An Apparent Redshift Dependence of Quasar Continuum: Implication for Cosmic Dust Extinction?

We investigate the luminosity and redshift dependence of the quasar continuum by means of composite spectrum using a large non-BAL radio-quiet quasar sample drawn from the Sloan Digital Sky Survey. Quasar continuum slopes in the UV-Opt band are measured at two different wavelength ranges, i.e., $\alpha_{\nu12}$ ($1000\sim 2000 \rm\AA$) and $\alpha_{\nu24}$ ($2000 \sim 4000 \rm\AA$) derived from power law fitting. Generally, the UV spectra slope becomes harder (higher $\alpha_{\nu}$) towards higher bolometric luminosity. On the other hand, when quasars are further grouped into luminosity bins, we find both $\alpha_{\nu12}$ and $\alpha_{\nu24}$ show significant anti-correlation with redshift (i.e., quasar continuum becomes redder towards higher redshift). We suggest that the cosmic dust extinction is very likely the cause of this observed $\alpha_\nu-z$ relation. We build a simple cosmic dust extinction model to quantify the observed reddening tendency and find an effective dust density $n\sigma_v \sim 10^{-5}h~\rm Mpc^{-1}$ at $z<1.5$. The other possibilities that could produce such a reddening effect have also been discussed.Comment: 6 pages, 5 figures; published in ApJ

A novel nutritional inflammation index for predicting mortality in acute ischemic stroke patients: insights into advanced lung cancer inflammation index from the Medical Information Mart for Intensive Care-IV database

ObjectiveThis investigation aimed to delineate the association between the advanced lung cancer inflammation index (ALI) and all-cause mortality (ACM) in individuals experiencing acute ischemic stroke (AIS).MethodsDrawing on information from the Medical Information Mart for Intensive Care (MIMIC)-IV database, release 2.2, covering the years 2012 to 2019, this research assessed the advanced lung cancer inflammation index (ALI) by factoring in body mass index (BMI), serum albumin levels (ALB), and the neutrophil-to-lymphocyte ratio (NLR). Patients with AIS were identified using codes from the International Classification of Diseases (ICD). To address potential confounding factors, a 1:1 propensity score matching (PSM) method was utilized. The investigation identified the pivotal ALI level impacting patient survival using maximally selected rank statistics. It then examined the effects on short- and long-term ACM through multivariate Cox proportional hazards regression models and Kaplan–Meier (K–M) survival analysis. Additionally, restricted cubic spline (RCS) methods were applied to delve into the linear or nonlinear nature of the relationship between ALI and ACM, with further insights gained from interaction and subgroup analyses.ResultsThe cohort comprised 838 AIS patients. Post-PSM, analysis involved 199 matched patient pairs. Adjusted Cox proportional hazard models indicated a significant association of low ALI (&lt;10.38) with increased in-hospital ACM, both before (HR: 1.98; 95% CI: 1.36–2.88; p &lt; 0.001) and after PSM (HR: 2.16; 95% CI: 1.32–3.52; p = 0.002). Associations of low ALI with elevated risk were consistent across ICU, 30 days, 90 days, and 1 year ACM pre- and post-PSM. Subsequent RCS analysis post-PSM underscored a negative nonlinear relationship between ALI and ACM over both short and long terms, without significant interaction effects across different subgroups for ACM.ConclusionIn this retrospective cohort study, by utilizing a nationally representative sample of United States patients with AIS, our analysis elucidates a negative correlation between the ALI and ACM in individuals with AIS, underscoring the utility of ALI as a novel, efficacious, and accessible inflammatory biomarker for prognosticating ACM. These results carry profound implications for public health policy and practice. A deeper comprehension of these associations can empower public health practitioners and researchers to devise more targeted interventions and policies, aimed specifically at catering to the distinct needs of the AIS patient population, thereby enhancing their health outcomes. The further research in other races/ethnicity is urgent, particularly before applying these findings in clinical practice

Altered cofactor regulation with disease-associated p97/VCP mutations

Dominant mutations in p97/VCP (valosin-containing protein) cause a rare multisystem degenerative disease with varied phenotypes that include inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. p97 disease mutants have altered N-domain conformations, elevated ATPase activity, and altered cofactor association. We have now discovered a previously unidentified disease-relevant functional property of p97 by identifying how the cofactors p37 and p47 regulate p97 ATPase activity. We define p37 as, to our knowledge, the first known p97-activating cofactor, which enhances the catalytic efficiency (k_(cat)/K_m) of p97 by 11-fold. Whereas both p37 and p47 decrease the K_m of ATP in p97, p37 increases the k_(cat) of p97. In contrast, regulation by p47 is biphasic, with decreased k_(cat) at low levels but increased k_(cat) at higher levels. By deleting a region of p47 that lacks homology to p37 (amino acids 69–92), we changed p47 from an inhibitory cofactor to an activating cofactor, similar to p37. Our data suggest that cofactors regulate p97 ATPase activity by binding to the N domain. Induced conformation changes affect ADP/ATP binding at the D1 domain, which in turn controls ATPase cycling. Most importantly, we found that the D2 domain of disease mutants failed to be activated by p37 or p47. Our results show that cofactors play a critical role in controlling p97 ATPase activity, and suggest that lack of cofactor-regulated communication may contribute to p97-associated disease pathogenesis

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwid

Deletion of the epigenetic regulator GcnE in Aspergillus niger FGSC A1279 activates the production of multiple polyketide metabolites

Epigenetic modification is an important regulatory mechanism in the biosynthesis of secondary metabolites in Aspergillus species, which have been considered to be the treasure trove of new bioactive secondary metabolites. In this study, we reported that deletion of the epigenetic regulator gcnE, a histone acetyltransferase in the SAGA/ADA complex, resulted in the production of 12 polyketide secondary metabolites in A. niger FGSC A1279, which was previously not known to produce toxins or secondary metabolites. Chemical workup and structural elucidation by 1D/2D NMR and high resolution electrospray ionization mass (HR-ESIMS) yielded the novel compound nigerpyrone (1) and five known compounds: carbonarone A (2), pestalamide A (3), funalenone (4), aurasperone E (5), and aurasperone A (6). Based on chemical information and the literature, the biosynthetic gene clusters of funalenone (4), aurasperone E (5), and aurasperone A (6) were located on chromosomes of A. niger FGSC A1279. This study found that inactivation of GcnE activated the production of secondary metabolites in A. niger. The biosynthetic pathway for nigerpyrone and its derivatives was identified and characterized via gene knockout and complementation experiments. A biosynthetic model of this group of pyran-based fungal metabolites was proposed. [Abstract copyright: Crown Copyright © 2018. Published by Elsevier GmbH. All rights reserved.

An Integrated Study on the Differential Expression of the <i>FOX</i> Gene Family in Cancer and Their Response to Chemotherapy Drugs

The Forkhead-box (FOX) transcription factors, as one of the largest gene families in humans, play key roles in cancer. Although studies have suggested that several FOX transcription factors have a significant impact on cancer, the functions of most of the FOX genes in cancer remain elusive. In the study, the expression of 43 FOX genes in 63 kinds of cancer diseases (including many subtypes of same cancer) and in response to 60 chemical substances was obtained from the Gene Expression Atlas database of the European Bioinformatics Institute. Based on the high degree of overlap in FOXO family members differentially expressed in various cancers and their particular responses to chemotherapeutic drugs, our data disclosed the FOX genes that played an important role in the development and progression of cancer. More importantly, we predicted the role of one or several combinatorial FOX genes in the diagnosis and prognostic assessment of a specific cancer and evaluated the potential of a certain anticancer drug therapy for this type of cancer by integrating patterns of FOX genes expression with anticancer drugs sensitivity