SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple ...cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.
We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.
SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.
SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
Evidence of nonthermal X-ray emission and TeV gamma rays from supernova remnants (SNRs) have strengthened the hypothesis that primary Galactic cosmic- ray electrons are accelerated in SNRs. ...High-energy electrons lose energy via synchrotron and inverse Compton processes during propagation in the Galaxy. Because of these radiative losses, TeV electrons liberated from SNRs at distances larger than approx1 kpc, or times older than approx10 super(5) yr, cannot reach the solar system. We investigated the cosmic-ray electron spectrum observed in the solar system using an analytical method and considered several candidate sources among nearby SNRs that may contribute to the high-energy electron flux. In particular, we discuss the effects for the release time from SNRs after the explosion, as well as the deviation of a source spectrum from a simple power law. From this calculation, we found that some nearby sources, such as Vela, Cygnus Loop, or Monogem, could leave unique signatures in the form of identifiable structure in the energy spectrum of TeV electrons and show anisotropies toward the sources, depending on when the electrons were liberated from the remnant. This suggests that, in addition to providing information on the mechanisms of acceleration and propagation of cosmic rays, specific cosmic- ray sources can be identified through the precise electron observation in the TeV region.
Copy number variants (CNVs) are a well-recognized cause of genetic disease; however, methods for their identification are often gene-specific, excluded as 'routine' in screens of genetically ...heterogeneous disorders, and not implemented in most next-generation sequencing pipelines. For this reason, the contribution of CNVs to non-syndromic hearing loss (NSHL) is most likely under-recognized. We aimed to incorporate a method for CNV identification as part of our standard analysis pipeline and to determine the contribution of CNVs to genetic hearing loss.
We used targeted genomic enrichment and massively parallel sequencing to isolate and sequence all exons of all genes known to cause NSHL. We completed testing on 686 patients with hearing loss with no exclusions based on type of hearing loss or any other clinical features. For analysis we used an integrated method for detection of single nucleotide changes, indels and CNVs. CNVs were identified using a previously published method that utilizes median read-depth ratios and a sliding-window approach.
Of 686 patients tested, 15.2% (104) carried at least one CNV within a known deafness gene. Of the 38.9% (267) of individuals for whom we were able to determine a genetic cause of hearing loss, a CNV was implicated in 18.7% (50). We identified CNVs in 16 different genes including 7 genes for which no CNVs have been previously reported. CNVs of STRC were most common (73% of CNVs identified) followed by CNVs of OTOA (13% of CNVs identified).
CNVs are an important cause of NSHL and their detection must be included in comprehensive genetic testing for hearing loss.
ABSTRACT The BESS-Polar Collaboration measured the energy spectra of cosmic-ray protons and helium during two long-duration balloon flights over Antarctica in 2004 December and 2007 December at ...substantially different levels of solar modulation. Proton and helium spectra probe the origin and propagation history of cosmic rays in the galaxy, and are essential to calculations of the expected spectra of cosmic-ray antiprotons, positrons, and electrons from interactions of primary cosmic-ray nuclei with the interstellar gas, and to calculations of atmospheric muons and neutrinos. We report absolute spectra at the top of the atmosphere for cosmic-ray protons in the kinetic energy range 0.2-160 GeV and helium nuclei in the range 0.15-80 GeV/nucleon. The corresponding magnetic-rigidity ranges are 0.6-160 GV for protons and 1.1-160 GV for helium. These spectra are compared to measurements from previous BESS flights and from ATIC-2, PAMELA, and AMS-02. We also report the ratio of the proton and helium fluxes from 1.1 to 160 GV and compare this to the ratios from PAMELA and AMS-02.
We review recent developments in the type IIB matrix model, which was conjectured to be a nonperturbative formulation of superstring theory. In the first part we review the recent results for the ...Euclidean model, which suggest that SO(10) symmetry is spontaneously broken. In the second part we review the recent results for the Lorentzian model. In particular, we discuss Monte Carlo results, which suggest that (3+1)‐dimensional expanding universe emerges dynamically. We also discuss some results suggesting the emergence of exponential expansion and the power‐law expansion at later times. The behaviors at much later times are studied by the classical equation of motion. We discuss a solution representing 3d expanding space, which suggests a possible solution to the cosmological constant problem.
The energy spectrum of cosmic-ray antiprotons (p's) from 0.17 to 3.5 GeV has been measured using 7886 p's detected by BESS-Polar II during a long-duration flight over Antarctica near solar minimum in ...December 2007 and January 2008. This shows good consistency with secondary p calculations. Cosmologically primary p's have been investigated by comparing measured and calculated p spectra. BESS-Polar II data show no evidence of primary p's from the evaporation of primordial black holes.
We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One ...thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (
KCNQ4
,
TECTA
,
WFS1
) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in
KCNQ4
; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for
TECTA
and
WFS1
. Identifying the drivers of ethnic differences will refine our understanding of phenotype–genotype relationships and the biology of hearing and deafness.
AIMS: The aims of this study were to evaluate the effectiveness of nisin A to control the growth of spore‐forming bacteria, Bacillus and Paenibacillus, in chilled high‐fat, milk pudding and to reduce ...heat treatment to improve aroma and flavour. METHODS AND RESULTS: Nisin A was added to milk pudding containing 5·0 and 7·5% fat to final concentrations of 40, 80, 120 and 240 IU ml⁻¹. Spores from Bacillus thuringiensis, Bacillus cereus and Paenibacillus jamilae were inoculated into samples at 10 spores ml⁻¹prior to pasteurization at 130°C for 2 s. Milk pudding without inoculation was pasteurized using less heat condition (100, 110 and 120°C for 2 s) to measure the effect of adjusting the ingredients to prevent naturally occurring bacteria. The viable cells during storage at 15, 20 and 30°C showed nisin A inhibited spiked bacteria to varying degrees depending on species, sensitivities to nisin A concentration and fat content, and inhibited natural populations at 80 IU g⁻¹nisin A in 5·0% fat and at 120 IU g⁻¹in 7·5% fat milk pudding. An aroma compound analysis and organoleptic assessment showed processing at 110 and 120°C decreased the temperature‐dependent unpleasant odours, for example, reduced dimethyl sulfide and dimethyl disulfide by 1·2–1·5 times and increased rankings in taste tests compared with 130°C treated pudding. CONCLUSIONS: Nisin A was found to be effective as a natural preservative to control spoilage bacteria in high‐fat milk pudding and extend its shelf life, when using reduced heat treatments to improve the flavour and aroma without compromising food safety. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing nisin A is effective in reducing spoilage bacteria in high‐fat, chilled dessert, milk pudding. Therefore, nisin A can be used to improve milk puddings to satisfy both industry and consumer demand for food quality and safety.
Vertically aligned ZnO nanowires were successfully grown on the sapphire substrate by nanoparticle-assisted pulsed laser deposition (NAPLD), which were employed in fabricating the ZnO nanowire-based ...heterojunction structures.
p
-GaN/
n
-ZnO heterojunction light-emitting diodes (LEDs) with embedded ZnO nanowires were obtained by fabricating
p
-GaN:Mg film/ZnO nanowire/
n
-ZnO film structures. The current–voltage measurements showed a typical diode characteristic with a threshold voltage of about 2.5 V. Electroluminescence (EL) emission having the wavelength of about 380 nm was observed under forward bias in the heterojunction diodes and was intensified by increasing the applied voltage up to 30 V.
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