Overlapping enhancer/promoter and transcriptional termination signals in the lentiviral long terminal repeat

We have studied the effects associated with two single amino acid substitution mutations in HIV-1 capsid (CA), the E98A and E187G. Both amino acids are well conserved among all major HIV-1 subtypes. HIV-1 infectivity is critically dependent on proper CA cone formation and mutations in CA are lethal when they inhibit CA assembly by destabilizing the intra and/or inter molecular CA contacts, which ultimately abrogate viral replication. Glu98, which is located on a surface of a flexible cyclophilin A binding loop is not involved in any intra-molecular contacts with other CA residues. In contrast, Glu187 has extensive intra-molecular contacts with eight other CA residues. Additionally, Glu187 has been shown to form a salt-bridge with Arg18 of another N -terminal CA monomer in a N-C dimer. However, despite proper virus release, glycoprotein incorporation and Gag processing, electron microscopy analysis revealed that, in contrast to the E187G mutant, only the E98A particles had aberrant core morphology that resulted in loss of infectivity.     

Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive Bacteria in the Mealworm Beetle

In many vertebrates and invertebrates, offspring whose mothers have been exposed to pathogens can exhibit increased levels of immune activity and/or increased survival to infection. Such phenomena, called “Trans-generational immune priming” (TGIP) are expected to provide immune protection to the offspring. As the offspring and their mother may share the same environment, and consequently similar microbial threats, we expect the immune molecules present in the progeny to be specific to the microbes that immune challenged the mother. We provide evidence in the mealworm beetle Tenebrio molitor that the antimicrobial activity found in the eggs is only active against Gram-positive bacteria, even when females were exposed to Gram-negative bacteria or fungi. Fungi were weak inducers of TGIP while we obtained similar levels of anti-Gram-positive activity using different bacteria for the maternal challenge. Furthermore, we have identified an antibacterial peptide from the defensin family, the tenecin 1, which spectrum of activity is exclusively directed toward Gram-positive bacteria as potential contributor to this antimicrobial activity. We conclude that maternal transfer of antimicrobial activity in the eggs of T. molitor might have evolved from persistent Gram-positive bacterial pathogens between insect generations.     

Draft Genome Sequences of Actinomyces timonensis Strain 7400942T and Its Prophage

A draft genome sequence of Actinomyces timonensis, an anaerobic bacterium isolated from a human clinical osteoarticular sample, is described here. CRISPR-associated proteins, insertion sequence, and toxin-antitoxin loci were found on the genome. A new virus or provirus, AT-1, was characterized.     

Murine model of dextran sulfate sodium-induced colitis reveals Candida glabrata virulence and contribution of β-mannosyltransferases

Candida glabrata, like Candida albicans, is an opportunistic yeast pathogen that has adapted to colonize all segments of the human gastrointestinal tract and vagina. The C. albicans cell wall expresses β-1,2-linked mannosides (β-Mans), promoting its adherence to host cells and tissues. Because β-Mans are also present in C. glabrata, their role in C. glabrata colonization and virulence was investigated in a murine model of dextran sulfate sodium (DSS)-induced colitis. Five clustered genes of C. glabrata encoding β-mannosyltransferases, BMT2-BMT6, were deleted simultaneously. β-Man expression was studied by Western blotting, flow cytometry, and NMR analysis. Mortality, clinical, histologic, and colonization scores were determined in mice receiving DSS and different C. glabrata strains. The results show that C. glabrata bmt2-6 strains had a significant reduction in β-1,2-Man expression and a disappearance of β-1,2-mannobiose in the acid-stable domain. A single gavage of C. glabrata wild-type strain in mice with DSS-induced colitis caused a loss of body weight, colonic inflammation, and mortality. Mice receiving C. glabrata bmt2-6 mutant strains had normal body weight and reduced colonic inflammation. Lower numbers of colonies of C. glabrata bmt2-6 were recovered from stools and different parts of the gastrointestinal tract. Histopathologic examination revealed that the wild-type strain had a greater ability to colonize tissue and cause tissue damage. These results showed that C. glabrata has a high pathogenic potential in DSS-induced colitis, where β-Mans contribute to colonization and virulence.     

Face recognition: lessons from a wasp

The golden paper wasp is a social insect whose colony members have the remarkable ability to recognise each others' faces. New research shows that this species is singularly skilled at learning about faces, opening interesting perspectives on convergent evolution of specialist cognitive abilities in insects and vertebrates.     

Relevance of exocytotic glutamate release from retinal glia

Glial cells release molecules that influence brain?development, function, and disease. Calcium-dependent exocytosis has been proposed as potential release mechanism in astroglia, but the physiological relevance of "gliotransmission" in?vivo remains controversial. We focused on the impact of glial exocytosis on sensory transduction in the retina.?To this end, we generated transgenic mice to block exocytosis by Cre recombinase-dependent expression of the clostridial botulinum neurotoxin serotype?B light chain, which cleaves vesicle-associated membrane protein 1-3. Ubiquitous and neuronal toxin expression caused perinatal lethality and?a reduction of synaptic transmission thus validating transgene function. Toxin expression in Müller cells inhibited vesicular glutamate release and impaired glial volume regulation but left retinal histology and visual processing unaffected. Our model to study gliotransmission in?vivo reveals specific functions of exocytotic glutamate release in retinal glia.     

Glutamic acid 709 substitutions highlight the importance of the interaction between androgen receptor helices H3 and H12 for androgen and antiandrogen actions

The mutation of a single amino acid in the ligand binding domain of the human androgen receptor (AR) can induce functional abnormalities; for example, in androgen binding or interactions with coregulators. We report here on the structure/function analysis of the ARE709K substitution that is associated with partial androgen insensitivity syndrome. We introduced several mutations at position 709 and tested the consequences of these changes on AR structure and activity in the presence of androgen and antiandrogens. Our results demonstrate that a strong interaction between helix H12 and residue 709 in H3 is required to obtain a fully functional AR. We show that glutamic acid 709 can be replaced by a bulky tyrosine residue without significant effect on the activation by agonists. In contrast, smaller or linear residues that are unable to maintain a tight interaction with H12 induce a substantial loss of androgen-induced AR activity. We also show that the agonist activity of partial antiandrogens is dependent on the side-chain residue at position 709. Strikingly, the ARE709Y substitution causes the conversion of cyproterone acetate into a pure antiandrogen and bicalutamide into a partial agonist. Together, our structural and functional data reveal the key role of glutamic acid 709 in androgenic and antiandrogenic activities.     

Sequence variant (CTAGGG)n in the human telomere favors a G-quadruplex structure containing a G·C·G·C tetrad

Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable in the male germline and somatic cells, suggesting formation of unusual structures by this repeat type. Here, we report on the structure of an intramolecular G-quadruplex formed by DNA sequences containing four human telomeric variant CTAGGG repeats in potassium solution. Our results reveal a new robust antiparallel G-quadruplex fold involving two G-tetrads sandwiched between a G·C base pair and a G·C·G·C tetrad, which could represent a new platform for drug design targeted to human telomeric DNA.