Expression and knockdown of zebrafish folliculin suggests requirement for embryonic brain morphogenesis.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited familial cancer syndrome characterised by the development of benign skin fibrofolliculomas, multiple lung and kidney cysts, spontaneous pneumothorax and susceptibility to renal cell carcinoma. BHD is caused by mutations in the gene encoding Folliculin (FLCN). Little is known about what FLCN does in a healthy individual and how best to treat those with BHD. As a first approach to developing a vertebrate model for BHD we aimed to identify the temporal and spatial expression of flcn transcripts in the developing zebrafish embryo. To gain insights into the function of flcn in a whole organism system we generated a loss of function model of flcn by the use of morpholino knockdown in zebrafish. RESULTS: flcn is expressed broadly and upregulated in the fin bud, somites, eye and proliferative regions of the brain of the Long-pec stage zebrafish embryos. Together with knockdown phenotypes, expression analysis suggest involvement of flcn in zebrafish embryonic brain development. We have utilised the zFucci system, an in vivo, whole organism cell cycle assay to study the potential role of flcn in brain development. We found that at the 18 somite stage there was a significant drop in cells in the S-M phase of the cell cycle in flcn morpholino injected embryos with a corresponding increase of cells in the G1 phase. This was particularly evident in the brain, retina and somites of the embryo. Timelapse analysis of the head region of flcn morpholino injected and mismatch control embryos shows the temporal dynamics of cell cycle misregulation during development. CONCLUSIONS: In conclusion we show that zebrafish flcn is expressed in a non-uniform manner and is likely required for the maintenance of correct cell cycle regulation during embryonic development. We demonstrate the utilisation of the zFucci system in testing the role of flcn in cell proliferation and suggest a function for flcn in regulating cell proliferation in vertebrate embryonic brain development.Funding for this project was provided by the Myrovlytis Trust and a KWF travel grant to Monique Luijten.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12861-016-0119-

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

PMCID: PMC3613350This 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 credited

The SAMI galaxy survey: Rules of behaviour for spin-ellipticity radial tracks in galaxies

We study the behaviour of the spin-ellipticity radial tracks for 507 galaxies from the Sydney AAO Multiobject Integral Field (SAMI) Galaxy Survey with stellar kinematics out to ≥1.5Re. We advocate for a morpho-dynamical classification of galaxies, relying on spatially resolved photometric and kinematic data. We find the use of spin-ellipticity radial tracks is valuable in identifying substructures within a galaxy, including embedded and counter-rotating discs, that are easily missed in unilateral studies of the photometry alone. Conversely, bars are rarely apparent in the stellar kinematics but are readily identified on images. Consequently, we distinguish the spin-ellipticity radial tracks of seven morpho-dynamical types: elliptical, lenticular, early spiral, late spiral, barred spiral, embedded disc, and 2σ galaxies. The importance of probing beyond the inner radii of galaxies is highlighted by the characteristics of galactic features in the spin-ellipticity radial tracks present at larger radii. The density of information presented through spin-ellipticity radial tracks emphasizes a clear advantage to representing galaxies as a track, rather than a single point, in spin-ellipticity parameter space

Acidithiobacillus thiooxidans secretome containing a newly described lipoprotein Licanantase enhances chalcopyrite bioleaching rate

The nature of the mineral–bacteria interphase where electron and mass transfer processes occur is a key element of the bioleaching processes of sulfide minerals. This interphase is composed of proteins, metabolites, and other compounds embedded in extracellular polymeric substances mainly consisting of sugars and lipids (Gehrke et al., Appl Environ Microbiol 64(7):2743–2747, 1998). On this respect, despite Acidithiobacilli—a ubiquitous bacterial genera in bioleaching processes (Rawlings, Microb Cell Fact 4(1):13, 2005)—has long been recognized as secreting bacteria (Jones and Starkey, J Bacteriol 82:788–789, 1961; Schaeffer and Umbreit, J Bacteriol 85:492–493, 1963), few studies have been carried out in order to clarify the nature and the role of the secreted protein component: the secretome. This work characterizes for the first time the sulfur (meta)secretome of Acidithiobacillus thiooxidans strain DSM 17318 in pure and mixed cultures with Acidithiobacillus ferrooxidans DSM 16786, identifying the major component of these secreted fractions as a single lipoprotein named here as Licanantase. Bioleaching assays with the addition of Licanantase-enriched concentrated secretome fractions show that this newly found lipoprotein as an active protein additive exerts an increasing effect on chalcopyrite bioleaching rate

Alleviating the new user problem in collaborative filtering by exploiting personality information

The final publication is available at Springer via http://dx.doi.org/10.1007/s11257-016-9172-zThe new user problem in recommender systems is still challenging, and there is not yet a unique solution that can be applied in any domain or situation. In this paper we analyze viable solutions to the new user problem in collaborative filtering (CF) that are based on the exploitation of user personality information: (a) personality-based CF, which directly improves the recommendation prediction model by incorporating user personality information, (b) personality-based active learning, which utilizes personality information for identifying additional useful preference data in the target recommendation domain to be elicited from the user, and (c) personality-based cross-domain recommendation, which exploits personality information to better use user preference data from auxiliary domains which can be used to compensate the lack of user preference data in the target domain. We benchmark the effectiveness of these methods on large datasets that span several domains, namely movies, music and books. Our results show that personality-aware methods achieve performance improvements that range from 6 to 94 % for users completely new to the system, while increasing the novelty of the recommended items by 3-40 % with respect to the non-personalized popularity baseline. We also discuss the limitations of our approach and the situations in which the proposed methods can be better applied, hence providing guidelines for researchers and practitioners in the field.This work was supported by the Spanish Ministry of Economy and Competitiveness (TIN2013-47090-C3). We thank Michal Kosinski and David Stillwell for their attention regarding the dataset

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Cognitive ability and physical health:A Mendelian randomization study

Causes of the association between cognitive ability and health remain unknown, but may reflect a shared genetic aetiology. This study examines the causal genetic associations between cognitive ability and physical health. We carried out two-sample Mendelian randomization analyses using the inverse-variance weighted method to test for causality between later life cognitive ability, educational attainment (as a proxy for cognitive ability in youth), BMI, height, systolic blood pressure, coronary artery disease, and type 2 diabetes using data from six independent GWAS consortia and the UK Biobank sample (N = 112 151). BMI, systolic blood pressure, coronary artery disease and type 2 diabetes showed negative associations with cognitive ability; height was positively associated with cognitive ability. The analyses provided no evidence for casual associations from health to cognitive ability. In the other direction, higher educational attainment predicted lower BMI, systolic blood pressure, coronary artery disease, type 2 diabetes, and taller stature. The analyses indicated no causal association from educational attainment to physical health. The lack of evidence for causal associations between cognitive ability, educational attainment, and physical health could be explained by weak instrumental variables, poorly measured outcomes, or the small number of disease cases

Rational Redesign of Glucose Oxidase for Improved Catalytic Function and Stability

Glucose oxidase (GOx) is an enzymatic workhorse used in the food and wine industries to combat microbial contamination, to produce wines with lowered alcohol content, as the recognition element in amperometric glucose sensors, and as an anodic catalyst in biofuel cells. It is naturally produced by several species of fungi, and genetic variants are known to differ considerably in both stability and activity. Two of the more widely studied glucose oxidases come from the species Aspergillus niger (A. niger) and Penicillium amagasakiense (P. amag.), which have both had their respective genes isolated and sequenced. GOx from A. niger is known to be more stable than GOx from P. amag., while GOx from P. amag. has a six-fold superior substrate affinity (KM) and nearly four-fold greater catalytic rate (kcat). Here we sought to combine genetic elements from these two varieties to produce an enzyme displaying both superior catalytic capacity and stability. A comparison of the genes from the two organisms revealed 17 residues that differ between their active sites and cofactor binding regions. Fifteen of these residues in a parental A. niger GOx were altered to either mirror the corresponding residues in P. amag. GOx, or mutated into all possible amino acids via saturation mutagenesis. Ultimately, four mutants were identified with significantly improved catalytic activity. A single point mutation from threonine to serine at amino acid 132 (mutant T132S, numbering includes leader peptide) led to a three-fold improvement in kcat at the expense of a 3% loss of substrate affinity (increase in apparent KM for glucose) resulting in a specify constant (kcat/KM) of 23.8 (mM−1 · s−1) compared to 8.39 for the parental (A. niger) GOx and 170 for the P. amag. GOx. Three other mutant enzymes were also identified that had improvements in overall catalysis: V42Y, and the double mutants T132S/T56V and T132S/V42Y, with specificity constants of 31.5, 32.2, and 31.8 mM−1 · s−1, respectively. The thermal stability of these mutants was also measured and showed moderate improvement over the parental strain

First Report of 13 Species of Culicoides (Diptera: Ceratopogonidae) in Mainland Portugal and Azores by Morphological and Molecular Characterization

The genus Culicoides (Diptera: Ceratopogonidae) contains important vectors of animal and human diseases, including bluetongue, African horse sickness and filariosis. A major outbreak of bluetongue occurred in mainland Portugal in 2004, forty eight years after the last recorded case. A national Entomological Surveillance Plan was initiated in mainland Portugal, Azores and the Madeira archipelagos in 2005 in order to better understand the disease and facilitate policy decisions. During the survey, the most prevalent Culicoides species in mainland Portugal was C. imicola (75.3%) and species belonging to the Obsoletus group (6.5%). The latter were the most prevalent in Azores archipelago, accounting for 96.7% of the total species identified. The Obsoletus group was further characterized by multiplex Polymerase Chain Reaction to species level showing that only two species of this group were present: C. obsoletus sensu strictu (69.6%) and C. scoticus (30.4%). Nine species of Culicoides were detected for the first time in mainland Portugal: C. alazanicus, C. bahrainensis, C. deltus, C. lupicaris, C. picturatus, C. santonicus, C. semimaculatus, C. simulator and C. subfagineus. In the Azores, C. newsteadi and C. circumscriptus were identified for the first time from some islands, and bluetongue vectors belonging to the Obsoletus group (C. obsoletus and C. scoticus) were found to be widespread

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-