Novel structurally designed vaccine for S. aureus α-hemolysin: protection against bacteremia and pneumonia

Staphylococcus aureus (S. aureus) is a human pathogen associated with skin and soft tissue infections (SSTI) and life threatening sepsis and pneumonia. Efforts to develop effective vaccines against S. aureus have been largely unsuccessful, in part due to the variety of virulence factors produced by this organism. S. aureus alpha-hemolysin (Hla) is a pore-forming toxin expressed by most S. aureus strains and reported to play a key role in the pathogenesis of SSTI and pneumonia. Here we report a novel recombinant subunit vaccine candidate for Hla, rationally designed based on the heptameric crystal structure. This vaccine candidate, denoted AT-62aa, was tested in pneumonia and bacteremia infection models using S. aureus strain Newman and the pandemic strain USA300 (LAC). Significant protection from lethal bacteremia/sepsis and pneumonia was observed upon vaccination with AT-62aa along with a Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) that is currently in clinical trials. Passive transfer of rabbit immunoglobulin against AT-62aa (AT62-IgG) protected mice against intraperitoneal and intranasal challenge with USA300 and produced significant reduction in bacterial burden in blood, spleen, kidney, and lungs. Our Hla-based vaccine is the first to be reported to reduce bacterial dissemination and to provide protection in a sepsis model of S. aureus infection. AT62-IgG and sera from vaccinated mice effectively neutralized the toxin in vitro and AT62-IgG inhibited the formation of Hla heptamers, suggesting antibody-mediated neutralization as the primary mechanism of action. This remarkable efficacy makes this Hla-based vaccine a prime candidate for inclusion in future multivalent S. aureus vaccine. Furthermore, identification of protective epitopes within AT-62aa could lead to novel immunotherapy for S. aureus infection.     

A fuzzy-genetic model for estimating forces from electromyographical activity of antagonistic muscles due to planar lower arm movements: the effect of nonlinear muscle properties

The aim of this paper is to create a model for mapping the surface electromyogram (EMG) signals to the force that generated by human arm muscles. Because the parameters of each person's muscle are individual, the model of the muscle must have two characteristics: (1) The model must be adjustable for each subject. (2) The relationship between the input and output of model must be affected by the force-length and the force-velocity behaviors are proven through Hill's experiments. Hill's model is a kinematic mechanistic model with three elements, i.e. one contractile component and two nonlinear spring elements.In this research, fuzzy systems are applied to improve the muscle model. The advantages of using fuzzy system are as follows: they are robust to noise, they prove an adjustable nonlinear mapping, and are able to model the uncertainties of the muscle.Three fuzzy coefficients have been added to the relationships of force-length (active and passive) and force-velocity existing in Hill's model. Then, a genetic algorithm (GA) has been used as a biological search method that can adjust the parameters of the model in order to achieve the optimal possible fit.Finally, the accuracy of the fuzzy genetic implementation Hill-based muscle model (FGIHM) is invested as following: the FGIHM results have 12.4% RMS error (in worse case) in comparison to the experimental data recorded from three healthy male subjects. Moreover, the FGIHM active force-length relationship which is the key characteristics of muscles has been compared to virtual muscle (VM) and Zajac muscle model. The sensitivity of the FGIHM has been evaluated by adding a white noise with zero mean to the input and FGIHM has proved to have lower sensitivity to input noise than the traditional Hill's muscle model.     

<Superscript>1</Superscript>H NMR metabolic fingerprinting of saffron extracts

The aim of this study was to explore feasibility of ¹H NMR metabolic fingerprinting for discrimination of authenticity of saffron using principal component analysis (PCA) modeling. Authentic reference Iranian saffron (n = 31) and commercial samples (n = 32) were used. Cross-validated PCA models based on ¹H NMR spectra of solutions prepared by direct extraction of grinded saffron with methanol-d ₄ distinguished reference Iranian saffron samples from commercial samples that formed several distinct clusters, some of which represent falsified samples as confirmed by microscopic analysis. The production sites and drying conditions of the authentic reference Iranian samples were not reflected in the current dataset. Picrocrocin and glycosyl esters of crocetin emerged as the most important ¹H NMR markers of authentic saffron by using statistical correlation spectroscopy. In conclusion, ¹H NMR spectra of saffron extracts combined with pattern recognition by PCA provide immediate means of unsupervised classification of saffron samples.     

Biocontrol of Ascochyta blight by Azospirillum sp. depending on the degree of resistance of chickpea genotypes

Throughout arable land that was devoted to chickpea (Cicer arietinum L. (Family: Leguminosae) production, Ascochyta blight (Ascochyta rabiei (Pass.) L. (Order: Sphaeriales; Family: Mycosphaerellaceae) is a widespread disease that would lead to significant loss of chickpea yield. This study's purpose was to explain the responses of a resistant chickpea cultivar (ICC 12004) and a susceptible cultivar (Bivanij) in terms of disease resistance, disease symptoms appearance and expression pattern of two defence‐related genes (DEF0442 and Snakin2) after the Azospirillum brasilense seeds inoculation. In this research, the Snakin2 gene expression was affected by Azospirillum inoculation. The gene expression has been enhanced in plants inoculated with Azospirillum in both cultivars in comparison with non‐inoculated plants, but this change in ICC 12004 and Bivanij were significant and non‐significant, respectively. Although, Azospirillum would up regulate the DEF0422 gene expression in ICC 12004, but it would down regulate the expression of this gene in Bivanij. A. brasilense inoculation decreased the A. rabiei disease severity, regardless of the chickpea cultivar. Bivanij still could be classified as susceptible, even if treated with A. brasilense.     

Edge influence on herbaceous plant species,diversity and soil properties in sparse oak forest fragments in Iran

伊朗稀疏橡木林片段对草本植物物种多样性和土壤特性的边缘影响 温带和热带森林中的森林边缘现象已经得到了很好的研究,但在稀疏的橡木林片段中的相关研究却较为缺乏。本文研究了稀疏橡木林片段对植物物种多样性和土壤特性的边缘影响。本研究沿着伊朗克尔曼沙赫省3个小型(<10 ha)和3个大型(>10 ha)橡木林片段的3个横断面收集了从边缘到内部的相 关数据,测量了0(森林边缘)、25、50、100和150 m处的草本植物(高度<0.5 m)和土壤特性。使用香农指数量化了物种多样性,使用稀疏标准化方法比较了两个大小不同片段中的物种丰富度,并应用了非度量多维测度排序研究了物种组成的变化。通过随机化测试估算了边缘影响的距离,并利用Tukey HSD事后检验法的广义线性混合模型评估了距边缘距离和片段大小对多样性和土壤特性的影响。研究结果表明,大小片段边缘具有较高的物种丰富度、多样性和均匀度,而大片段边缘的土壤氮和有机碳含量则较内部更低(边缘50 m范围内的变化最大)。大小片段的物种组成、土壤有机碳和氮总量都存在显 著差异。本研究关于这些稀疏森林对草本植物和土壤特性产生显著边缘影响的发现,对于边缘研究,尤其是边缘和草本植物的相关研究具有重大贡献。     

Formation of embryoid bodies from mouse embryonic stem cells cultured on silicon-coated surfaces

Embryoid bodies (EBs) are primitive embryonic structures derived from differentiating embryonic stem cells (ESCs). Many techniques have been used to obtain EBs. Improving the technique of EB formation can help in achieving better results in ESCs differentiation into neurons, myocardiocytes, haemopoeitic cells, and others. We evaluated the use of Sigmacote™ as a hydrophobic substrate to improve EB formation. CCE and P19 cell lines were used to obtain EBs and retinoic acid was used to induce neural differentiation. The results revealed that Sigmacote™, as a hydrophobic substrate, can improve EB formation from ESCs. Our results demonstrate that the silicon-coating of glass petri dishes by Sigmacote™ is an easy and reproducible technique to enhance EB formation from murine ESCs and EC cells.     

Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress,microRNA, and long noncoding RNA

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the β cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic β-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic β-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic β-cell dysfunction.