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Neuronal remodeling is a fundamental process by which the brain responds to environmental influences, e.g., during stress. In the hippocampus, chronic stress causes retraction of dendrites in CA3 pyramidal neurons. We have recently identified the glycoprotein M6a as a stress-responsive gene in the hippocampal formation. This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment. In the present work, we analyzed the biological function of the M6a protein. Immunohistochemistry showed that the M6a protein is abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia/ spines). Transfection experiments revealed that M6a overexpression induces neurite formation and increases filopodia density in hippocampal neurons. M6a knockdown with small interference RNA methodology showed that M6a low-expressing neurons display decreased filopodia number and a lower density of synaptophysin clusters. Taken together, our findings indicate that M6a plays an important role in neurite/filopodium outgrowth and synapse formation. Therefore, reduced M6a expression might be responsible for the morphological alterations found in the hippocampus of chronically stressed animals. Potential mechanisms that might explain the biological effects of M6a are discussed. chronic stress | hippocampus

Optical spectroscopic data on a series of designed beta-hairpins were shown by NMR to contain a substantial population of beta-sheet structure. The models contain a designed hydrophobic cluster and a (super d)Pro-Gly sequence to promote formation of a turn geometry.

Ketosteroid Isomerase (KSI) catalyzes proton abstraction from the C-H function adjacent to carbonyl group at a rate approaching diffusion limit. The two mechanisms proposed for the KSI reaction are the catalytic and the cooperative hydrogen bond mechanism. Results from the molecular dynamics (MD) simulations of the enzyme bound substrate and dienolate intermediate strongly support the cooperative hydrogen bond mechanism.

Equilibrium and kinetic isotope effects were measured for several phosphorothioate esters of p-nitrophenol (pNPPT) and the results were compared with data from phosphate esters to study the comparative inherent chemistry of the two types of esters. Results of the study suggested that leading a group bond fission in the transition state of reactions of the monoester pNPPT was more advanced than for its phosphate counterpart pNNP, while alkaline hydrolysis of the phosphorothioate diester and triester somewhat less advanced bond fission than that of their phosphate ester counterparts.

A group of new DNA enzymes that possess a synchronized RNA-cleavage flourescence-signaling ability and exhibit wide-ranging metal-ion and pH dependences is reported. The demonstration of DNA enzymes that are functional under extremely high acidity indicates that DNA has the ability to perform efficient catalysts even under harsh reaction conditions.

The nervous system monitors the environment to maintain homeostasis, which can be affected by stressful conditions. Using mammalian models of chronic stress, we previously observed altered brain levels of GPM6A, a protein involved in neuronal morphology. However, GPM6A's role in systemic stress responses remains unresolved. The nematode Caenorhabditis elegans expresses a GPM6A ortholog, the neuronal membrane glycoprotein 1 (NMGP‐1). Because of the shared features between nematode and mammalian nervous systems and the vast genetic tools available in C. elegans, we used the worm to elucidate the role of GPM6A in the stress response. We first identified nmgp‐1 expression in different amphid and phasmid neurons. To understand the nmgp‐1 role, we characterized the behavior of nmgp‐1(RNAi) animals and two nmgp‐1 mutant alleles. Compared to control animals, mutant and RNAi‐treated worms exhibited increased recovery time from the stress‐resistant dauer stage, altered SDS chemosensation and reduced egg‐laying rate resulting in egg retention (bag‐of‐worms phenotype). Silencing of nmgp‐1 expression induced morphological abnormalities in the ASJ sensory neurons, partly responsible for dauer exit. These results indicate that nmgp‐1 is required for neuronal morphology and for behaviors associated with chemosensation. Finally, we propose nmgp‐1 mutants as a tool to screen drugs for human nervous system pathologies. [ABSTRACT FROM AUTHOR]

Abstract Background Members of the proteolipid protein family, including the four-transmembrane glycoprotein M6a, are involved in neuronal plasticity in mammals. Results from our group previously demonstrated that M6, the only proteolipid protein expressed in Drosophila, localizes to the cell membrane in follicle cells. M6 loss triggers female sterility, which suggests a role for M6 in follicular cell remodeling. These results were the basis of the present study, which focused on the function and requirements of M6 in the fly nervous system. Results The present study identified two novel, tissue-regulated M6 isoforms with variable N- and C- termini, and showed that M6 is the functional fly ortholog of Gpm6a. In the adult brain, the protein was localized to several neuropils, such as the optic lobe, the central complex, and the mushroom bodies. Interestingly, although reduced M6 levels triggered a mild rough-eye phenotype, hypomorphic M6 mutants exhibited a defective response to light. Conclusions Based on its ability to induce filopodium formation we propose that M6 is key in cell remodeling processes underlying visual system function. These results bring further insight into the role of M6/M6a in biological processes involving neuronal plasticity and behavior in flies and mammals.

Difference between FT-IR spectroscopy was used to show that oxidation of a redox-active tyrosine in photosystem II (PSII) causes perturbations of the peptide bond. The perturbations were attributed to spin delocalization, as proposed earlier for typtophan cation radicals and tyrosyl radicals in vitro.

The enzyme kinetics of wild type trans-sialidase from Trypanosoma cruzi (TcTS) is demonstrated by using the concentrations of two different donor aryl [alpha]-sialoside substrates and the acceptor substrate lactose. The results provide insight into ping-pong mechanism of TcTS, identify of acid/base catalyst, and the formation of a sialyl-enzyme intermediate with an unmodified sialic acid.

The solution structure of TcUBP1 is determined and by nuclear magnetic resonance (NMR) chemical shift mapping its interactions with the GU-rich RNA element from one of its target mRNAs, TcSMUG is analyzed. A structural framework for further biochemical studies of TcUBP1 function is provided.

Observations that alkaline earth metal orgonometallics are efficient initiators for the anionic living polymerization of styrene and butadiene have led a number of reports of calcium, strontium, and barium complexes, includingbenzylic, acetylenic, and heterometallic 'ate' derivatives, as well as carbene adducts of the decamethylmetallocenes.

It is shown that Trypanosoma cruzi trans-sialidase (TcTS) operates through a double displacement mechanism involving the transient formation of a covalent sialyl-enzyme intermediate with Tyr342. The relay of charge required for the generation of the novel intermediate is likely a consequence of the structure of sialic acid.