Molecular Architecture of Spinal Cord Injury Protein Interaction Network

Spinal cord injury (SCI) is associated with complex pathophysiological processes that follow the primary traumatic event and determine the extent of secondary damage and functional recovery. Numerous reports have used global and hypothesis-driven approaches to identify protein changes that contribute to the overall pathology of SCI in an effort to identify potential therapeutic interventions. In this study, we use a semi-automatic annotation approach to detect terms referring to genes or proteins dysregulated in the SCI literature and develop a curated SCI interactome. Network analysis of the SCI interactome revealed the presence of a rich-club organization corresponding to a “powerhouse” of highly interacting hub-proteins. Studying the modular organization of the network have shown that rich-club proteins cluster into modules that are specifically enriched for biological processes that fall under the categories of cell death, inflammation, injury recognition and systems development. Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI. In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy. Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.     

Modulational Instability,Ion-Acoustic Envelope Solitons,and Rogue Waves in Four-Component Plasmas

Plasma Physics Reports - Modulational instability (MI) of ion-acoustic waves (IAWs) has been theoretically investigated in a plasma system which is composed of inertial warm adiabatic ions,...     

A Genetic RNAi Screen for IP3/Ca2+ Coupled GPCRs in Drosophila Identifies the PdfR as a Regulator of Insect Flight

Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP₃ receptor mediated Ca²⁺ signaling and store-operated Ca²⁺ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca²⁺ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP₃ receptor. Among the 108 GPCRs screened, we discovered 5 IP₃/Ca²⁺ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior.     

The effect of carvacrol on healthy neurons and N2a cancer cells: some biochemical, anticancerogenicity and genotoxicity studies

Carvacrol (CVC) is a phenolic monoterpene present in many essential oils of medicinal and aromatic plants and has attracted attention because of its beneficial biological activities. To date, although various biological activities of CVC have been demonstrated, its neurotoxicity on cultured primary rat neurons and N2a neuroblastoma cells has never been explored. Therefore, in this present study, we aimed to describe in vitro antiproliferative and/or cytotoxic properties (by 3-(4,5 dimetylthiazol -2-yl)-2,5 diphenlytetrazolium bromide (MTT) test), genotoxic damage potentials (by single cell gel electrophoresis (SCGE) or Comet assay) and antioxidant activities (by total antioxidant capacity (TAC) and total oxidative stress (TOS) analysis) of CVC in vitro. Dose (0–400 mg/L) dependent effects of CVC were tested on both cultured primary rat neurons and N2a neuroblastoma cells. Statistical analysis of MTT assay results indicated significant (p < 0.05) decreases of cell proliferation rates in both cell types treated with CVC at 200 and 400 mg/L. On the other hand, the mean values of the total scores of cells showing DNA damage (for comet assay) was not found significantly different from the control values for both cells (p > 0.05). In addition, our results indicated that 10, 25 and 50 mg/L of CVC treatment caused increases of TAC levels in cultured primary rat neurons but not in the N2a cell line. However, CVC treatments led to increases of TOS levels in cultured primary rat neurons at only 400 mg/L while they led to increases of TOS levels in N2a neuroblastoma cells at 200 and 400 mg/L. The present findings demonstrated that CVC could be a source of antioxidant and chemopreventive activities to be studied on cancer diseases.     

Fungicide inhibition of aflatoxins,diacetoxyscirpenol and zearalenone production

The effect of fungicides on the production of aflatoxin byAspergillus flavus IMI 89717, diacetoxyscirpenol and zearalenone byFusarium graminearum was studied. In a yeast extract - sucrose medium, dicloran, iprodione and vinclozolin fungicides significantly inhibited mycelial growth ofA. flavus at 250 ppm and significantly decreased aflatoxin production at 100, 250 and 500 ppm, respectively. In potato — dextrose broth, these fungicides diminished the mycelial growth ofF. graminearum and production of diacetoxyscirpenol and zearalenone at 100 ppm. Sensitivity of toxigenic mycelia to fungicides increased approximately five-fold in a yeast extract-starch medium with an appreciable reduction in sugar uptake andα-amylase activity.     

Biological and computational studies provide insights into Caesalphinia digyna Rottler stems

Caesalpinia digyna (Rottl.) (Family: Fabaceae) is an essential medicinal plant for it's conventional uses against a kind of human disorders. This research aims to investigate the antidiarrheal, antibacterial and antifungal properties of the methanol extract of the stems extracts of the C. digyna (MECD). The in vivo antidiarrheal activity of the stem extracts were evaluated by using castor oil-induced diarrhea, castor oil-induced enteropooling and charcoal induced intestinal transit in mice model. Besides, in vitro antimicrobial potentiality of MECD was investigated by the disc diffusion method. In silico activity of the isolated compounds were performed by Schrödinger-Maestro (Version 11.1) software. In addition, The ADME/T analysis and PASS prediction were implemented by using pass online tools. In the antidiarrheal investigation, the MECD exhibited a notable inhibition rate in all test approaches which were statistically significant (p < 0.05, p < 0.1, p < 0.01). MECD 400 mg/kg showed the maximum antidiarrheal potency in all the test methods. In vitro antimicrobial analysis unveiled that, MECD revealed higher potentiality against almost all pathogens and indicates dose-dependent activity against almost all the bacteria and fungi. In the case of in silico evaluation of anti-diarrheal, anti-bacterial and anti-fungal activity, all three isolated compounds met the pre-conditions of Lipinski's five rules for drug discovery. Pass predicted study also employed for all compounds. However, The chemical constituents of the C. digyna can be a potent source of anti-diarrheal, anti-bacterial and anti-fungal medicine and further modification and simulation studies are required to establish the effectiveness of bioactive compounds.     

Synthesis and carbonic anhydrase inhibitory properties of amino acid – coumarin/quinolinone conjugates incorporating glycine,alanine and phenylalanine moieties

N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid–coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (K_Is?>?50?μM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92?nM and 1.19?μM for hCA IV, and between 0.11 and 0.79?μM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.     

Rosin Surfactant QRMAE Can Be Utilized as an Amorphous Aggregate Inducer: A Case Study of Mammalian Serum Albumin

Quaternary amine of diethylaminoethyl rosin ester (QRMAE), chemically synthesized biocompatible rosin based cationic surfactant, has various biological applications including its use as a food product additive. In this study, we examined the amorphous aggregation behavior of mammalian serum albumins at pH 7.5, i.e., two units above their isoelectric points (pI ~5.5), and the roles played by positive charge and hydrophobicity of exogenously added rosin surfactant QRMAE. The study was carried out on five mammalian serum albumins, using various spectroscopic methods, dye binding assay, circular dichroism and electron microscopy. The thermodynamics of the binding of mammalian serum albumins to cationic rosin modified surfactant were established using isothermal titration calorimetry (ITC). It was observed that a suitable molar ratio of protein to QRMAE surfactant enthusiastically induces amorphous aggregate formation at a pH above two units of pI. Rosin surfactant QRMAE-albumins interactions revealed a unique interplay between the initial electrostatic and the subsequent hydrophobic interactions that play an important role towards the formation of hydrophobic interactions-driven amorphous aggregate. Amorphous aggregation of proteins is associated with varying diseases, from the formation of protein wine haze to the expansion of the eye lenses in cataract, during the expression and purification of recombinant proteins. This study can be used for the design of novel biomolecules or drugs with the ability to neutralize factor(s) responsible for the aggregate formation, in addition to various other industrial applications.