented in CEDA-MOLES) and its limitations. Key drivers for the MOLES3 development included the necessity for improved data provenance, for further structured information to support ISO19115 discovery metadata export (for EU INSPIRE compliance), and to provide appropriate fixed landing pages for Digital Object Identifiers (DOIs) in the presence of evolving datasets. Key lessons learned included the importance of minimising information structure in free text fields, and the necessity to support as much agility in the information infrastructure as possible without compromising on maintainability both by those using the systems internally and externally (e.g. citing in to the information infrastructure), and those responsible for the systems themselves. The migration itself needed to ensure continuity of service and traceability of archived assets

A Near-Infrared Template Derived from I Zw 1 for the FeII Emission in Active Galaxies

In AGN spectra, a series of FeII multiplets form a pseudo-continuum that extends from the ultraviolet to the near-infrared (NIR). This emission is believed to originate in the Broad Line Region (BLR), and it has been known for a long time that pure photoionization fails to reproduce it in the most extreme cases, as does the collisional-excitation alone. The most recent models by Sigut & Pradhan (2003) include details of the FeII ion microphysics and cover a wide range in ionization parameter log U_ion= (-3.0 -> -1.3) and density log n_H = (9.6 -> 12.6). With the aid of such models and a spectral synthesis approach, we study for the first time in detail the NIR emission of I Zw 1. The main goals are to confirm the role played by Ly\alpha-fluorescence mechanisms in the production of the FeII spectrum and to construct the first semi-empirical NIR FeII template that best represents this emission and can be used to subtract it in other sources. A good overall match between the observed FeII+MgII features with those predicted by the best fitted model is obtained, corroborating the Ly\alpha-fluorescence as a key process to understand the FeII spectrum. The best model is then adjusted by applying a deconvolution method on the observed FeII+MgII spectrum. The derived semi-empirical template is then fitted to the spectrum of Ark 564, suitably reproducing its observed FeII+MgII emission. Our approach extends the current set of available FeII templates into the NIR region.Comment: 47 pages, 5 tables, 12 figures. Accepted for publication in The Astrophysical Journa

Evidencing a place for the hippocampus within the core scene processing network

Functional neuroimaging studies have identified several “core” brain regions that are preferentially activated by scene stimuli, namely posterior parahippocampal gyrus (PHG), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS). The hippocampus (HC), too, is thought to play a key role in scene processing, although no study has yet investigated scene-sensitivity in the HC relative to these other “core” regions. Here, we characterised the frequency and consistency of individual scene-preferential responses within these regions by analysing a large dataset (n = 51) in which participants performed a one-back working memory task for scenes, objects, and scrambled objects. An unbiased approach was adopted by applying independently-defined anatomical ROIs to individual-level functional data across different voxel-wise thresholds and spatial filters. It was found that the majority of subjects had preferential scene clusters in PHG (max = 100% of participants), RSC (max = 76%), and TOS (max = 94%). A comparable number of individuals also possessed significant scene-related clusters within their individually defined HC ROIs (max = 88%), evidencing a HC contribution to scene processing. While probabilistic overlap maps of individual clusters showed that overlap “peaks” were close to those identified in group-level analyses (particularly for TOS and HC), inter-individual consistency varied across regions and statistical thresholds. The inter-regional and inter-individual variability revealed by these analyses has implications for how scene-sensitive cortex is localised and interrogated in functional neuroimaging studies, particularly in medial temporal lobe regions, such as the H

Bulk perturbations of N=2 branes

The evolution of supersymmetric A-type D-branes under the bulk renormalization group flow between two different N=2 minimal models is studied. Using the Landau-Ginzburg description we show that a specific set of branes decouples from the infrared theory, and we make detailed predictions for the behavior of the remaining branes. The Landau-Ginzburg picture is then checked against a direct conformal field theory analysis. In particular we construct a natural index pairing which is preserved by the RG flow, and show that the branes that decouple have vanishing index with the surviving branes.Comment: 35 pages (30 pages plus title and references), 8 figure

NACA Research Memorandums

Report presenting the results of a wind-tunnel investigation to determine the effects of a variation in wing taper ratio on the longitudinal characteristics of a wing-body combination at a variety of Mach numbers. The wings had an aspect ratio of 3, an unswept midchord line, and an NACA 64A003 profile. Results regarding the lift and pitching-moment characteristics and drag characteristics are provided

Cognitive and white-matter compartment models reveal selective relations 1 between corticospinal tract microstructure and simple reaction time

The speed of motor reaction to an external stimulus varies substantially between individuals and is slowed in ageing. However, the neuroanatomical origins of inter-individual variability in reaction time (RT) remain unclear. Here, we combined a cognitive model of RT and a biophysical compartment model of diffusion-weighted MRI (DWI) to characterize the relationship between RT and microstructure of the corticospinal tract (CST) and the optic radiation (OR), the primary motor output and visual input pathways associated with visual-motor responses. We fitted an accumulator model of RT to 46 female human participants' behavioral performance in a simple reaction time task. The non-decision time parameter (Ter) derived from the model was used to account for the latencies of stimulus encoding and action initiation. From multi-shell DWI data, we quantified tissue microstructure of the CST and OR with the neurite orientation dispersion and density imaging (NODDI) model as well as the conventional diffusion tensor imaging (DTI) model. Using novel skeletonization and segmentation approaches, we showed that DWI-based microstructure metrics varied substantially along CST and OR. The Ter of individual participants was negatively correlated with the NODDI measure of the neurite density in the bilateral superior CST. Further, we found no significant correlation between the microstructural measures and mean RT. Thus, our findings suggest a link between inter-individual differences in sensorimotor speed and selective microstructural properties in white matter tracts