Gaussian Markov random field spatial models in GAMLSS

This paper describes the modelling and fitting of Gaussian Markov random field spatial components within a Generalized Additive-Model for Location, Scale and Shape (GAMLSS) model. This allows modelling of any or all the parameters of the distribution for the response variable using explanatory variables and spatial effects. The response variable distribution is allowed to be a non-exponential family distribution. A new package developed in R to achieve this is presented. We use Gaussian Markov random fields to model the spatial effect in Munich rent data and explore some features and characteristics of the data. The potential of using spatial analysis within GAMLSS is discussed. We argue that the flexibility of parametric distributions, ability to model all the parameters of the distribution and diagnostic tools of GAMLSS provide an ideal environment for modelling spatial features of data

Integrated transcriptomics establish macrophage polarization signatures and have potential applications for clinical health and disease

Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution

Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability

BACKGROUND: The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting. METHODS: Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry. RESULTS: A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older ( 6565 years) subjects (ROC area: 0.584; 95% CI: 0.399-0.769). Among the young, assays have different optimal thresholds (120 \u3bcg/g for ELISA, 50 \u3bcg/g for CLIA and 100 \u3bcg/g for turbidimetry). CONCLUSIONS: We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV

Role of microstructure in the electron–hole interaction of hybrid lead halide perovskites

Organic–inorganic metal halide perovskites have demonstrated high power conversion efficiencies in solar cells and promising performance in a wide range of optoelectronic devices. The existence and stability of bound electron–hole pairs in these materials and their role in the operation of devices with different architectures remains a controversial issue. Here we demonstrate, through a combination of optical spectroscopy and multiscale modelling as a function of the degree of polycrystallinity and temperature, that the electron–hole interaction is sensitive to the microstructure of the material. The long-range order is disrupted by polycrystalline disorder and the variations in electrostatic potential found for smaller crystals suppress exciton formation, while larger crystals of the same composition demonstrate an unambiguous excitonic state. We conclude that fabrication procedures and morphology strongly influence perovskite behaviour, with both free carrier and excitonic regimes possible, with strong implications for optoelectronic devices

Detección de leptospiras patógenas en tejido renal de murciélagos de Corrientes, Argentina

Existen muchos animales que participan en la transmisión de diferentes serovares de leptospiras. Los murciélagos han acrecentado su presencia en zonas urbanas; este cambio de hábitat se atribuye a razones de origen antropogénico y ha elevado las probabilidades de contacto entre quirópteros, seres humanos y animales domésticos. El objetivo del trabajo fue identificar, mediante una reacción en cadena de la polimerasa (PCR sencilla), la infección natural de especies de leptospiras patógenas en quirópteros colectados durante los años 2010 a 2012 en la ciudad de Corrientes. Para la captura se utilizaron redes de mano y trampas balde. La identificación de los quirópteros se efectuó en base a su características fenotípicas y morfométricas, determinándose la presencia de ejemplares de tres de las cuatro familias existentes en Argentina. Los animales fueron sacrificados bajo anestesia de hidrato de cloral 20%, obteniéndose muestras de tejido renal. Se realizó el procedimiento de extracción de ácido desoxirribonucleico; se amplificaron 2 genes en PCR sencillas separadas, un gen mitocondrial, mt DNA 12S/16S como control de especie y luego, en las mismas muestras, se amplificó parte de los genes LipL32. Se detectó presencia de ADN de leptospiras en el 20% de los quirópteros, siendo éste el primer hallazgo por PCR publicado para murciélagos del país. Revelar la presencia de ADN de leptospiras resulta de gran importancia, debido a su utilidad en los casos en que la búsqueda molecular del patógeno ha sido no detectable

Detección de Leishmania (Viannia) braziliensis en gato doméstico de Corrientes, Argentina, por técnicas de biología molecular

Ruiz, R.M.; Ramírez, N.N.; Alegre, A.E.; Bastiani, C.E.; De Biasio, M.B.: Detección de Leishmania (Viannia) braziliensis en gato doméstico de Corrientes, Argentina, por técnicas de biología molecular. Rev vet 26: 2, 147-150, 2015

Detección y diferenciación molecular de Leptospira sp. utilizando diferentes técnicas de extracción de ADN

Existen diversas estrategias diagnósticas para identificar leptospiras, siendo la reacción en cadena de la polimerasa (PCR) una técnica de alta sensibilidad y especificidad. El presente trabajo tuvo como objetivo optimizar técnicas de extracción de ADN a partir de cultivos bacterianos y establecer condiciones de PCR multiplex para diferenciar leptospiras saprófitas de patógenas. Para ello se ensayaron técnicas de bromuro de cetiltrimetil amonio (CTAB) y hervido (boiling). Se analizaron dos secuencias de ácidos nucleicos, correspondientes a una fracción de un gen conservado en ambos grupos de bacterias (ARNr 16S) y otra procedente de una fracción de un gen (LipL32) presente sólo en especies de leptospiras patógenas, las cuales dieron amplicones de 474 y 430 pb respectivamente, utilizándose como controles positivos de amplificación muestras de cultivos bacterianos de Leptospira icteroahemorragiae, L. canicola y apatógena (Patoc I), utilizando agua como control negativo. Se concluyó que no existen diferencias en la perdurabilidad del ADN extraído a partir de cepas de referencia al comparar el método de digestión con el detergente CTAB y el de boiling y sus variantes. Considerando el más bajo costo y menor tiempo de desarrollo, este último resultó la mejor alternativa para la obtención de moldes para amplificación por PCR

Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas

Lifelong exposure to a low-dose of the glyphosate-based herbicide RoundUp® causes intestinal damage, gut dysbiosis, and behavioral changes in mice

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders

Eficácia de herbicidas pré-emergentes no controle de caruru resistente ao glifosato e efeito carryover sobre azevém em sucessão.

O objetivo do trabalho foi investigar o efeito residual de herbicidas pré-emergentes no controle de caruru e o efeito carryover sobre azevém em sucessão ao cultivo de soja