Changes in CNS cells in Hyperammonemic portal hypertensive rats

Rats with pre‐hepatic portal hypertension because of partial portal vein ligation develop minimal hepatic encephalopathy (MHE) with hyperammonemia, impaired blood–brain barrier, mild brain edema, and severe mitochondrial changes in the hippocampus. The aim of this study was to evaluate changes of different neural cells in the cerebral cortex and the hippocampus. Animals were divided into two groups, MHE and sham. Astrocytes were studied by immunostaining with glial fibrillary acidic protein and S100β protein; neurons were immunostained with neuronal nuclear marker, microtubule associated protein‐2, and NF‐200 and capillaries with Nestin. The hypoxia‐inducible factor 1α (HIF‐1α) and its downstream proteins, P‐glycoprotein (P‐gp) and erythropoietin receptor (Epo‐R), were also evaluated. Astrocytes were increased in area and number only in the hippocampus, while S100β increased in both brain areas in MHE animals. Microtubule associated protein‐2 and NF‐200 immunoreactivities (‐ir) were significantly reduced in both areas. Hippocampal Nestin‐ir was increased in MHE animals. These cellular changes were similar to those described in ischemic conditions, thus HIF‐1α, P‐gp, and Epo‐R were also evaluated. A high expression of HIF‐1α in cortical neurons was observed in the MHE group. It is likely that this hypoxia‐like state is triggered via ammonia occupying the binding domain of HIF‐1α and thereby preventing its degradation and inducing its stabilization, leading to the over‐expression of P‐gp and the Epo‐R.

     

Biotic and abiotic factors modulating wild boar relative abundance in Atlantic Spain

The population dynamics of wild ungulates, particularly wild boar (Sus scrofa), are modulated by biotic (e.g. predation) and abiotic (environmental) determinants. Despite the evident potential interference of predation in the environmental patterns of wild boar population abundance, studies including both predation and abiotic factors are scarce. Here, using spatially explicit predictive models, we investigated the effects of habitat features on the relative abundance of wild boar populations and how the abundance of boars is related to frequency of Iberian wolf (Canis lupus signatus; hereafter, wolf) in the area. Wild boar relative abundance was determined by hunting bag statistics, including hunting effort-related variables (in order to avoid problems derived from modeling rates) as covariates, while wolf attacks to livestock were considered as a proxy of wolf frequency in the drive. After modeling, variation partitioning procedures were used to determine the relative importance of each factor and their overlaid effects. Our results showed that wild boar and wolf relative abundances are associated. According to previous knowledge on the wild boar ecology, we found that the species abundance is positively related to the percentage of surface occupied by mature forest and heather providing high food diversity and refuge, but these environmental variables achieved a low explanatory capacity in the models in relation to wolf frequency. The holistic approach followed in this study was attended to open new perspectives for thinking on the wolf-livestock conflict and to adequate wild boar management strategies taking into account hunting interests and natural processes.     

A combination of chitosan,coating and modified atmosphere packaging for prolonging Fior di latte cheese shelf life

In this work, the addition of chitosan into cheese making, combined with either coating or active coating (lysozyme and ethylenediamine tetraacetic acid, disodium salt) and MAP (modified atmosphere packaging) was used to prolong the shelf life of “Fior di latte” cheese. On the packaged cheese stored at 4 °C microbiological, pH, gas composition and sensory changes were monitored over an 8-day period. Results showed that the combination of chitosan, active coating and MAP improved “Fior di latte” cheese preservation by increasing the shelf life in comparison with the traditional packaging. In fact, the latter showed a very short shelf life limited to more or less 1 day, whereas the integrated approach developed in this study allowed us to obtain a significant shelf life prolongation to 5 days, most probably due to the synergic effect between the active compounds and the atmospheric conditions in the package headspace.     

Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes

Cytolytic T cells play a major role in controlling herpes simplex virus type 2 (HSV-2) infections in humans. In an effort to more thoroughly evaluate the response to HSV-2 directly, ex vivo, we developed an enzyme-linked immunospot (ELISPOT) assay that utilized pools of overlapping synthetic peptides presented by autologous dendritic cells to purified CD8(+) T cells. Donor response rates to individual open reading frames (ORFs) ranged from fewer than 5% responding to as many as 70% responding, with the greatest frequency of responses (by ORF) being directed against UL39, UL25, UL27, ICP0, UL46, and UL47 in descending order of frequency. HSV-2-seropositive subjects responded to as few as 3 or as many as 46 of the 48 ORFs tested, with a median of 11 ORFs recognized. HLA-B*07 expression correlated with stronger responses overall that were directed primarily against UL49 and UL46. Cumulative precursor frequencies in the blood ranged from 500 to almost 6,000 HSV-2 spot-forming units/10(6) CD8(+) T cells. The magnitude and breadth of the response in the infected population were greater than previously appreciated. Whether this variability in the CD8(+) T-cell response within individuals is associated with the frequency of viral reactivation warrants further study.     

p120-catenin mediates inflammatory responses in the skin

Although p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo. Using conditional targeting in mice, we show that p120 null neonatal epidermis exhibits reduced intercellular AJ components but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they display epidermal hyperplasia and chronic inflammation, typified by hair degeneration and loss of body fat. Using skin engraftments and anti-inflammatory drugs, we show that these features are not attributable to reductions in junctional cadherins and catenins, but rather NFkB activation. Both in vivo and in vitro, p120 null epidermal cells activate nuclear NFkB, triggering a cascade of proinflammatory NFkB targets. Although the underlying mechanism is likely complex, we show that p120 affects NFkB activation and immune homeostasis in part through regulation of Rho GTPases. These findings provide important new insights into p120 function.     

Prevention of invasive candidiasis in the critically ill non neutropenic patient

Prevention of invasive candidiasis (IC) in the setting of critically ill non neutropenic patients should be based on evidenced-based recommendations, namely improved hand hygiene, optimal catheter care, and rational and reduced use of broad-spectrum antibiotics. Concomitant interventions aimed at reducing risk factors are important to decrease IC.     

The emerging role of auxins as bacterial signal molecules: Potential biotechnological applications

Microorganisms are exposed in their natural niches to a wide diversity of signal molecules. Specific detection of these signals results in alterations in microbial metabolism and physiology. Auxins like indole-3-acetic acid are key phytohormones that regulate plant growth and development. Nonetheless, auxin biosynthesis is not restricted to plants but is ubiquitous in all kingdoms of life. This wide phylogenetic distribution of auxins production, together with the diversity of regulated cellular processes, have made auxins key intra- and inter-kingdom signal molecules in life modulating, for example microbial physiology, metabolism and virulence. Despite their increasing importance as global signal molecules, the mechanisms by which auxins perform their regulatory functions in microorganisms are largely unknown. In this article, we outline recent research that has advanced our knowledge of the mechanisms of bacterial auxin perception. We also highlight the potential applications of this research in aspects such as antibiotic production, biosensor design, plant microbiome engineering and antivirulence therapies.     

Zoledronic acid repolarizes tumour‐associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway

It is unknown whether zoledronic acid (ZA) at clinically relevant doses is active against tumours not located in bone. Mice transgenic for the activated ErbB‐2 oncogene were treated with a cumulative number of doses equivalent to that recommended in human beings. A significant increase in tumour‐free and overall survival was observed in mice treated with ZA. At clinically compatible concentrations, ZA modulated the mevalonate pathway and affected protein prenylation in both tumour cells and macrophages. A marked reduction in the number of tumour‐associated macrophages was paralleled by a significant decrease in tumour vascularization. The local production of vascular endothelial growth factor and interleukin‐10 was drastically down‐regulated in favour of interferon‐γ production. Peritoneal macrophages and tumour‐associated macrophages of ZA‐treated mice recovered a full M1 antitumoral phenotype, as shown by nuclear translocation of nuclear factor kB, inducible nitric oxide synthase expression and nitric oxide production. These data indicate that clinically achievable doses of ZA inhibit spontaneous mammary cancerogenesis by targeting the local microenvironment, as shown by a decreased tumour vascularization, a reduced number of tumour‐associated macrophages and their reverted polarization from M2 to M1 phenotype.