Dendritic Cells Transduced to Express Interleukin 4 Reduce Diabetes Onset in Both Normoglycemic and Prediabetic Nonobese Diabetic Mice

Background: We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown. Methodology/Principal Findings: DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 106 DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals. Conclusions: Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D. © 2010 Ruffner, Robbins

Cellulase recycling in biorefineriesis : is it possible?

On a near future, bio-based economy will assume a key role in our lives. Lignocellulosic materials (e.g., agroforestry residues, industrial/solid wastes) represent a cheaper and environmentally friendly option to fossil fuels. Indeed, following suitable processing, they can be metabolized by different microorganisms to produce a wide range of compounds currently obtained by chemical synthesis. However, due to the recalcitrant nature of these materials, they cannot be directly used by microorganisms, the conversion of polysaccharides into simpler sugars being thus required. This conversion, which is usually undertaken enzymatically, represents a significant part on the final cost of the process. This fact has driven intense efforts on the reduction of the enzyme cost following different strategies. Here, we describe the fundamentals of the enzyme recycling technology, more specifically, cellulase recycling. We focus on the main strategies available for the recovery of both the liquid- and solid-bound enzyme fractions and discuss the relevant operational parameters (e.g., composition, temperature, additives, and pH). Although the efforts from the industry and enzyme suppliers are primarily oriented toward the development of enzyme cocktails able to quickly and effectively process biomass, it seems clear by now that enzyme recycling is technically possible.Financial support from FEDER and Fundação para a Ciência e a Tecnologia (FCT): GlycoCBMs Project PTDC/AGR-FOR/3090/2012–FCOMP-01-0124- FEDER-027948 and Strategic Project PEst-OE/EQB/LA0023/2013, Project BBioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028 Cofunded by the Programa Operacional Regional do Norte (ON.2–O Novo Norte), QREN, FEDER and the PhD grant to DG (SFRH/BD/88623/ 2012) and ACR (SFRH/BD/89547/2012)

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries, in which chronic conditions such as obesity, hypertension and diabetes are more common. Many rural residents with Chagas disease have now migrated to cities, taken on new habits and may suffer from both types of disease. We studied heart disease among 394 adults seen by cardiologists in a public hospital in the city of Santa Cruz, Bolivia; 64% were infected with T. cruzi, the parasite that causes Chagas disease. Both T. cruzi infected and uninfected patients had a high rate of hypertension (64%) and overweight (67%), with no difference by infection status. Nearly 60% of symptomatic congestive heart failure was due to Chagas disease; mortality was also higher for infected than uninfected patients. Males and older patients had more severe Chagas heart disease. Chagas heart disease remains an important cause of congestive heart failure in this hospital population, but often occurs in patients who also have obesity, hypertension and/or other cardiac risk factors

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005