Near-IR spectroscopic ages of massive star clusters in M82

Like other starburst galaxies, M82 hosts compact, massive young star clusters that are interesting both in their own right and as benchmarks for population synthesis models. Can spectral synthesis models at resolutions around 1000 adequately reproduce the near-IR spectral features and the energy distribution of these clusters between 0.8 and 2.4 microns? How do the derived cluster properties compare with previous results from optical studies? We analyse the spectra of 5 massive clusters in M82, using data acquired with the spectrograph SpeX on the InfraRed Telescope Facility (NASA/IRTF) and a new population synthesis tool with a highly improved near-IR extension, based on a recent collection of empirical and theoretical spectra of red supergiant stars. We obtain excellent fits across the near-IR with models at quasi-solar metallicity and a solar neighbourhood extinction law. Spectroscopy breaks a strong degeneracy between age and extinction in the near-IR colours in the red supergiant-dominated phase of evolution. The estimated near-IR ages cluster between 9 and 30 Myr, i.e. the ages at which the molecular bands due to luminous red supergiants are strongest in the current models. They do not always agree with optical spectroscopic ages. Adding optical data sometimes leads to the rejection of the solar neighbourhood extinction law. This is not surprising considering small-scale structure around the clusters, but it has no significant effect on the near-IR based spectroscopic ages. [abridged]Comment: 14 pages, 20 figures, uses aa.cl

Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BACKGROUND: Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. METHODS: This observational, prospective surveillance study recruited hospitalized adults aged \u3e /=18years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. RESULTS: Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1years and 52.7% were aged \u3e /=65years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged \u3e /=65years. Among patients aged 18-64years PCV13 serotypes were detected in 3.8-5.3% of patients depending on their risk status. CONCLUSIONS: After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population

The Relation Between the Surface Brightness and the Diameter for Galactic Supernova Remnants

In this work, we have constructed a relation between the surface brightness ($\Sigma$) and diameter (D) of Galactic C- and S-type supernova remnants (SNRs). In order to calibrate the $\Sigma$-D dependence, we have carefully examined some intrinsic (e.g. explosion energy) and extrinsic (e.g. density of the ambient medium) properties of the remnants and, taking into account also the distance values given in the literature, we have adopted distances for some of the SNRs which have relatively more reliable distance values. These calibrator SNRs are all C- and S-type SNRs, i.e. F-type SNRs (and S-type SNR Cas A which has an exceptionally high surface brightness) are excluded. The Sigma-D relation has 2 slopes with a turning point at D=36.5 pc: $\Sigma$(at 1 GHz)=8.4$^{+19.5}_{-6.3}$$\times10^{-12}$ D$^{{-5.99}^{+0.38}_{-0.33}}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ (for $\Sigma$$\le3.7\times10^{-21}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ and D$\ge$36.5 pc) and $\Sigma$(at 1 GHz)=2.7$^{+2.1}_{-1.4}$$\times$ 10$^{-17}$ D$^{{-2.47}^{+0.20}_{-0.16}}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ (for $\Sigma$$>3.7\times10^{-21}$ Wm$^{-2}$Hz$^{-1}$ster$^{-1}$ and D$<$36.5 pc). We discussed the theoretical basis for the $\Sigma$-D dependence and particularly the reasons for the change in slope of the relation were stated. Added to this, we have shown the dependence between the radio luminosity and the diameter which seems to have a slope close to zero up to about D=36.5 pc. We have also adopted distance and diameter values for all of the observed Galactic SNRs by examining all the available distance values presented in the literature together with the distances found from our $\Sigma$-D relation.Comment: 45 pages, 2 figures, accepted for publication in Astronomical and Astrophysical Transaction

Non-Small Cell Lung Carcinoma Cell Motility, Rac Activation and Metastatic Dissemination Are Mediated by Protein Kinase C Epsilon

Background: Protein kinase C (PKC) e, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCe in lung cancer metastasis has not yet been established. Principal Findings: Here we show that RNAi-mediated knockdown of PKCe in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCe depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCe with eV1-2, a specific PKCe inhibitor. PKCe was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCe-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Conclusions: Our results implicate PKCe as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target

Action ability modulates time‑to‑collision judgments

Time-to-collision (TTC) underestimation has been interpreted as an adaptive response that allows observers to have more time to engage in a defensive behaviour. This bias seems, therefore, strongly linked to action preparation. There is evidence that the observer’s physical fitness modulates the underestimation effect so that people who need more time to react (i.e. those with less physical fitness) show a stronger underestimation effect. Here we investigated whether this bias is influenced by the momentary action capability of the observers. In the first experiment, participants estimated the time-to-collision of threatening or non-threatening stimuli while being mildly immobilized (with a chin rest) or while standing freely. Having reduced the possibility of movement led participants to show more underestimation of the approaching stimuli. However, this effect was not stronger for threatening relative to non-threatening stimuli. The effect of the action capability found in the first experiment could be interpreted as an expansion of peripersonal space (PPS). In the second experiment, we thus investigated the generality of this effect using an established paradigm to measure the size of peripersonal space. Participants bisected lines from different distances while in the chin rest or standing freely. The results replicated the classic left-to-right gradient in lateral spatial attention with increasing viewing distance, but no effect of immobilization was found. The manipulation of the momentary action capability of the observers influenced the participants’ performance in the TTC task but not in the line bisection task. These results are discussed in relation to the different functions of PPS

Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation

The results of many studies support the influence of the corticotropin-releasing factor (CRF) system on ethanol (EtOH) consumption and EtOH-induced neuroadaptations that are critical in the addiction process. This review summarizes the preclinical data in this area after first providing an overview of the components of the CRF system. This complex system involves hypothalamic and extra-hypothalamic mechanisms that play a role in the central and peripheral consequences of stressors, including EtOH and other drugs of abuse. In addition, several endogenous ligands and targets make up this system and show differences in their involvement in EtOH drinking and in the effects of chronic or repeated EtOH treatment. In general, genetic and pharmacological approaches paint a consistent picture of the importance of CRF signaling via type 1 CRF receptors (CRF1) in EtOH-induced neuroadaptations that result in higher levels of intake, encourage alcohol seeking during abstinence and alter EtOH sensitivity. Furthermore, genetic findings in rodents, non-human primates and humans have provided some evidence of associations of genetic polymorphisms in CRF-related genes with EtOH drinking, although additional data are needed. These results suggest that CRF1 antagonists have potential as pharmacotherapeutics for alcohol use disorders. However, given the broad and important role of these receptors in adaptation to environmental and other challenges, full antagonist effects may be too profound and consideration should be given to treatments with modulatory effects.The authors were supported by the Department of Veterans Affairs; NIH NIAAA grants P60AA010760, R24AA020245 and U01AA013519 and NIH NIDA grant P50DA018165, during the writing of this manuscript. The authors have no financial conflict of interest to disclose

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100