3D Structure Prediction of Human β1-Adrenergic Receptor via Threading-Based Homology Modeling for Implications in Structure-Based Drug Designing

Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied by impairment of the β₁-adrenergic receptor (β₁-AR) signal cascade. The disturbed β₁-AR function may be based on an elevated sympathetic tone observed in patients with heart failure. Prolonged adrenergic stimulation may induce metabolic and electrophysiological disturbances in the myocardium, resulting in tachyarrhythmia that leads to the development of heart failure in human and sudden death. Hence, β₁-AR is considered as a promising drug target but attempts to develop effective and specific drug against this tempting pharmaceutical target is slowed down due to the lack of 3D structure of Homo sapiens β₁-AR (hsβADR1). This study encompasses elucidation of 3D structural and physicochemical properties of hsβADR1 via threading-based homology modeling. Furthermore, the docking performance of several docking programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and cross-docking experiments. GOLD and Surflex-Dock performed best in re-docking and cross docking experiments, respectively. Consequently, Surflex-Dock was used to predict the binding modes of four hsβADR1 agonists. This study provides clear understanding of hsβADR1 structure and its binding mechanism, thus help in providing the remedial solutions of cardiovascular, effective treatment of asthma and other diseases caused by malfunctioning of the target protein.     

Towards the development of a biobased economy in Europe and India

India has emerged as a key player with a high potential to develop a biomass and biobased economy due to its large geographic size and the massive amounts of agricultural and non agricultural biomass produced. India has joined hands with Europe to synchronize its efforts to create and facilitate the development of a biobased economy in this country. This paper aims to examine common research and development actions between the European Union (EU) and India to facilitate the development of these biobased economies. As a base, a thorough study has been performed considering the biomass potential and current status of the bioeconomy in both the EU and India based on the distillation of a series of 80 potential recommendations. The recommendations were grouped into four major categories: (1) biomass production, (2) by-products/waste, (3) biorefineries and (4) policy, market, and value-added products. A questionnaire was designed and distributed to key stakeholders belonging to: academia, industry, and policymakers in both India and the EU. A total of 231 responses were received and analyzed, based on the key recommendations made for the essential research and development topics that are of prime importance to develop biobased economies in both the EU and India. The findings of this study suggest recognizing the value-added contributions made by biobased products such as: food, feed, valuable materials and chemicals in both regions. It is important to reduce the overall process costs and minimize the environmental impacts of such a biobased economy.     

Ultrastructure and histochemistry of the lymph system and parenchyma of juvenile paramphistomes (paramphistomidae: digenea) during migration in indian ruminants

, and 1992. Ultrastructure and histochemistry of the lymph system and parenchyma of juvenile paramphistomes (Paramphistomidae: Digenea) during migration in Indian ruminants. International Journal for Parasitology 22: 1117–1135. The lymph system of juvenile Paramphistomum epiclitum and Fischoederius elongatus consists of a single pair of longitudinal primary vessels from which sub-dividing branches extend laterally to associate with most major tissues and organs. The system originates shortly after excystation in the definitive host and is fully developed in day 14 juveniles. Lymph vessels are syncytial and membrane limited, with a matrix which contains autophagic-like inclusions, clusters of SER and free nuclei. Similar organelies are evident in the matrix of parenchyma and specialized cells juxta-posing the pharynx (JP cells). These tissues are intimately associated and perhaps functionally integrated. Parenchyma represents a major site for carbohydrate storage and turnover, whilst the lymph appears to perform a similar role for proteins. The JP cells of juveniles display prolific autophagic-like activity only during migration, which coincides with the depletion of carbohydrate reserves in parenchyma. Key mitochondrial enzymes were histochemically demonstrated in the lymph despite the apparent absence of mitochondria from this system in post-day 14 juveniles. Succinate dehydrogenase activity was cytolocalized in mitochondria, whilst attempts to perform a similar localization of this enzyme in lymph were unsuccessful. The possibility of non-enzymatic interference in the histochemical demonstration of dehydrogenase is examined.     

Sodium dodecylbenzenesulfonate–based silver nanoparticles and their potent application as antibiofilm,antimicrobial agent,and trace level determination of amlodipine

Herein, we presented the synthesis and application of sodium dodecylbenzenesulfonate–based silver nanoparticles (termed as SDBS-AgNPs). The SDBS reverse micelles (RMs) in ethanol was used as nanoreactor for green AgNPs synthesis. The size, structure, and shape of SDBS-AgNPs were well distinct by UV/visible (UV/Vis), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) techniques. The SDBS-AgNPs were quite stable even at high temperature (80 °C), salt concentration (up to 300 μM), and wide pH range (2 to 12). Moreover, SDBS-AgNPs were found to be highly sensitive and selective colorimetric sensor for antihypertensive drug amlodipine (AML). The interaction of AML with SDBS-AgNPs resulted as a substantial increase in the absorbance and a prominent blue shift in wavelength from 426 to 400 nm. DLS results were further confirmed that the SDBS-AgNPs break into smaller sized particles. Similarly, FTIR results also verified the SDBS-AgNPs etching–based sensing of AML molecules due to the strong attraction by amine and carbonyl functional groups on the target drug. The proposed sensor exhibited linear response in the range of 0.001–200 μM (R² = 0.9917) with limit of detection (LOD) and quantification (LOQ) of 0.161 and 0.49 μM, respectively. The probe remained selective against AML, even in the presence of equimolar interfering species (including other drugs and metal ions). Furthermore, findings proposed that the SDBS-AgNPs might be used as effective substitute to minimize infection severity by obstructing the biofilm formation against nosocomial and urinary tract infection (UTI) causing pathogens.

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A HARP SEAL × HOODED SEAL HYBRID

In this study we report the first documentation of mating between harp ( Phoca groenlandica ) and hooded seals ( Cystophora cristata ). The production of this hybrid was quite unusual, being the result of a cross between parents of different genera which are morphologically dissimilar and have quite different mating behavior and dramatically different body sizes. The molecular techniques (mtDNA and macrosatellite nuclear DNA banding patterns) used in this study will undoubtedly be applied widely to many different taxa in the near future, allowing us to re-examine many suspected cases of hybridization among marine mammals and, in a larger context, the meaning of the species concept.     

A comparative study of the protein content of some helminths and the suitability of assay methods

The protein content of fresh homogenates and their corresponding TCA precipitated fractions of 10 different species of helminths was estimated by the methods of Lowry et al. and Spector using the Folin phenol reagent and Coomassie brilliant blue G-250 respectively. The former method gives exaggerated values as compared to the latter method. The parasite phenols, phenolic proteins and catecholamines could be responsible for interference in the Lowry's procedure. The TCA noln-precipitable moieties also give colour only with the Folin phenol assay. The pronounced intra-specific differences in the total protein content of helminths reflect their metabolic variations and adaptations. Habitat does not appear to influence the protein content of parasites, however, the effect of host variation was evident in the pouched amphistome G. crumenifer. It is concluded that the dye binding method gives more consistent results and it can be conveniently applied to crude tissue homogenates of helminths.     

Studies on the ultrastructure and histochemistry of the lymph system in three species of amphistome (Trematoda: Digenea) Gigantocotyle explanatum, Gastrothylax crumenifer and Srivastavaia indica from the Indian water buffalo Bubalus bubalis

The lymph system of three amphistome parasites from buffaloes, Gigantocotyle explanatum, Gastrothylax crumenifer and Srivastavaia indica was studied using light microscope histochemistry and electron microscopy. In each case the system comprised a single pair of main longitudinal vessels which gave rise to numerous sub-dividing lateral branches. Although the finer lymph channels associated with most internal systems, they did not penetrate the basement membrane of any organ. The lymph vessels were delimited by a unit membrane and separated from adjacent cells by interstitial material. The lymph fluid consisted of an amorphous proteinaceous, lipid-rich matrix, containing naked nuclei and granules of various sizes. Complexes of endoplasmic reticulum were frequently associated with the nuclei. No distinct Golgi bodies or mitochondria were evident. The granules noted throughout the lymph morphologically resembled autophagosomes and lysosomes. Autophagy within the lymph system presumably mobilizes amino acids for subsequent transport to tissues undergoing active protein synthesis. The lymph channels displayed an intimate relationship with the general parenchyma. In particular, numerous protrusions of lymph occurred into the cytoplasm of certain specialized parenchymal cells surrounding the pharynx. Within these 'juxtapharyngeal' cells autophagic degradation of sequestered lymph cytoplasm apparently occurred. In the three species of amphistome studied, the lymph system appears to function in storage and mobilization of amino acids and possibly lipids. It may also serve to distribute other small molecules throughout the body. The detection of haemoglobin in the lymph system of G. crumenifer and S. indica, but not in Gigantocotyle explanatum, suggests a further role in oxygen storage and transport.