ABSTRACT
SN 2018hti is a Type I superluminous supernova (SLSN I) with an absolute g-band magnitude of −22.2 at maximum brightness, discovered by the Asteroid Terrestrial-impact Last Alert System in a ...metal-poor galaxy at a redshift of 0.0612. We present extensive photometric and spectroscopic observations of this supernova, covering the phases from ∼−35 d to more than +340 d from the r-band maximum. Combining our BVgri-band photometry with Swift UVOT optical/ultraviolet photometry, we calculated the peak luminosity as ∼3.5 × 1044 erg s−1. Modelling the observed light curve reveals that the luminosity evolution of SN 2018hti can be produced by an ejecta mass of 5.8 M⊙ and a magnetar with a magnetic field of B = 1.8 × 1013 G having an initial spin period of P0 = 1.8 ms. Based on such a magnetar-powered scenario and a larger sample, a correlation between the spin of the magnetar and the kinetic energy of the ejecta can be inferred for most SLSNe I, suggesting a self-consistent scenario. Like for other SLSNe I, the host galaxy of SN 2018hti is found to be relatively faint (Mg = −17.75 mag) and of low metallicity (Z = 0.3 Z⊙), with a star formation rate of 0.3 M⊙ yr−1. According to simulation results of single-star evolution, SN 2018hti could originate from a massive, metal-poor star with a zero-age main sequence (ZAMS) mass of 25–40 M⊙, or from a less massive rotating star with MZAMS ≈ 16–25 M⊙. For the case of a binary system, its progenitor could also be a star with $M_\mathrm{ZAMS} \gtrsim 25\, \mathrm{ M}_\odot$.
BACKGROUND AND PURPOSE 3‐Hydroxy‐octanoate, recently identified as a ligand for, the orphan GPCR, HCA3, is of particular interest given its ability to treat lipid disorders and atherosclerosis. Here ...we demonstrate the pathway of HCA3‐mediated activation of ERK1/2.
EXPERIMENTAL APPROACH Using CHO‐K1 cells stably expressing HCA3 receptors and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA3 receptors, HCA3‐mediated activation of ERK1/2 was measured by Western blot.
KEY RESULTS HCA3‐mediated activation of ERK1/2 was rapid, peaking at 5 min, and was Pertussis toxin sensitive. Our data, obtained by time course analyses in combination with different kinase inhibitors, demonstrated that on agonist stimulation, HCA3 receptors evoked ERK1/2 activation via two distinct pathways, the PLC/PKC pathway at early time points (≤2 min) and the MMP/ epidermal growth factor receptor (EGFR) transactivation pathway with a maximum response at 5 min. Furthermore, our present results also indicated that the βγ‐subunits of the Gi protein play a critical role in HCA3‐activated ERK1/2 phosphorylation, whereas β‐arrestins and Src were not required for ERK1/2 activation.
CONCLUSIONS AND IMPLICATIONS We have described the molecular mechanisms underlying the coupling of human HCA3 receptors to the ERK1/2 MAP kinase pathway in CHO‐K1 and A431 cells, which implicate the Gi protein‐initiated, PLC/PKC‐ and platelet‐derived growth factor receptor/EGFR transactivation‐dependent pathways. These observations may provide new insights into the pharmacological effects and the physiological functions modulated by the HCA3‐mediated activation of ERK1/2.
The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable ...techniques for pre-operative determination of tumor grade may enhance clinical decision-making.
A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype. Area under the curve (AUC) and odd ratios (OR) were computed with multiple-hypothesis correction. Random-forest classifiers were developed and validated on an independent dataset (n = 44).
Twelve radiographic features (eight radiomic and four semantic) were significantly associated with meningioma grade. High-grade tumors exhibited necrosis/hemorrhage (ORsem = 6.6, AUCrad = 0.62-0.68), intratumoral heterogeneity (ORsem = 7.9, AUCrad = 0.65), non-spherical shape (AUCrad = 0.61), and larger volumes (AUCrad = 0.69) compared to low-grade tumors. Radiomic and sematic classifiers could significantly predict meningioma grade (AUCsem = 0.76 and AUCrad = 0.78). Furthermore, combining them increased the classification power (AUCradio = 0.86). Clinical variables alone did not effectively predict tumor grade (AUCclin = 0.65) or show complementary value with imaging data (AUCcomb = 0.84).
We found a strong association between imaging features of meningioma and histopathologic grade, with ready application to clinical management. Combining qualitative and quantitative radiographic features significantly improved classification power.
Henosepilachna vigintioctopunctata is a serious pest of Solanaceae and Cucurbitaceae in many Asian countries. RNA interference (RNAi) can effectively reduce transcript abundance in this beetle, ...offering opportunities to explore the biological function of specific genes. The white gene encodes a half‐type ATP‐binding cassette transporter that plays an essential role in tryptophan, guanine and uric acid transport across membranes. Mutations that disrupt the function of white are known to cause eye pigmentation phenotypes in many insect species. Here, we found evidence for five white gene paralogues present in H. vigintioctopunctata transcriptome datasets sequenced from a range of developmental stages. We individually knocked down each of the five white genes through the injection of corresponding double‐stranded RNAs (dsRNAs) to the fourth‐instar larvae to determine whether functional divergence has occurred. We found that injecting 1 μg dswhite3 caused compound eye colour of pupae and adults to develop as red/brown and brown, respectively, compared with black eyes in control beetles. Injection of 2 μg dswhite3 increased RNAi efficacy and produced a clearer eye colour phenotype. At both doses, the ocular diaphragm (a ring of black pigment surrounding each eye) did not change in the white3 RNAi hypomorphs. Moreover, our data revealed that injection of dswhite2 at the fourth‐instar larval stage impaired the climbing ability of both male and female adults. Our results confirmed, for the first time, functional divergence of duplicated white genes in an insect species.
Five white genes were detectable from embryo (egg) to adults. Injection of dswhite3 caused obvious eye color phenotype. Silencing dswhite2 impaired climbing ability of adults.
. Chang S‐N, Tsai C‐T, Wu C‐K, Lee J‐K, Lai L‐P, Huang S‐W, Huang L‐Y, Tseng C‐D, Lin J‐L, Chiang F‐T, Hwang J‐J (National Taiwan University Hospital Yun‐Lin Branch, Yun‐Lin; National Taiwan ...University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C‐reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315.
Objectives. In a large population‐based cohort, the level of C‐reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown.
Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association.
Results. Three polymorphisms (T‐861C, A‐821G and C‐390A/C‐390T) were found in the 1‐kb promoter of CRP. A triallelic polymorphism (C‐390A/C‐390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L‐type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts.
Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.
Summary
Low bone mineral density (BMD) and osteoporosis have become a public health problem. We found that non-Hispanic white, black, and Asian adults with extremely low education and personal income ...are more likely to have lower BMD. This relationship is gender-specific. These findings are valuable to guide bone health interventions.
Introduction
The evidence is limited regarding the relationship between socioeconomic status (SES) and bone mineral density (BMD) for minority populations in the USA, as well as the relationship between SES and BMD for men. This study explored and examined the relationship between SES and BMD by race/ethnicity and gender.
Methods
Data (
n
= 6568) from the Louisiana Osteoporosis Study (LOS) was examined, including data for non-Hispanic whites (
n
= 4153), non-Hispanic blacks (
n
= 1907), and non-Hispanic Asians (
n
= 508). General linear models were used to estimate the relationship of SES and BMD (total hip and lumbar spine) stratified by race/ethnicity and gender. Adjustments were made for physiological and behavioral factors.
Results
After adjusting for covariates, men with education levels below high school graduate experienced relatively low hip BMD than their counterparts with college or graduate education (
p
< 0.05). In addition, women reporting a personal annual income under $20,000 had relatively low hip and spine BMD than their counterparts with higher income level(s) (
p
< 0.05).
Conclusions
Establishing a conclusive positive or negative association between BMD and SES proved to be difficult. However, individuals who are at an extreme SES disadvantage are the most vulnerable to have relatively low BMD in the study population. Efforts to promote bone health may benefit from focusing on men with low education levels and women with low individual income.
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
The US Food and Drug Administration (FDA) is currently developing a guidance for industry to replace a previous guidance, “Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data ...Analysis, and Impact on Dosing and Labeling” (renal guidance) issued in May 1998. The impact of the 1998 renal guidance was assessed following a survey of 94 new drug applications (NDAs) for small‐molecule new molecular entities (NMEs) approved over the past 5 years (2003–2007). The survey results indicate that 57% of these NDAs included renal impairment study data, that 44% of those with renal data included evaluation in patients on hemodialysis, and that 41% of those with renal data resulted in recommendation of dose adjustment in renal impairment. In addition, the survey results provided evidence that renal impairment can affect the pharmacokinetics of drugs that are predominantly eliminated by nonrenal processes such as metabolism and/or active transport. The latter finding supports our updated recommendation to evaluate pharmacokinetic/pharmacodynamic alterations in renal impairment for those drugs that are mainly eliminated by nonrenal processes, in addition to those that are mainly excreted unchanged by the kidney.
Clinical Pharmacology & Therapeutics (2009); 85, 3, 305–311 doi:10.1038/clpt.2008.208
Previous reviews of childhood obesity prevention have focused largely on schools and findings have been inconsistent. Funded by the US Agency for Healthcare Research and Quality (AHRQ) and the ...National Institutes of Health, we systematically evaluated the effectiveness of childhood obesity prevention programmes conducted in high‐income countries and implemented in various settings. We searched MEDLINE®, Embase, PsycINFO, CINAHL®, ClinicalTrials.gov and the Cochrane Library from inception through 22 April 2013 for relevant studies, including randomized controlled trials, quasi‐experimental studies and natural experiments, targeting diet, physical activity or both, and conducted in children aged 2–18 in high‐income countries. Two reviewers independently abstracted the data. The strength of evidence (SOE) supporting interventions was graded for each study setting (e.g. home, school). Meta‐analyses were performed on studies judged sufficiently similar and appropriate to pool using random effect models. This paper reported our findings on various adiposity‐related outcomes. We identified 147 articles (139 intervention studies) of which 115 studies were primarily school based, although other settings could have been involved. Most were conducted in the United States and within the past decade. SOE was high for physical activity‐only interventions delivered in schools with home involvement or combined diet–physical activity interventions delivered in schools with both home and community components. SOE was moderate for school‐based interventions targeting either diet or physical activity, combined interventions delivered in schools with home or community components or combined interventions delivered in the community with a school component. SOE was low for combined interventions in childcare or home settings. Evidence was insufficient for other interventions. In conclusion, at least moderately strong evidence supports the effectiveness of school‐based interventions for preventing childhood obesity. More research is needed to evaluate programmes in other settings or of other design types, especially environmental, policy and consumer health informatics‐oriented interventions.
Well-crystallized, homogeneous nanocomposites of lithium iron(II) phosphate and carbon was synthesized by solid state reaction, and the obtained particles are spherical. Measurement of both CV and ...EIS shows that the lithium ion diffusion coefficient in the nanocomposites is affected by the incorporated carbon, and markedly increases with the carbon content. Meanwhile, the kinetics of lithium intercalation and de-intercalation is greatly ameliorated. These data provide strong evidence of the potential use of this kind of nanocomposite cathode in lithium ion battery.
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