The complex roles of neurosteroids in depression and anxiety disorders

The role of neurosteroids in neuropsychiatric disorders has been thoroughly investigated in many research studies that have stressed their significant pathophysiological function in neuropsychiatry. In this review, we will focus mainly on the steroids active on the GABA(A) receptors studied in anxiety and depression. The aim is to discuss the controversial results reported in research on anxiety and depressive disorders. We suggest the combined use of biological parameters linked to psychopathological dimensions to make more homogeneous diagnoses and to develop more precise therapies for the treatment of depression and anxiety disorders. We discuss the role of neurosteroids in the pathophysiology and therapy of anxiety and depression. Finally, we consider the possibility of using quantification of mRNA expression of steroidogenic enzymes from peripheral sources in neuropsychiatry.     

α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.     

Trichomycete insect symbionts in Great Smoky Mountains National Park and vicinity

Collections of trichomycete symbionts of larval aquatic insects in Great Smoky Mountains National Park and vicinity in the southern Appalachian region of the USA resulted in finding many taxa of Harpellales, including an unusual new monotypic genus, Barbatospora ambicaudata in Simuliidae, and five new species in Thaumaleidae or Chironomidae, Harpellomyces montanus, Smittium lentaquaticum, Sm. minutisporum, Stachylina gravicaudata and St. stenospora. In addition a new species of Amoebidium (Amoebidiales), A. appalachense, attached to the anal tubules of bloodworms (Chironomidae) is described. Axenic cultures of three of the new taxa were obtained, plus Sm. culisetae. Fourteen identified species representing 13 genera of previously known Harpellales are recorded from Plecoptera, Ephemeroptera and Diptera, as well as a new Dipteran host record for an unidentified harpellid that was found in a Blephariceridae. Also identified were Paramoebidium corpulentum and many undetermined species of Paramoebidium (Amoebidiales) from four orders of aquatic insect larvae. The occurrence of an Enterobryus species in Diplopoda and another Eccrinales from an aquatic beetle is noted. Amoebidiales,     

Hydraulic Lift in Cork Oak Trees in a Savannah-Type Mediterranean Ecosystem and its Contribution to the Local Water Balance

The aim of this study was to identify the sources and depth of water uptake by 15-years old Quercus suber L. trees in southern Portugal under a Mediterranean climate, measuring δ¹⁸O and δD in the soil–plant-atmosphere continuum. Evidence for hydraulic lift was substantiated by the daily fluctuations observed in Ψ_s at 0.4 and 1 m depth and supported by similar δ¹⁸O values found in tree xylem sap, soil water in the rhizosphere and groundwater. From 0.25 m down to a depth of 1 m, δD trends differed according to vegetation type, showing a more depleted value in soil water collected under the evergreen trees (−47‰) than under dead grasses (−35‰). The hypothesis of a fractionation process occurring in the soil due to diffusion of water vapour in the dry soil is proposed to explain the more depleted soil δD signature observed under trees. Hydraulically lifted water was estimated to account for 17–81% of the water used during the following day by tree transpiration at the peak of the drought season, i.e., 0.1–14 L tree⁻¹ day⁻¹. Significant relationships found between xylem sap isotopic composition and leaf water potential in early September emphasized the positive impact of the redistribution of groundwater in the rhizosphere on tree water status.     

A novel system for large-scale gene expression analysis: bacterial colonies array

In the present work, we report the use of bacterial colonies to optimize macroarray technique. The devised system is significantly cheaper than other methods available to detect large-scale differential gene expression. Recombinant Escherichia coli clones containing plasmid-encoded copies of 4,608 individual expressed sequence tag (ESTs) were robotically spotted onto nylon membranes that were incubated for 6 and 12 h to allow the bacteria to grow and, consequently, amplify the cloned ESTs. The membranes were then hybridized with a beta-lactamase gene specific probe from the recombinant plasmid and, subsequently, phosphorimaged to quantify the microbial cells. Variance analysis demonstrated that the spot hybridization signal intensity was similar for 3,954 ESTs (85.8%) after 6 h of bacterial growth. Membranes spotted with bacteria colonies grown for 12 h had 4,017 ESTs (87.2%) with comparable signal intensity but the signal to noise ratio was fivefold higher. Taken together, the results of this study indicate that it is possible to investigate large-scale gene expression using macroarrays based on bacterial colonies grown for 6 h onto membranes.     

International NeuroAIDS: prospects of HIV-1 associated neurological com-plications

INTRODUCTION AND NEUROEPIDEMIO- LOGY OF HIV/AIDS AIDS was first recognized as a new and distinct clini- cal entity in 1981 [1] and the HIV-1 as their casual agent in 1983 [2]. Since then, the HIV/AIDS epidemic has reached epidemic proportions with a total accumulative number of more than 60 million people, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) and WHO. The extensive spread of HIV-1 epidemics in Asia was not appreciated in the 1980s,…     

Efficient synthesis and biological evaluation of two modafinil analogues

Non classical bioisosters of modafinil featuring interesting biological profile have been easily produced through replacement of the sulfoxide function with a carbonyl group and modification of the carboxylic acid amide functionality.     

Diphenyl Diselenide-Induced Seizures in Rat Pups: Possible Interaction with Glutamatergic System

The aims of the present study were to investigate the possible involvement of glutamatergic system in seizures induced by diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight) administered in association with diphenyl diselenide (500 mg/kg of body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and catalase, Na⁺,K⁺-ATPase and δ-ALA-D activities. At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the appearance of seizure episodes induced by glutamate but did not alter the latency for the onset of the first episode. Glutamate uptake was inhibited in glutamate, diphenyl diselenide (the highest dose) and in the association of diphenyl diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-NMDA receptor antagonist, DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by diphenyl diselenide. The results of the present study demonstrated that: (a) when diphenyl diselenide and glutamate were administered concomitantly in pups, glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic receptors, were at least in part, involved in diphenyl diselenide- induced seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures induced by glutamate.     

Algicide production by the filamentous cyanobacteriumFischerellasp. CENA 19

The biosynthesis of algicides produced by a novelFischerellastrain was investigated. Two allelochemicals were identified, the aminoacylpolyketide fischerellin A (FsA) and the alkaloid 12-epi-hapalindole F (HapF). Based on the structure of FsA, genes that could be involved in its biosynthesis, including those encoding nonribosomal peptide synthetases (NRPSs) and a polyketide synthase (PKS), were identified by the polymerase chain reaction (PCR). By showing that the expression of NRPSs and PKSs is concomitant with algicide production we suggest that the identified genes may be involved in algicide biosynthesis. Analysis of an algicide preparation of the Brazilian-Amazonian strainFischerellasp. CENA 19 revealed the production of FsA,m/z409 (MH⁺), HapF,m/z370 (MH⁺), and other potential isoforms of the latter compounds, which were identified by high-performance liquid chromatography (HPLC) and matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass-spectrometry. The production of HapF was confirmed after purification by HPLC, analysis by NMR, and high-resolution mass-spectrometry (HRMS). Two-NRPS and a PKS gene were identified after specific amplification using a degenerate PCR. The expression of these synthetases was confirmed by Western blot analysis employing enzyme family-specific antibodies. These analyses revealed the presence of three NRPSs and a single PKS inFischerellasp. CENA 19. The structure of FsA indicates both aminoacyl- and polyketide moeities, suggesting that its biosynthesis may require an integrated NRPS/PKS enzyme system, possibly involving the genes and the synthetases identified.     

Atomic resolution (1.1 A) structure of the ribosome-inactivating protein PD-L4 from Phytolacca dioica L. leaves

The ribosome inactivating protein PD-L4 from Phytolacca dioica is a N-beta-glycosidase, probably involved in plant defence. The crystal structures of wild type PD-L4 and of the S211A PD-L4 mutant with significantly decreased catalytic activity were determined at atomic resolution. To determine the structural determinants for the reduced activity of S211A PD-L4, both forms have also been co-crystallized with adenine, the major product of PD-L4 catalytic reaction. In the structure of the S211A mutant, the cavity formed by the lack of the Ser hydroxyl group is filled by a water molecule; the insertion of this non-isosteric group leads to small albeit concerted changes in the tightly packed active site of the enzyme. These changes have been correlated to the different activity of the mutant enzyme. This work highlights the importance of atomic resolution studies for the deep understanding of enzymatic properties.