Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei

published_or_final_versio

Hemolysis and methemoglobinemia due to hepatitis E virus infection in patient with G6PD deficiency

published_or_final_versionSpringer Open Choice, 21 Feb 201

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Controllable Synthesis of Single-Crystalline CdO and Cd(OH)2Nanowires by a Simple Hydrothermal Approach

Single-crystalline Cd(OH)2 or CdO nanowires can be selectively synthesized at 150 °C by a simple hydrothermal method using aqueous Cd(NO3)2 as precursor. The method is biosafe, and compared to the conventional oil-water surfactant approach, more environmental-benign. As revealed by the XRD results, CdO or Cd(OH)2 nanowires can be generated in high purity by varying the time of synthesis. The results of FESEM and HRTEM analysis show that the CdO nanowires are formed in bundles. Over the CdO-nanowire bundles, photoluminescence at ~517 nm attributable to near band-edge emission of CdO was recorded. Based on the experimental results, a possible growth mechanism of the products is proposed

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Developing Literacy Learning Model Based on Multi Literacy, Integrated, and Differentiated Concept at Primary School

The main issue addressed in this research is the low writing skills of primary school students. One of the reasons for this condition is that the existing model of writing literacy learning is not appropriate. The purpose of this study is to explain MID-based literacy teaching model and the impact of the model in increasing primary school students\u27 writing skills. This study used combined methods of exploratory type. The samples were elementary school students coming from six schools with three different characteristics. Based on the data analysis, it can be concluded that the implementation of MID-based literacy learning model has proven to signi cantly contribute to the improvement of students\u27 writing skills. Taking place in all sample schools, the improvement may suggest that the model ts not only to students with high- ability but also those with low-ability. Therefore, the MID-based literacy learning model is needed to improve the ability to write various text types appropriately

A wild derived quantitative trait locus on mouse chromosome 2 prevents obesity

<p>Abstract</p> <p>Background</p> <p>The genetic architecture of multifactorial traits such as obesity has been poorly understood. Quantitative trait locus (QTL) analysis is widely used to localize loci affecting multifactorial traits on chromosomal regions. However, large confidence intervals and small phenotypic effects of identified QTLs and closely linked loci are impeding the identification of causative genes that underlie the QTLs. Here we developed five subcongenic mouse strains with overlapping and non-overlapping wild-derived genomic regions from an F2 intercross of a previously developed congenic strain, B6.Cg-<it>Pbwg1</it>, and its genetic background strain, C57BL/6J (B6). The subcongenic strains developed were phenotyped on low-fat standard chow and a high-fat diet to fine-map a previously identified obesity QTL. Microarray analysis was performed with Affymetrix GeneChips to search for candidate genes of the QTL.</p> <p>Results</p> <p>The obesity QTL was physically mapped to an 8.8-Mb region of mouse chromosome 2. The wild-derived allele significantly decreased white fat pad weight, body weight and serum levels of glucose and triglyceride. It was also resistant to the high-fat diet. Among 29 genes residing within the 8.8-Mb region, <it>Gpd2, Upp2, Acvr1c, March7 </it>and <it>Rbms1 </it>showed great differential expression in livers and/or gonadal fat pads between B6.Cg-<it>Pbwg1 </it>and B6 mice.</p> <p>Conclusions</p> <p>The wild-derived QTL allele prevented obesity in both mice fed a low-fat standard diet and mice fed a high-fat diet. This finding will pave the way for identification of causative genes for obesity. A further understanding of this unique QTL effect at genetic and molecular levels may lead to the discovery of new biological and pathologic pathways associated with obesity.</p

Protein Hydrolysates Are Avoided by Herbivores but Not by Omnivores in Two-Choice Preference Tests

Background: The negative sensory properties of casein hydrolysates (HC) often limit their usage in products intended for human consumption, despite HC being nutritious and having many functional benefits. Recent, but taxonomically limited, evidence suggests that other animals also avoid consuming HC when alternatives exist. Methodology/Principal Findings: We evaluated ingestive responses of five herbivorous species (guinea pig, mountain beaver, gopher, vole, and rabbit) and five omnivorous species (rat, coyote, house mouse, white-footed mouse, and deer mouse; N = 16–18/species) using solid foods containing 20% HC in a series of two-choice preference tests that used a nonprotein, cellulose-based alternative. Individuals were also tested with collagen hydrolysate (gelatin; GE) to determine whether it would induce similar ingestive responses to those induced by HC. Despite HC and GE having very different nutritional and sensory qualities, both hydrolysates produced similar preference score patterns. We found that the herbivores generally avoided the hydrolysates while the omnivores consumed them at similar levels to the cellulose diet or, more rarely, preferred them (HC by the white-footed mouse; GE by the rat). Follow-up preference tests pairing HC and the nutritionally equivalent intact casein (C) were performed on the three mouse species and the guinea pigs. For the mice, mean HC preference scores were lower in the HC v C compared to the HC v Cel tests, indicating that HC’s sensory qualities negatively affected its consumption. However, responses were species-specific. For the guinea pigs, repeated exposure to HC or C (4.7-h sessions; N = 10) were found to increase subsequent HC preference scores in an HC v C preference test, which was interpreted in the light of conservative foraging strategies thought to typify herbivores. Conclusions/Significance: This is the first empirical study of dietary niche-related taxonomic differences in ingestive responses to protein hydrolysates using multiple species under comparable conditions. Our results provide a basis for future work in sensory, physiological, and behavioral mechanisms of hydrolysate avoidance and on the potential use of hydrolysates for pest management

Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1–6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1–6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418–446 and aa611–616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434–446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410–425. The isolation of four HC-84 HMAbs binding to the peptide, aa434–446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus

Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

<p>Abstract</p> <p>Background</p> <p>Highly active anti-retroviral therapy (HAART) is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication.</p> <p>Methods</p> <p>Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to identify potential anti-HIV mechanisms of these extracts.</p> <p>Results</p> <p>Two extracts, one from <it>Euphorbiaceae</it>, <it>Trigonostema xyphophylloides </it>(TXE) and one from <it>Dipterocarpaceae</it>, <it>Vatica astrotricha </it>(VAD) inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus.</p> <p>Conclusion</p> <p>These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.</p