ABSTRACT
We studied the 2018 outburst of the black hole transient H 1743 − 322 with a series of Insight-HXMT, NICER, and NuSTAR observations, covering the 1–120 keV band. With our broad-band X-ray ...spectral modelling, we confirm that the source remained in the low/hard state throughout the month-long outburst, although it became marginally softer at peak flux. We detected Type-C quasi-periodic oscillations (QPOs) and followed the evolution of their properties. The QPO frequency increased from ∼0.1 to ∼0.4 Hz during the rising phase of the outburst and decreased again in the decline. Continuum X-ray flux, power-law photon index, QPO frequency, and QPO root-mean-square amplitude were positively correlated. The QPO amplitude was slightly higher in the soft X-ray band (typical values of 12–16 per cent, compared with 8–10 per cent in the hard band). Our spectral-timing results shed light on the initial rising phase in the low/hard state, which has rarely been monitored with such high cadence, time resolution, and broad-band coverage. Combining spectral and timing properties, we find that ‘failed’ (hard state only) and ‘successful’ outbursts follow the same initial evolutionary track, although the former class of outburst never reaches the threshold for a transition to softer (thermally dominated) accretion regimes.
The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: ...Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear.
To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed.
Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression.
Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.
Congenital scoliosis (CS) is a spinal deformity present at birth due to underlying congenital vertebral malformation (CVM) that occurs during embryonic development. Hemivertebrae is the most common ...anomaly that causes CS. Recently, compound heterozygosity in TBX6 has been identified in Northern Chinese, Japanese, and European CS patient cohorts, which explains about 7%‐10% of the affected population. In this report, we recruited 67 CS patients characterized with hemivertebrae in the Southern Chinese population and investigated the TBX6 variant and risk haplotype. We found that two patients with hemivertebrae in the thoracic spine and one patient with hemivertebrae in the lumbar spine carry the previously defined pathogenic TBX6 compound heterozygous variants. In addition, whole exome sequencing of patients with CS and their family members identified a de novo missense mutation (c.G47T: p.R16L) in another member of the T‐box family, TBXT. This rare mutation compromised the binding of TBXT to its target sequence, leading to reduced transcriptional activity, and exhibited dominant‐negative effect on wild‐type TBXT. Our findings further highlight the importance of T‐box family genes in the development of congenital scoliosis.
Reliability of parentage test panels is usually based on its power to exclude wrong parentage assignments based on allele frequencies. We evaluated the rates of false exclusions and inclusions in ...parentage assignments, and how these results are affected by allele frequencies, panel sizes and the number of allowed mismatches. We also evaluated the reliability of parentage testing by comparing populations with distinct genetic backgrounds using pure and composite families of cattle and sheep. Allowing for 1% genotype mismatches in true parent–offspring relations provided the best compromise between false‐positive and false‐negative assignments. Pure breeds needed at least 200–210 single‐nucleotide polymorphism (SNP) markers to correctly assign relations, but between 700 and 890 markers to avoid assigning incorrect relationships. Composite breeds needed between 220 (sheep) and 500 (cattle) markers for correct assignment; 680 (cattle) to 4400 (sheep) SNPs were needed to eliminate false‐positive assignments. Allowing 0% genotype mismatches decreased false‐positive but increased false‐negative assignments, whilst a higher threshold of 2% showed the opposite effects. Panels with high minor allele frequencies (0.35–0.45) provided the best chance for correct parentage resolutions requiring fewer markers. Further, we propose that a dynamic threshold would allow adapting to population specific error rates. A comparison to the performance of the official International Society for Animal Genetics SNP panel for cattle and a recently published SNP panel for sheep showed that randomly selected markers performed only slightly worse for the applied parentage test based on opposing homozygotes. This suggests that even with carefully selected panels, only marginal assignment improvements are obtainable for a particular number of SNPs. The main point for improvement is the number of markers used. We recommend using at least 200 SNP markers for parentage testing if the aim is to reduce false‐negative results. To fully exclude false positives at least 700 markers are required.
Abstract
We report the energy-resolved broadband timing analysis of the black hole X-ray transient MAXI J1631-479 during its 2019 outburst from February 11 to April 9, using data from the ...Insight−Hard X-ray Modulation Telescope (Insight-HXMT), which caught the source from its hard-intermediate state to the soft state. Thanks to the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of fast variability up to ∼100 keV. Type-C quasi-periodic oscillations (QPOs) with a frequency varying between 4.9 and 6.5 Hz are observed in the 1–100 keV energy band. While the QPO fractional rms increases with photon energy from 1 keV to ∼10 keV and remains more or less constant from ∼10 keV to ∼100 keV, the rms of the flat-top noise first increases from 1 keV to ∼8 keV and then drops to less than 0.1% above ∼30 keV. We suggest that the disappearance of the broadband variability above 30 keV could be caused by the nonthermal acceleration in the Comptonizing plasma. At the same time, the QPOs could be produced by the precession of either a small-scale jet or a hot inner flow model.
Lysophosphatidylcholine (LPC) has been suggested to serve as a useful prognostic marker for sepsis. However, existing LPC assays are complicated, time-consuming, and of limited application in real ...clinical situations. Thus, we investigated the serum LPC levels in sepsis patients using an enzymatic assay and analyzed the correlations between the serum LPC concentration and clinical characteristics. We prospectively collected blood samples from suspected sepsis patients, commencing on day 1 of sepsis. We analyzed all samples using an enzymatic assay. Additionally, we analyzed the serum LPC concentrations in a control group of 21 healthy blood donors. A total of 105 patients who fulfilled the sepsis criteria were included. The mean serum LPC concentration was 43.49 ± 33.09 μmol/L in sepsis patients, which was much lower than that of 21 healthy controls (234.68 ± 30.33 μmol/L,
p
< 0.001). Bacteremic sepsis was associated with a lower serum LPC concentration than non-bacteremic sepsis (34.81 ± 26.85 vs. 49.05 ± 35.63 μmol/L,
p
< 0.05). No difference in serum LPC concentration was evident between survivors and non-survivors. The serum LPC concentration tended to decrease with the severity of sepsis. The day 1 serum LPC concentration was decreased in patients with sepsis, especially when bacteremia was present. However, the serum LPC level did not correlate with disease severity and did not predict mortality from sepsis.
To evaluate existing evidence of prospective cohort studies on associations between insomnia and multiple health outcomes.
An umbrella review of meta-analyses of prospective cohort studies.
A ...systematic search was undertaken in Pubmed, Embase, Cochrane, and Web of Science from inception to October 2021 to find meta-analyses of prospective cohort studies investigating the association of insomnia with any health outcome. The summary relative risk (SRR) for each meta-analysis was recalculated with random-effects model. The methodological quality and the quality of evidence were assessed by the A Measurement Tool to Assess Systematic Reviews and Grading of Recommendations, Assessment, Development and Evaluation, respectively.
A total of 25 published meta-analyses of prospective cohort studies, reporting 63 SRRs for 29 unique outcomes were included. Insomnia was mainly related to cardiovascular outcomes and mental disorders. The former comprised atrial fibrillation (SRR: 1.30, 95% confidence interval: 1.26 to 1.35), cardiovascular diseases (1.45, 1.29 to 1.64), coronary heart disease (1.28, 1.10 to 1.50), myocardial infarction (1.42, 1.17 to 1.72), and stroke (1.55, 1.39 to 1.72). The latter involved alcohol abuse (1.35, 1.08 to 1.67), all mental disorders (2.16, 1.70 to 3.97), anxiety (3.23, 1.52 to 6.85), depression (2.31, 1.90 to 2.81), suicidal ideation (2.26, 1.79 to 2.86), suicidal attempt (1.99, 1.31 to 3.02), and suicidal death (1.72, 1.42 to 2.08). Besides, insomnia enhanced the risk of Alzheimer's disease (1.51, 1.06 to 2.14) and hyperlipidemia (1.64, 1.53 to 1.76).
Insomnia exhibits considerable adverse outcomes, primarily comprises cardiovascular outcomes and mental disorders, but further studies with robustly designed trials are needed to draw firmer conclusions.
Abstract
We present a spectral study of the black hole candidate MAXI J1348−630 during its 2019 outburst, based on monitoring observations with Insight-HXMT and Swift. Throughout the outburst, the ...spectra are well fitted with power-law plus disk-blackbody components. In the soft-intermediate and soft states, we observed the canonical relation
L
∝
T
in
4
between disk luminosity
L
and peak color temperature
T
in
, with a constant inner radius
R
in
(traditionally identified with the innermost stable circular orbit). At other stages of the outburst cycle, the behavior is more unusual, inconsistent with the canonical outburst evolution of black hole transients. In particular, during the hard rise, the apparent inner radius is smaller than in the soft state (and increasing), and the peak color temperature is higher (and decreasing). This anomalous behavior is found even when we model the spectra with self-consistent Comptonization models, which take into account the upscattering of photons from the disk component into the power-law component. To explain both anomalous trends at the same time, we suggest that the hardening factor for the inner-disk emission was larger than the canonical value of ≈1.7 at the beginning of the outburst. A more physical trend of radii and temperature evolution requires a hardening factor evolving from ≈3.5 at the beginning of the hard state to ≈1.7 in the hard-intermediate state. This could be evidence that the inner disk was in the process of condensing from the hot, optically thin medium and had not yet reached a sufficiently high optical depth for its emission spectrum to be described by the standard optically thick disk solution.
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof‐of‐concept has been established in nonhuman primates. However, significant ...barriers to xenoislet transplantation remain, including the poorly understood instant blood‐mediated inflammatory reaction and a thorough understanding of early xeno‐specific immune responses. A paucity of data exist comparing xeno‐specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling)‐positive cells) of NPIs compared with AIs. Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (wild‐type) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (α1,3‐galactosyltransferase knockout) compared with AIs. These findings demonstrate an augmented macrophage and antibody response toward xenografts compared with allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.
A nonhuman primate dual transplant model of islet transplantation compares allogeneic islets to porcine xenogeneic islets and demonstrates an augmented macrophage and antibody response toward xenografts and an early increase in xenograft cell death.
Abstract
The X9.3 flare SOL20170906T11:55 was observed by the CsI detector aboard the first Chinese X-ray observatory Hard X-ray Modulation telescope (Insight-HXMT). Using the wavelets method, we ...report 22 s quasiperiodic pulsations during the impulsive phase. The spectra from 100 keV to 800 keV show the evolution with the gamma-ray flux of a power-law photon index from ∼1.8 before the peak, ∼2.0 around the flare peak, to ∼1.8 again. The gyrosynchrotron microwave spectral analysis reveals a 36.″6 ± 0.″6 radius gyrosynchrotron source with mean transverse magnetic field around 608.2 Gauss. The penetrated ≥10 keV non-thermal electron density is about 10
6.7
cm
−3
at peak time. The magnetic field strength followed the evolution of high-frequency radio flux. Further gyrosynchrotron source modeling analysis implies that there exists a quite steady gyrosynchrotron source, and the non-thermal electron density and transverse magnetic field evolution are similar to higher-frequency light curves. The temporal spectral analysis reveals that those non-thermal electrons are accelerated by repeated magnetic reconnection, likely from a lower corona source.
PDF
