Caste-Specific Expression of Na<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase in the Asian Weaver Ant, <Emphasis Type="Italic">Oecophylla smaragdina</Emphasis> (Fabricius, 1775)

Social insect colonies adopt different levels of survival strategies and exhibit well-defined reproductive division of labour. Oecophylla smaragdina (Fabricius, 1775) has physiological and behavioral adaptations that enable them to forage at extreme environmental conditions and are lethal to most other insects. Ion homeostasis is the key process in an organism’s survival mechanism. Among ion pumps, the ATP-dependent sodium–potassium ion pump is essential for maintaining the Na⁺ and K⁺ ionic balance and is well known as the primary consumer of energy. Oecophylla smaragdina plays pivotal role as a model among social insects for understanding ion homeostasis at the organization level of the castes. We have evaluated the expression and activity of Na⁺/K⁺-ATPase among various castes of O. smaragdina (worker subcastes, queen and male). Real-time PCR and immunoblotting analyses revealed the differential expression of Na⁺/K⁺-ATPase in the castes. Significantly higher expression of Na⁺/K⁺-ATPase mRNA and protein were observed in the minor workers, queen, major workers and males respectively. These results suggest that in the weaver ant colony, the castes might have variously adapted and evolved with a well-developed ion transport mechanism which allows them to perform allocated tasks within the nest and could be a key to their adaptive benefits towards division of labour.     

Fluorescence microscopy applied to intracellular transport by microtubule motors

Long-distance transport of many organelles inside eukaryotic cells is driven by the dynein and kinesin motors on microtubule filaments. More than 30 years since the discovery of these motors, unanswered questions include motor–organelle selectivity, structural determinants of processivity, collective behaviour of motors and track selection within the complex cytoskeletal architecture, to name a few. Fluorescence microscopy has been invaluable in addressing some of these questions. Here we present a review of some efforts to understand these sub-microscopic machines using fluorescence.     

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Cardiometabolic Risk Factors: A Study Among Bhil Tribal Population from Two Environmental Settings

Studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and cardiometabolic risk factors (CMRFs), however with varying results, which could be due to ethnicity differences. Therefore, the present study was conducted among Bhil tribal population (a mendelian population with the common gene pool and same sociocultural attributes), residing in two different environmental settings. The study attempts to understand the distribution and extent of association of ACE I/D gene polymorphism with cardiometabolic risk factors among Bhils from rural and urban settings. All the obesity and blood pressure variables were collected form 432 recruited subjects from both sexes aged 25–65 years and ACE I/D polymorphism was analysed on 299 subjects. Almost all the studied CMRFs were found to be significantly higher among urban Bhils. ACE gene was found to be polymorphic in the studied groups. DD genotype was found to pose more than threefold significant risk for low HDLC only in rural area. Estimate change analysis revealed an increasing D allele dose leads to more than one unit increase in Blood Pressure, and more than three units decrease in HDLC. The study highlights the differential effect of ACE I/D gene polymorphism in different environmental settings.     

Preparation,characterization and cytotoxic evaluation of bovine serum albumin nanoparticles encapsulating 5-methylmellein: A secondary metabolite isolated from Xylaria psidii

In this study, 5-methylmellein (5-MM) loaded bovine serum albumin nanoparticles (BSA NPs) were developed using desolvation technique. The developed nanoparticles were characterized for their mean particle size, polydispersity, zeta potential, loading efficiency, X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and release profile. The developed nanoparticles were spherical in shape under transmission electron microscopy (TEM) and atomic force microscopy (AFM). The developed 5-MM loaded BSA NPs demonstrated a mean particle size with a diameter of 154.95?±?4.44?nm. The results from XRD and DSC studies demonstrated that the crystal state of the 5-MM was converted to an amorphous state in polymeric matrix. The encapsulation and loading efficiency was found to be 73.26?±?4.48% and 7.09?±?0.43%. The in vitro cytotoxicity in human prostate cancer cell line (PC-3), human colon cancer cells (HCT-116) and human breast adenocarcinoma cell line (MCF-7) cells demonstrated enhanced cytotoxicity of 5-MM BSA NPs as compared to native 5-MM after 72-h treatment. The enhancement in cytotoxicity of 5-MM BSA NPs was also supported by increase in cellular apoptosis, mitochondrial membrane potential loss and generation of high reactive oxygen species (ROS). In conclusion, these findings collectively indicated that BSA nanoparticles may serve as promising drug delivery system for improving the efficacy of 5-methylmellein.     

Wet chemical synthesis of chitosan hydrogel–hydroxyapatite composite membranes for tissue engineering applications

Chitosan, a deacetylated derivative of chitin is a commonly studied biomaterial for tissue-engineering applications due to its biocompatibility, biodegradability, low toxicity, antibacterial activity, wound healing ability and haemostatic properties. However, chitosan has poor mechanical strength due to which its applications in orthopedics are limited. Hydroxyapatite (HAp) is a natural inorganic component of bone and teeth and has mechanical strength and osteoconductive property. In this work, HAp was deposited on the surface of chitosan hydrogel membranes by a wet chemical synthesis method by alternatively soaking the membranes in CaCl₂ (pH 7.4) and Na₂HPO₄ solutions for different time intervals. These chitosan hydrogel–HAp membranes were characterized using SEM, AFM, EDS, FT-IR and XRD analyses. MTT assay was done to evaluate the biocompatibility of these membranes using MG-63 osteosarcoma cells. The biocompatibility studies suggest that chitosan hydrogel–HAp composite membranes can be useful for tissue-engineering applications.     

First generation 5-vinyl-3-pyridinecarbonitrile PKCθ inhibitors

A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCθ inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCθ inhibitor with good selectivity over PKCδ.     

C-5 substituted heteroaryl-3-pyridinecarbonitriles as PKCθ inhibitors: Part II

We previously reported that a 3-pyridinecarbonitrile analog with a furan substituent at C-5 and a 4-methylindol-5-ylamino substituent at C-4, 1, was a potent inhibitor of PKCθ (IC₅₀ = 4.5 nM). Replacement of the C-5 furan ring of 1 with bicyclic heteroaryl rings, led to compounds with significantly improved potency against PKCθ. Analog 6b with a 4-methylindol-5-ylamino group at C-4 and a 5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl group at C-5 had an IC₅₀ value of 0.28 nM for the inhibition of PKCθ.     

BMP-13 Emerges as a Potential Inhibitor of Bone Formation

Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation.