Genetics THE INFLUENCE OF WEANING WEIGHT ON GROWTH OF THE HYPLUS BROILER RABBIT

ABSTRACT The final crossbreds of the broiler rabbit HYPLUS (product of the company Grimaud Frères) were fattened from 42 to 84 days of age. The following traits were weekly recorded: body weight, average daily weight gain, average daily consumption of feed and feed conversion ratio with regard to the effect of the genotype (♂PS59 × ♀PS19; ♂PS119 × ♀PS19), replication, interaction genotype x replication and weight at 42 days of age (group 1: weight lower then 1300 g and group 2: weight greater then 1300 g). The highest difference in body weight between both genotypes was found at the age of 70 days, when the difference was 5.6%. During the whole fattening period the genotype (59 x 19) showed lower feed conversion ratio (P<0.001) and higher average daily gain (P<0.05). The effect of replication was not-significant in most of the traits. The first replication showed a significantly higher value in the average daily gains than the second replication (P<0.05). The interaction genotype x replication was significant in the body weight at 42, 56, 63 and 70 days of age and in the feed consumption from 49 to 56 days. Rabbits of group 1 weighed 2655 g at the end of fattening period and rabbits of group 2 weighed 2892 g respectively. No growth compensation during the fattening period was observed in group 1. The body weight at 42 days of age had a significant influence on body weight at the end of fattening

KRAS Inhibitor that Simultaneously Inhibits Nucleotide Exchange Activity and Effector Engagement

We describe a small molecule ligand ACA-14 (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, ACA-14 impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, ACA-14 inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and inhibits the growth of pancreatic and colon cancer cells harboring mutant KRAS. We thus propose compound ACA-14 as a useful initial lead for the development of broad-acting inhibitors that target multiple KRAS mutants and simultaneously deplete the fraction of GTP-loaded KRAS while abrogating the effector-binding ability of the already GTP-loaded fraction

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe – Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive

The relationship between greenspace and the mental wellbeing of adults: A systematic review

INTRODUCTION: The view that interacting with nature enhances mental wellbeing is commonplace, despite a dearth of evidence or even agreed definitions of 'nature'. The aim of this review was to systematically appraise the evidence for associations between greenspace and mental wellbeing, stratified by the different ways in which greenspace has been conceptualised in quantitative research. METHODS: We undertook a comprehensive database search and thorough screening of articles which included a measure of greenspace and validated mental wellbeing tool, to capture aspects of hedonic and/or eudaimonic wellbeing. Quality and risk of bias in research were assessed to create grades of evidence. We undertook detailed narrative synthesis of the 50 studies which met the review inclusion criteria, as methodological heterogeneity precluded meta-analysis. RESULTS: Results of a quality assessment and narrative synthesis suggest associations between different greenspace characteristics and mental wellbeing. We identified six ways in which greenspace was conceptualised and measured: (i) amount of local-area greenspace; (ii) greenspace type; (iii) visits to greenspace; (iv) views of greenspace; (v) greenspace accessibility; and (vi) self-reported connection to nature. There was adequate evidence for associations between the amount of local-area greenspace and life satisfaction (hedonic wellbeing), but not personal flourishing (eudaimonic wellbeing). Evidence for associations between mental wellbeing and visits to greenspace, accessibility, and types of greenspace was limited. There was inadequate evidence for associations with views of greenspace and connectedness to nature. Several studies reported variation in associations between greenspace and wellbeing by life course stage, gender, levels of physically activity or attitudes to nature. CONCLUSIONS: Greenspace has positive associations with mental wellbeing (particularly hedonic wellbeing), but the evidence is not currently sufficient or specific enough to guide planning decisions. Further studies are needed, based on dynamic measures of greenspace, reflecting access and uses of greenspace, and measures of both eudaimonic and hedonic mental wellbeing

Formation of multi-compartmental drug carriers by hetero-aggregation of polyelectrolyte microgels

The formation of drug carriers able to incorporate multiple molecular payloads in separate compartments was investigated, using the hetero-aggregation of oppositely charged hydrogel microparticles as the building blocks. The primary particles – negatively charged alginate and positively charged chitosan microgels with a mean diameter of 6–7 μm – were produced by spray drying with in situ cross-linking. The kinetics of their hetero-aggregation was measured on-line by static light scattering. The effects of the starting stoichiometry (positive:negative particle ratio), hydrodynamic conditions (agitation intensity), and pre-conditioning (dry vs. pre-hydrated primary particles) on the aggregate growth rate were systematically investigated. An optimum stoichiometric ratio of the primary particles was found in each case. The structure of the resulting hetero-aggregates was characterised by laser scanning confocal microscopy and found to strongly depend on the pre-conditioning of the primary particles. While dry primary particles resulted in open, floccular structures, pre-hydrated primary particles gave rise to relatively dense, compact aggregates. The ability to incorporate multiple molecular payloads was demonstrated, providing a platform for the formation of well-defined structures that can be further used in applications such as the encapsulation and release of multiple actives from a single carrier

EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel

The ER membrane protein complex (EMC) is required for the biogenesis of a subset of tail anchored (TA) and polytopic membrane proteins, including Rhodopsin-1 (Rh1) and the TRP channel. To understand the physiological implications of EMC-dependent membrane protein biogenesis, we perform a bioinformatic identification of Drosophila TA proteins. From 254 predicted TA proteins, screening in larval eye discs identified two proteins that require EMC for their biogenesis: fan and Xport-A. Fan is required for male fertility in Drosophila and we show that EMC is also required for this process. Xport-A is essential for the biogenesis of both Rh1 and TRP, raising the possibility that disruption of Rh1 and TRP biogenesis in EMC mutants is secondary to the Xport-A defect. We show that EMC is required for Xport-A TMD membrane insertion and that EMC-independent Xport-A mutants rescue Rh1 and TRP biogenesis in EMC mutants. Finally, our work also reveals a role for Xport-A in a glycosylation-dependent triage mechanism during Rh1 biogenesis in the endoplasmic reticulum