C-Nucleoside Analogues of Nicotinamide Mononucleotide (NMN)

Abstract

5-(β-D-Ribofuranosyl)nicotinamide (lie) and 6-(β-D-ribo-furanosyDpicolinamide (IId) and their corresponding o-isomers (III) were synthesized from ribonolactone. The C-nucleoside lie was further converted to its 5′-monophosphate Up which is isosteric to NMN Ip).     

Role of FSH and triiodothyronine in Sertoli cell development expressed by formation of connexin 43-based gap junctions

Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Connexin 43 (Cx43) is the most ubiquitous constitutive protein of gap junctions in the testis. This study evaluates the effects of the hyperstimulation of FSH and T3 during testicular maturation on Cx43 expression in the testis. The newborn, male Wistar rats were divided randomly into four experimental groups: FSH group-daily injections of FSH 7.5?IU/animal; T3 group-100?μg T3/kg body weight; FSH+T3 group-both substances; A control group-received vehicles in the same volume. Proliferating cell nuclear antigen immunohistochemistry and toluidine blue staining were used to determine the germ cell proliferation and degeneration. Cx43 immunolocalization was evaluated to find Cx43 maturational changes. Under FSH treatment, the proliferation rate was high so the total number of Sertoli cells increased with a low level of degeneration and lumen formation. T3 stimulation evoked a reduction in the proliferation rate and a decrease in Sertoli cell number but with intensive formation of lumen. T3+FSH inhibited the proliferation rate and stimulated lumen formation together with degeneration, which negatively influenced the number of germ cells in the seminiferous epithelium. We conclude that T3 action seems to be particularly connected with the maturation of Cx43 gap junctions. FSH stimulates maturation of Sertoli cell function, but this effect may take place regardless of the presence of Cx43-dependent intercellular communication. The hyperstimulation of both FSH and T3 damages Cx43 connections and hence evokes regressional changes in the seminiferous epithelium.     

DEVELOPMENT,FUNCTION, AND THE QUANTITATIVE GENETICS OF WING MELANIN PATTERN IN PIERIS BUTTERFLIES

Do genetic correlations among phenotypic characters reflect developmental organization or functional coadaptation of the characters? We test these hypotheses for the wing melanin pattern of Pieris occidentalis butterflies, by comparing estimated genetic correlations among wing melanin characters with a priori predictions of the developmental organization and the functional (thermoregulatory) organization of melanin pattern. There were significant broad-sense heritabilities and significant genetic correlations for most melanin characters. Matrix correlation tests revealed significant agreement between the observed genetic correlations and both developmental and functional predictions in most cases; this occurred even when the overlap between developmental and functional predictions was eliminated. These results suggest that both developmental organization and functional coadaptation among melanin characters influence the genetic correlation structure of melanin pattern in this species. These results have two important implications for the evolution of melanin pattern in P. occidentalis and other butterflies: 1) most phenotypic variation in pattern may reflect variation among, rather than within, sets of developmentally homologous wing melanin characters; and 2) in a changing selective environment, genetic correlations may retard the disruption of functionally coupled melanin characters, thus affecting the evolutionary response to selection.     

Metallo-beta-lactamases of Pseudomonas aeruginosa--a novel mechanism resistance to beta-lactam antibiotics

Since about twenty years, following the introduction into therapeutic of news beta-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems), a very significant number of new beta-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-beta-enzymes (IMP, VIM, SPM, GIM types) are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron) and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all beta-lactamases because they confer resistance to carbapenems and all the beta-lactams (with the exception of aztreonam) and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended--spectrum antibiotics (e.g. cephalosporins and carbapenems), and therefore care must be taken that these drugs are not used unnecessarily.     

Dioecy and the evolution of sex ratios in ants

Split sex ratios, when some colonies produce only male and others only female reproductives, is a common feature of social insects, especially ants. The most widely accepted explanation for split sex ratios was proposed by Boomsma and Grafen, and is driven by conflicts of interest among colonies that vary in relatedness. The predictions of the Boomsma–Grafen model have been confirmed in many cases, but contradicted in several others. We adapt a model for the evolution of dioecy in plants to make predictions about the evolution of split sex ratios in social insects. Reproductive specialization results from the instability of the evolutionarily stable strategy (ESS) sex ratio, and is independent of variation in relatedness. We test predictions of the model with data from a long-term study of harvester ants, and show that it correctly predicts the intermediate sex ratios we observe in our study species. The dioecy model provides a comprehensive framework for sex allocation that is based on the pay-offs to the colony via production of males and females, and is independent of the genetic variation among colonies. However, in populations where the conditions for the Boomsma–Grafen model hold, kin selection will still lead to an association between sex ratio and relatedness.     

The role of group I metabotropic glutamate receptors in memory consolidation and reconsolidation in the passive avoidance task in 1-day-old chicks

Although reconsolidation of memory after reminder does not seem to be the simple reiteration of the sequential stages occurring during memory consolidation, both phenomena probably employ similar mechanisms including activation of glutamate receptors and protein synthesis. It is known that group I metabotropic glutamate receptors (mGluRs) are involved in memory consolidation and modulation of protein synthesis. The aim of present study was to investigate the role of mGluR5 in memory consolidation and reconsolidation and to determine whether inhibition of these receptors may affect protein synthesis in these processes. The one-trial passive avoidance task on chicks was used as the experimental model of learning. Injection of the mGluR5 antagonist MPEP into a specific chick brain region IMM resulted in amnesia, provided the injection was made either shortly before or after training, or approximately 4 h after training. This amnesia was permanent, resembling the effects of protein synthesis inhibitors. MPEP injection immediately after reminder resulted in only a transient amnesia revealed 1h later. Increased expression of Zif/268 and c-Fos proteins 2 h after initial training was abolished bilaterally in chicks injected with MPEP. Injection of MPEP immediately after reminder did not inhibit c-Fos and Zif/268 expression, on the contrary, their expression was increased, specifically in left IMM and was similar to that observed after initial training. These results show that at least in the chick model mGluR5 play an important role in both consolidation and reconsolidation of memory but the mechanisms triggered by their activation in these processes differ. It is suggested that Ca(2+) signal derived from mGluR5 stimulation is necessary for complete memory consolidation, whereas during reconsolidation other mGluR5 triggered mechanisms of protein synthesis activation and regulation may be involved.     

Seed-expressed fluorescent proteins as versatile tools for easy (co)transformation and high-throughput functional genomics in Arabidopsis

We demonstrate that fluorescent proteins can be used as visual selection markers for the transformation of Arabidopsis thaliana by the floral dip method. Seed-specific expression of green fluorescent protein (GFP) variants, as well as DsRed, permits the identification of mature transformed seeds in a large background of untransformed seeds by fluorescence microscopy. In planta visualization of transformed seeds in siliques shows that susceptibility to floral dip transformation is limited to a small, defined window in flower development. In the competent stage, the random transformation of up to 25% of the seeds within a single silique may occur. The use of fluorescent proteins with different spectral characteristics allows a rapid identification and genetic analysis of seeds that have received multiple genes-of-interest in co-transformation experiments. The data reveal that co-transformation does not occur at random, since the co-transformed genes are integrated at a single genetic locus in approximately 70% of the cases. This genetic linkage of the co-transformed genes greatly simplifies metabolic pathway engineering by reverse genetics in Arabidopsis. Additional advantages of using visual selection instead of antibiotic resistance include a rapid identification of the effect of the T-DNA insertion or the transgene on seed development and/or germination. This technology, of tagging and identifying transformed seeds by fluorescence provides a novel high-throughput screening system with many potential applications in plant biotechnology.