The VMC Survey. V. First results for Classical Cepheids

The VISTA Magellanic Cloud (VMC, PI M.R. Cioni) survey is collecting deep Ks-band time-series photometry of the pulsating variable stars hosted by the system formed by the two Magellanic Clouds (MCs) and the "bridge" connecting them. In this paper we present the first results for Classical Cepheids, from the VMC observations of two fields in the Large Magellanic Cloud (LMC). The VMC Ks-band light curves of the Cepheids are well sampled (12-epochs) and of excellent precision. We were able to measure for the first time the Ks magnitude of the faintest Classical Cepheids in the LMC (Ks\sim17.5 mag), which are mostly pulsating in the First Overtone (FO) mode, and to obtain FO Period-Luminosity (PL), Period-Wesenheit (PW), and Period-Luminosity-Color (PLC) relations, spanning the full period range from 0.25 to 6 day. Since the longest period Cepheid in our dataset has a variability period of 23 day, we have complemented our sample with literature data for brighter F Cepheids. On this basis we have built a PL relation in the Ks band that, for the first time, includes short period pulsators, and spans the whole range from 1.6 to 100 days in period. We also provide the first ever empirical PW and PLC relations using the (V-Ks) color and time-series Ks photometry. The very small dispersion (\sim0.07 mag) of these relations makes them very well suited to study the three-dimensional (3D) geometry of the Magellanic system. The use of "direct" (parallax- and Baade-Wesselink- based) distance measurements to both Galactic and LMC Cepheids, allowed us to calibrate the zero points of the PL, PW, and PLC relations obtained in this paper, and in turn to estimate an absolute distance modulus of (m-M)0=18.46\pm0.03 for the LMC. This result is in agreement with most of the latest literature determinations based on Classical Cepheids.Comment: 12 pages, 7 figures: MNRAS in pres

TRPM2 channel deficiency prevents delayed cytosolic Zn²⁺ accumulation and CA1 pyramidal neuronal death after transient global ischemia

Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn²⁺ level ([Zn²⁺]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia-reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn²⁺]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn²⁺]c but abolished the cytosolic Zn²⁺ accumulation during reperfusion as well as ROS-elicited increases in the [Zn²⁺]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn²⁺]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury

Surveying the Agents of Galaxy Evolution in the Tidally-Stripped, Low Metallicity Small Magellanic Cloud (SAGE-SMC) II. Cool Evolved Stars

We investigate the infrared (IR) properties of cool, evolved stars in the Small Magellanic Cloud (SMC), including the red giant branch (RGB) stars and the dust-producing red supergiant (RSG) and asymptotic giant branch (AGB) stars using observations from the Spitzer Space Telescope Legacy program entitled: "Surveying the Agents of Galaxy Evolution in the Tidally-stripped, Low Metallicity SMC", or SAGE-SMC. The survey includes, for the first time, full spatial coverage of the SMC bar, wing, and tail regions at infrared (IR) wavelengths (3.6 - 160 microns). We identify evolved stars using a combination of near-IR and mid-IR photometry and point out a new feature in the mid-IR color-magnitude diagram that may be due to particularly dusty O-rich AGB stars. We find that the RSG and AGB stars each contribute ~20% of the global SMC flux (extended + point-source) at 3.6 microns, which emphasizes the importance of both stellar types to the integrated flux of distant metal-poor galaxies. The equivalent SAGE survey of the higher-metallicity Large Magellanic Cloud (SAGE-LMC) allows us to explore the influence of metallicity on dust production. We find that the SMC RSG stars are less likely to produce a large amount of dust (as indicated by the [3.6]-[8] color). There is a higher fraction of carbon-rich stars in the SMC, and these stars appear to able to reach colors as red as their LMC counterparts, indicating that C-rich dust forms efficiently in both galaxies. A preliminary estimate of the dust production in AGB and RSG stars reveals that the extreme C-rich AGB stars dominate the dust input in both galaxies, and that the O-rich stars may play a larger role in the LMC than in the SMC.Comment: Accepted for publication in AJ. 25 pages, 36 figures, Table 4 will be available electronically from A

Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Bioremediation of PCP by Trichoderma and Cunninghamella Strains Isolated from Sawdust

Four fungal isolates, SD12, SD14, SD19 and SD20 isolated from the aged sawdust grew on agar plates supplemented with PCP up to a concentration of 100 mg L-1. At high PCP concentration, isolate SD12 showed the highest radial growth rate of 10 mm day-1, followed by SD14 and SD19 both with 4.5 mm day-1 and SD20 with 4.2 mm day-1. Ultrastructural study on the effect of PCP on the PCP tolerant fungi using scanning electron microscope showed that high concentration of PCP caused the collapse of both fungal hyphae and spores. Among the four PCP tolerant fungi examined, isolate SD12 showed the least structural damage at high PCP concentration of 100 mg L-1. This fungal isolate was further characterized and identified as Cunninghamella sp. UMAS SD12. Preliminary PCP biodegradation trial performed in liquid minimal medium supplemented with 20 mg L-1 of PCP using Cunninghamella sp. UMAS SD12 showed that the degradation up to 51.7% of PCP in 15 days under static growth condition