The frequency of transforming growth factor-TGF-B gene polymorphisms in a normal southern Iranian population

Several single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele frequencies in different ethnic groups is useful for both population genetic analyses and association studies with immunological diseases. In this study, five SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian population using polymerase chain reaction-restriction fragment length polymorphism method. This population was in Hardy-Weinberg equilibrium for these SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in the normal southern Iranian population. Comparison of genotype and allele frequencies of TGFB SNPs between Iranian and other populations (meta-analysis) showed significant differences, and in this case the southern Iranian population seems genetically similar to Caucasoid populations. However, neighbour-joining tree using Nei's genetic distances based on TGF-β1 allele frequencies showed that southern Iranians are genetically far from people from the USA, Germany, UK, Denmark and the Czech Republic. In conclusion, this is the first report of the distribution of TGFB1 SNPs in an Iranian population and the results of this investigation may provide useful information for both population genetic and disease studies. © 2008 The Authors

Balo's Concentric Sclerosis In A Woman From Papua New Guinea

We report a case of Balo's concentric sclerosis (a variant of multiple sclerosis) from Papua New Guinea. A 42-year-old woman with a past episode of optic neuritis presented with a left hemiparesis. Magnetic resonance imaging revealed a solitary large tumour-like right cerebral lesion with a pattern of concentric bands of different signal intensities. The diagnosis was established by biopsy of the lesion. To our knowledge, this is the first reported case of Balo's concentric sclerosis in the indigenous population of Papua New Guinea

Development of the Sandia Cooler.

This report describes an FY13 effort to develop the latest version of the Sandia Cooler, a breakthrough technology for air-cooled heat exchangers that was developed at Sandia National Laboratories. The project was focused on fabrication, assembly and demonstration of ten prototype systems for the cooling of high power density electronics, specifically high performance desktop computers (CPUs). In addition, computational simulation and experimentation was carried out to fully understand the performance characteristics of each of the key design aspects. This work culminated in a parameter and scaling study that now provides a design framework, including a number of design and analysis tools, for Sandia Cooler development for applications beyond CPU cooling

Matrix metalloproteinases and their tissue inhibitors after selective laser trabeculoplasty in pseudoexfoliative secondary glaucoma

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess changes in metalloproteinases (MMP-2) and tissue inhibitor of metalloproteinases (TIMP-2) following selective laser trabeculoplasty (SLT) in patients with pseudoexfoliative glaucoma (PEXG).</p> <p>Methods</p> <p>We enrolled 15 patients with PEXG and cataracts (PEXG-C group) and good intraocular pressure (IOP) controlled with β-blockers and dorzolamide eye drops who were treated by cataract phacoemulsification and 15 patients with pseudoexfoliative glaucoma (PEXG-SLT group). The PEXG-SLT patients underwent a trabeculectomy for uncontrolled IOP in the eye that showed increased IOP despite the maximum drug treatment with β-blockers and dorzolamide eye drops and after ineffective selective laser trabeculoplasty (SLT). The control group consisted of 15 subjects with cataracts. Aqueous humor was aspirated during surgery from patients with PEXG-C, PEXG-SLT and from matched control patients with cataracts during cataract surgery or trabeculectomy. The concentrations of MMP-2 and TIMP-2 in the aqueous humor were assessed with commercially available ELISA kits.</p> <p>Results</p> <p>In PEXG-SLT group in the first 10 days after SLT treatment a significant reduction in IOP was observed: 25.8 ± 1.9 vs 18.1.0 ± 1.4 mm/Hg (p < 0.001), but after a mean time of 31.5 ± 7.6 days IOP increased and returned to pretreatment levels: 25.4 ± 1.6 mm/Hg (p < 0.591). Therefore a trabeculectomy was considered necessary.</p> <p>The MMP-2 in PEXG-C was 57.77 ± 9.25 μg/ml and in PEXG-SLT was 58.52 ± 9.66 μg/ml (p < 0.066). TIMP-2 was 105.19 ± 28.53 μg/ml in PEXG-C and 105.96 ± 27.65 μg/ml in PEXG-SLT (p < 0.202). The MMP-2/TIMP-2 ratio in the normal subjects was 1.11 ± 0.44. This ratio increase to 1.88 ± 0.65 in PEXG-C (p < 0.001) and to 1.87 ± 0.64 in PEXG-SLT (p < 0.001). There was no statistically significant difference between the PEXG-C and PEXG-SLT ratios (p < 0.671).</p> <p>Conclusion</p> <p>This case series suggest that IOP elevation after SLT can be a serious adverse event in some PEXG patients. The IOP increase in these cases would be correlated to the failure to decrease the TIMP-2/MMP-2 ratio.</p> <p>Trial registration</p> <p>Current Controlled Trials <b>ISRCTN79745214</b></p

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Anti‑algal activity of the 12‑5‑12 gemini surfactant results from its impact on the photosynthetic apparatus

A rapid amplification of algal population has a negative impact on the environment and the global economy. Thus, control of algal proliferation is an important issue and effective procedures which reduce algal blooms and control algal fouling are highly desired. Gemini surfactants are considered to have a low environmental impact, therefore they seem to be a promising group of detergents which could reduce algal blooms in water systems. Furthermore, due to their emulsifying properties they could replace algaecides added to antifouling paints and decrease algae adhesion to various surfaces. In this study the toxic effect of the 12-5-12 gemini surfactant was investigated on Chlorella cells and close attention was paid to a potential mechanism of its action. At the high cell density (10.05 × 107 cells/mL) a dose-dependent cell death was found and the IC50 value was reached at the concentration of 19.6 µmol/L after 72-h exposure to the surfactant. The decrease in chlorophyll autofluorescence shows that the photosynthetic apparatus seems to be the target of the tested compound. The presented studies indicate that gemini surfactants could effectively reduce algal blooms in water systems, and if added to paints, they could decrease algal growth on external building walls or other water immersed surfaces

Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination

Multiple sclerosis (MS) is a progressive inflammatory-demyelinating disease of the central nervous system. Increasing evidence suggests that vulnerable neurons in MS exhibit fatal metabolic exhaustion over time, a phenomenon hypothesized to be caused by chronic hyperexcitability. Axonal Kv7 (outward rectifying) and oligodendroglial Kir4.1 (inward rectifying) potassium channels have important roles in regulating neuronal excitability at and around nodes of Ranvier. Here, we studied the spatial and functional relationship between neuronal Kv7 and oligodendroglial Kir4.1 channels and assessed the transcriptional and functional signatures of cortical and retinal projection neurons under physiological and inflammatory-demyelinating conditions. We found that both channels became dysregulated in MS and experimental autoimmune encephalomyelitis (EAE) with Kir4.1 channels being chronically downregulated and Kv7 channel subunits being transiently upregulated during inflammatory demyelination. Further, we observed that pharmacological Kv7 channel opening with retigabine reduced neuronal hyperexcitability in human and EAE neurons, improved clinical EAE signs and rescued neuronal pathology in oligodendrocyte-Kir4.1-deficient mice. In summary, our findings indicate that neuron-oligodendrocyte compensatory interactions promote resilience through Kv7 and Kir4.1 channels and suggest pharmacological activation of nodal Kv7 channels as a neuroprotective strategy against inflammatory demyelination