Preterm infants have deficient monocyte and lymphocyte cytokine responses to Group B Streptococcus

Group B streptococcus GBS) is an important cause of early-and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS HKGBS) of preterm infants gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants GA, < 30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection

Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis

Application of transcriptomics for predicting protein interaction networks, drug targets and drug candidates

Protein interaction pathways and networks are critically-required for a vast range of biological processes. Improved discovery of candidate druggable proteins within specific cell, tissue and disease contexts will aid development of new treatments. Predicting protein interaction networks from gene expression data can provide valuable insights into normal and disease biology. For example, the resulting protein networks can be used to identify potentially druggable targets and drug candidates for testing in cell and animal disease models. The advent of whole-transcriptome expression profiling techniques—that catalogue protein-coding genes expressed within cells and tissues—has enabled development of individual algorithms for particular tasks. For example,: (i) gene ontology algorithms that predict gene/protein subsets involved in related cell processes; (ii) algorithms that predict intracellular protein interaction pathways; and (iii) algorithms that correlate druggable protein targets with known drugs and/or drug candidates. This review examines approaches, advantages and disadvantages of existing gene expression, gene ontology, and protein network prediction algorithms. Using this framework, we examine current efforts to combine these algorithms into pipelines to enable identification of druggable targets, and associated known drugs, using gene expression datasets. In doing so, new opportunities are identified for development of powerful algorithm pipelines, suitable for wide use by non-bioinformaticians, that can predict protein interaction networks, druggable proteins, and related drugs from user gene expression datase

Improvement in Performance of ZnO Based DSC Prepared by Spraying Method

This paper reports the effect of TiCl4 on the performance of ZnO based DSC. ZnO was used due to its stability against photo-corrosion&nbsp; and&nbsp; photochemical&nbsp; properties&nbsp; similar&nbsp; to&nbsp; TiO2.&nbsp; Thin&nbsp; films&nbsp; of&nbsp; nanocrystalline&nbsp; ZnO&nbsp; were&nbsp; deposited&nbsp; on transparent conducting oxide glass using spray&nbsp; method. The ZnO&nbsp; films&nbsp; were treated using TiCl4. The cell&rsquo;s efficiency was found to be 2.5% with TiCl4 post-treatment and 1.9% without TiCl4 post-treatment

An XPS Study of the Ag-S interface of L-Cysteine Films on Silver Surface

L-cysteine has gained much attention as a versatile amino acid to create bioactive surfaces by assisting the bonding of proteins to metal surfaces. When L-cysteine interacts with metallic partners such as gold, silver and copper, the SH functional group is known to interact strongly with the metallic surface. The interaction of the L-cysteine with silver surfaces is particularly interesting because, L-cysteine adsorption on silver has been suggested to be stronger than on gold or copper surfaces and the interactions may strongly influence the formation of novel interface states of the L-cysteine-Ag interface. On the other hand, some studies report a weakening of silver-sulfur bond with increasing coverage. However, research has not been sufficiently addressed for experimental investigation to understand the interaction of L-cysteine with silver metallic surfaces. As the first step, we reported the results of experimental investigation of L-cysteine and silver interface electronic structure by thickness-dependent ultraviolet photoelectron spectroscopy (UPS) with a clear spectral feature in between Fermi edge and highest occupied molecular orbital (HOMO) of L-cysteine due to the formation of Ag-S bonding together with a weakening of the silver-sulfur bond with increasing of L-cysteine. In this study, the formation of Ag-S bond at the L-cysteine modified silver surface was systematically elucidated by X-ray photoelectron spectroscopy (XPS) for three different coverages, namely monolayer, two-layered and multi-layered. A prominent shoulder at 2475.2 eV of the main peak at 2473.2 eV was observed for the S 1s XPS spectrum for monolayer film, while only a single peak was observed in the case of two- layered and multi-layered. The spectral feature at 2475.2 eV can be attributed to the interaction of L-cysteine with silver. In addition, the disappearance of the spectral feature for the two-layered film can be attributed to the weakening of silver-sulfur bond by over layer of L-cysteine

Updates on the Morphometric Characterization of Indian Pangolin (Manis crassicaudata) in Sri Lanka

An accurate morphological description and analysis based on reliable data are unavailable for the geographically isolated population of M. crassicaudata in Sri Lanka. This study provides the most updated morphological description of M. crassicaudata with special reference to body measurements directly obtained from 27 specimens collected island-wide. Morphological parameters were recorded under three age classes that were defined based on their body weight (BW) and total body length (TBL); juvenile (BW: 7.3 kg TBL: >101 cm) and gender to reveal sexual dimorphism based on morphometric parameters. The TBL of adult males ranged between 137 and 177 cm while body weight ranged between 20.4 and 48.8 kg. The average count of body scales was 511 ± 21. The body scales were found arranged in 13 longitudinal rows with the highest number of scales observed on the vertebral scale row (16 ± 1). Three major scale morphs were identified; broad rhombic scales, elongated kite-shaped scales, and folded shaped scales. Broad rhombic shaped scales was the dominant scale type (80.49%) on the body (405 ± 7). The tail-length to body-length ratio of an Indian pangolin was 0.87. The tail length of an Indian pangolin is a reliable predictor of the TBL and has potential implications in quick field data gathering

The Effect of Strategic Flexibility on Strategy-Performance Nexus: A Conceptual Model

Many of the business strategies adopted by organizations fail as a result of inflexibility of such strategies in responding to market dynamics. Although there is a considerable number of research to indicate that the strategic clarity has a strong positive association with firm performance, there remains little theoretical and empirical evidence to explain the effect of strategic flexibility on firm performance. Hence, this concept paper draws on the Porter’s typology and the Miles and Snow’s typology to analyze how the strategic flexibility moderates the association between strategic clarity and firm performance. The paper concludes with a conceptual model that enables the testing of the discrete effect of strategic flexibility on firm performance which in turn will add insights to the said models in the study.</p

Developing an economic, environmental and agronomic case for the increased use of organic amendments in South Asia

Aggressive fertilizer subsidies throughout South Asia have led to a rapid increase in the use of synthetic nitrogen fertilizers such as urea at the farm level. While this has been successful in increasing yields, significant yield gaps remain between potential and actual farm yields, while unbalanced or over application of fertilizers potentially damages soil and environmental health. This project examined organic amendment (OA) application in India and Sri Lanka on productivity, soil properties and greenhouse gas emissions. In India, poultry, farm-yard manure and vermi-compost were applied to a paddy rice crop, and the potential benefits followed through to a post-rice chickpea crop. In Sri Lanka, we tested the optimal combination of synthetic nitrogen fertilizer rates when using municipal-waste compost in a multi-year maize-soybean rotation. Results at both trial sites saw an increase in crop yields under OA application; in particular chickpea yields from farm-yard manure and after repeated application of municipal-waste compost. However, all OA treatments increased emissions of the greenhouse gases nitrous oxide and methane due to additional nitrogen or carbon availability. Furthermore, the low nutrient content and relatively high cost of the OA’s, particularly the composts, made them uneconomical as nutrient sources compared to conventional fertilizers