Gene expression differs in susceptible and resistant amphibians exposed to Batrachochytrium dendrobatidis.

Chytridiomycosis, the disease caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has devastated global amphibian biodiversity. Nevertheless, some hosts avoid disease after Bd exposure even as others experience near-complete extirpation. It remains unclear whether the amphibian adaptive immune system plays a role in Bd defence. Here, we describe gene expression in two host species-one susceptible to chytridiomycosis and one resistant-following exposure to two Bd isolates that differ in virulence. Susceptible wood frogs (Rana sylvatica) had high infection loads and mortality when exposed to the more virulent Bd isolate but lower infection loads and no fatal disease when exposed to the less virulent isolate. Resistant American bullfrogs (R. catesbeiana) had high survival across treatments and rapidly cleared Bd infection or avoided infection entirely. We found widespread upregulation of adaptive immune genes and downregulation of important metabolic and cellular maintenance components in wood frogs after Bd exposure, whereas American bullfrogs showed little gene expression change and no evidence of an adaptive immune response. Wood frog responses suggest that adaptive immune defences may be ineffective against virulent Bd isolates that can cause rapid physiological dysfunction. By contrast, American bullfrogs exhibited robust resistance to Bd that is likely attributable, at least in part, to their continued upkeep of metabolic and skin integrity pathways as well as greater antimicrobial peptide expression compared to wood frogs, regardless of exposure. Greater understanding of these defences will ultimately help conservationists manage chytridiomycosis

Modeling the System Parameters of 2M1533+3759: A New Longer-Period Low-Mass Eclipsing sdB+dM Binary

We present new photometric and spectroscopic observations for 2M 1533+3759 (= NSVS 07826147). It has an orbital period of 0.16177042 day, significantly longer than the 2.3--3.0 hour periods of the other known eclipsing sdB+dM systems. Spectroscopic analysis of the hot primary yields Teff = 29230 +/- 125 K, log g = 5.58 +/- 0.03 and log N(He)/N(H) = -2.37 +/- 0.05. The sdB velocity amplitude is K1 = 71.1 +/- 1.0 km/s. The only detectable light contribution from the secondary is due to the surprisingly strong reflection effect. Light curve modeling produced several solutions corresponding to different values of the system mass ratio, q(M2/M1), but only one is consistent with a core helium burning star, q=0.301. The orbital inclination is 86.6 degree. The sdB primary mass is M1 = 0.376 +/- 0.055 Msun and its radius is R1 = 0.166 +/- 0.007 Rsun. 2M1533+3759 joins PG0911+456 (and possibly also HS2333+3927) in having an unusually low mass for an sdB star. SdB stars with masses significantly lower than the canonical value of 0.48 Msun, down to as low as 0.30 Msun, were theoretically predicted by Han et al. (2002, 2003), but observational evidence has only recently begun to confirm the existence of such stars. The existence of core helium burning stars with masses lower than 0.40--0.43 Msun implies that at least some sdB progenitors have initial main sequence masses of 1.8--2.0 Msun or more, i.e. they are at least main sequence A stars. The secondary is a main sequence M5 star.Comment: 47 pages, 7 figure

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Revealing the cold dust in low-metallicity environments: I. Photometry analysis of the Dwarf Galaxy Survey with Herschel

Context. We present new photometric data from our Herschel Guaranteed Time Key Programme, the Dwarf Galaxy Survey (DGS), dedicated to the observation of the gas and dust in low-metallicity environments. A total of 48 dwarf galaxies were observed with the PACS and SPIRE instruments onboard the Herschel Space Observatory at 70, 100, 160, 250, 350, and 500 µm. Aims. The goal of this paper is to provide reliable far infrared (FIR) photometry for the DGS sample and to analyse the FIR/submillimetre (submm) behaviour of the DGS galaxies. We focus on a systematic comparison of the derived FIR properties (FIR luminosity, LFIR, dust mass, Mdust , dust temperature, T, emissivity index, β) with more metal-rich galaxies and investigate the detection of a potential submm excess. Methods. The data reduction method is adapted for each galaxy in order to derive the most reliable photometry from the final maps. The derived PACS flux densities are compared with the Spitzer MIPS 70 and 160 µm bands. We use colour-colour diagrams to analyse the FIR/submm behaviour of the DGS galaxies and modified blackbody fitting procedures to determine their dust properties. To study the variation in these dust properties with metallicity, we also include galaxies from the Herschel KINGFISH sample, which contains more metal-rich environments, totalling 109 galaxies. Results. The location of the DGS galaxies on Herschel colour-colour diagrams highlights the differences in dust grain properties and/or global environments of low-metallicity dwarf galaxies. The dust in DGS galaxies is generally warmer than in KINGFISH galaxies (TDGS ∼ 32 K and TKINGFIS H ∼ 23 K). The emissivity index, β, is ∼ 1.7 in the DGS, however metallicity does not make a strong effect on β. The proportion of dust mass relative to stellar mass is lower in low-metallicity galaxies: Mdust /Mstar ∼ 0.02% for the DGS versus 0.1% for KINGFISH. However, per unit dust mass, dwarf galaxies emit about six times more in the FIR/submm than higher metallicity galaxies. Out of the 22 DGS galaxies detected at 500 µm, about 41% present an excess in the submm beyond the explanation of our dust SED model, and this excess can go up to 150% above the prediction from the model. The excess mainly appears in lower metallicity galaxies (12+log(O/H) ;S 8.3), and the strongest excesses are detected in the most metal-poor galaxies. However, we so stress the need for observations longwards of the Herschel wavelengths to detect any submm excess appearing beyond 500 .Norwegian Lis

Measurement of the t-channel single top quark production cross section in pp collisions at √s =7 TeV

Peer reviewe

Radial distribution of dust, stars, gas, and star-formation rate in DustPedia face-on galaxies

Aims. The purpose of this work is the characterization of the radial distribution of dust, stars, gas, and star-formation rate (SFR) in a sub-sample of 18 face-on spiral galaxies extracted from the DustPedia sample. Methods. This study is performed by exploiting the multi-wavelength DustPedia database, from ultraviolet (UV) to sub-millimeter bands, in addition to molecular (12CO) and atomic (Hi) gas maps and metallicity abundance information available in the literature. We fitted the surface-brightness profiles of the tracers of dust and stars, the mass surface-density profiles of dust, stars, molecular gas, and total gas, and the SFR surface-density profiles with an exponential curve and derived their scale-lengths. We also developed a method to solve for the CO-to-H2 conversion factor (αCO) per galaxy by using dust- and gas-mass profiles. Results. Although each galaxy has its own peculiar behavior, we identified a common trend of the exponential scale-lengths versus wavelength. On average, the scale-lengths normalized to the B-band 25 mag/arcsec2 radius decrease from UV to 70 μm, from 0.4 to 0.2, and then increase back up to ~0.3 at 500 microns. The main result is that, on average, the dust-mass surface-density scale-length is about 1.8 times the stellar one derived from IRAC data and the 3.6 μm surface brightness, and close to that in the UV. We found a mild dependence of the scale-lengths on the Hubble stage T: the scale-lengths of the Herschel bands and the 3.6 μm scale-length tend to increase from earlier to later types, the scale-length at 70 μm tends to be smaller than that at longer sub-mm wavelength with ratios between longer sub-mm wavelengths and 70 μm that decrease with increasing T. The scale-length ratio of SFR and stars shows a weak increasing trend towards later types. Our αCO determinations are in the range (0.3−9) M⊙ pc-2 (K km s-1)-1, almost invariant by using a fixed dust-to-gas ratio mass (DGR) or a DGR depending on metallicity gradient

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells

Background: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. Methods: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. Results: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. Conclusions: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer

Mutational analysis of the major soybean UreF paralogue involved in urease activation

The soybean genome duplicated ∼14 and 45 million years ago and has many paralogous genes, including those in urease activation (emplacement of Ni and CO2 in the active site). Activation requires the UreD and UreF proteins, each encoded by two paralogues. UreG, a third essential activation protein, is encoded by the single-copy Eu3, and eu3 mutants lack activity of both urease isozymes. eu2 has the same urease-negative phenotype, consistent with Eu2 being a single-copy gene, possibly encoding a Ni carrier. Unexpectedly, two eu2 alleles co-segregated with missense mutations in the chromosome 2 UreF paralogue (Ch02UreF), suggesting lack of expression/function of Ch14UreF. However, Ch02UreF and Ch14UreF transcripts accumulate at the same level. Further, it had been shown that expression of the Ch14UreF ORF complemented a fungal ureF mutant. A third, nonsense (Q2*) allelic mutant, eu2-c, exhibited 5- to 10-fold more residual urease activity than missense eu2-a or eu2-b, though eu2-c should lack all Ch02UreF protein. It is hypothesized that low-level activation by Ch14UreF is ‘spoiled’ by the altered missense Ch02UreF proteins (‘epistatic dominant-negative’). In agreement with active ‘spoiling’ by eu2-b-encoded Ch02UreF (G31D), eu2-b/eu2-c heterozygotes had less than half the urease activity of eu2-c/eu2-c siblings. Ch02UreF (G31D) could spoil activation by Chr14UreF because of higher affinity for the activation complex, or because Ch02UreF (G31D) is more abundant than Ch14UreF. Here, the latter is favoured, consistent with a reported in-frame AUG in the 5' leader of Chr14UreF transcript. Translational inhibition could represent a form of ‘functional divergence’ of duplicated genes

Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation

Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-κB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation- and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-κB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-κB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund’s adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-κB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-κB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-κB activity in astrocytes. Furthermore, we observed NF-κB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-κB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

Background: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns