Approaches to Type 1 Diabetes Prevention by Intervention in Cytokine Immunoregulatory Circuits

Type 1 (insulin-dependent) diabetes mellitus, like other organ specific autoimmune diseases, results from a disorder of immunoregulation. T cells specific for pancreatic islet ß cell constituents (autoantigens) exist normally but are restrained by regulatory mechanisms (self-tolerant state). When regulation fails, ß cell-specific autoreactive T cells become activated and expand clonally. Current evidence indicates that islet ß cell-specific autoreactive T cells belong to a T helper 1 (Th1) subset, and these Th1 cells and their characteristic cytokine products, IFNγ and IL-2, are believed to cause islet inflammation (insulitis) and ß cell destruction. Immune-mediated destruction of ß cells precedes hyperglycemia and clinical symptoms by many years because these become apparent only when most of the insulin-secreting ß cells have been destroyed. Therefore, several approaches are being tested or are under consideration for clinical trials to prevent or arrest complete autoimmune destruction of islet ß cells and insulin-dependent diabetes. Approaches that attempt to correct underlying immunoregulatory defects in autoimmune diabetes include interventions aimed at i) deleting ß cell autoreactive Th1 cells and cytokines (IFNγ and IL-2) and/or ii) increasing regulatory Th2 cells and/or Th3 cells and their cytokine products (IL-4, IL-10 and TGFßI)

East Asia and the global/transatlantic/Western crisis

This paper introduces the special collection on East Asia and the Global Crisis. After justifying why a focus on East Asia is appropriate, it draws out the main themes that run through the individual contributions. These are the extent to which the region is decoupling from the global economy (or the West), the increasing legitimacy of statist alternatives to neoliberal development strategies, and the impact of crises on the definition of ―region‖ and the functioning of regional institutions and governance mechanisms

Combination Therapy With Glucagon-Like Peptide-1 and Gastrin Restores Normoglycemia in Diabetic NOD Mice

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic β-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the β-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes

In pulmonary arterial hypertension, reduced BMPR2 promotes rndothelial-to-mesenchymal transition via HMGA1 and its target slug

Background—We previously reported high-throughput RNA sequencing analyses that identified heightened expression of the chromatin architectural factor High Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs) from patients who had idiopathic pulmonary arterial hypertension (PAH) in comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal transition in cancer, we hypothesized that increased HMGA1 could induce transition of PAECs to a smooth muscle (SM)–like mesenchymal phenotype (endothelial-to-mesenchymal transition), explaining both dysregulation of PAEC function and possible cellular contribution to the occlusive remodeling that characterizes advanced idiopathic PAH. Methods and Results—We documented increased HMGA1 in PAECs cultured from idiopathic PAH versus donor control lungs. Confocal microscopy of lung explants localized the increase in HMGA1 consistently to pulmonary arterial endothelium, and identified many cells double-positive for HMGA1 and SM22α in occlusive and plexogenic lesions. Because decreased expression and function of bone morphogenetic protein receptor 2 (BMPR2) is observed in PAH, we reduced BMPR2 by small interfering RNA in control PAECs and documented an increase in HMGA1 protein. Consistent with transition of PAECs by HMGA1, we detected reduced platelet endothelial cell adhesion molecule 1 (CD31) and increased endothelial-to-mesenchymal transition markers, αSM actin, SM22α, calponin, phospho-vimentin, and Slug. The transition was associated with spindle SM-like morphology, and the increase in αSM actin was largely reversed by joint knockdown of BMPR2 and HMGA1 or Slug. Pulmonary endothelial cells from mice with endothelial cell–specific loss of Bmpr2 showed similar gene and protein changes. Conclusions—Increased HMGA1 in PAECs resulting from dysfunctional BMPR2 signaling can transition endothelium to SM-like cells associated with PAH

Inativação seletiva de esporos mantendo atividade larvicida em Bt sorovar israelensis irradiada com raios gama

Bacillus thuringiensis is used to produce biopesticides against target-insects of importance in agroindustry and human health. However, B. thuringiensis can carry the same enterotoxin-encoding genes as Bacillus cereus, suggesting a potential risk of food poisoning. The objective of this work was to study the application of gamma radiation to eliminate spores in biopesticides based on B. thuringiensis serovar israelensis in order to avoid the liberation of these spores in the environment. The application of 20 kGy of radiation ensures total inactivation of the spores in the insecticide without changing the larvicidal activity. Results showed that it is possible to develop formulations containing B. thuringiensis serovar israelensis (IPS-82) eliminating viable spores with gamma radiation without affecting the larvicidal activity. Irradiated formulations would be safer for the environment and humans since the elimination of viable spores abolishes the pathogenic potential of B. thuringiensis strains.Keywords: biopesticides, gamma radiation, larvicidal insecticides.Bacillus thuringiensis é usado na produção de biopesticidas contra insetos-alvo de importância na agroindústria e na saúde pública. Contudo, B. thuringiensis pode apresentar os mesmos genes codificadores de enterotoxinas presentes em Bacillus cereus, sugerindo a possível existência de risco para intoxicação alimentar. O objetivo deste trabalho foi estudar a aplicação de radiação gama para a eliminação de esporos em preparações de biopesticidas de B. thuringiensis sorovar israelensis de forma a se evitar a liberação de esporos viáveis no ambiente. Observou-se que a aplicação de 20 kGy garante a inativação total dos esporos no inseticida sem que haja mudança na atividade larvicida. Os resultados obtidos demonstram que é possível desenvolver formulações contendo B. thuringiensis sorovar israelensis (IPS-82) eliminando-se esporos viáveis sem alteração da atividade larvicida. As formulações irradiadas seriam mais seguras para o meio-ambiente e para seres humanos uma vez que a eliminação dos esporos viáveis neutraliza o potencial patogênico de cepas de B. thuringiensis.Palavras-chave: biopesticidas, radiação gama, inseticidas larvicidas

Measurement of left ventricular ejection fraction in pediatric patients using the nuclear stethoscope

Left ventricular (LV) ejection fraction (EF) was measured in 25 patients, aged 2 weeks to 20 years (mean 8.6 years), using a portable nonimaging scintillation stethoscope. Technically satisfactory studies were obtained in 23 patients. LVEF was validated by cineangiography in 19 patients and by standard gated blood pool scintigraphy in 4. EF measured by the nuclear stethoscope correlated well with values obtained by cineangiography or scintigraphy (r = 0.869, p < 0.001) over a wide range of EF values (18 to 79%). In children younger than 5 years (n = 11), the correlation (r = 0.728, p < 0.02) was less satisfactory than in those older than 5 years (r = 0.926; p < 0.001). Although modifications in the instrument and further clinical trials with the stethoscope are needed before the device becomes clinically useful to pediatric cardiologists, our data indicate that the nuclear stethoscope can provide reliable assessment of LVEF in pediatric patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24989/1/0000416.pd

Sudden drop of fractal dimension of electromagnetic emissions recorded prior to significant earthquake

The variation of fractal dimension and entropy during a damage evolution process, especially approaching critical failure, has been recently investigated. A sudden drop of fractal dimension has been proposed as a quantitative indicator of damage localization or a likely precursor of an impending catastrophic failure. In this contribution, electromagnetic emissions recorded prior to significant earthquake are analysed to investigate whether they also present such sudden fractal dimension and entropy drops as the main catastrophic event is approaching. The pre-earthquake electromagnetic time series analysis results reveal a good agreement to the theoretically expected ones indicating that the critical fracture is approaching