Erythrocyte flow through the interendothelial slits of the splenic venous sinus

Biomechanics and Modeling in Mechanobiology - The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring...     

LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation

Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.     

Sustainable biosynthesis of chemicals from methane and glycerol via reconstruction of multi-carbon utilizing pathway in obligate methanotrophic bacteria

Obligate methanotrophic bacteria can utilize methane, an inexpensive carbon feedstock, as a sole energy and carbon substrate, thus are considered as the only nature-provided biocatalyst for sustainable biomanufacturing of fuels and chemicals from methane. To address the limitation of native C1 metabolism of obligate type I methanotrophs, we proposed a novel platform strain that can utilize methane and multi-carbon substrates, such as glycerol, simultaneously to boost growth rates and chemical production in Methylotuvimicrobium alcaliphilum 20Z. To demonstrate the uses of this concept, we reconstructed a 2,3-butanediol biosynthetic pathway and achieved a fourfold higher titer of 2,3-butanediol production by co-utilizing methane and glycerol compared with that of methanotrophic growth. In addition, we reported the creation of a methanotrophic biocatalyst for one-step bioconversion of methane to methanol in which glycerol was used for cell growth, and methane was mainly used for methanol production. After the deletion of genes encoding methanol dehydrogenase (MDH), 11.6 mM methanol was obtained after 72 h using living cells in the absence of any chemical inhibitors of MDH and exogenous NADH source. A further improvement of this bioconversion was attained by using resting cells with a significantly increased titre of 76 mM methanol after 3.5 h with the supply of 40 mM formate. The work presented here provides a novel framework for a variety of approaches in methane-based biomanufacturing.     

猴痘病毒CrmB蛋白的结构特征及其抗原表位分析

为深入了解猴痘病毒(Monkeypox virus, MPXV)的CrmB(cytokine response modifier B)蛋白的结构特征和抗原表位，运用ORF Finder、ExPaSy、SignalP 6.0、TMHMM 2.0、Cell-Ploc、Conserved Domains、 SOPMA、SWISS-MODEL、NetNGlyc 1.0、NetPhos 3.1、IEDB、SYFPEITHI、Clustalx、MEGA 11.0、Prankweb、DrugBank等多种生物信息学方法，分析CrmB蛋白的开放阅读框、理化性质、信号肽、跨膜区、亚细胞定位、结构域、糖基化/磷酸化位点、二级/三级结构、B/T细胞抗原表位、抗原决定簇、蛋白同源性、配体结合位点、小分子抑制药物等。CrmB蛋白是由349个氨基酸组成的不稳定蛋白质，相对分子量为38 308.75;理论等电点为6.24,分子式为C₁₆₂₁H₂₅₅₀N₄₆₀O₅₅₀S₃₂;二级结构以不规则卷曲为主，有信号肽...     

Designing a Community Engagement Framework for a New Dengue Control Method: A Case Study from Central Vietnam

Background

The Wolbachia strategy aims to manipulate mosquito populations to make them incapable of transmitting dengue viruses between people. To test its efficacy, this strategy requires field trials. Public consultation and engagement are recognized as critical to the future success of these programs, but questions remain regarding how to proceed. This paper reports on a case study where social research was used to design a community engagement framework for a new dengue control method, at a potential release site in central Vietnam.

Methodology/Principal Findings

The approach described here, draws on an anthropological methodology and uses both qualitative and quantitative methods to design an engagement framework tailored to the concerns, expectations, and socio-political setting of a potential trial release site for Wolbachia-infected Aedes aegypti mosquitoes. The process, research activities, key findings and how these were responded to are described. Safety of the method to humans and the environment was the most common and significant concern, followed by efficacy and impact on local lives. Residents expected to be fully informed and engaged about the science, the project, its safety, the release and who would be responsible should something go wrong. They desired a level of engagement that included regular updates and authorization from government and at least one member of every household at the release site.

Conclusions/Significance

Results demonstrate that social research can provide important and reliable insights into public concerns and expectations at a potential release site, as well as guidance on how these might be addressed. Findings support the argument that using research to develop more targeted, engagement frameworks can lead to more sensitive, thorough, culturally comprehensible and therefore ethical consultation processes. This approach has now been used successfully to seek public input and eventually support for releases Wolbachia-infected mosquitoes, in two different international settings - Australia and Vietnam.     

Atherosclerosis-Related Circulating miRNAs as Novel and Sensitive Predictors for Acute Myocardial Infarction

Background

The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the expressions of circulating miR-21-5p, miR-361-5p and miR-519e-5p in AMI patients, and assess their clinical applications for diagnosing and monitoring AMI.

Results

Two different cohorts were enrolled in this study. The first cohort included 17 AMI patients and 28 healthy volunteers, and the second cohort included 9 AMI patients, 9 ischemic stroke patients, 8 patients with pulmonary embolism, and 12 healthy volunteers. Quantitative real-time PCR and ELISA assays were preformed to detect the concentrations of plasma miRNAs and cardiac troponin I (cTnI), respectively. The results showed that the plasma levels of miR-21-5p and miR-361-5p were significantly increased in AMI patients, whereas the concentration of circulating miR-519e-5p was reduced. Interestingly, the levels of these circulating miRNAs correlated with the concentrations of plasma cTnI. Receiver operating characteristic (ROC) analysis revealed that these three circulating miRNAs had considerable diagnostic accuracy for AMI with high values of area under ROC curve (AUC). Importantly, combining the three miRNAs significantly increased the diagnostic accuracy. Furthermore, cell experiments demonstrated that these plasma miRNAs may originate from injured cardiomyocytes induced by hypoxia. In addition, the levels of all the three circulating miRNAs in ischemic stroke (IS) and pulmonary embolism (PE) were elevated, whereas the decreased level of plasma miR-519e-5p was only detected in AMI. ROC analysis demonstrated that circulating miR-519e-5p may be a useful biomarker for distinguishing AMI from other ischemic diseases.

Conclusions

Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.     

Isolating Fungal Pathogens from a Dynamic Disease Outbreak in a Native Plant Population to Establish Plant-Pathogen Bioassays for the Ecological Model Plant Nicotiana attenuata

The wild tobacco species Nicotiana attenuata has been intensively used as a model plant to study its interaction with insect herbivores and pollinators in nature, however very little is known about its native pathogen community. We describe a fungal disease outbreak in a native N. attenuata population comprising 873 plants growing in an area of about 1500 m². The population was divided into 14 subpopulations and disease symptom development in the subpopulations was monitored for 16 days, revealing a waxing and waning of visible disease symptoms with some diseased plants recovering fully. Native fungal N. attenuata pathogens were isolated from diseased plants, characterized genetically, chemotaxonomically and morphologically, revealing several isolates of the ascomycete genera Fusarium and Alternaria, that differed in the type and strength of the disease symptoms they caused in bioassays on either detached leaves or intact soil-grown plants. These isolates and the bioassays will empower the study of N. attenuata-pathogen interactions in a realistic ecological context.     

Intra-Individual Double Burden of Overweight and Micronutrient Deficiencies among Vietnamese Women

Background

Vietnamese Living Standard Surveys showed that the rate of overweight and obese in Vietnamese adults doubled between 1992 and 2002, from 2% to 5.5%, respectively with no significant difference in the proportions of overweight/obesity between men and women.

Objectives

Considering the increasing public health concern over the double burden of malnutrition in Vietnam, we investigated micronutrient deficiencies among women of reproductive age according to their Body Mass Index.

Methods

A transversal study was conducted in 2010 among 1530 women of reproductive age from 19 provinces. Participating women were asked to give a non-fasting blood sample for plasma iron, vitamin A, folate, vitamin B₁₂ and zinc assessment.

Results

Although % body fat was associated with haemoglobin, ferritin, retinol and zinc concentrations, BMI category was only associated with marginal vitamin A status (19% among underweight vs 7% among overweight/obese; p<0.0001) and not with iron deficiency anemia, zinc deficiency, vitamin B₁₂ deficiency or folate status. The prevalence of iron, and vitamin B₁₂ deficiencies was respectively 11.4% and 15% among the 20% overweight/obese women; prevalence of zinc deficiency and marginal/deficient folate status was much higher, affecting respectively 61.1% and 25.8%. Intra-individual double burden of malnutrition (overweight/obesity (OW) and micronutrient deficiency) was observed among 2.0% for OW-anemia, 2.3% OW-iron deficient, 3.0% for OW-Vitamin B₁₂ deficiency, 12.2% for OW-Zinc deficiency and 5.2% for OW-marginal/deficient folate status.

Conclusions

This large, cross-sectional survey demonstrated that micronutrient deficiencies are an issue across the weight spectrum among women in Vietnam, with only vitamin A status being better among overweight than underweight women. It is therefore essential for Vietnam to actively prevent women of reproductive age from overweight/obesity and at same time to control micronutrient deficiencies in this population to limit their economic and health consequences.     

Mutation of the Dictyostelium fbxA gene affects cell-fate decisions and spatial patterning

Cell-fate decisions and spatial patterning in Dictyostelium are regulated by a number of genes. Our studies have implicated a gene called fbxA, which codes for an F-box protein, in these pathways. The FbxA protein is one of the controls on a cAMP phosphodiesterase called RegA, mediating its degradation via ubiquitin-linked proteolysis. Using marked strains, we showed that the fbxA^– mutant has defective cell-type proportioning, with a dearth of prestalk cells compared to prespore cells. In this work, we show that this effect occurs earlier during the 24 hour developmental cycle than previously thought. The normal sorting of the prestalk and prespore cells in aggregates and mounds is not affected by the mutation. The mutant cells sort abnormally at the tipped mound stage, when prespore and prestalk cells normally distribute into their proper compartments. The fbxA^– mutant forms prestalk cells in low numbers when not in chimeras, but in the presence of wild-type amoebae the mutant preferentially forms viable spores, driving the wild type to form non-viable stalk cells. In an attempt to identify the signal transduction pathway that mediates proportionality in prestalk and prespore cells, we asked whether certain signal transduction mutants were immune to the effects of the fbxA^–cells and formed spores in chimeras.