Synthesis of Hybrid Inositol Glycan Analogues

Inositol glycans (IGs) are small oligosaccharides exhibiting insulin-like metabolic activities in insulin-sensitive cells. The signal transduction pathways activated by IGs in these cells are still under study, but it is known that there is cross talk between the IG-signaling pathway and the insulin-signaling pathway downstream of the insulin receptor. Therefore, IGs may have potential for use in the treatment of type II diabetes mellitus. However, natural IGs are heterogeneous and difficult to isolate. Hence, synthetic IGs and their analogues have been chemically synthesized and evaluated for insulin-mimetic properties by various research groups. Unfortunately, the most biologically active IG analogues are structurally complex and difficult to synthesize. The present work reports the progress towards designing and preparing biologically active IG analogues with short and relatively simple synthetic pathways. The strategy is to synthesize a small library of hybrid inositol glycan analogues (HIGAs) where each HIGA consists of an inositol core covalently tethered to a variety of readily available non-carbohydrate moieties. Synthesis of one such HIGA (compound 16) was successfully accomplished. Initial results from mass spectrometric analysis provide evidence of molecular mass of compound 16

Optimium Planning of Hybrid Renewable Energy System Using HOMER

A hybrid renewable energy system may be used to reduce dependency on either conventional energy or renewable system. Optimization of hybrid renewable energy systems looks into the process of selecting the best components and its sizing with appropriate operation strategy to provide cheap, efficient, reliable and cost effective alternative energy. In this paper a methodology has been develop for optimum planning of hybrid PV-Wind system with some battergy backup. The local solar radiation, wind data and components database from different manufactures are analyzed and simulated in HOMER to assess the technical and economic viability of the integrated system. Performance of each component will be evaluated and finally sensitivity analysis will be performed to optimize the system at different conditions. Keywords:Optimization, Hybrid system,Renewable system, HOMER, Cost of energy.DOI:http://dx.doi.org/10.11591/ijece.v2i1.15

Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response.

Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins, as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR/Cas9 system to generate a precise deletion of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance

Study of blood donor complications after whole blood donation in our center

Background: Despite the advent of many synthetic and semi-synthetic products, the importance of biological blood products cannot be undermined in the current era. The blood donors are the backbone of any health care delivery system that has a well-organized blood transfusion service.Methods: A prospective study conducted for the period of 16 months aimed to find out various complications and their frequencies before, during or after the blood donations. The donors who developed any complications were followed up for at least three weeks to assess the late reactions if any. Blood donation was carried out with proper precautions and asepsis by experienced phlebotomists.Results: Out of 10346 blood donations, 9887 were from replacement donors, while 459 were from voluntary donors. Total donation associated complications were 113, out of which the majority were VVRs (n=74), followed by venous hematomas (n=34) and arterial punctures (n=5). Of the 74 donors who had a VVR after blood donation, the incidence was higher in females (1.64% versus 0.69%). A higher incidence of VVRs was seen among the donors who had a history of previous blood donation.Conclusions: This study strengthened the fact that though blood donation is relatively safe, it still has a complication rate of nearly 1%. To encourage for blood donation at a regular interval, all the possible steps should be taken to minimize the rate of complications. More medical attention should be given to the “at-risk” donors

Peptic Ulcers and their Complications

Peptic ulcer disease (PUD) is an uncommon disorder of early life. Peptic ulceration of the stomach or duodenum is usually associated with abnormalities of the gastric mucosa such as gastritis and/or gastropathy. Gastritis and ulcers of the stomach and duodenum can be classified into either primary or secondary depending on their aetiologies. The majority of primary or unexplained peptic ulcers are the result of chronic inflammation caused by Helicobacter pylori infection. However, an increasing number of children with PUD without evidence of H. Pylori infection are now being seen. Rarely PUD is caused by hypersecretory states. Secondary ulceration occurs in response to acute stress from severe systemic illnesses such as sepsis, head injury, burns, and as sequelae to use of certain drugs. The prognosis for recovery from peptic ulcers is good as most patients will respond to treatment. Keywords:  Peptic ulcer disease, Complication, Helicobacter pylori, NSAIDs, Management

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

AbstractBone marrow stromal cell (BMSC) adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38) and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions