Impact of sar and agr on methicillin resistance in Staphylococcus aureus

Abstract The global regulators agr and sar control expression of cell wall and extracellular proteins. Inactivation of either sar and/or agr in a typical heterogeneously methicillin-resistant Staphylococcus aureus resulted in a small but reproducible decrease in the number of cells in the subpopulation expressing high methicillin resistance. The amount of low affinity penicillin-binding protein PBP2', the prerequisite for methicillin resistance, was apparently not affected, however, a reduction in PBP1 and PBP3 production was observed, suggesting that these resident PBPs of the cells might be involved somehow together with PBP2' in high level methicillin resistance.     

Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype

We recently demonstrated that ω-3-polyunsaturated fatty acids ameliorate obesity-induced adipose tissue inflammation and insulin resistance. In this study, we report novel mechanisms underlying ω-3-polyunsaturated fatty acid actions on adipose tissue, adipocytes, and stromal vascular cells (SVC). Inflamed adipose tissue from high-fat diet-induced obese mice showed increased F4/80 and CD11b double-positive macrophage staining and elevated IL-6 and MCP-1 levels. Docosahexaenoic acid (DHA; 4 μg/g) did not change the total number of macrophages but significantly reduced the percentage of high CD11b/high F4/80-expressing cells in parallel with the emergence of low-expressing CD11b/F4/80 macrophages in the adipose tissue. This effect was associated with downregulation of proinflammatory adipokines in parallel with increased expression of IL-10, CD206, arginase 1, resistin-like molecule α, and chitinase-3 like protein, indicating a phenotypic switch in macrophage polarization toward an M2-like phenotype. This shift was confined to the SVC fraction, in which secretion of Th1 cytokines (IL-6, MCP-1, and TNF-α) was blocked by DHA. Notably, resolvin D1, an anti-inflammatory and proresolving mediator biosynthesized from DHA, markedly attenuated IFN-γ/LPS-induced Th1 cytokines while upregulating arginase 1 expression in a concentration-dependent manner. Resolvin D1 also stimulated nonphlogistic phagocytosis in adipose SVC macrophages by increasing both the number of macrophages containing ingested particles and the number of phagocytosed particles and by reducing macrophage reactive oxygen species production. No changes in adipocyte area and the phosphorylation of hormone-sensitive lipase, a rate-limiting enzyme regulating adipocyte lipolysis, were observed. These findings illustrate novel mechanisms through which resolvin D1 and its precursor DHA confer anti-inflammatory and proresolving actions in inflamed adipose tissue.     

Population dynamics of Stylaria lacustris (Linnaeus, 1767) (Oligochaeta,Naididae) in Los Talas,Argentina

Population dynamics of Stylaria lacustris were analyzed over 2 years in a pond located at Los Talas, Argentina. In both years, the peak in abundance, due to intense asexual reproduction, fell at the end of winter, and was followed by mature individuals. The species was not collected during summer. Temperature was the main factor regulating the population through both sexual and asexual reproduction. In the second year, density was lower and correlated with a lower water level and a reduced vegetation development. Individuals were randomly distributed in periods of high abundance and contagious when density was low. Generation time was 15 days.     

Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat

Background & Aims

Secretin induces bicarbonate-rich hydrocholeresis in healthy individuals, but not in untreated patients with primary biliary cirrhosis (PBC). Ursodeoxycholic acid (UDCA) – the first choice treatment for PBC – restores the secretin response. Compared with humans, secretin has poor effect in experimental normal-rat models with biliary drainage, although it may elicit hydrocholeresis when the bile-acid pool is maintained. In view of the benefits of UDCA in PBC, we used normal-rat models to unravel the acute contribution of UDCA (and/or taurine-conjugated TUDCA) for eliciting the biliary secretin response.

Methods

Intravascular and/or intrabiliary administration of agonists and inhibitors was performed in normal rats with biliary monitoring. Secretin/bile-acid interplay was analyzed in 3D cultured rat cholangiocytes that formed expansive cystic structures with intralumenal hydroionic secretion.

Results

In vivo, secretin stimulates hydrocholeresis upon UDCA/TUDCA infusion, but does not modify the intrinsic hypercholeretic effect of dehydrocholic acid (DHCA). The former effect is dependent on microtubule polymerization, and involves PKCα, PI3K and MEK pathways, as shown by colchicine (i.p.) and retrograde biliary inhibitors. In vitro, while secretin alone accelerates the spontaneous expansion of 3D-cystic structures, this effect is enhanced in the presence of TUDCA, but not UDCA or DHCA. Experiments with inhibitors and Ca²⁺-chelator confirmed that the synergistic effect of secretin plus TUDCA involves microtubules, intracellular Ca²⁺, PKCα, PI3K, PKA and MEK pathways. Gene silencing also demonstrated the involvement of the bicarbonate extruder Ae2.

Conclusions

UDCA is conjugated in order to promote secretin-stimulated hydrocholeresis in rats through Ae2, microtubules, intracellular Ca²⁺, PKCα, PI3K, PKA, and MEK.     

A network-based approach to integrate nutrient microenvironment in the prediction of synthetic lethality in cancer metabolism

Synthetic Lethality (SL) is currently defined as a type of genetic interaction in which the loss of function of either of two genes individually has limited effect in cell viability but inactivation of both genes simultaneously leads to cell death. Given the profound genomic aberrations acquired by tumor cells, which can be systematically identified with -omics data, SL is a promising concept in cancer research. In particular, SL has received much attention in the area of cancer metabolism, due to the fact that relevant functional alterations concentrate on key metabolic pathways that promote cellular proliferation. With the extensive prior knowledge about human metabolic networks, a number of computational methods have been developed to predict SL in cancer metabolism, including the genetic Minimal Cut Sets (gMCSs) approach. A major challenge in the application of SL approaches to cancer metabolism is to systematically integrate tumor microenvironment, given that genetic interactions and nutritional availability are interconnected to support proliferation. Here, we propose a more general definition of SL for cancer metabolism that combines genetic and environmental interactions, namely loss of gene functions and absence of nutrients in the environment. We extend our gMCSs approach to determine this new family of metabolic synthetic lethal interactions. A computational and experimental proof-of-concept is presented for predicting the lethality of dihydrofolate reductase (DHFR) inhibition in different environments. Finally, our approach is applied to identify extracellular nutrient dependences of tumor cells, elucidating cholesterol and myo-inositol depletion as potential vulnerabilities in different malignancies.     

Bone Loss at Implant with Titanium Abutments Coated by Soda Lime Glass Containing Silver Nanoparticles: A Histological Study in the Dog

The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression.     

Morphostructural constraints and phylogenetic overprint on sutural frilling in Late Jurassic ammonites

The functional significance of frilled septa and complex sutures in ammonoids has generated ongoing debate. The 'classic' hypothesis envisages ammonoid shells and septa as designed for resisting ambient hydrostatic pressure, complex sutures being the evidence of strength in shells for colonization of deep habitats. Here we address the 'suture problem', focusing on the analysis and interpretation of variables in our database of Late Jurassic ammonites not included in previous studies, such as whorl height ( W h ), whorl shape ( S ), shell coiling ( WD ), taxonomic grouping and basic planispiral shell shape. The results indicate that sutural complexity, as measured by the fractal dimension ( D f ) value of the suture line, is positively correlated with W h , and that the sutures of oceanic shells tend to provide, for a given W h value, lower D f estimates than do those of neritic shells. No general trend of increase in sutural complexity was noted for specimens recovered from swell areas belonging to oceanic fringes with respect to those that inhabited epicontinental shelves. In fact, Perisphinctoidea, the clade best represented in the database analysed, shows a higher D f mean value in neritic species than in epioceanic ones. Significant differences in sutural complexity were detected for groups of ammonites classified according to shell shapes ( WD , S ). Oxycones and discocones, streamlined potential swimmers, show the highest D f mean values, while spherocones and cadicones, which were presumably vertical vagrants, present the lowest ones. This indicates that sutural complexity was more related to shell geometry than to bathymetry.     

Sensory lateralization in pain subjective perception for noxious heat stimulus

The aim of the present study was to identify and characterize hemispheric lateralization for pain intensity perception. A sample of 351 healthy volunteers was tested by the immersion of the right hand for 10 s followed by the same test for the left hand (RL group; n = 199) or in a random sequence (RND group; n = 152) into a water bath (48 degrees C, 15 s). Pain intensity was self-reported by the Visual Analogue Scale (VAS). The motor hemispherical Lateralization Index (LI) was obtained by the Edinburgh Inventory. Gender, hand skin fold, interstimulus time and menstrual cycle data in case of female subjects were recorded. The sample, 60.7% females and 39.3% males, 20.4 +/- 0.18 (mean +/- SEM) years old, showed 92.1% right-handed subjects. Left hand VAS was significantly higher than right hand VAS for RL (7.24 +/- 1.31 vs 6.74 +/- 1.52; p < 0.01) and RND (7.24 +/- 0.82 vs 6.73 +/- 1.25; p < 0.01) both for right- and left-handed subjects. A low but significant correlation for VAS scores and LI was found (r = 0.14; p < 0.05 or r = 0.18; p < 0.05, for left or right hand, respectively). Skin fold was statistically similar in both hands (p > 0.05) being highly correlated with each other (r = 0.68; p < 0.05). Pain subjective perception was not correlated to interstimulus time (r = -0.01; p > 0.05). Females showed significantly higher values than males for both left and right hand VAS scores. Periovulatory phase VAS value was significantly higher than luteal phase VAS only for the right hand test (7.57 +/- 0.20 vs 6.47 +/- 0.33; p < 0.01). The results of the present study suggest a lateralization of pain intensity perception to the right hemisphere not correlated with the motor hemispheric lateralization.     

Both foliar and residual applications of herbicides that inhibit amino acid biosynthesis induce alternative respiration and aerobic fermentation in pea roots

The objective of this work was to ascertain whether there is a general pattern of carbon allocation and utilisation in plants following herbicide supply, independent of the site of application: sprayed on leaves or supplied to nutrient solution. The herbicides studied were the amino acid biosynthesis‐inhibiting herbicides (ABIH): glyphosate, an inhibitor of aromatic amino acid biosynthesis, and imazamox, an inhibitor of branched‐chain amino acid biosynthesis. All treated plants showed impaired carbon metabolism; carbohydrate accumulation was detected in both leaves and roots of the treated plants. The accumulation in roots was due to lack of use of available sugars as growth was arrested, which elicited soluble carbohydrate accumulation in the leaves due to a decrease in sink strength. Under aerobic conditions, ethanol fermentative metabolism was enhanced in roots of the treated plants. This fermentative response was not related to a change in total respiration rates or cytochrome respiratory capacity, but an increase in alternative oxidase capacity was detected. Pyruvate accumulation was detected after most of the herbicide treatments. These results demonstrate that both ABIH induce the less‐efficient, ATP‐producing pathways, namely fermentation and alternative respiration, by increasing the key metabolite, pyruvate. The plant response was similar not only for the two ABIH but also after foliar or residual application.     

Molecular identification and morphological variations of Dermacentor albipictus collected from two deer species in northern Mexico

Experimental and Applied Acarology - In total, 57 ticks were collected from six white-tailed deer (Odocoileus virginianus) and three mule deer (O. hemionus) in northern Mexico during the 2017, 2018...