Of Least Concern? Range Extension by Rhesus Macaques (<Emphasis Type="BoldItalic">Macaca mulatta</Emphasis>) Threatens Long-Term Survival of Bonnet Macaques (<Emphasis Type="BoldItalic">M. radiata</Emphasis>) in Peninsular India

Rhesus and bonnet macaques are the 2 most common and widely distributed of the 8 macaque species of India. Rhesus macaques are widely distributed across southern and southeastern Asia, whereas bonnet macaques are restricted to peninsular India. We studied the current distributional limits of the 2 species, examined patterns of their coexistence in the interspecific border zones, and evaluated losses in the distributional range of bonnet macaques over the last 3 decades. Our results indicate that whereas rhesus macaques have extended their geographical range into the southern peninsula, bonnet macaques have been displaced from many areas within their former distributional range. The southern and the northern distributional limits for rhesus and bonnet macaques, respectively, currently run parallel to each other in the western part of the country, are separated by a large gap in central India, and converge on the eastern coast of the peninsula to form a distribution overlap zone. This overlap region is characterized by the presence of mixed-species troops, with pure troops of both species sometimes occurring even in close proximity to one another. The range extension of rhesus macaque—a natural process in some areas and a direct consequence of introduction by humans in other regions—poses grave implications for the endemic and declining populations of bonnet macaques in southern India.     

Ligand-switchable Substrates for a Ubiquitin-Proteasome System

Cellular maintenance of protein homeostasis is essential for normal cellular function. The ubiquitin-proteasome system (UPS) plays a central role in processing cellular proteins destined for degradation, but little is currently known about how misfolded cytosolic proteins are recognized by protein quality control machinery and targeted to the UPS for degradation in mammalian cells. Destabilizing domains (DDs) are small protein domains that are unstable and degraded in the absence of ligand, but whose stability is rescued by binding to a high affinity cell-permeable ligand. In the work presented here, we investigate the biophysical properties and cellular fates of a panel of FKBP12 mutants displaying a range of stabilities when expressed in mammalian cells. Our findings correlate observed cellular instability to both the propensity of the protein domain to unfold in vitro and the extent of ubiquitination of the protein in the non-permissive (ligand-free) state. We propose a model in which removal of stabilizing ligand causes the DD to unfold and be rapidly ubiquitinated by the UPS for degradation at the proteasome. The conditional nature of DD stability allows a rapid and non-perturbing switch from stable protein to unstable UPS substrate unlike other methods currently used to interrogate protein quality control, providing tunable control of degradation rates.     

Novel lipase-catalysed highly selective acetylation studies on D-arabino- and D-threo-polyhydroxyalkyltriazoles

Capabilities of lipases from Candida antarctica, Candida rugosa and porcine pancreas have been evaluated for regioselective acetylation of 2-phenyl-4-(D-arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-O-1',2'-isopropylidene-3',4'-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-threo-trihydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of triazolylacyclonucleosides. C. antarctica lipase and porcine pancreatic lipase exhibited exclusive selectivity for the acetylation of primary hydroxyl group over secondary hydroxyl group(s) in all the three cases.     

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.     

Nodes occupying central positions in human tissue specific PPI networks are enriched with many splice variants

The functional repertoire of genes in the eukaryotic organisms is enhanced by the phenomenon of alternative splicing. Hence, a node in a tissue specific protein–protein interaction (TS PPIN) network can be thought of as an ensemble of various spliced protein products of the corresponding gene expressed in that tissue. Here we demonstrate that the nodes that occupy topologically central positions characterized by high degree, betweenness, closeness, and eigenvector centrality values in TS PPINs of Homo sapiens are associated with high number of splice variants. We also show that the high “centrality” of these genes/nodes could in part be explained by the presence of a large number of promiscuous domains.     

Structural and photoluminescence study of Mn2+‐activated CaYAl3O7 blue phosphors

The structural and photoluminescence properties of CaYAl₃O₇ phosphor material doped with varying concentration of Mn²⁺ have been studied. The phosphor material was synthesized by the combustion method at 500 °C and was characterized using X‐ray diffraction, Fourier transform infrared spectroscopy and photoluminescence spectroscopy (PL). X‐ray diffraction showed that the crystallites have average sizes in the range of ~58–70 nm. Corresponding Fourier transform infrared spectroscopy investigations confirm the phase formation and the presence of aluminate group (Al‐O bands) in CaYAl₃O₇:Mn²⁺ phosphor. Under the excitation at 356 nm wavelength, the PL spectra show the occurrence of two emission peaks obtained in the blue region at 389 nm and 412 nm, which is attributed to the 4 T1(G) → 6A1 transition of Mn²⁺ ion. Upon increasing Mn²⁺ concentration, the relative PL intensity shows an initial decrement followed by an increase displaying the effect of concentration quenching. Overall the results suggest the possibility of using this material in white lighting devices and plasma display panels. Copyright © 2013 John Wiley & Sons, Ltd.     

Nanomedicine Scale-up Technologies: Feasibilities and Challenges

Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage. The bioactive agent can be combined with a diagnostic agent in a nanodevice for theragnostic applications. However, the formulation scientist faces numerous challenges related to their development, scale-up feasibilities, regulatory aspects, and commercialization. This article reviews recent progress in the method of development of nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up techniques, and challenges in their commercialization.KEY WORDS: lipid nanoparticles, nanomedicine, polymeric nanoparticles, scale-up production     

Titanium Dioxide Nanoparticles As Guardian against Environmental Carcinogen Benzo[alpha]Pyrene

Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO₂ NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO₂ NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO₂ NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order to explore the mechanism of protection by TiO₂ NP against BaP, we performed in silico studies. BaP and other PAHs are known to enter the cell via aromatic hydrocarbon receptor (AHR). TiO₂ NP showed a much higher docking score with AHR (12074) as compared to the docking score of BaP with AHR (4600). This indicates a preferential binding of TiO₂ NP with the AHR, in case if both the TiO₂ NP and BaP are present. Further, we have done the docking of BaP with the TiO₂ NP bound AHR-complex (score 4710), and observed that BaP showed strong adsorption on TiO₂ NP itself, and not at its original binding site (at AHR). TiO₂ NPs thereby prevent the entry of BaP in to the cell via AHR and hence protect cells against the deleterious effects induced by BaP.