Spectroscopic confirmation of a substantial population of luminous red galaxies at redshifts z ≳ 2

We confirm spectroscopically the existence of a population of galaxies at z greater than or similar to 2 with rest-frame optical colors similar to normal nearby galaxies. The galaxies were identified by their red near-infrared colors in deep images obtained with the Infrared Spectrometer and Array Camera on the Very Large Telescope of the field around the foreground cluster MS 1054-03. Redshifts of six galaxies with J(s)-K-s > 2.3 were measured from optical spectra obtained with the W. M. Keck telescope. Five out of six are in the range, demonstrating that the 2.43 = z = 3.52 J(s)-K-s color selection is quite efficient. The rest-frame ultraviolet spectra of confirmed z > 2 galaxies display a range of properties, with two galaxies showing emission lines characteristic of active galactic nuclei, two having Lyalpha in emission, and one showing interstellar absorption lines only. Their full spectral energy distributions are well described by constant star formation models with ages 1.4-2.6 Gyr, except for one galaxy whose colors indicate a dusty starburst. The confirmed z > 2 galaxies are very luminous: their K-s magnitudes are in the range 19.2-19.9, corresponding to rest-frame absolute V magnitudes from -24.8 to -23.2. Assuming that our bright spectroscopic sample is representative for the general population of J(s)-K-s selected objects, we find that the surface density of red z greater than or similar to 2 galaxies is approximate to0.9 arcmin(-2) to K-s = 21. The surface density is comparable to that of Lyman break-selected galaxies with K-s < 21, when corrections are made for the different redshift distributions of the two samples. Although there will be some overlap between the two populations, most "optical-break" galaxies are too faint in the rest-frame ultraviolet to be selected as Lyman break galaxies. The most straightforward interpretation is that star formation in typical optical-break galaxies started earlier than in typical Lyman break galaxies. Optical-break galaxies may be the oldest and most massive galaxies yet identified at, and they z 1 2 could evolve into early-type galaxies and bulges

A new cell primo-culture method for freshwater benthic diatom communities

A new cell primo-culture method was developed for the benthic diatom community isolated from biofilm sampled in rivers. The approach comprised three steps: (1) scraping biofilm from river pebbles, (2) diatom isolation from biofilm, and (3) diatom community culture. With a view to designing a method able to stimulate the growth of diatoms, to limit the development of other microorganisms, and to maintain in culture a community similar to the original natural one, different factors were tested in step 3: cell culture medium (Chu No 10 vs Freshwater “WC” medium modified), cell culture vessel, and time of culture. The results showed that using Chu No 10 medium in an Erlenmeyer flask for cell culture was the optimal method, producing enough biomass for ecotoxicological tests as well as minimising development of other microorganisms. After 96 h of culture, communities differed from the original communities sampled in the two rivers studied. Species tolerant of eutrophic or saprobic conditions were favoured during culture. This method of diatom community culture affords the opportunity to assess, in vitro, the effects of different chemicals or effluents (water samples andindustrial effluents) on diatom communities, as well as on diatom cells, from a wide range of perspectives

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

<p>Abstract</p> <p>Background</p> <p>Interferon gamma is a major macrophage-activating cytokine during infection with <it>Mycobacterium tuberculosis</it>, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as <it>M. tuberculosis</it>. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.</p> <p>Methods</p> <p>Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan^®SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.</p> <p>Results</p> <p>A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.</p> <p>Conclusions</p> <p>This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.</p

The role of passion in exercise addiction, exercise volume, and exercise intensity in long-term exercisers

Recent studies have shown a relationship between the risk for exercise addiction (REA) and passion. This research examined whether levels of REA, volume of exercise (in weekly hours), and self-reported exercise intensities yield differences in obsessive passion and harmonious passion among individuals with long history of exercise. Respondents (n = 360) completed the Exercise Addiction Inventory, Passion Scale, and Borg Scale (assessing their usual exercise intensity), and reported their volume of exercise (hours per week). Regression analysis demonstrated that exercise intensity, obsessive passion, and harmonious passion were significant predictors (r2 = .381, p < .001) of the REA scores with obsessive passion being the strongest predictor (r2 = .318). Exercisers classified as at REA reported higher obsessive passion, harmonious passion, and exercise intensity (p ≤ .001) than those classified as symptomatic, who in turn scored higher on these measures (p ≤ .006) than asymptomatic exercisers. Participants reporting greater volumes of exercise also scored higher on obsessive passion, harmonious passion (p < .001), exercise intensity (p = .032), and REA scores (p = .042) than individuals who exercised less. Finally, women exercising between low and high intensities exhibited greater obsessive passion, as well as harmonious passion (p ≤ .005) than men reporting similar exercise intensities. These findings support the recently reported relationship between passion and REA. They also expand the current knowledge by demonstrating that obsessive passion and harmonious passion are greater in the individuals who exercise at higher volumes and with higher intensities

Using Expression and Genotype to Predict Drug Response in Yeast

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross

A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas

The cancer immunoediting hypothesis has gained significant footing over the past decade as a result of work performed using sarcomas induced by 3-methylcholanthrene (3-MCA) in mice. Despite the progress made by several groups in establishing evidence for the three phases of immunoediting (elimination, equilibrium and escape), there continues to be active controversy on the nature of interaction between spontaneously formed tumour cells and the immune system during the early phases of tumourigenesis. At the root of this controversy is conflicting and unresolved evidence spanning back to the 1970s regarding the incidence and frequency of 3-MCA-induced sarcomas in immunocompetent mice as compared to immunodeficient mice. In this mini review we provide a critical analysis of both sides of this controversy

Progressive Visceral Leishmaniasis Is Driven by Dominant Parasite-induced STAT6 Activation and STAT6-dependent Host Arginase 1 Expression

The clinicopathological features of the hamster model of visceral leishmaniasis (VL) closely mimic active human disease. Studies in humans and hamsters indicate that the inability to control parasite replication in VL could be related to ineffective classical macrophage activation. Therefore, we hypothesized that the pathogenesis of VL might be driven by a program of alternative macrophage activation. Indeed, the infected hamster spleen showed low NOS2 but high arg1 enzyme activity and protein and mRNA expression (p<0.001) and increased polyamine synthesis (p<0.05). Increased arginase activity was also evident in macrophages isolated from the spleens of infected hamsters (p<0.05), and arg1 expression was induced by L. donovani in primary hamster peritoneal macrophages (p<0.001) and fibroblasts (p<0.01), and in a hamster fibroblast cell line (p<0.05), without synthesis of endogenous IL-4 or IL-13 or exposure to exogenous cytokines. miRNAi-mediated selective knockdown of hamster arginase 1 (arg1) in BHK cells led to increased generation of nitric oxide and reduced parasite burden (p<0.005). Since many of the genes involved in alternative macrophage activation are regulated by Signal Transducer and Activator of Transcription-6 (STAT6), and because the parasite-induced expression of arg1 occurred in the absence of exogenous IL-4, we considered the possibility that L. donovani was directly activating STAT6. Indeed, exposure of hamster fibroblasts or macrophages to L. donovani resulted in dose-dependent STAT6 activation, even without the addition of exogenous cytokines. Knockdown of hamster STAT6 in BHK cells with miRNAi resulted in reduced arg1 mRNA expression and enhanced control of parasite replication (p<0.0001). Collectively these data indicate that L. donovani infection induces macrophage STAT6 activation and STAT6-dependent arg1 expression, which do not require but are amplified by type 2 cytokines, and which contribute to impaired control of infection

An examination of the factorial and convergent validity of four measures of conspiracist ideation, with recommendations for researchers

A number scales have been developed to measure conspiracist ideation, but little attention has been paid to the factorial validity of these scales. We reassessed the psychometric properties of four widely-used scales, namely the Belief in Conspiracy Theories Inventory (BCTI), the Conspiracy Mentality Questionnaire (CMQ), the Generic Conspiracist Beliefs Scale (GCBS), and the One-Item Conspiracy Measure (OICM). Eight-hundred-and-three U. S. adults completed all measures, along with measures of endorsement of 9/11 and anti- vaccination conspiracy theories. Through both exploratory and confirmatory factor analysis, we found that only the BCTI had acceptable factorial validity. We failed to confirm the factor structures of the CMQ and the GBCS, suggesting these measures had poor factorial valid- ity. Indices of convergent validity were acceptable for the BCTI, but weaker for the other measures. Based on these findings, we provide suggestions for the future refinement in the measurement of conspiracist ideation