RNA-Seq analysis of ileocecal valve and peripheral blood from Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis revealed dysregulation of the CXCL8/IL8 signaling pathway

17 páginas, 5 tablas, 5 figuras.Paratuberculosis is chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Whole RNA-sequencing (RNA-Seq) is a promising source of novel biomarkers for early MAP infection and disease progression in cattle. Since the blood transcriptome is widely used as a source of biomarkers, we analyzed whether it recapitulates, at least in part, the transcriptome of the ileocecal valve (ICV), the primary site of MAP colonization. Total RNA was prepared from peripheral blood (PB) and ICV samples, and RNA-Seq was used to compare gene expression between animals with focal or diffuse histopathological lesions in gut tissues versus control animals with no detectable signs of infection. Our results demonstrated both shared, and PB and ICV-specific gene expression in response to a natural MAP infection. As expected, the number of differentially expressed (DE) genes was larger in the ICV than in the PB samples. Among the DE genes in the PB and ICV samples, there were some common genes irrespective of the type of lesion including the C-X-C motif chemokine ligand 8 (CXCL8/IL8), apolipoprotein L (APOLD1), and the interferon inducible protein 27 (IF127). The biological processes (BP) enriched in the PB gene expression profiles from the cows with diffuse lesions included the killing of cells of other organism, defense response, immune response and the regulation of neutrophil chemotaxis. Two of these BP, the defense and immune response, were also enriched in the ICV from the cows with diffuse lesions. Metabolic analysis of the DE genes revealed that the N-glycan biosynthesis, bile secretion, one-carbon pool by folate and purine metabolism were significantly enriched in the ICV from the cows with focal lesions. In the ICV from cows with diffuse lesions; the valine, leucine and isoleucine degradation route, purine metabolism, vitamin digestion and absorption and the cholesterol routes were enriched. Some of the identified DE genes, BP and metabolic pathways will be studied further to develop novel diagnostic tools, vaccines and immunotherapeutics.This work was supported by grants from the Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA) and by European Funds for Regional Development (FEDER) (INIA RTA2014-00009-C02 and RTA2018-094192). The study is partially funded by the Principado de Asturias (PCTI 2018-2020, GRUPIN: IDI2018-000237). Maria Canive and Cristina Blanco-Vazquez are recipients of INIA fellowships. The authors thank ASTEGA Veterinary services for their assistance on sample collection. We are also grateful to Kyle Hearn for the careful editing of the manuscript

Evaluation of a lime-mediated sewage sludge stabilisation process. Product characterisation and technological validation for its use in the cement industry

This paper describes an industrial process for stabilising sewage sludge (SS) with lime and evaluates the viability of the stabilised product, denominated Neutral, as a raw material for the cement industry. Lime not only stabilised the sludge, raised the temperature of the mix to 80-100 °C, furthering water evaporation, portlandite formation and the partial oxidation of the organic matter present in the sludge. Process mass and energy balances were determined. Neutral, a white powder consisting of portlandite (49.8%), calcite (16.6%), inorganic oxides (13.4%) and organic matter and moisture (20.2%), proved to be technologically apt for inclusion as a component in cement raw mixes. In this study, it was used instead of limestone in raw mixes clinkerised at 1400, 1450 and 1500 °C. These raw meals exhibited greater reactivity at high temperatures than the limestone product and their calcination at 1500 °C yielded clinker containing over 75% calcium silicates, the key phases in Portland clinker. Finally, the two types of raw meal (Neutral and limestone) were observed to exhibit similar mineralogy and crystal size and distribution. © 2011.Peer Reviewe

The ALHAMBRA survey : Estimation of the clustering signal encoded in the cosmic variance

The relative cosmic variance ($\sigma_v$) is a fundamental source of uncertainty in pencil-beam surveys and, as a particular case of count-in-cell statistics, can be used to estimate the bias between galaxies and their underlying dark-matter distribution. Our goal is to test the significance of the clustering information encoded in the $\sigma_v$ measured in the ALHAMBRA survey. We measure the cosmic variance of several galaxy populations selected with $B-$band luminosity at $0.35 \leq z < 1.05$ as the intrinsic dispersion in the number density distribution derived from the 48 ALHAMBRA subfields. We compare the observational $\sigma_v$ with the cosmic variance of the dark matter expected from the theory, $\sigma_{v,{\rm dm}}$. This provides an estimation of the galaxy bias $b$. The galaxy bias from the cosmic variance is in excellent agreement with the bias estimated by two-point correlation function analysis in ALHAMBRA. This holds for different redshift bins, for red and blue subsamples, and for several $B-$band luminosity selections. We find that $b$ increases with the $B-$band luminosity and the redshift, as expected from previous work. Moreover, red galaxies have a larger bias than blue galaxies, with a relative bias of $b_{\rm rel} = 1.4 \pm 0.2$. Our results demonstrate that the cosmic variance measured in ALHAMBRA is due to the clustering of galaxies and can be used to characterise the $\sigma_v$ affecting pencil-beam surveys. In addition, it can also be used to estimate the galaxy bias $b$ from a method independent of correlation functions.Comment: Astronomy and Astrophysics, in press. 9 pages, 4 figures, 3 table

The ALHAMBRA survey: Accurate merger fractions by PDF analysis of photometric close pairs

Our goal is to develop and test a novel methodology to compute accurate close pair fractions with photometric redshifts. We improve the current methodologies to estimate the merger fraction f_m from photometric redshifts by (i) using the full probability distribution functions (PDFs) of the sources in redshift space, (ii) including the variation in the luminosity of the sources with z in both the selection of the samples and in the luminosity ratio constrain, and (iii) splitting individual PDFs into red and blue spectral templates to deal robustly with colour selections. We test the performance of our new methodology with the PDFs provided by the ALHAMBRA photometric survey. The merger fractions and rates from the ALHAMBRA survey are in excellent agreement with those from spectroscopic work, both for the general population and for red and blue galaxies. With the merger rate of bright (M_B <= -20 - 1.1z) galaxies evolving as (1+z)^n, the power-law index n is larger for blue galaxies (n = 2.7 +- 0.5) than for red galaxies (n = 1.3 +- 0.4), confirming previous results. Integrating the merger rate over cosmic time, we find that the average number of mergers per galaxy since z = 1 is N_m = 0.57 +- 0.05 for red galaxies and N_m = 0.26 +- 0.02 for blue galaxies. Our new methodology exploits statistically all the available information provided by photometric redshift codes and provides accurate measurements of the merger fraction by close pairs only using photometric redshifts. Current and future photometric surveys will benefit of this new methodology.Comment: Submitted to A&A, 15 pages, 15 figures, 6 tables. Comments are welcome. Close pair systems available at https://cloud.iaa.csic.es/alhambra/catalogues/ClosePairs

The ALHAMBRA survey : B−B-band luminosity function of quiescent and star-forming galaxies at 0.2≤z<10.2 \leq z < 1 by PDF analysis

Our goal is to study the evolution of the $B-$band luminosity function (LF) since $z=1$ using ALHAMBRA data. We used the photometric redshift and the $I-$band selection magnitude probability distribution functions (PDFs) of those ALHAMBRA galaxies with $I\leq24$ mag to compute the posterior LF. We statistically studied quiescent and star-forming galaxies using the template information encoded in the PDFs. The LF covariance matrix in redshift-magnitude-galaxy type space was computed, including the cosmic variance. That was estimated from the intrinsic dispersion of the LF measurements in the 48 ALHAMBRA sub-fields. The uncertainty due to the photometric redshift prior is also included in our analysis. We modelled the LF with a redshift-dependent Schechter function affected by the same selection effects than the data. The measured ALHAMBRA LF at $0.2\leq z<1$ and the evolving Schechter parameters both for quiescent and star-forming galaxies agree with previous results in the literature. The estimated redshift evolution of $M_B^* \propto Qz$ is $Q_{\rm SF}=-1.03\pm0.08$ and $Q_{\rm Q}=-0.80\pm0.08$, and of $\log \phi^* \propto Pz$ is $P_{\rm SF}=-0.01\pm0.03$ and $P_{\rm Q}=-0.41\pm0.05$. The measured faint-end slopes are $\alpha_{\rm SF}=-1.29\pm0.02$ and $\alpha_{\rm Q}=-0.53\pm0.04$. We find a significant population of faint quiescent galaxies, modelled by a second Schechter function with slope $\beta=-1.31\pm0.11$. We find a factor $2.55\pm0.14$ decrease in the luminosity density $j_B$ of star-forming galaxies, and a factor $1.25\pm0.16$ increase in the $j_B$ of quiescent ones since $z=1$, confirming the continuous build-up of the quiescent population with cosmic time. The contribution of the faint quiescent population to $j_B$ increases from 3% at $z=1$ to 6% at $z=0$. The developed methodology will be applied to future multi-filter surveys such as J-PAS.Comment: Accepted for publication in Astronomy and Astrophysics. 25 pages, 20 figures, 7 table

Rules, Standards, and the Internal Point of View

Large scale structure and cosmolog

Formación de taumasita en morteros hidráulicos mediante la deposición de SO2 atmosférico

Sulphation of mortars and concretes is a function of diverse environmental factors (SO2 aerosol, temperature, etc) as well as some material characteristics. One of the phases that could be formed as consequence of the sulphation of the hydraulic binder is thaumasite. In this paper different hydraulic mortars have been exposed to laboratory exposure chambers in order to reproduce thaumasite formation due to atmospheric SO2. Under the laboratory exposure conditions, thaumasite was formed in hydraulic lime mortars, and mortars elaborated with ordinary Portland cement as well as mineralized white portland cement. However, thaumasite was not formed in mortars made of lime and pozzolan. The first product formed as a result of the SO2-mortar interaction was gypsum. Gypsum reacted with calcite and C-S-H gel, present in the samples, giving place to thaumasite. Low temperature promotes thaumasite formation.La sulfatación de morteros y hormigones depende de las condiciones ambientales (SO2 aerosol, temperatura, etc.), así como de las características del material. Una de las fases que se puede formar como consecuencia de la sulfatación de los ligantes hidráulicos es la taumasita. En este trabajo se han expuesto diferentes morteros hidráulicos en cámaras de laboratorio con el fin de reproducir la formación de taumasita por efecto del SO2 atmosférico. Bajo las condiciones de laboratorio se formó taumasita en los morteros de cal hidráulica y en los morteros fabricados con cemento portland y cemento blanco mineralizado. Sin embargo, cuando el ligante utilizado en los morteros fue cal y puzolana, no se formó taumasita. El yeso fue el primer producto formado en la interacción entre los morteros y el SO2. A continuación, este yeso reaccionó con la calcita y el gel C-S-H dando lugar a la formación de taumasita. Las bajas temperaturas favorecieron la formación de taumasita

Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide

Deletion of glycine N-methyltransferase (GNMT) in mice, the main gene involved in liver S-adenosylmethionine (SAMe) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis. To demonstrate that the excess of hepatic SAMe is the main agent contributing to liver disease in GNMT-KO mice, we treated 1.5-month old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAMe content, prevented DNA-hypermethylation and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis. More important, NAM treatment prevented the development of fatty liver and fibrosis in GNMT-KO mice. Because GNMT expression is down-regulated in patients with cirrhosis and there are subjects with GNMT mutations who have spontaneous liver disease, the clinical implication of the present findings is obvious at least with respect to these latter individuals. Especially since NAM has been used for many years to treat a broad spectrum of diseases including pellagra and diabetes without significant side effects, it should be considered in subjects with GNMT mutations.ConclusionsThese results indicate that the anomalous accumulation of SAMe in GNMT-KO mice can be corrected by NAM treatment leading to the normalization of the expression of many genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation and apoptosis, and to the reversion of the appearance of the pathologic phenotype

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice