Aims/hypothesis
The associations between adiponectin polymorphisms and type 2 diabetes have been studied widely; however, results are inconsistent.
Methods
We searched electronic literature databases ...and reference lists of relevant articles. A fixed or random effects model was used on the basis of heterogeneity. Sub-group and meta-regression analyses were conducted to explore the sources of heterogeneity.
Results
There were no statistically significant associations between +45T>G (rs2241766), +276G>T (rs1501299), −11391G>A (rs17300539) and type 2 diabetes risk. However, for −11377C>G (rs266729), the pooled OR (95% CI) for G vs C allele was 1.07 (1.03–1.11,
p
= 0.001). Subgroup analysis by study design revealed that −11377C>G (rs266729) dominant model (CG+GG vs CC,
p
= 0.0008) and G vs C allele (
p
= 0.0004) might be associated with type 2 diabetes risk in population-based case–control studies. After stratification by ethnicity, we found that −11377C>G (rs266729) dominant model (CG+GG vs CC,
p
= 0.004) and G vs C allele (
p
= 0.001) might be associated with type 2 diabetes risk in white individuals. In individuals with a family history of diabetes, the presence of −11391G>A (rs17300539) dominant model (GA+AA vs GG) and A vs G allele might be associated with increased risk of type 2 diabetes.
Conclusions/interpretation
The presence of +45T>G (rs2241766), +276G>T (rs1501299) and −11391G>A (rs17300539) do not appear to influence the development of type 2 diabetes. However, G vs C allele of −11377C>G (rs266729) might be a risk factor for type 2 diabetes.
RATIONALE:Duchenne muscular dystrophy is a severe inherited form of muscular dystrophy caused by mutations in the reading frame of the dystrophin gene disrupting its protein expression. Dystrophic ...cardiomyopathy is a leading cause of death in Duchenne muscular dystrophy patients, and currently no effective treatment exists to halt its progression. Recent advancement in genome editing technologies offers a promising therapeutic approach in restoring dystrophin protein expression. However, the impact of this approach on Duchenne muscular dystrophy cardiac function has yet to be evaluated. Therefore, we assessed the therapeutic efficacy of CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing on dystrophin expression and cardiac function in mdx/Utr mice after a single systemic delivery of recombinant adeno-associated virus.
OBJECTIVE:To examine the efficiency and physiological impact of CRISPR-mediated genome editing on cardiac dystrophin expression and function in dystrophic mice.
METHODS AND RESULTS:Here, we packaged SaCas9 (clustered regularly interspaced short palindromic repeat–associated 9 from Staphylococcus aureus) and guide RNA constructs into an adeno-associated virus vector and systemically delivered them to mdx/Utr neonates. We showed that CRIPSR-mediated genome editing efficiently excised the mutant exon 23 in dystrophic mice, and immunofluorescence data supported the restoration of dystrophin protein expression in dystrophic cardiac muscles to a level approaching 40%. Moreover, there was a noted restoration in the architecture of cardiac muscle fibers and a reduction in the extent of fibrosis in dystrophin-deficient hearts. The contractility of cardiac papillary muscles was also restored in CRISPR-edited cardiac muscles compared with untreated controls. Furthermore, our targeted deep sequencing results confirmed that our adeno-associated virus-CRISPR/Cas9 strategy was very efficient in deleting the ≈23 kb of intervening genomic sequences.
CONCLUSIONS:This study provides evidence for using CRISPR-based genome editing as a potential therapeutic approach for restoring dystrophic cardiomyopathy structurally and functionally.
Context.
No robust detection of prompt electromagnetic counterparts to fast radio bursts (FRBs) has yet been obtained, in spite of several multi-wavelength searches having been carried out so far. ...Specifically, X/
γ
-rays counterparts are predicted by some models.
Aims.
We aim to search for prompt
γ
-ray counterparts in the Insight-Hard X-ray Modulation Telescope (Insight-HXMT) data, taking advantage of the unique combination of the large effective area in the keV–MeV energy range, and of sub-ms time resolution.
Methods.
We selected 39 FRBs that were promptly visible from the High-Energy (HE) instrument aboard Insight-HXMT. After calculating the expected arrival times at the location of the spacecraft, we searched for a significant excess in both individual and cumulative time profiles over a wide range of time resolutions, from several seconds down to sub-ms scales. Using the dispersion measures in excess of the Galactic terms, we estimated the upper limits on the redshifts.
Results.
No convincing signal was found, and for each FRB we constrained the
γ
-ray isotropic-equivalent luminosity and the released energy as a function of emission timescale. For the nearest FRB source, the periodic repeater FRB 180916.J0158+65, we find
L
γ
, iso
< 5.5 × 10
47
erg s
−1
over 1 s, whereas
L
γ
, iso
< 10
49
− 10
51
erg s
−1
for the bulk of FRBs. The same values scale up by a factor of ∼100 for a ms-long emission.
Conclusions.
Even on a timescale comparable with that of the radio pulse itself, no keV–MeV emission is observed. A systematic association with either long or short GRBs is ruled out with high confidence, except for sub-luminous events, as is the case for the core-collapse of massive stars (long) or binary neutron star mergers (short) viewed off axis. Only giant flares from extragalactic magnetars at least ten times more energetic than Galactic siblings are ruled out for the nearest FRB.
The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that ...alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, whereas exogenous Bmp4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this brake is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair, the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal crucial roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium.
OBJECTIVE: To prospectively examine the relation between television watching and body fat change in children from preschool to early adolescence. METHODS: In a longitudinal study, 106 children were ...enrolled during preschool years (mean age 4.0 y) and followed into early adolescence (mean age 11.1 y). Parents completed an annual questionnaire on the child's television and video habits. Body mass index (BMI), triceps skinfolds, and sum of five skinfolds were recorded yearly at annual clinic visits. Longitudinal statistical analyses were carried out using mixed modeling procedures to control for potential confounding by a number of factors. RESULTS: Television watching was an independent predictor of the change in the child's BMI, triceps, and sum of five skinfolds throughout childhood. Its effect was only slightly attenuated by controlling for the baseline body fat, level of physical activity (as measured repeatedly by Caltrac accelerometer), percent of calories from fat, total calorie intake, or the parents' BMI or education. By age 11, children who watched 3.0 h or more of television per day had a mean sum of skinfolds of 106.2 mm, compared with a mean sum of skinfolds of 76.5 mm for those who watched less than 1.75 h per day (P=0.007). Furthermore, the adverse effect of television viewing was worse for those children who were also sedentary or had a higher-fat diet. CONCLUSIONS: Children who watched the most television during childhood had the greatest increase in body fat over time. Healthy lifestyle education designed to prevent obesity and its consequences should target television-watching habits of children.
•HE behavior of localized zones in SUS301L-MT stainless steel was investigated using SSRT tests during in situ electrochemical hydrogen charging.•HE cracks in BM and HAZ specimens initiated along ...αˊ/γ interface near the specimen edge.•HE cracks in WM specimen initiated along the δ-ferrites distributed at austenitic grain boundaries.•HE cracks propagated in BM, HAZ and WM exhibited hydrogen enhanced local plastic deformation and hydrogen induced decohesion mechanisms controlled by the hydrogen diffusion behavior in the front of cracks tips.
Hydrogen induced stress corrosion cracking behavior of SUS301L-MT laser-arc hybrid welded (LAHW) joints has been investigated in our previous works. However, the hydrogen embrittlement (HE) behavior in each zone of this joint is still unclear. In this work, in combination with microstructures, cracks propagation paths and fracture surface morphologies analysis, in situ electrochemical hydrogen charging during slow strain rate tensile (SSRT) tests were performed on the specimens cut from base metal (BM), heat-affected zone (HAZ) and weld metal (WM) in SUS301L-MT stainless steel LAHW joints to investigate the HE behavior of each zone. The results indicated that deformation induced martensite transformation occurred in BM and HAZ specimens during SSRT tests, resulted in cleavage morphologies on the fracture center and dimples on other areas. The fracture surface of WM specimen was all covered with dimples. During in situ hydrogen charging, the cracks in BM and HAZ specimens initiated along αˊ/γ interface near the specimen edge. The cracks in WM specimen initiated along the δ-ferrites distributed at austenitic grain boundaries. After the cracks initiated, the hydrogen concentration distribution in combination with stress field at the front of cracks tips would induce the cracks propagation by “hydrogen enhanced local plastic deformation” and “hydrogen enhanced decohesion” mechanisms. As a result, mainly fracture characterizations of intergranular cracking, transgranular cleavage and secondary cracks formed on the fracture surface.
We report on the observation of the accreting pulsar GRO J1008-57 performed by Insight-Hard X-ray Modulation Telescope (HXMT) at the peak of the source's 2017 outburst. Pulsations are detected with a ...spin period of 93.283(1) s. The pulse profile shows double peaks at soft X-rays, and only one peak above 20 keV. The spectrum is well described by the phenomenological models of X-ray pulsars. A cyclotron resonant scattering feature (CRSF) is detected with very high statistical significance at a centroid energy of keV, for the reference continuum and line models, HIGHECUT and GABS, respectively. Detection is very robust with respect to different continuum models. The line energy is significantly higher than what is suggested from previous observations, which provided very marginal evidence for the line. This establishes a new record for the centroid energy of a fundamental CRSF observed in accreting pulsars. We also discuss the accretion regime of the source during the Insight-HXMT observation.
beta decay of proton-rich nuclei plays an important role in exploring isospin mixing. The beta decay of P-26 at the proton drip line is studied using double-sided silicon strip detectors operating in ...conjunction with high-purity germanium detectors. The T = 2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in Si-26 are unambiguously identified through beta-delayed two-proton emission (beta 2p). Angular correlations of two protons emitted from Si-26 excited states populated by P-26 beta decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the Si-26 IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in beta-decay experiments.
Context.
A link has finally been established between magnetars and fast radio burst (FRB) sources. Within this context, a major issue that remains unresolved pertains to whether sources of ...extragalactic FRBs exhibit X/
γ
-ray outbursts and whether this is correlated with radio activity. If so, the subsequent goal is to identify these sources.
Aims.
We aim to constrain possible X/
γ
-ray burst activity from one of the nearest extragalactic FRB sources currently known. This is to be done over a broad energy range by looking for bursts over a range of timescales and energies that are compatible with those of powerful flares from extragalactic magnetars.
Methods.
We followed up on the observation of the as-yet nearest extragalactic FRB source, located at a mere 149 Mpc distance, namely, the periodic repeater
FRB 180916.J0158+65
. This took place during the active phase between 4 and 7 February 2020, using the Insight–Hard X-ray Modulation Telescope (Insight–HXMT). By taking advantage of the combination of broad-band wavelengths, a large effective area, and several independent detectors at our disposal, we searched for bursts over a set of timescales from 1 ms to 1.024 s with a sensitive algorithm that had been previously characterised and optimised. Moreover, through simulations, we studied the sensitivity of our technique in the released energy-duration phase space for a set of synthetic flares and assuming a range of different energy spectra.
Results.
We constrain the possible occurrence of flares in the 1−100 keV energy band to
E
< 10
46
erg for durations Δ
t
< 0.1 s over several tens of ks exposure.
Conclusions.
We can rule out the occurrence of giant flares similar to the ones that were observed in the few cases of Galactic magnetars. The absence of reported radio activity during our observations prevents us from making any determinations regarding the possibility of simultaneous high-energy emission.
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