Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials.     

Ballistic transfection of avian primordial germ cellin ovo

In the fowl the primordial germ cells accumulate in the germinal crescent to the anterior of the two-day embryo. A simple ballistic device has been used to fire tungsten particles (mean diameter 1.5 m) into this region. By coating these projectiles with vector DNA it is possible to transfect these cells. Hatchlings produced by this technique were raised to sexual maturity and shown to contain the foreign DNA in their sperm. G₁ offspring containing this DNA were also produced in roughly 20% of these cockerels. In the majority of cases the vector DNA disappeared from the G₁ generation as they matured suggesting that in these cases it had been transmitted episomally.     

Review and future prospects on the mechanisms related to cold stress resistance and tolerance in medicinal plants

Medicinal plants play important role in industrial production of medicines. Moreover, they consume without complicated processes around the world. They are considered as healthy cure without any harmful side effects at least among ordinary people. Cold stress is one the harmful abiotic stresses and constrains medicinal plants yielding geographically. Cold acclimation is a process that induces cold stress resistance in temperate plants. Various structural and morphological alterations are involved in this process. Also, enzymatic and non-enzymatic agents play role in cold acclimation. Cell membrane modification and compatible solutes accumulation and so many other changes occur through cold acclimation. Growing under different stressful conditions, medicinal plants synthesize different components such as metabolites. Moreover, ROS can be generated in plant cells under stressful conditions. The accumulation of bioactive components, biosynthesis of phytohormones, ion hemostasis, osmolyte (compatible solutes) accumulation and changes in nutrient uptake, root system modification and systemic resistance are some of new investigations that are considered in this review.     

The Crosstalk Between Brain Mediators Regulating Food Intake Behavior in Birds: A Review

International Journal of Peptide Research and Therapeutics - Appetite is controlled by a complex system of central and peripheral signals interacting to modulate the ingestion response. Several...     

A Dermal Gel Made of Rutilus Kutum Skin Collagen-Chitosan for Deep Burn Healing

International Journal of Peptide Research and Therapeutics - Natural compounds extracted from marine organisms consisting of biological active materials like collagen provide a major source of...     

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.     

Evaluation of the effects of weak and moderate static magnetic fields on the characteristics of human low density lipoprotein in vitro

It has been suggested that exposure to electromagnetic fields may be a risk factor for cardiovascular disease in humans. Low density lipoprotein (LDL) modifications such as peroxidation and aggregation have been implicated in the pathogenesis of atherosclerosis. The present study investigated the effects of weak (0.125–0.5 mT) and moderate (1–4 mT) static magnetic fields (SMFs) on LDL oxidation, aggregation and zeta potential in vitro. Our results demonstrated that magnetic flux densities of 0.25 and 0.5 mT decreased, and magnetic flux densities of 3 and 4 mT increased the zeta potential and LDL oxidation in comparison with the control samples. All doses of SMFs increased the LDL aggregation in a time‐ and dose‐dependent manner. It is concluded that SMFs can alter the susceptibility of LDL to oxidation and this alteration is dependent on the applied magnetic flux density. The SMF, in addition to its role in the production and stabilization of free radicals and promotion of lipid peroxidation, may influence the metabolism of lipoproteins and their interaction with other molecules such as apolipoproteins, enzymes and receptors through the alteration of the LDL zeta potential and its particles tendency to aggregation. Bioelectromagnetics 34:397–404, 2013. © 2012 Wiley Periodicals, Inc.     

An efficient system for selection and culture of Schwann cells from adult rat peripheral nerves

Schwann cells (SCs), the supporting cells of the peripheral nerves, are indispensable for regenerating the peripheral and central nervous system. Copious preparation of these cells in a well-defined manner is to be a privileged position. SCs cultivation is overwhelmed by contaminating fibroblasts which are often outgrowing as the predominant cell type in an in vitro culture. This study introduces a technically simple and efficient procedure for SCs isolation and enrichment based on implementing recombinant and defined supplements. Collected adult rat sciatic nerves were cultured for 10 days as in vitro predegeneration. After dissociation and plating, the medium changed to knockout serum replacement supplemented DMDM/F12 medium containing various growth factors. The whole procedure took 3 weeks and SCs purity was then evaluated through implementing specific cytoplasmic and membranous markers. The viability of enriched SCs were evaluated by MTT assay. Within 10 days, over 99 % homogenous SCs were achieved and confirmed through immunofluorescence staining and flow-cytometry for P75^NTR and S100 markers, respectively. MTT data revealed that the viability and metabolic activities of purified SCs were increased in expansion medium. This study provides a technically easy and efficient method with the benefits of not utilizing bovine serum or other animal products for SCs isolation and enrichment.     

An evaluation of sequencing coverage and genotyping strategies to assess neutral and adaptive diversity

Whole genome sequences (WGS) greatly increase our ability to precisely infer population genetic parameters, demographic processes, and selection signatures. However, WGS may still be not affordable for a representative number of individuals/populations. In this context, our goal was to assess the efficiency of several SNP genotyping strategies by testing their ability to accurately estimate parameters describing neutral diversity and to detect signatures of selection. We analysed 110 WGS at 12× coverage for four different species, i.e., sheep, goats and their wild counterparts. From these data we generated 946 data sets corresponding to random panels of 1K to 5M variants, commercial SNP chips and exome capture, for sample sizes of five to 48 individuals. We also extracted low‐coverage genome resequencing of 1×, 2× and 5× by randomly subsampling reads from the 12× resequencing data. Globally, 5K to 10K random variants were enough for an accurate estimation of genome diversity. Conversely, commercial panels and exome capture displayed strong ascertainment biases. Besides the characterization of neutral diversity, the detection of the signature of selection and the accurate estimation of linkage disequilibrium (LD) required high‐density panels of at least 1M variants. Finally, genotype likelihoods increased the quality of variant calling from low coverage resequencing but proportions of incorrect genotypes remained substantial, especially for heterozygote sites. Whole genome resequencing coverage of at least 5× appeared to be necessary for accurate assessment of genomic variations. These results have implications for studies seeking to deploy low‐density SNP collections or genome scans across genetically diverse populations/species showing similar genetic characteristics and patterns of LD decay for a wide variety of purposes.     

Long‐term ethanol consumption promotes changes in β‐defensin isoform gene expression and induces structural changes and oxidative DNA damage to the epididymis of rats

Chronic alcohol ingestion causes sexual dysfunction, impairs sperm motility and fertility, and changes semen quality. Considering the key role of epididymis in sperm development, the aim of the present study was to evaluate the effects of long‐term ethanol consumption on epididymis changes, including alterations in β‐defensin isoform gene expression, oxidative stress, and pathological changes, such as cell proliferation and fibrosis in the epididymis of rats. In this study, male Wistar rats were equally divided into control and ethanol (4.5 g/kg BW) groups. After six weeks of treatment, the results revealed the proliferation of epididymis cells, fibrosis in the epididymis tissue, and a significant rise in the level of 8‐OHdG and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the ethanol group, compared with the control group. Moreover, the ethanol group showed an increase in the gene expression of epididymal β‐defensin isoforms 15 and 21 and a reduction in the gene expression of β‐defensin isoforms 27 and 30, compared with the controls. These findings indicate that ethanol‐induced epididymal damage and sperm abnormalities might be partly associated with changes in β‐defensin isoforms and epididymal structure, mediated by the increased activities of 8‐OHdG and NADPH oxidase.