asense, a member of the Drosophila achaete-scute complex, is a proneural and neural differentiation gene.

The asense (ase) gene of the achaete-scute complex (AS-C) is expressed in the precursors of all adult sensory organs (SOs), the sensory mother cells (SMCs) and in their immediate progeny. Its deletion causes the loss of some SOs and the abnormal differentiation of part of the remaining ones. These defects, which include malformations of the external part of the SOs, duplication of the innervating neuron etc, are enhanced by the haploid condition for the other AS-C genes and are corrected by an ase transgene. We conclude that ase participates, in combination with other members of the AS-C, in implementing the neural program of differentiation of the SMCs. ase also has a proneural function that participates in the singling out of the SMCs that give rise to the recurved bristles of the anterior wing margin. The proneural potential of ase is shown, in addition, by the generation of SOs induced by the generalized expression of an ase gene driven by a hsp70 promoter.     

Interspecies recombination In nature: a meningococcus that has acquired a gonococcal PIB porin

A. vaginal isolate of Neisseria has been reported to resemble Neisseria meningitidis in biochemical characteristics but to react with serological reagents that are specific to the PI porin from Neisseria gonorrhoeae. We have confirmed that this isolate has the biochemical attributes of a meningococcus and have shown that it clusters among meningococcal Isolates on a dendrogram based on isoenzyme variation within housekeeping enzymes from populations of N. meningitidis and N. gonorrhoeae. Furthermore, the sequences of the fbp and adk genes were typical of those of N. meningitidis and were distinct from those of N. gonorrhoeae. However, the porB gene was very similar to the por genes of N. gonorrhoeae isolates that express the PIB class of outer-membrane porin (differing from one gonococcal por allele at only a single nucleotide site), and was clearly distinct from the porB genes of N. meningitidis. The isolate therefore appears to be a typical meningococcus, except that its porB gene has been replaced with the por gene from a gonococcus.     

DNA map of mutations at the scute locus of Drosophila melanogaster

The achaete-scute gene complex (AS-C) of Drosophila melanogaster is involved in the differentiation of innervated elements in the adult (chaetes) and in the embryo (central nervous system). Genetically, the AS-C is subdivided into four regions: achaete, scute α, lethal of scute, and scute β. Using a previously cloned fragment of scute DNA, we have now cloned 62 kb of wild-type DNA from the scute region. No repetitive sequences have been detected in this stretch of DNA. Of 16 scute mutants with chromosomal rearrangements studied (inversions, deletions, and translocations), nine, included genetically in scute β, have breakpoints in the cloned region. The remaining rearrangements, which genetically correspond to scute α, map outside and to the left of the cloned region. Of nine scute `point mutants' studied, eight have large DNA alterations within the cloned region. These alterations include insertions (five) and deletions (three). The DNA alterations found in both `point mutants' and rearrangements are interspersed and scattered over 40 kb. The relationship between the sites of the DNA alterations and the mutant phenotypes are discussed.     

The serine hydroxymethyltransferase of Plasmodium lophurae.

Plasmodium lophurae serine hydroxymethyltransferase (EC 2.1.2.1) was partially purified and characterized by (NH4)2SO4 fractionation and chromatography on Sephadex G-100. The enzyme, precipitated by 3.0.3.3 M (NH4)2SO4, had a molecular weight of 68,300 as estimated by exclusion chromatography on G-100. The pH optimum of the enzyme was 6.8-7.6 in sodium phosphate-citrate buffer. Citrate stabilized the enzyme during storage in phosphate buffer at 4 C. The Km was 4.3 X 10(-3) M for L-serine and 2.5 X 10(-4) M for tetrahydrofolate.     

Use of RT-Defective HIV Virions: New Tool to Evaluate Specific Response in Chronic Asymptomatic HIV-Infected Individuals

Background

Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.

Methods

We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.

Results

The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: “full-responders” (positive response against both viral particles), “partial-responders” (positive response only against NL4-3/ΔRT virions) and “non-responders” (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.

Conclusions

In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.     

Synthesis and cytotoxic activity of metallic complexes of lawsone

In the present study, a series of metallic complexes of the 1,4-naphthoquinone lawsone (2–6) were synthesized and evaluated for potential cytotoxicity in a mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by the MTT assay. Significant growth inhibition was observed for the copper complex (4) with an IC₅₀ value of 2.5 μM. This compound was selected for further evaluation of cytotoxic activity on several human cancer cells including HT-29 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease was also observed in HepG2 cells. The apoptotic potential of this complex was evaluated in these cells. Compound 4 induced apoptosis by a mechanism that involves the activation of caspases 3, 8 and 9 and modulation of apoptotic-related proteins such as Bax, Bad, and p53. These results indicate that metal complexes of lawsone derivatives, in particular compound 4, might be used for the design of new antitumoral agents.