ALMaQUEST. IV. The ALMA-MaNGA QUEnching and STar Formation (ALMaQUEST) Survey

The ALMaQUEST (ALMA-MaNGA QUEnching and STar formation) survey is a program with spatially-resolved $^{12}$CO(1-0) measurements obtained with the Atacama Large Millimeter Array (ALMA) for 46 galaxies selected from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) DR15 optical integral-field spectroscopic survey. The aim of the ALMaQUEST survey is to investigate the dependence of star formation activity on the cold molecular gas content at kpc scales in nearby galaxies. The sample consists of galaxies spanning a wide range in specific star formation rate (sSFR), including starburst (SB), main-sequence (MS), and green valley (GV) galaxies. In this paper, we present the sample selection and characteristics of the ALMA observations, and showcase some of the key results enabled by the combination of spatially-matched stellar populations and gas measurements. Considering the global (aperture-matched) stellar mass, molecular gas mass, and star formation rate of the sample, we find that the sSFR depends on both the star formation efficiency (SFE) and the molecular gas fraction ($f_{\rm H_{2}}$), although the correlation with the latter is slightly weaker. Furthermore, the dependence of sSFR on the molecular gas content (SFE or $f_{\rm H_{2}}$) is stronger than that on either the atomic gas fraction or the molecular-to-atomic gas fraction, albeit with the small HI sample size. On kpc scales, the variations in both SFE and $f_{\rm H_{2}}$ within individual galaxies can be as large as 1-2 dex thereby demonstrating that the availability of spatially-resolved observations is essential to understand the details of both star formation and quenching processes.STFC ER

SDSS-IV MaNGA-resolved Star Formation and Molecular Gas Properties of Green Valley Galaxies: A First Look with ALMA and MaNGA

We study the role of cold gas in quenching star formation in the green valley by analyzing ALMA 12 CO (1-0) observations of three galaxies with resolved optical spectroscopy from the MaNGA survey. We present resolution-matched maps of the star formation rate and molecular gas mass. These data are used to calculate the star formation efficiency (SFE) and gas fraction (f gas ) for these galaxies separately in the central "bulge" regions and outer disks. We find that, for the two galaxies whose global specific star formation rate (sSFR) deviates most from the star formation main sequence, the gas fraction in the bulges is significantly lower than that in their disks, supporting an "inside-out" model of galaxy quenching. For the two galaxies where SFE can be reliably determined in the central regions, the bulges and disks share similar SFEs. This suggests that a decline in f gas is the main driver of lowered sSFR in bulges compared to disks in green valley galaxies. Within the disks, there exist common correlations between the sSFR and SFE and between sSFR and f gas on kiloparsec scales - the local SFE or f gas in the disks declines with local sSFR. Our results support a picture in which the sSFR in bulges is primarily controlled by f gas , whereas both SFE and f gas play a role in lowering the sSFR in disks. A larger sample is required to confirm if the trend established in this work is representative of the green valley as a whole.The work is supported by the Ministry of Science & Technology of Taiwan under the grant MOST 103-2112-M-001-031-MY3 and 106-2112-M-001-034. R.M. and F.B. acknowledge support by the UK Science and Technology Facilities Council (STFC). R.M. acknowledges ERC Advanced Grant 695671 "QUENCH.

Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-kB Activity

The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis.Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment.NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis

Novel, synergistic antifungal combinations that target translation fidelity

There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8 fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone

In vitro measurement of temperature changes during implantation of cemented glenoid components

Background and purpose It is unclear whether the increase in temperature during cement curing may cause osteonecrosis, leading to loosening of the glenoid component in shoulder arthroplasty. We therefore analyzed the temperature during implantation of cemented glenoid implants

The candidate antimalarial drug MMV665909 causes oxygen-dependent mRNA mistranslation and synergises with quinoline-derived antimalarials

To cope with growing resistance to current antimalarials, new drugs with novel modes of action are urgently needed. Molecules targeting protein synthesis appear to be promising candidates. We identified a compound (MMV665909) from the MMV Malaria Box of candidate antimalarials that could produce synergistic growth inhibition with the aminoglycoside antibiotic paromomycin, suggesting a possible action of the compound in mRNA mistranslation. This mechanism of action was substantiated with the yeast cell model using available reporters of mistranslation and other genetic tools. Mistranslation induced by MMV665909 was oxygen-dependent, suggesting a role for reactive oxygen species (ROS). Overexpression of Rli1 (a ROS-sensitive, conserved FeS protein essential in mRNA translation) rescued inhibition by MMV665909, consistent with the drug’s action on translation fidelity being mediated through Rli1. The MMV drug also synergised with major quinoline-derived antimalarials which can perturb amino acid availability or promote ROS stress: chloroquine, amodiaquine and primaquine. The data collectively suggest translation-fidelity as a novel target of antimalarial action and support MMV665909 as a promising drug candidate

Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-1β-activated human mast cells were inhibited by Baicalein via regulation of the NF-κB pathway

Background: Human mast cells are capable of a wide variety of inflammatory responses and play a vital role in the pathogenesis of inflammatory diseases such as allergy, asthma, and atherosclerosis. We have reported that cigarette smoke extract (CSE) significantly increased IL-6 and IL-8 production in IL-1β-activated human mast cell line (HMC-1). Baicalein (BAI) has anti-inflammatory properties and inhibits IL-1β- and TNF-α-induced inflammatory cytokine production from HMC-1. The goal of the present study was to examine the effect of BAI on IL-6 and IL-8 production from CSE-treated and IL-1β-activated HMC-1.Methods: Main-stream (Ms) and Side-stream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI-1640 medium. Two ml of HMC-1 at 1 × 10 6 cells/mL were cultured with CSE in the presence or absence of IL-1β (10 ng/mL) for 24 hrs. A group of HMC-1 cells stimulated with both IL-1β (10 ng/ml) and CSE was also treated with BAI. The expression of IL-6 and IL-8 was assessed by ELISA and RT-PCR. NF-κB activation was measured by electrophoretic mobility shift assay (EMSA) and IκBα degradation by Western blot.Results: Both Ms and Ss CSE significantly increased IL-6 and IL-8 production (p \u3c 0.001) in IL-1β-activated HMC-1. CSE increased NF-κB activation and decreased cytoplasmic IκBα proteins in IL-1β-activated HMC-1. BAI (1.8 to 30 μM) significantly inhibited production of IL-6 and IL-8 in a dose-dependent manner in IL-1β-activated HMC-1 with the optimal inhibition concentration at 30 μM, which also significantly inhibited the enhancing effect of CSE on IL-6 and IL-8 production in IL-1β-activated HMC-1. BAI inhibited NF-κB activation and increased cytoplasmic IκBα proteins in CSE-treated and IL-1β-activated HMC-1.Conclusions: Our results showed that CSE significantly increased inflammatory cytokines IL-6 and IL-8 production in IL-1β-activated HMC-1. It may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. BAI inhibited the production of inflammatory cytokines through inhibition of NF-κB activation and IκBα phosphorylation and degradation. This inhibitory effect of BAI on the expression of inflammatory cytokines induced by CSE suggests its usefulness in the development of novel anti-inflammatory therapies