464 research outputs found
Local modulation of the Wnt/β‐catenin and bone morphogenic protein (BMP) pathways recapitulates rib defects analogous to cerebro‐costo‐mandibular syndrome
Ribs are seldom affected by developmental disorders, however, multiple defects in rib structure are observed in the spliceosomal disease cerebro‐costo‐mandibular syndrome (CCMS). These defects include rib gaps, found in the posterior part of the costal shaft in multiple ribs, as well as missing ribs, shortened ribs and abnormal costotransverse articulations, which result in inadequate ventilation at birth and high perinatal mortality. The genetic mechanism of CCMS is a loss‐of‐function mutation in SNRPB, a component of the major spliceosome, and knockdown of this gene in vitro affects the activity of the Wnt/β‐catenin and bone morphogenic protein (BMP) pathways. The aim of the present study was to investigate whether altering these pathways in vivo can recapitulate rib gaps and other rib abnormalities in the model animal. Chick embryos were implanted with beads soaked in Wnt/β‐catenin and BMP pathway modulators during somitogenesis, and incubated until the ribs were formed. Some embryos were harvested in the preceding days for analysis of the chondrogenic marker Sox9, to determine whether pathway modulation affected somite patterning or chondrogenesis. Wnt/β‐catenin inhibition manifested characteristic rib phenotypes seen in CCMS, including rib gaps (P < 0.05) and missing ribs (P < 0.05). BMP pathway activation did not cause rib gaps but yielded missing rib (P < 0.01) and shortened rib phenotypes (P < 0.05). A strong association with vertebral phenotypes was also noted with BMP4 (P < 0.001), including scoliosis (P < 0.05), a feature associated with CCMS. Reduced expression of Sox9 was detected with Wnt/β‐catenin inhibition, indicating that inhibition of chondrogenesis precipitated the rib defects in the presence of Wnt/β‐catenin inhibitors. BMP pathway activators also reduced Sox9 expression, indicating an interruption of somite patterning in the manifestation of rib defects with BMP4. The present study demonstrates that local inhibition of the Wnt/β‐catenin and activation of the BMP pathway can recapitulate rib defects, such as those observed in CCMS. The balance of Wnt/β‐catenin and BMP in the somite is vital for correct rib morphogenesis, and alteration of the activity of these two pathways in CCMS may perturb this balance during somite patterning, leading to the observed rib defects
Self-Diffusion of a Polymer Chain in a Melt
Self-diffusion of a polymer chain in a melt is studied by Monte Carlo
simulations of the bond fluctuation model, where only the excluded volume
interaction is taken into account. Polymer chains, each of which consists of
segments, are located on an simple cubic lattice
under periodic boundary conditions, where each segment occupies unit cells. The results for
and 512 at the volume fraction are reported, where
for and L=192 for . The -dependence of the
self-diffusion constant is examined. Here, is estimated from the mean
square displacements of the center of mass of a single polymer chain at the
times larger than the longest relaxation time. From the data for , 384
and 512, the apparent exponent , which describes the apparent power
law dependence of on as , is estimated as
. The ratio seems to be a
constant for and 512, where and
denote the longest relaxation time and the mean square end-to-end distance,
respectively.Comment: 4 pages, 3 figures, submitted to J. Phys. Soc. Jp
Electricity and disinfectant production from wastewater: Microbial Fuel Cell as a self-powered electrolyser
This study presents a simple and sustainable Microbial Fuel Cell as a standalone, self-powered reactor for in situ wastewater electrolysis, recovering nitrogen from wastewater. A process is proposed whereby the MFC electrical performance drives the electrolysis of wastewater towards the self-generation of catholyte within the same reactor. The MFCs were designed to harvest the generated catholyte in the internal chamber, which showed that liquid production rates are largely proportional to electrical current generation. The catholyte demonstrated bactericidal properties, compared to the control (open-circuit) diffusate, and reduced observable biofilm formation on the cathode electrode. Killing effects were confirmed using bacterial kill curves constructed by exposing a bioluminescent Escherichia coli target, as a surrogate coliform, to catholyte where a rapid kill rate was observed. Therefore, MFCs could serve as a water recovery system, a disinfectant/cleaner generator that limits undesired biofilm formation and as a washing agent in waterless urinals to improve sanitation. This simple and ready to implement MFC system can convert organic waste directly into electricity and self-driven nitrogen along with water recovery. This could lead to the development of energy positive bioprocesses for sustainable wastewater treatment
Common and Distant Structural Characteristics of Feruloyl Esterase Families from Aspergillus oryzae
Background: Feruloyl esterases (FAEs) are important biomass degrading accessory enzymes due to their capability of cleaving the ester links between hemicellulose and pectin to aromatic compounds of lignin, thus enhancing the accessibility of plant tissues to cellulolytic and hemicellulolytic enzymes. FAEs have gained increased attention in the area of biocatalytic transformations for the synthesis of value added compounds with medicinal and nutritional applications. Following the increasing attention on these enzymes, a novel descriptor based classification system has been proposed for FAEs resulting into 12 distinct families and pharmacophore models for three FAE sub-families have been developed. Methodology/Principal Findings: The feruloylome of Aspergillus oryzae contains 13 predicted FAEs belonging to six sub-families based on our recently developed descriptor-based classification system. The three-dimensional structures of the 13 FAEs were modeled for structural analysis of the feruloylome. The three genes coding for three enzymes, viz., A.O.2, A.O.8 and A.O.10 from the feruloylome of A. oryzae, representing sub-families with unknown functional features, were heterologously expressed in Pichia pastoris, characterized for substrate specificity and structural characterization through CD spectroscopy. Common feature-based pharamacophore models were developed according to substrate specificity characteristics of the three enzymes. The active site residues were identified for the three expressed FAEs by determining the titration curves of amino acid residues as a function of the pH by applying molecular simulations. Conclusions/Significance: Our findings on the structure-function relationships and substrate specificity of the FAEs of A. oryzae will be instrumental for further understanding of the FAE families in the novel classification system. The developed pharmacophore models could be applied for virtual screening of compound databases for short listing the putative substrates prior to docking studies or for post-processing docking results to remove false positives. Our study exemplifies how computational predictions can complement to the information obtained through experimental methods. © 2012 Udatha et al.published_or_final_versio
Search for the Invisible Decay of Neutrons with KamLAND
The Kamioka Liquid scintillator Anti-Neutrino Detector (KamLAND) is used in a
search for single neutron or two neutron intra-nuclear disappearance that would
produce holes in the -shell energy level of C nuclei. Such holes
could be created as a result of nucleon decay into invisible modes (),
e.g. or . The de-excitation of the corresponding
daughter nucleus results in a sequence of space and time correlated events
observable in the liquid scintillator detector. We report on new limits for
one- and two-neutron disappearance: years
and years at 90% CL. These results
represent an improvement of factors of 3 and over previous
experiments.Comment: 5 pages, 3 figure
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Biological, clinical and population relevance of 95 loci for blood lipids.
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD
Measurement of Neutrino Oscillation with KamLAND: Evidence of Spectral Distortion
We present results of a study of neutrino oscillation based on a 766 ton-year
exposure of KamLAND to reactor anti-neutrinos. We observe 258 \nuebar\
candidate events with energies above 3.4 MeV compared to 365.2 events expected
in the absence of neutrino oscillation. Accounting for 17.8 expected background
events, the statistical significance for reactor \nuebar disappearance is
99.998%. The observed energy spectrum disagrees with the expected spectral
shape in the absence of neutrino oscillation at 99.6% significance and prefers
the distortion expected from \nuebar oscillation effects. A two-neutrino
oscillation analysis of the KamLAND data gives \DeltaMSq =
7.9 eV. A global analysis of data from KamLAND
and solar neutrino experiments yields \DeltaMSq =
7.9 eV and \ThetaParam =
0.40, the most precise determination to date.Comment: 5 pages, 4 figures; submitted to Phys.Rev.Letter
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