Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial.

Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction (LEADER) trial. Three polymorphisms in the peroxisome proliferator activated receptor alpha (PPARalpha) gene were investigated (L162V, G>A in intron 2 and G>C in intron 7), two in the apolipoprotein CIII (APOC3) gene (-482C>T and -455T>C) and one in the beta-fibrinogen (FIBB) gene (-455G>A). The presence of diabetes (n=158) was associated with 15% higher triglyceride levels at baseline compared to non-diabetics (n=654) (PC substitution. In the non-diabetic patients, the PPARalpha V162 allele was significantly associated with 9% higher baseline triglyceride levels (P<0.03) and a similar, but non-significant trend was seen for the intron 7 polymorphism. Overall, triglyceride levels fell by 26% with 3 months of bezafibrate treatment, and current smokers showed a poorer response compared to ex/non-smokers (23% fall compared to 28% P=0.03), but none of the genotypes examined had a significant influence on the magnitude of response. Carriers of the -455A polymorphism of the FIBB gene had, as expected, marginally higher baseline fibrinogen levels, 3.43 versus 3.36 g/l (P=0.055), but this polymorphism did not affect response to treatment. Overall, fibrinogen levels fell by 12%, with patients with the highest baseline fibrinogen levels showing the greatest decrease in response to bezafibrate. For both the intron 2 and the L162V polymorphisms of the PPARalpha gene there was a significant interaction (both P<0.01) between genotype and baseline levels of fibrinogen on the response of fibrinogen levels to bezafibrate, such that individuals carrying the rare alleles in the lowest tertile showed essentially no overall decrease compared to a 0.18 g/l fall in homozygotes for the common allele. Thus while these genotypes are a minor determinant of baseline triglyceride and fibrinogen levels, there is little evidence from this study that the magnitude of response to bezafibrate treatment in men with peripheral vascular disease is determined by variation at these loci

Netflix and Chilling: Binge-Watching Behaviors and the Cultivation Effects of Horror Television Shows.

M.A. Thesis. University of Hawaiʻi at Mānoa 2018

Demonstration of the Presence of the "Deleted" MIR122 Gene in HepG2 Cells

MicroRNA 122 (miR-122) is highly expressed in the liver where it influences diverse biological processes and pathways, including hepatitis C virus replication and metabolism of iron and cholesterol. It is processed from a long non-coding primary transcript (~7.5 kb) and the gene has two evolutionarily-conserved regions containing the pri-mir-122 promoter and pre-mir-122 hairpin region. Several groups reported that the widely-used hepatocytic cell line HepG2 had deficient expression of miR-122, previously ascribed to deletion of the pre-mir-122 stem-loop region. We aimed to characterise this deletion by direct sequencing of 6078 bp containing the pri-mir-122 promoter and pre-mir-122 stem-loop region in HepG2 and Huh-7, a control hepatocytic cell line reported to express miR-122, supported by sequence analysis of cloned genomic DNA. In contrast to previous findings, the entire sequence was present in both cell lines. Ten SNPs were heterozygous in HepG2 indicating that DNA was present in two copies. Three validation isolates of HepG2 were sequenced, showing identical genotype to the original in two, whereas the third was different. Investigation of promoter chromatin status by FAIRE showed that Huh-7 cells had 6.2 ± 0.19- and 2.7 ± 0.01- fold more accessible chromatin at the proximal (HNF4α-binding) and distal DR1 transcription factor sites, compared to HepG2 cells (p=0.03 and 0.001, respectively). This was substantiated by ENCODE genome annotations, which showed a DNAse I hypersensitive site in the pri-mir-122 promoter in Huh-7 that was absent in HepG2 cells. While the origin of the reported deletion is unclear, cell lines should be obtained from a reputable source and used at low passage number to avoid discrepant results. Deficiency of miR-122 expression in HepG2 cells may be related to a relative deficiency of accessible promoter chromatin in HepG2 versus Huh-7 cells

Empirical model for quasi direct current interruption with a convoluted arc

This contribution considers various aspects of a quasi direct current, convoluted arc produced by a magnetic field (B-field) connected in parallel with an RLC circuit that have not been considered in combination. These aspects are the arc current limitation due to the arc convolution, changes in arc resistance due to the B-field and material ablation, and the relative significance of the RLC circuit in producing an artificial current zero. As a result, it has been possible to produce an empirical equation for predicting the current interruption capability in terms of the B-field magnitude and RLC components

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

Discordant inflammatory changes in the apophyseal and sacroiliac joints: serial observations in enthesitis-related arthritis

OBJECTIVE: To determine the extent to which inflammation of the sacroiliac joints (SIJs) and apophyseal joints (AJs) changes concordantly after treatment in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. 31 young patients with ERA who had been scanned between March 2009 and November 2014 were included. All patients had post-contrast imaging of the SIJs and lumbar spine and short tau inversion-recovery (STIR) images of the SIJs. The severity of sacroiliitis was scored using a modification of an established technique, and inflammation of the AJs was evaluated using a recently described grading system. The changes in SIJ and AJ scores after treatment were classified as either concordant or discordant, and the proportion of scan pairs in these groups was recorded. In addition, the correlation between change in SIJ STIR score (Δnfla) and change in AJ score (ΔAJ) was assessed using Spearman's correlation coefficient. RESULTS: Of a total of 43 scan pairs, the changes in inflammation were concordant in 16 scan pairs and discordant in 27 scan pairs. There was no significant correlation between Δnfla and ΔAJ (R = 0.14, p = 0.37). CONCLUSION: Inflammatory changes in the SIJs and AJs are often discordant. This may be a reason why patients experience ongoing back pain despite apparent improvement in one or the other site. ADVANCES IN KNOWLEDGE: Inflammation may behave differently at different anatomical sites. The SIJs and AJs should both be imaged in patients with ERA with back pain

Index

The interest in relativistic beam-plasma instabilities has been greatly rejuvenated over the past two decades by novel concepts in laboratory and space plasmas. Recent advances in this long-standing field are here reviewed from both theoretical and numerical points of view. The primary focus is on the two-dimensional spectrum of unstable electromagnetic waves growing within relativistic, unmagnetized, and uniform electron beam-plasma systems. Although the goal is to provide a unified picture of all instability classes at play, emphasis is put on the potentially dominant waves propagating obliquely to the beam direction, which have received little attention over the years. First, the basic derivation of the general dielectric function of a kinetic relativistic plasma is recalled. Next, an overview of two-dimensional unstable spectra associated with various beam-plasma distribution functions is given. Both cold-fluid and kinetic linear theory results are reported, the latter being based on waterbag and Maxwell–Jüttner model distributions. The main properties of the competing modes (developing parallel, transverse, and oblique to the beam) are given, and their respective region of dominance in the system parameter space is explained. Later sections address particle-in-cell numerical simulations and the nonlinear evolution of multidimensional beam-plasma systems. The elementary structures generated by the various instability classes are first discussed in the case of reduced-geometry systems. Validation of linear theory is then illustrated in detail for large-scale systems, as is the multistaged character of the nonlinear phase. Finally, a collection of closely related beam-plasma problems involving additional physical effects is presented, and worthwhile directions of future research are outlined.Original Publication: Antoine Bret, Laurent Gremillet and Mark Eric Dieckmann, Multidimensional electron beam-plasma instabilities in the relativistic regime, 2010, Physics of Plasmas, (17), 12, 120501-1-120501-36. http://dx.doi.org/10.1063/1.3514586 Copyright: American Institute of Physics http://www.aip.org/</p

Breeding for quantitative variables. Part 4: Breeding for nutritional quality traits

Yusuf Genc, Julia M. Humphries, Graham H. Lyons and Robin D. Grahamhttp://www.fao.org/docrep/012/i1070e/i1070e00.ht