13C-nuclear magnetic resonance study of glycophorins AM and AN modified with various pyrylium salts

The environment of the N-terminal amino groups of glycophorins A^M and A^N has been studied using¹³C-NMR spectroscopy and pyrylium salts as amino-blocking agents. The extent of amino blocking was monitored by¹³C-reductive methylation of the residual free amino groups. The pyrylium ions reacted with the N-terminal amino groups of the two glycophorins at almost identical rates, which is thought to indicate that the overriding steric bulk of the pyrylium salt may determine the rate of the reaction. The difference in the rates of modification of lysine residues of glycophorins A^M and A^N by the pyrylium ions did indicate that there may exist an environmental difference around the lysine residues between the two glycophorins. This environmental difference may result from solution aggregation of the glycophorin A molecules or from some differences in the pK_a values of the five lysine residues found in glycophorins A^M and A^N.     

Adaptive foraging tactics of greater short-nosed fruit bats on a spiny shrub and its effect on seed dispersal

Journal of Ethology - Many plant species have seeds embedded in their fleshy pulp to attract frugivores, which enhances the chance of seed dispersal. However, some tropical plants are evolved with...     

Selection of herbal therapeutics against deltatoxin mediated Clostridial infections

Clostridium perfringens (a versatile pathogenic bacterium) secretes enterotoxins (the deltatoxin, virulent factor) and causes food borne gastroenteritis and gasgangrene. The organism was isolated and characterized from improperly cooked meat and poultry samples. The isolated organism showed multiple drug resistance indicating that the treatment is challenging. Hence, there is need for improved therapeutic agents. The rational design of improved therapeutics requires the crystal structure for the toxin. However, the structure for the toxin is not yet available in its native form. Thus, we modeled the toxin structure using α- hemolysin of Staphylococcus aureus (PDB: 3M4D chain A) as template. The docking of the toxin with the herbal extract curcumin (1,7-bis(4-hydroxy-3- methoxyphenyl)hepta-1,6-diene-3,5-dione) showed a binding energy of -8.6 Kcal/mol, in comparison to the known antibiotic Linezolid with binding energy of -6.1 Kcal/mol. This data finds application in the design and development of novel compounds against the deltatoxin from Clostridium perfringens.     

3D printing of self-standing and vascular supportive multimaterial hydrogel structures for organ engineering

Three dimensional printable formulation of self-standing and vascular-supportive structures using multi-materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self-standing and vascular-supportive structures using an in-house formulated multi-material combination of albumen/alginate/gelatin-based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed before the printing process. The suitability of the hydrogel in 3D printing of various customizable and self-standing structures, including a human ear model, was examined by extrusion-based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self-standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion-based 3D printing technique for manufacturing complex shapes and structures using multi-materials with high fidelity, which have great potential in organ engineering.     

Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience

Background aimsPrevious clinical studies have reported that the injection of bone marrow (BM)-derived mononuclear cells (MNC) results in improvement in symptoms and healing of ulcers in patients with critical limb ischemia (CLI) up to stage IV of Fontaine's classification. However, most patients with Fontaine stage IV CLI limbs had to undergo amputation even after stem cell therapy. We report on six patients, who had poorly controlled diabetes with extensive ulceration and gangrene of limbs because of Fontaine stage IV CLI and had been advised amputation elsewhere, who underwent injection of autologous BM MNC.MethodsIn all six patients, BM was aspirated and the isolated MNC from the BM were injected intralesionally at various sites of the ulcer and its surroundings after necessary debridement. The patients were followed up at regular intervals for at least 6 months.ResultsAt the end of the 6-month follow-up, the lower limb pain and ulcers had improved significantly in all patients. The mean toe–brachial index had increased from 0.26 to 0.36. One patient died a month after therapy because of causes unrelated to the procedure. Limb salvage was possible in the remaining five patients and they had a pain-free walking distance of 100 m within 6 months.ConclusionsLimb salvage was possible in all six diabetic patients with Fontaine stage IV CLI following autologous BM MNC injection. The procedure was safe without any adverse outcomes.     

Plk1-targeted small molecule inhibitors: molecular basis for their potency and specificity

Members of polo-like kinases (collectively, Plks) have been identified in various eukaryotic organisms and play pivotal roles in cell proliferation. They are characterized by the presence of a distinct region of homology in the C-terminal noncatalytic domain, called polo-box domain (PBD). Among them, Plk1 and its functional homologs in other organisms have been best characterized because of its strong association with tumorigenesis. Plk1 is overexpressed in a wide spectrum of cancers in humans, and is thought to be an attractive anti-cancer drug target. Plk1 offers, within one molecule, two functionally different drug targets with distinct properties-the N-terminal catalytic domain and the C-terminal PBD essential for targeting the catalytic activity of Plk1 to specific subcellular locations. In this review, we focused on discussing the recent development of small-molecule and phosphopeptide inhibitors for their potency and specificity against Plk1. Our effort in understanding the binding mode of various inhibitors to Plk1 PBD are also presented.     

Toxicity of Acalypha indica (Euphorbiaceae) and Achyranthes aspera (Amaranthaceae) leaf extracts to Aedes aegypti (Diptera: Culicidae)

Alternative control strategies for the dengue vector Aedes aegypti L. (Diptera: Culicidae) include botanical insecticides. They are believed to pose little threat to the environment or to human health and may provide practical substitutes for synthetic insecticides. In this study, we determined the biological activities of methanol extracts of Acalypha indica L. (Euphorbiaceae) and Achyranthes aspera L (Amaranthaceae) leaves individually and in combination as botanical insecticides against Ae. aegypti. Based on LC₅₀ values for 4th instar Ae. aegypti, the combined extracts showed the strongest larvicidal activity (277 ppm). A. aspera and A. indica extracts individually gave similar results (409 and 420 ppm, respectively). Respective LC₅₀ values for pupae were 326 ppm, 456 ppm, and 467 ppm. In studies of smoke toxicity, 64% of females exposed to negative control smoke (no extract) blood fed on chicken, whereas 17% blood fed when exposed to smoke containing A. aspera extract and to positive control smoke (0.2% d-allethrin). In the field, treatment of water storage tanks (≈ 0.5 m³) with combined plant extract reduced larval and pupal populations by 97% and 81%, respectively, after 5 days. Given the results of this study, further evaluation of the combined (A. indica + A. aspera) extract as a mosquito larvicide is warranted. Mosquito coils with A. aspera extract also show promise as a practical and potentially economical means for mitigating mosquito blood feeding.     

Functionalization of biomolecules on nanoparticles: specialized for antibacterial applications

Biological efficiency of existing antimicrobial agents is still inadequate to ensure optimal therapeutic index. Developing biocompatible advanced functional materials with antimicrobial properties could be promising for environmentally benign applications. Nanoparticles and other nanoscale materials are of great interest due to their multiple potential applications in material science, medicine, and industry. Nanomaterials possess well renowned antimicrobial activity against several microorganisms; however, it has some non-specific toxicity. Biofunctionalization of nanomaterials is one such topic to address this issue. Rational selection of therapeutically active biomolecules for design of nanoparticles will certainly increase the biological applicability. The present paper describes the current status of different types of biofunctionalized nanoparticles and their antibacterial applications. Key principles such as strategies involved at bio-/nanointerface, the structural activity relationship, and mechanism of action involved in the antibacterial activity of functionalized nanoparticles are briefly discussed. This knowledge is important from the objective of generation of advanced functional nanomaterials with antimicrobial properties.