Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

The LSST DESC data challenge 1: Generation and analysis of synthetic images for next-generation surveys

Data Challenge 1 (DC1) is the first synthetic data set produced by the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC). DC1 is designed to develop and validate data reduction and analysis and to study the impact of systematic effects that will affect the LSST data set. DC1 is comprised of r-band observations of 40 deg2 to 10 yr LSST depth. We present each stage of the simulation and analysis process: (a) generation, by synthesizing sources from cosmological N-body simulations in individual sensor-visit images with different observing conditions; (b) reduction using a development version of the LSST Science Pipelines; and (c) matching to the input cosmological catalogue for validation and testing. We verify that testable LSST requirements pass within the fidelity of DC1. We establish a selection procedure that produces a sufficiently clean extragalactic sample for clustering analyses and we discuss residual sample contamination, including contributions from inefficiency in star-galaxy separation and imperfect deblending. We compute the galaxy power spectrum on the simulated field and conclude that: (i) survey properties have an impact of 50 per cent of the statistical uncertainty for the scales and models used in DC1; (ii) a selection to eliminate artefacts in the catalogues is necessary to avoid biases in the measured clustering; and (iii) the presence of bright objects has a significant impact (2-6) in the estimated power spectra at small scales (> 1200), highlighting the impact of blending in studies at small angular scales in LSST

Charged, conformal non-relativistic hydrodynamics

We embed a holographic model of an U(1) charged fluid with Galilean invariance in string theory and calculate its specific heat capacity and Prandtl number. Such theories are generated by a R-symmetry twist along a null direction of a N=1 superconformal theory. We study the hydrodynamic properties of such systems employing ideas from the fluid-gravity correspondence.Comment: 31 pages, 1 figure, JHEP3 style, refs added, typos corrected, missing terms in spatial charge current and field corrections added, to be published in JHE

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Non-abelian T-duality, Ramond Fields and Coset Geometries

We extend previous work on non-abelian T-duality in the presence of Ramond fluxes to cases in which the duality group acts with isotropy such as in backgrounds containing coset spaces. In the process we generate new supergravity solutions related to D-brane configurations and to standard supergravity compactifications.Comment: 35 pages, Late

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Smeared versus localised sources in flux compactifications

We investigate whether vacuum solutions in flux compactifications that are obtained with smeared sources (orientifolds or D-branes) still survive when the sources are localised. This seems to rely on whether the solutions are BPS or not. First we consider two sets of BPS solutions that both relate to the GKP solution through T-dualities: (p+1)-dimensional solutions from spacetime-filling Op-planes with a conformally Ricci-flat internal space, and p-dimensional solutions with Op-planes that wrap a 1-cycle inside an everywhere negatively curved twisted torus. The relation between the solution with smeared orientifolds and the localised version is worked out in detail. We then demonstrate that a class of non-BPS AdS_4 solutions that exist for IASD fluxes and with smeared D3-branes (or analogously for ISD fluxes with anti-D3-branes) does not survive the localisation of the (anti) D3-branes. This casts doubts on the stringy consistency of non-BPS solutions that are obtained in the limit of smeared sources.Comment: 23 pages; v2: minor corrections, added references, version published in JHE