Physical mapping and cloning of RAD56

Here we report the physical mapping of the rad56-1 mutation to the NAT3 gene, which encodes the catalytic subunit of the NatB N-terminal acetyltransferase in Saccharomyces cerevisiae. Mutation of RAD56 causes sensitivity to X-rays, methyl methanesulfonate, zeocin, camptothecin and hydroxyurea, but not to UV light, suggesting that N-terminal acetylation of specific DNA repair proteins is important for efficient DNA repair.     

Fatal-Mixed Cutaneous Zygomycosis–Aspergillosis: A Case Report

Mucorales and Aspergillus are molds responsible for infections in immunocompromised patients. In this report, we describe a case of a rare extensively mixed cutaneous infection caused by Lichtheimia ramosa, Aspergillus fumigatus and Aspergillus terreus in a neutropenic patient suffering from an acute leukemia. The fatal outcome of this patient can be attributed to its hematologic malignancy, the extensive nature of the lesions and the resistance of the strains to antifungals.     

Stereoselective Covalent Binding of Anti-benzo(a)pyrene Diol Epoxide to DNA Conformation of Enantiomer Adducts

Abstract

The conformation of adducts derived from the reactions and covalent binding of the (+) and (-) enantiomers of 7β, 8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BaPDE) with double-stranded calf thymus DNA in vitro were investigated utilizing the electric linear dichroism technique. The linear dichroism and absorption spectra of the covalent DNA complexes are interpreted in terms of a superposition of two types of binding sites. One of these conformations (site I) is a complex in which the plane of the pyrene residue is close to parallel (within 30°) to the planes of the DNA bases (quasi-intercalation), while the other (site II) is an external binding site; this latter type of adduct is attributed to the covalent binding of anti-BaPDE to the exocyclic amino group of deoxyguanine (N2-dG), while site I adducts are attributed to the 06-deoxyguanine and N6-deoxyadenine adducts identified in the product analysis of P. Brookes and M.R. Osborne (Carcinogenesis (1982) 3, 1223–1226). Site II adducts are dominant (~90% in the covalent complexes derived from the (+) enantiomer), but account for only 50±5% of the adducts in the case of the (—)-enantiomer. The orientation of site II complexes is different by 20±10° in the adducts derived from the binding of the (+) and the (—) enantiomers to DNA, the long axis of the pyrene chromophore being oriented more parallel to the axis of the DNA helix in the case of the (+) enantiomer. These findings support the proposals by Brookes and Osborne that the difference in spatial orientation of the N2-dG adducts of (-)-anti-BaPDE together with their lower abundance may account for the lower biological activity of the (—) enantiomer. The external site II adducts, rather than site I adducts, appear to be correlated with the biological activity of these comoounds.     

Do species of Neacratus with anchor-shaped sclerite of endophallus really belong to Neacratus (Coleoptera: Brentidae: Acratini)?

A small group of nine nominal species belonging to the genus Neacratus Alonso-Zarazaga, Lyal, Sforzi & Bartolozzi, 1999 is studied in detail from a morphological point of view. Lectotypes are designated for Brentus obtusus Lund, 1800 and Nemocephalus fulgidus Kleine, 1928. Three new synonymies are proposed: Nemocephalus brevicostatus Kleine, 1922 n. syn. for Brenthus obtusus Lund, 1800, Nemocephalus longiceps Perroud, 1853 n. syn. for Brenthus famulus Boheman, 1840, and Nemocephalus fulgidus Kleine, 1928 n. syn. for B. famulus Boheman, 1840. A new species, Neacratus pascali n. sp., is described from French Guiana. New country records are provided for Neacratus obtusus (Bolivia, Ecuador, French Guiana, Grenada, Peru, Trinidad and Tobago, Venezuela), N. puncticeps (Sharp, 1895) (Colombia, Ecuador, Venezuela), N. guatemalensis (Senna, 1893) (Belize, Colombia, El Salvador), N. deplanatus (Sharp, 1895) (Colombia, Costa Rica, French Guiana, Mexico, Panama, Venezuela) and N. famulus (Paraguay). A phylogenetic analysis carried out on this group shows it forms a monophyletic lineage included in a clade containing most of other species of Neacratus, of which it is the type species; it is therefore not justified to create a new generic name. The possible polyphyletism of the genus Neacratus as a whole and the development of an excessively long rostrum in some male Acratini are discussed.     

The roots of contemporary attitudes toward immigration in Australia: contextual and individual-level influencesÞ

This paper examines the roots of attitudes toward immigration among Australians of English-speaking background using the 1998, 2001, 2004, and 2007 Australian Election Studies. The paper demonstrates that attitudes toward immigration in Australia have their roots in multiple sources, some of them relating to the local context in which individuals reside, others in the socio-economic and financial situation experienced by individuals. Attitudes toward immigration in Australia are also related to attitudinal factors and historical legacies that manifest themselves in mistrust and suspicion toward Asian neighbours. Finally, the paper demonstrates that the presence of immigrants and ethnic minorities influences Australians' attitudes toward immigration but that this effect must be understood in conjunction with the educational context of the areas of residence. While in high education areas Australians tend to react positively to the presence of immigrants, in low education areas they tend to react negatively to the presence of immigrants.     

In Human Pseudouridine Synthase 1 (hPus1), a C-Terminal Helical Insert Blocks tRNA from Binding in the Same Orientation as in the Pus1 Bacterial Homologue TruA,Consistent with Their Different Target Selectivities

Human pseudouridine (Ψ) synthase Pus1 (hPus1) modifies specific uridine residues in several non-coding RNAs: tRNA, U2 spliceosomal RNA, and steroid receptor activator RNA. We report three structures of the catalytic core domain of hPus1 from two crystal forms, at 1.8 Å resolution. The structures are the first of a mammalian Ψ synthase from the set of five Ψ synthase families common to all kingdoms of life. hPus1 adopts a fold similar to bacterial Ψ synthases, with a central antiparallel β-sheet flanked by helices and loops. A flexible hinge at the base of the sheet allows the enzyme to open and close around an electropositive active-site cleft. In one crystal form, a molecule of Mes [2-(N-morpholino)ethane sulfonic acid] mimics the target uridine of an RNA substrate. A positively charged electrostatic surface extends from the active site towards the N-terminus of the catalytic domain, suggesting an extensive binding site specific for target RNAs. Two α-helices C-terminal to the core domain, but unique to hPus1, extend along the back and top of the central β-sheet and form the walls of the RNA binding surface. Docking of tRNA to hPus1 in a productive orientation requires only minor conformational changes to enzyme and tRNA. The docked tRNA is bound by the electropositive surface of the protein employing a completely different binding mode than that seen for the tRNA complex of the Escherichia coli homologue TruA.     

Protease‐activated receptor‐1 modulates hippocampal memory formation and synaptic plasticity

Protease‐activated receptor‐1 (PAR1) is an unusual G‐protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1?/? mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1?/? mice have deficits in hippocampus‐dependent memory. We also show that while PAR1?/? mice have normal baseline synaptic transmission at Schaffer collateral‐CA1 synapses, they exhibit severe deficits in N‐methyl‐d ‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR‐mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR‐dependent processes subserving memory formation and synaptic plasticity.