Multispectroscopic insight,morphological analysis and molecular docking studies of CuII-based chemotherapeutic drug entity with human serum albumin (HSA) and bovine serum albumin (BSA)

The interaction studies of Cu^II nalidixic acid–DACH chemotherapeutic drug entity, [C₃₆H₅₀N₈O₆Cu] with serum albumin proteins, viz., human serum albumin (HSA) and bovine serum albumin (BSA) employing UV–vis, fluorescence, CD, FTIR and molecular docking techniques have been carried out. Complex [C₃₆H₅₀N₈O₆Cu] demonstrated strong binding affinity towards serum albumin proteins via hydrophobic contacts with binding constants, K?=?3.18?×?10⁵ and 7.44?×?10⁴ M^–1 for HSA and BSA, respectively implicating a higher binding affinity for HSA. The thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were also calculated and the interaction of complex [C₃₆H₅₀N₈O₆Cu] with HSA and BSA was found to be enthalpy and entropy favoured, nevertheless, complex [C₃₆H₅₀N₈O₆Cu] demonstrated higher binding affinity towards HSA than BSA evidenced from its higher binding constant values. Time resolved fluorescence spectroscopy (TRFS) was carried out to validate the static quenching mechanism of HSA/BSA fluorescence. The collaborative results of spectroscopic studies indicated that the microenvironment and the conformation of HSA and BSA (α–helix) were significantly perturbed upon interaction with complex [C₃₆H₅₀N₈O₆Cu]. Hirshfeld surfaces analysis and fingerprint plots revealed various intermolecular interactions viz., N–H····O, O–H····O and C–H····O linkages in a 2–dimensional framework that provide crucial information about the supramolecular architectures in the complex. Molecular docking studies were carried out to ascertain the preferential binding mode and affinity of complex [C₃₆H₅₀N₈O₆Cu] at the target site of HSA and BSA. Furthermore, only for Transmission electroscopy microscopy micrographs of HSA and BSA in presence of complex [C₃₆H₅₀N₈O₆Cu] revealed major protein morphological transitions and aggregation which validates efficient delivery of complex by serum proteins to the target site.

Communicated by Ramaswamy H. Sarma     

ImShot: An Open-Source Software for Probabilistic Identification of Proteins In Situ and Visualization of Proteomics Data

Imaging mass spectrometry (IMS) has developed into a powerful tool allowing label-free detection of numerous biomolecules in situ. In contrast to shotgun proteomics, proteins/peptides can be detected directly from biological tissues and correlated to its morphology leading to a gain of crucial clinical information. However, direct identification of the detected molecules is currently challenging for MALDI–IMS, thereby compelling researchers to use complementary techniques and resource intensive experimental setups. Despite these strategies, sufficient information could not be extracted because of lack of an optimum data combination strategy/software. Here, we introduce a new open-source software ImShot that aims at identifying peptides obtained in MALDI–IMS. This is achieved by combining information from IMS and shotgun proteomics (LC–MS) measurements of serial sections of the same tissue. The software takes advantage of a two-group comparison to determine the search space of IMS masses after deisotoping the corresponding spectra. Ambiguity in annotations of IMS peptides is eliminated by introduction of a novel scoring system that identifies the most likely parent protein of a detected peptide in the corresponding IMS dataset. Thanks to its modular structure, the software can also handle LC–MS data separately and display interactive enrichment plots and enriched Gene Ontology terms or cellular pathways. The software has been built as a desktop application with a conveniently designed graphic user interface to provide users with a seamless experience in data analysis. ImShot can run on all the three major desktop operating systems and is freely available under Massachusetts Institute of Technology license.     

Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA

Vibrio cholerae is a noninvasive intestinal pathogen extensively studied as the causative agent of the human disease cholera. Our recent work identified MakA as a potent virulence factor of V. cholerae in both Caenorhabditis elegans and zebrafish, prompting us to investigate the potential contribution of MakA to pathogenesis also in mammalian hosts. In this study, we demonstrate that the MakA protein could induce autophagy and cytotoxicity of target cells. In addition, we observed that phosphatidic acid (PA)-mediated MakA-binding to the host cell plasma membranes promoted macropinocytosis resulting in the formation of an endomembrane-rich aggregate and vacuolation in intoxicated cells that lead to induction of autophagy and dysfunction of intracellular organelles. Moreover, we functionally characterized the molecular basis of the MakA interaction with PA and identified that the N-terminal domain of MakA is required for its binding to PA and thereby for cell toxicity. Furthermore, we observed that the ΔmakA mutant outcompeted the wild-type V. cholerae strain A1552 in the adult mouse infection model. Based on the findings revealing mechanistic insights into the dynamic process of MakA-induced autophagy and cytotoxicity we discuss the potential role played by the MakA protein during late stages of cholera infection as an anti-colonization factor.     

Folate: Metabolism,genes, polymorphisms and the associated diseases

Folate being an important vitamin of B Complex group in our diet plays an important role not only in the synthesis of DNA but also in the maintenance of methylation reactions in the cells. Folate metabolism is influenced by several processes especially its dietary intake and the polymorphisms of the associated genes involved. Aberrant folate metabolism, therefore, affects both methylation as well as the DNA synthesis processes, both of which have been implicated in the development of various diseases. This paper reviews the current knowledge of the processes involved in folate metabolism and consequences of deviant folate metabolism, particular emphasis is given to the polymorphic genes which have been implicated in the development of various diseases in humans, like vascular diseases, Down's syndrome, neural tube defects, psychiatric disorders and cancers.     

Temperature Gradient Measurements by Using Thermoelectric Effect in CNTs-Silicone Adhesive Composite

This work presents the fabrication and investigation of thermoelectric cells based on composite of carbon nanotubes (CNT) and silicone adhesive. The composite contains CNT and silicon adhesive 1∶1 by weight. The current-voltage characteristics and dependences of voltage, current and Seebeck coefficient on the temperature gradient of cell were studied. It was observed that with increase in temperature gradient the open circuit voltage, short circuit current and the Seebeck coefficient of the cells increase. Approximately 7 times increase in temperature gradient increases the open circuit voltage and short circuit current up to 40 and 5 times, respectively. The simulation of experimental results is also carried out; the simulated results are well matched with experimental results.     

Singlet oxygen damages the function of Photosystem II in isolated thylakoids and in the green alga Chlorella sorokiniana

Photosynthesis Research - Singlet oxygen (1O2) is an important damaging agent, which is produced during illumination by the interaction of the triplet excited state pigment molecules with molecular...     

Importation,colonization and establishment ofAnagyrus indicus [Hym.: Encyrtidae] onNipaecoccus viridis [Hom.: Pseudococcidae] in Jordan

Anagyrus indicus Shafeeet al. was collected on the island of Guam and released in the Jordan River Valley of Jordan in order to regulateNipaecoccus viridis (Newstead) on citrus.A. indicus was originally released in February 1984 and became colonized by April of the same year. It also dispersed by natural means up to 61 km following the original release and colonized that same year on infestedZizyphus sp. By spring of 1985 it became the dominant parasitoid attackingN. viridis. Another parasitoid,Anagyrus kamali Moursi, was collected in Jordan in June of 1985 for the first time. This latter parasitoid apparently moved into the Jordan River Valley by means of natural dispersal from a neighboring country. Infestations ofN. viridis have been greatly reduced in areas whereA. indicus became established. This paper reports the results of research only. Mention of a proprietary product does not constitute an endorsement for its use by USDA.     

Involvement of excitatory amino acid receptors in long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices.

The present article reviews studies from our laboratory, which have shown that excitatory amino acids receptors of the N-methyl-D-aspartate type are involved in the induction of long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices. The nature of the excitatory amino acid receptors that mediate the response that is modified by the induction of long-term potentiation is also considered. The mechanism of induction of long-term potentiation is discussed, as are some possible stages that are required for the maintenance of this process. Some new data are presented concerning the ability of N-methyl-D-aspartate to potentiate synaptic transmission and to depress the amplitude of the presynaptic fibre volley. Concerning the potentiation, it is shown that brief (1-2 min) perfusion of slices with N-methyl-D-aspartate is sufficient to potentiate synaptic transmission for at least 3 h. The N-methyl-D-aspartate induced depression of the presynaptic fibre volley is shown to be transient and independent of synaptic transmission.