R7-binding protein targets the G protein β5/R7-regulator of G protein signaling complex to lipid rafts in neuronal cells and brain

Background  

Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), composed of Gα, Gβ, and Gγ subunits, are positioned at the inner face of the plasma membrane and relay signals from activated G protein-coupled cell surface receptors to various signaling pathways. Gβ5 is the most structurally divergent Gβ isoform and forms tight heterodimers with regulator of G protein signalling (RGS) proteins of the R7 subfamily (R7-RGS). The subcellular localization of Gβ 5/R7-RGS protein complexes is regulated by the palmitoylation status of the associated R7-binding protein (R7BP), a recently discovered SNARE-like protein. We investigate here whether R7BP controls the targeting of Gβ5/R7-RGS complexes to lipid rafts, cholesterol-rich membrane microdomains where conventional heterotrimeric G proteins and some effector proteins are concentrated in neurons and brain.     

Chemical elements of Algerian Mentha spicata L. used in the treatment of digestive system disorders by employing instrumental neutron activation analysis technique

Journal of Radioanalytical and Nuclear Chemistry - The objectives of this research were to study the elemental concentrations of Mentha spicata L., using a sensitive nuclear analytical technique...     

Elemental analysis of traditional medicinal seeds by instrumental neutron activation analysis

Traditional medicinal seeds prescribed for specific treatment purposes, were purchased from local markets and analyzed by INAA. The samples were irradiated at Es-Salam research reactor, at a power of 5 MW for 6 h. The accuracy of the method was established by analyzing reference materials. Twenty elements were measured, with good accuracy and reproducibility. The concentration of elements determined, was found to vary depending on the seeds. The daily intake of essential and toxic elements was determined, and compared with the recommended values. The probable cumulative intake of toxic elements is well below the tolerance limits.     

Anticancer Cytotoxic Activity of Bispidine Derivatives Associated with the Increasing Catabolism of Polyamines

Polyamine (PA) catabolism is often reduced in cancer cells. The activation of this metabolic pathway produces cytotoxic substances that might cause apoptosis in cancer cells. Chemical compounds able to restore the level of PA catabolism in tumors could become potential antineoplastic agents. The search for activators of PA catabolism among bicyclononan-9-ones is a promising strategy for drug development. The aim of the study was to evaluate the biological activity of new 3,7-diazabicyclo[3.3.1]nonan-9-one derivatives that have antiproliferative properties by accelerating PA catabolism. Eight bispidine derivatives were synthetized and demonstrated the ability to activate PA catabolism in regenerating rat liver homogenates. However, only three of them demonstrated a potent ability to decrease the viability of cancer cells in the MTT assay. Compounds 4c and 4e could induce apoptosis more effectively in cancer HepG2 cells rather than in normal WI-38 fibroblasts. The lead compound 4e could significantly enhance cancer cell death, but not the death of normal cells if PAs were added to the cell culture media. Thus, the bispidine derivative 4e 3-(3-methoxypropyl)-7-[3-(1H-piperazin-1-yl)ethyl]-3,7-diazabicyclo[3.3.1]nonane could become a potential anticancer drug substance whose mechanism relies on the induction of PA catabolism in cancer cells.     

Ditopic Chelators of Dicopper Centers for Enhanced Tyrosinases Inhibition

Tyrosinase enzymes (Tys) are involved in the key steps of melanin (protective pigments) biosynthesis and molecules targeting the binuclear copper active site on tyrosinases represent a relevant strategy to regulate enzyme activities. In this work, the possible synergic effect generated by a combination of known inhibitors is studied. For this, derivatives containing kojic acid (KA) and 2-hydroxypyridine-N-oxide (HOPNO) combined with a thiosemicarbazone (TSC) moiety were synthetized. Their inhibition activities were evaluated on purified tyrosinases from different sources (mushroom, bacterial, and human) as well as on melanin production by lysates from the human melanoma MNT-1 cell line. Results showed significant enhancement of the inhibitory effects compared with the parent compounds, in particular for HOPNO-TSC. To elucidate the interaction mode with the dicopper(II) active site, binding studies with a tyrosinase bio-inspired model of the dicopper(II) center were investigated. The structure of the isolated adduct between one ditopic inhibitor (KA-TSC) and the model complex reveals that the binding to a dicopper center can occur with both chelating sites. Computational studies on model complexes and docking studies on enzymes led to the identification of KA and HOPNO moieties as interacting groups with the dicopper active site.     

Experimental and MCNP calculations of neutron flux parameters in irradiation channel at Es-Salam reactor

The Algerian research reactor (Es-Salam) is a 15 MW heavy water reactor type, operating since 1992. It became essential to characterize the neutron field in the most useful irradiation positions, in order to guarantee the accuracy in the application of k ₀-neutron activation analysis (k ₀-NAA). Experimental value of the thermal to epithermal neutron flux ratio (f) and of the deviation of the epithermal neutron spectrum from 1/E shape (α) were determined using different methods. This work focuses the verification of Monte Carlo neutron flux calculation in typical irradiation channel. Comparison of the results for parameter f obtained experimentally and by Monte Carlo simulations shows good agreement in the irradiation channel studied. The difference between both results is about 2.08%.     

Determination of trace elements in cigarette tobacco with the <Emphasis Type="Italic">k</Emphasis><Subscript>0</Subscript>-based NAA method using Es-Salam research reactor

The k ₀-standardization method of NAA is known as one of the most remarkable progress of NAA with its many advantages. Recently, our laboratory is highly involved in various areas of application of k ₀-NAA. This paper focuses on the application of the k ₀-NAA method in Nutritional and Health-Related Environmental field. Tobacco holds a leading position among different commodities of human consumption. The adverse health effects of toxic and trace elements in tobacco smoke on smokers and non-smokers are a special concern. In the present study, the concentration of 24 trace elements in cigarette tobacco of five different brands of Algerian and American cigarettes have been determined by k ₀-based INAA method. The results were compared with those obtained for samples from Iranian, Turkish, Brazilian and Mexican cigarettes tobacco. To evaluate the accurate of the results the SRM IAEA-140/TM was executed. The analytical results showed that the relative error of most of the elements was less than 10%.     

Characterization of neutron spectrum at Es-Salam Research Reactor using Høgdahl convention and Westcott formalism for the k<Subscript>0</Subscript>-based neutron activation analysis

For the general applicability of the k ₀-NAA method two formalisms were carried out to deal with “1/ν and non-l/ν ((n,γ)” reaction nuclides, respectively. In the Høgdahl-formalism the reactor neutron spectrum parameters, such as α and f were measured using three methods: Cd-ratio, Cdcovered and bare triple monitors. In addition, bare bi-isotopic method using Zr is also utilized for the calculation of f. According to the Westcottformalism the modified spectral index r(α)√T _n /T ₀ and g(T _n ) factor for monitoring neutron temperature T _n , were measured employing Lu as non “1/v” monitor and ¹⁹⁷Au, ⁹⁶Zr and ⁹⁴Zr as “1/v” monitors. The reduced resonance integral of lutetium s _0,Lu was also calculated. To evaluate the applicability of k ₀-NAA in our analytical system, the analysis of two kinds of SRMs was executed. The analytical results showed that the relative error of most of the elements was less than 10%.     

Trace and essential elements determination in baby formulas milk by INAA and k 0-INAA techniques

As a part of the food analysis program executed at Es-Salam research reactor by neutron activation analysis laboratory, the concentration of As, Ba, Br, Ca, Fe, K, La, Rb and Zn in baby formulas milk have been determined by using INAA and k ₀-NAA techniques. It was found that the concentration of all elements obtained by both techniques was relatively identical for the three brands of the 0–6 and 6–12 months of analyzed samples. In addition, the analytical results have been compared with those given by producers.