Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor

© 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Aceros al molibdeno sinterizados con gradiente funcional

Las propiedades que se solicitan a las piezas y productos exigen, la mayoría de las veces, una combinación de materiales que respondan a requerimientos específicos en función de su posición. La fabricación de materiales compuestos y materiales con gradiente funcional proporciona grandes posibilidades de respuesta a las necesidades demandas, tanto de satisfacción de requerimientos como de reducción de materias primas necesarias. En este sentido, satisfacer las propiedades demandadas, de manera localizada geométricamente, puede suponer un ahorro de materias primas y de los residuos relacionados en su fabricación. En el presente estudio de la sinterización a 1120 ºC de un compacto de dos aceros de diferentes composiciones (un acero con un 0,3 % C y un 2 % de cobre y un acero al molibdeno con un 0,7 % carbono y un 2 % de cobre) ofrece unas posibilidades muy atractivas de eficiencia, al reducir en el interior la composición que se requiere en la superficie de las piezas. Se han caracterizado las propiedades mecánicas de este acero sinterizado con gradiente funcional: densidad, variación dimensional, durezas y resistencia mecánica; ilustradas con el análisis de imagen mediante microscopía óptica y electrónica de barrido

Metabolomics Reveals Differential Levels of Oral Metabolites in HIV-Infected Patients: Toward Novel Diagnostic Targets

The objective of the current study was to characterize the profile of oral metabolites in HIV-infected patients using metabolomics. Oral wash samples were collected from 12 HIV-infected and 12 healthy individuals (matched for age, sex, and ethnicity), processed, and analyzed by metabolomics. We detected 198 identifiable and 85 nonidentifiable metabolites; 27 identifiable metabolites were differentially present (12 increased, 15 decreased) in HIV-infected patients. Elevated metabolites included p-cresol sulfate, nucleotides (e.g., allantoin), and amino acids (e.g., phenylalanine, tryptophan), whereas decreased oral metabolites included fucose, fumarate, and N-acetylglucosamine. Pathway network analysis revealed the largest multinode network in healthy versus HIV-infected patients to involve carbohydrate biosynthesis and degradation. HIV-infected patients on antiretroviral therapy (ART) showed the largest number (12) of statistically significant metabolite correlation differences compared with healthy controls. Interestingly, the oral phenlyalanine:tyrosine ratio increased in ART-naive HIV-infected patients (mean ± SEM = 2.58 ± 0.87) compared with healthy individuals (1.33 ± 0.10, p = 0.062) or ART-experienced patients (1.78 ± 0.30, p = 0.441). This is the first study to reveal differential levels of oral metabolites in HIV-infected patients compared withj healthy volunteers, and that oral phenlyalanine:tyrosine ratio may be a useful marker for noninvasive monitoring of the immune status during HIV infection

Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs

A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic.MDA972-03-C-010 (Defense Advanced Research Programs Agency-DARPA)Neurobiotechnology Program of Louisian

Candida parapsilosis Characterization in an Outbreak Setting

Candida parapsilosis is an important non-albicans species which infects hospitalized patients. No studies have correlated outbreak infections of C. parapsilosis with multiple virulence factors. We used DNA fingerprinting to determine genetic variability among isolates from a C. parapsilosis outbreak and from our clinical database. We compared phenotypic markers of pathogenesis, including adherence, biofilm formation, and protein secretion (secretory aspartic protease [SAP] and phospholipase). Adherence was measured as colony counts on silicone elastomer disks immersed in agar. Biofilms formed on disks were quantified by dry weight. SAP expression was measured by hydrolysis of bovine albumin; a colorimetric assay was used to quantitate phospholipase. DNA fingerprinting indicated that the outbreak isolates were clonal and genetically distinct from our database. Biofilm expression by the outbreak clone was greater than that of sporadic isolates (p < 0.0005). Adherence and protein secretion did not correlate with strain pathogenicity. These results suggest that biofilm production plays a role in C. parapsilosis outbreaks

Characterization of the Oral Fungal Microbiome (Mycobiome) in Healthy Individuals

The oral microbiome–organisms residing in the oral cavity and their collective genome–are critical components of health and disease. The fungal component of the oral microbiota has not been characterized. In this study, we used a novel multitag pyrosequencing approach to characterize fungi present in the oral cavity of 20 healthy individuals, using the pan-fungal internal transcribed spacer (ITS) primers. Our results revealed the “basal” oral mycobiome profile of the enrolled individuals, and showed that across all the samples studied, the oral cavity contained 74 culturable and 11 non-culturable fungal genera. Among these genera, 39 were present in only one person, 16 genera were present in two participants, and 5 genera were present in three people, while 15 genera (including non-culturable organisms) were present in ≥4 (20%) participants. Candida species were the most frequent (isolated from 75% of participants), followed by Cladosporium (65%), Aureobasidium, Saccharomycetales (50% for both), Aspergillus (35%), Fusarium (30%), and Cryptococcus (20%). Four of these predominant genera are known to be pathogenic in humans. The low-abundance genera may represent environmental fungi present in the oral cavity and could simply be spores inhaled from the air or material ingested with food. Among the culturable genera, 61 were represented by one species each, while 13 genera comprised between 2 and 6 different species; the total number of species identified were 101. The number of species in the oral cavity of each individual ranged between 9 and 23. Principal component (PCO) analysis of the obtained data set followed by sample clustering and UniFrac analysis revealed that White males and Asian males clustered differently from each other, whereas both Asian and White females clustered together. This is the first study that identified the “basal mycobiome” of healthy individuals, and provides the basis for a detailed characterization of the oral mycobiome in health and disease

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Purified arginine permease of Candida albicans is functionally active in a reconstituted system

We have for the first time purified arginine permease from a pathogenic yeast, Candida albicans, to homogeneity by affinity chromatography using L-arginine-linked agarose matrix as affinity column. The purified protein (PP) was of 66 kDa with no subunit structure. Two kinetically distinct binding affinities of PP were evident where high affinity binding (S1) revealed a dependence on acidic pH while pH did not have dramatic effect on low affinity (S2) binding. The specificity of L-arginine binding to PP with regard to other amino acids, structural analogues and inhibitors, was essentially similar to arginine transport observed in the intact cells of C. albicans (Rao et al., 1986). The purified arginine permease was reconstituted into proteoliposomes and its functionality was tested by imposing a valinomycin-induced membrane potential. All the characteristic features of L-arginine transport displayed by the reconstituted system were similar to those observed in intact cells. Thus homogeneous purified arginine permease was also functionally active