A monomeric 3(10)-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41

The peptide gp41(659-671) (ELLELDKWASLWN) comprises the entire epitope for one of the three known antibodies capable of neutralizing a broad spectrum of primary HIV-1 isolates and is the only such epitope that is sequential. Here we present the NMR structure of gp41(659-671) in water. This peptide forms a monomeric 3(10)-helix stabilized by i,i+3 side chain-side chain interactions favored by its primary sequence. In this conformation the peptide presents an exposed surface, which is mostly hydrophobic and consists of conserved HIV-1 residues. The presence of the 3(10)-helix is confirmed by its characteristic CD pattern. Studies of the 3(10)-helix have been hampered by the absence of a model peptide adopting this conformation. gp41(659-671) can serve as such a model to investigate the spectral characteristics of the 3(10)-helix, the factors that influence its stability, and the propensity of different amino acids to form a 3(10)-helix. The observation that the 3(10)-helical conformation is highly populated in the peptide gp41(659-671) indicates that the corresponding segment in the cognate protein is an autonomous folding unit. As such, it is very likely that the helical conformation is maintained in gp41 throughout the different tertiary structures of the envelope protein that form during the process of viral fusion. However, the exposure of the gp41(659-671) segment may vary, leading to changes in the reactivity of anti-gp41 antibodies in the different stages of viral fusion. Since gp41(659-671) is an autonomous folding unit, peptide immunogens consisting of the complete gp41(659-671) sequence are likely to induce antibodies highly cross-reactive with HIV-1.     

The Econo-Environmental Return (EER)

Aim and Background  

Many analytical tools have been developed to support the implementation of sustainable development. Principal among these are the ones that are based on physical aspects such as life cycle assessment (LCA), while others focus on non-physical aspects, namely on monetary concepts, such as life cycle costing and total cost assessment. Each kind of tool is designed to assess a specific aspect (environmental or economic) of the entire life of a good or a service. Unfortunately, even if the literature clearly states the advantage of combining these tools, case studies with global conclusions considering both aspects are still rare. Most often, studies conclude separately on each aspect; environmental impact and cost assessment.     

Formation of plant cuticle: evidence for the occurrence of the peroxygenase pathway

Cuticle plays a major role as a protective barrier in plants. Despite its physiological importance, the mode of formation of this complex structure remains poorly understood. In particular, none of the putative enzymes involved in the biosynthesis of the cutin, the matrix of cuticle, have been cloned. We have shown previously that peroxygenase is able to catalyze in vitro the epoxidation step required for the biosynthesis of C18 cutin monomers. In the present work, we have confirmed in planta that this oxidase is indeed a key enzyme involved in the formation of cutin. Thus, in maize leaves, the specific inactivation of peroxygenase by organophosphorothioates resulted in a dramatic decrease of cuticular epoxide content, as visualized by a specific histochemical technique that was accompanied by a reduced thickness of the cuticle. A strict correlation could also be established between the extent of inhibition of the peroxygenase and the modification of the cuticle triggered by a family of structurally related inhibitors. Importantly, these effects were restricted to plants that contain a cutin originating from C18 monomers. The altered cuticle of maize, treated with the peroxygenase inhibitor, was characterized by an increased permeability to pesticides. In addition, such plants became largely susceptible to infection by fungi, implying that the cuticle represents a crucial target for the modulation of the response in plant-pathogen interactions.     

Gene transfer to suppress bone marrow alkylation sensitivity

Alkylating agents represent a highly cytotoxic class of chemotherapeutic compounds that are extremely effective anti-tumor agents. Unfortunately, alkylating agents damage both malignant and non-malignant tissues. Bone marrow is especially sensitive to damage by alkylating agent chemotherapy, and is a dose-limiting tissue when treating cancer patients. One strategy to overcome bone marrow sensitivity to alkylating agent exposure involves gene transfer of the DNA repair protein O(6)-methylguanine DNA methyltransferase (O(6)MeG DNA MTase) into bone marrow cells. O(6)MeG DNA MTase is of particular interest because it functions to protect against the mutagenic, clastogenic and cytotoxic effects of many chemotherapeutic alkylating agents. By increasing the O(6)MeG DNA MTase repair capacity of bone marrow cells, it is hoped that this tissue will become alkylation resistant, thereby increasing the therapeutic window for the selective destruction of malignant tissue. In this review, the field of O(6)MeG DNA MTase gene transfer into bone marrow cells will be summarized with an emphasis placed on strategies used for suppressing the deleterious side effects of chemotherapeutic alkylating agent treatment.     

Evidence for 3' untranslated region-dependent autoregulation of the Drosophila gene encoding the neuronal nuclear RNA-binding protein ELAV.

The Drosophila locus embryonic lethal abnormal visual system (elav) encodes a nuclear RNA-binding protein essential for normal neuronal differentiation and maintenance of neurons. ELAV is thought to play its role by binding to RNAs produced by other genes necessary for neuronal differentiation and consequently to affect their metabolism by an as yet unknown mechanism. ELAV structural homologues have been identified in a wide range of organisms, including humans, indicating an important conserved role for the protein. Analysis of elav germline transformants presented here shows that one copy of elav minigenes lacking a complete 3'' untranslated region (3'' UTR) rescues null mutations at elav, but that two copies are lethal. Additional in vivo experiments demonstrate that elav expression is regulated through the 3'' UTR of the gene and indicate that this level of regulation is dependent upon ELAV itself. Because ELAV is an RNA-binding protein, the simplest model to account for these findings is that ELAV binds to the 3'' UTR of its own RNA to autoregulate its expression. I discuss the implications of these results for normal elav function.     

Reduction of Presynaptic Action Potentials by PAD: Model and Experimental Study

A compartmental model of myelinated nerve fiber was used to show that primary afferent depolarization (PAD), as elicited by axo-axonic synapses, reduces the amplitude of propagating action potentials primarily by interfering with ionic current responsible for the spike regeneration. This reduction adds to the effect of the synaptic shunt, increases with the PAD amplitude, and occurs at significant distances from the synaptic zone. PAD transiently enhances the sodium current activation, which partly accounts for the PAD-induced fiber hyperexcitability, and enhances sodium inactivation on a slower time course, thus reducing the amplitude of action potentials. In vivo, intra-axonal recordings from the intraspinal portion of group I afferent fibers were carried out to verify that depolarizations reduced the amplitude of propagating action potentials as predicted by the model. This article suggests PAD might play a major role in presynaptic inhibition.     

Specific EEG Sleep Pattern in the Prefrontal Cortex in Primary Insomnia

Objective

To assess the specific prefrontal activity in comparison to those in the other main cortical areas in primary insomnia patients and in good sleepers.

Methods

Fourteen primary insomnia patients and 11 good sleepers were included in the analysis. Participants completed one night of polysomnography in the sleep lab. Power spectra were calculated during the NREM (Non-rapid eyes movements) and the REM (Rapid eyes movements) sleep periods at prefrontal, occipital, temporal and central electrode positions.

Results

During the NREM sleep, the power spectra did not differ between groups in the prefrontal cortex; while primary insomnia patients exhibited a higher beta power spectrum and a lower delta power spectrum compared to good sleepers in other areas. During the REM sleep, the beta1 power spectrum was lower in the prefrontal cortex in primary insomnia patients compared to good sleepers; while no significant difference between groups was obtained for the other areas.

Conclusions

The present study shows a specific prefrontal sleep pattern during the whole sleep period. In addition, we suggest that primary insomnia patients displayed a dysfunction in the reactivation of the limbic system during the REM sleep and we give additional arguments in favor of a sleep-protection mechanism displayed by primary insomnia patients.