Heat shock proteins and neurodegenerative disorders

10.1100/tsw.2008.48TheScientificWorldJournal8270-27

Magnetoresistive and magnetic properties of La0.67A0.33MnO3 (A= Ba, Ca, and Sr) prepared by co-precipitation method.

We have prepared perovskite structured La0.67A0.33MnO3 manganite (A = Ba, Ca and Sr) using co-precipitation method. The samples were characterized using x-ray diffraction (XRD) and scanning electron microscope (SEM) to identify the structure and microstructure. The magnetic and magnetoresistance properties were measured by vibrations sample magnetometer (VSM) and four point probe methods. From the XRD spectrum, samples are in single phase pervoskite structure where LBMO and LCMO showed orthorhombic whereas LSMO has rhombohedral phase. LSMO has average grain size range of 0.5μm -2.5μm. However, for LBMO and LCMO, the grain boundaries are not well define and connected. The difference in the microstructure image might be due to the different activation energy and variance A-site cation that differs in grain growth. The Curie temperature of LBMO and LSMO are 343K and 371K, respectively. LCMO system gives the highest CMR value (-10.1% at 1 tesla) at room temperature. A significantly low field magnetoresistance effect (LFMR) which is -13.9% (at 0.1T, 90K) has been observed in LBMO and this LFMR effect is believed to be due to the disorder layers at the grain boundaries in the samples

Healthcare Worker Seroconversion in SARS Outbreak

Serum samples were obtained from healthcare workers 5 weeks after exposure to an outbreak of severe acute respiratory syndrome (SARS). A sensitive dot blot enzyme-linked immunosorbent assay, complemented by a specific neutralization test, shows that only persons in whom probable SARS was diagnosed had specific antibodies and suggests that subclinical SARS is not an important feature of the disease

Low-field magnetoresistive and magnetic properties in (La1-xErx)0.67Sr0.33MnO3 manganites perovskite.

Polycrystalline manganites of (La1-xErx)0.67Sr0.33MnO3 (x=0.00, 0.05 and 0.10) had been prepared by conventional solid-state reaction method. X-ray diffraction analysis confirms that all samples are in single phase with distorted perovskite rhombohedral structure. Scanning electron microscope shows that small amount of Er substitution in La site affect the grain formation and this might affect the grain boundaries layer which resulting the reduction of Tc. All sample shows quite similar Low-field magnetoresistance (MR) effect with a large negative MR at low field (0-0.1T) region followed by a slower varying MR at high field (0.1-1T) region. The highest low-field MR value of -3% (at 0.1T, 300K) and high-field MR value of -8.3% (at 1T, 300K) are observed for sample X=0.10

Passive and active ventricular elastances of the left ventricle

BACKGROUND: Description of the heart as a pump has been dominated by models based on elastance and compliance. Here, we are presenting a somewhat new concept of time-varying passive and active elastance. The mathematical basis of time-varying elastance of the ventricle is presented. We have defined elastance in terms of the relationship between ventricular pressure and volume, as: dP = EdV + VdE, where E includes passive (E(p)) and active (E(a)) elastance. By incorporating this concept in left ventricular (LV) models to simulate filling and systolic phases, we have obtained the time-varying expression for E(a )and the LV-volume dependent expression for E(p). METHODS AND RESULTS: Using the patient's catheterization-ventriculogram data, the values of passive and active elastance are computed. E(a )is expressed as: [Image: see text]; E(p)is represented as: [Image: see text]. E(a )is deemed to represent a measure of LV contractility. Hence, Peak dP/dt and ejection fraction (EF) are computed from the monitored data and used as the traditional measures of LV contractility. When our computed peak active elastance (E(a,max)) is compared against these traditional indices by linear regression, a high degree of correlation is obtained. As regards E(p), it constitutes a volume-dependent stiffness property of the LV, and is deemed to represent resistance-to-filling. CONCLUSIONS: Passive and active ventricular elastance formulae can be evaluated from a single-beat P-V data by means of a simple-to-apply LV model. The active elastance (E(a)) can be used to characterize the ventricle's contractile state, while passive elastance (E(p)) can represent a measure of resistance-to-filling

Social Cognitive Role of Schizophrenia Candidate Gene GABRB2

10.1371/journal.pone.0062322PLoS ONE84

Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations

10.1371/journal.pone.0062378PLoS ONE86

A Single Nucleotide Polymorphism within the Acetyl-Coenzyme A Carboxylase Beta Gene Is Associated with Proteinuria in Patients with Type 2 Diabetes

It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4×10−6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33–1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35×10−8, odds ratio = 1.61, 95% Cl: 1.35–1.91). Rs2268388 was also associated with type 2 diabetes–associated end-stage renal disease (ESRD) in European Americans (p = 6×10−4, odds ratio = 1.61, 95% Cl: 1.22–2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes

Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical

Vaginally Administered PEGylated LIF Antagonist Blocked Embryo Implantation and Eliminated Non-Target Effects on Bone in Mice

Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice