Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

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Sustained release varnish containing chlorhexidine for prevention of Streptococcus mutans biofilm formation on voice prosthesis surface: an in vitro study

International Microbiology - In this study, we aimed to develop a novel, sustained release varnish (SRV) for voice prostheses (VP) releasing chlorhexidine (CHX), for the prevention of biofilm...     

Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl-CoA availability and increases plant polyphenol synthesis

In recent years microorganisms have been engineered towards synthesizing interesting plant polyphenols such as flavonoids and stilbenes from glucose. Currently, the low endogenous supply of malonyl-CoA, indispensable for plant polyphenol synthesis, impedes high product titers. Usually, limited malonyl-CoA availability during plant polyphenol production is avoided by supplementing fatty acid synthesis-inhibiting antibiotics such as cerulenin, which are known to increase the intracellular malonyl-CoA pool as a side effect. Motivated by the goal of microbial polyphenol synthesis being independent of such expensive additives, we used rational metabolic engineering approaches to modulate regulation of fatty acid synthesis and flux into the tricarboxylic acid cycle (TCA cycle) in Corynebacterium glutamicum strains capable of flavonoid and stilbene synthesis. Initial experiments showed that sole overexpression of genes coding for the native malonyl-CoA-forming acetyl-CoA carboxylase is not sufficient for increasing polyphenol production in C. glutamicum. Hence, the intracellular acetyl-CoA availability was also increased by reducing the flux into the TCA cycle through reduction of citrate synthase activity. In defined cultivation medium, the constructed C. glutamicum strains accumulated 24 mg·L ⁻¹ (0.088 mM) naringenin or 112 mg·L ⁻¹ (0.49 mM) resveratrol from glucose without supplementation of phenylpropanoid precursor molecules or any inhibitors of fatty acid synthesis.     

Ontogeny of odorant receptor gene expression in zebrafish,Danio rerio

We cloned three putative odorant receptor (OR) genes from the zebrafish to use as in situ hybridization probes to follow the temporal patterns of neurons expressing OR genes through a developmental progression from embryo (12 h postfertilization) to adult. The identification of these genes is supported by sequence homology to previously reported ORs and by the morphology and location of labeled cells in in situ hybridization experiments. Cells expressing OR mRNA were first observed in the olfactory placodes between 31 and 38 h after fertilization (fish reared at 26°C). Initially, only single cells were observed to hybridize the probe; the number of labeled cells increased throughout the remainder of embryogenesis and through postembryonic growth and morphogenesis of the olfactory organ. At all ages, the positively hybridizing cells were scattered throughout the olfactory epithelium but not in the nonsensory epithelium of the olfactory organ. © 1996 John Wiley & Sons, Inc.     

Polydactyly in the Strong's luxoid mouse is suppressed by limb deformity alleles

The study of limb development has provided insight into pattern formation during vertebrate embryogenesis. Genetic approaches offer powerful ways to identify the critical molecules and their pathways of action required to execute a complex morphogenetic program. We have applied genetic analysis to the process of limb development by studying two mouse mutants, limb deformity (Id) and Strong's luxoid (Ist). These mutations confer contrasting phenotypic alterations to the anteroposterior limb pattern. The six mutant Id alleles are fully recessive and result in oligosyndactyly of all four limbs. By contrast, the two mutant Ist alleles result in a mirror-image polydactylous limb phenotype inherited in a semidominant fashion. Morphological and molecular analysis of embryonic limbs has shown that the Id and Ist alleles affect the extent and distribution of two key signaling centers differentially: the apical ectodermal ridge and the zone of polarizing activity. Molecular characterization of the Id gene has defined a new family of evolutionarily conserved proteins termed the formins. The underlying molecular defect in the Ist mutation has not been identified; however, both loci are tightly linked on mouse chromosome 2, suggesting the possibility that they may be allelic. In this study, we have used genetic analysis to examine the epistatic and allelic relationships of Id and Ist. We observed that in + Id/Ist + double heterozygotes, a single mutant Id allele is able to suppress the semi-dominant polydactylous Ist limb phenotype. By segregating the Ist and Id loci in a backcross, we observed that these loci recombine and are separated by a genetic distance of approximately 6 cM. Therefore, while our observations demonstrate a genetic interaction between Id and Ist, it is probable that Id and Ist are not allelic. Instead, Ist and Id may be operating either in a linear or in a parallel (bypass) genetic pathway to affect the limb signaling centers. © 1996 Wiley-Liss, Inc.     

A role for the polyproline domain of p53 in its regulation by Mdm2

The p53 protein plays a key role in the cellular response to stress by inducing cell growth arrest or apoptosis. The polyproline region of p53 has been shown to be important for its growth suppression activity. p53 protein lacking the polyproline region has impaired apoptotic activity and altered specificity for certain apoptotic target genes. Here we describe the role of this region in the regulation of p53 by its inhibitor Mdm2. p53 lacking the polyproline region was identified to be more susceptible to inhibition by Mdm2. Furthermore, the absence of this region renders p53 more accessible to ubiquitination, nuclear export, and Mdm2-mediated degradation. This increased sensitivity to Mdm2 results from an enhanced affinity of Mdm2 toward p53 lacking the polyproline region. Our results provide a new explanation for the impaired growth suppression activity of p53 lacking this region. The polyproline region is proposed to be important in the modulation of the inhibitory effects of Mdm2 on p53 activities and stability.     

Strategy for membrane protein crystallization exemplified with OmpA and OmpX

The bacterial outer membrane proteins OmpA and OmpX were modified in such a manner that they yielded bulky crystals diffracting X-rays isotropically beyond 2 A resolution and permitting detailed structural analyses. The procedure involved semi-directed mutagenesis, mass production into inclusion bodies, and (re)naturation therefrom; it should be applicable for a broader range of membrane proteins.     

Life stages and reproductive components of the Marmorkrebs (marbled crayfish), the first parthenogenetic decapod crustacean

Recently, we briefly reported on the first case of parthenogenesis in the decapod Crustacea which was found in the Marmorkrebs or marbled crayfish, a cambarid species of unknown geographic origin and species identity. Curiously, this animal is known only from aquarium populations, where it explosively propagates. By means of light and electron microscopic techniques we have now investigated the reproductive components of this crayfish, using more than 100 specimens ranging from hatchling to repeatedly spawned adult. Additionally, we documented its principal life stages. Our results revealed that the external sexual characters and also the gonads of the marbled crayfish are purely female, making this fast-reproducing species a good model for investigating female reproductive features in crayfish. Testicular tissues, ovotestes, or male gonoducts, gonopores, or gonopods were never found, either in small juveniles or large adult specimens, confirming the parthenogenetic nature of this crayfish. Parthenogenesis may have arisen spontaneously or by interspecific hybridization since Wolbachia-like feminizing microorganisms were not found in the ovaries. The external sexual characters of the marbled crayfish are first recognized in Stage 4 juveniles and are structurally complete approximately 2 months after hatching in specimens of approximately 2 cm total length. In the same life stage the ovary is fully differentiated as well, although the oocytes are in previtellogenic and primary vitellogenic stages only. The architecture of the mature ovary and also the synchronous maturation of cohorts of primary vitellogenic oocytes by secondary vitellogenesis are in general agreement with data published on ovaries of bisexual crayfish. New results were obtained with respect to the muscular nature of the ovarian envelope and its extensive proliferation after the first spawning, the distribution of hemal sinuses in the ovarian envelope and in the interstitium around the oogenetic pouches, the high transport activity of the follicle cells, and the colonization of oogenetic pouches by previtellogenic oocytes that originate in the germaria. Investigation of the nuclei of oocytes in the germaria and oogenetic pouches revealed no signs of meiosis, as usually found in females of bisexual decapods, suggesting that parthenogenesis in the marbled crayfish might be an apomictic thelytoky. The detection of new rickettsial and coccidian infections in the ovary and further organs raises fears that the marbled crayfish might endanger native European species by transmission of pathogens once escaped into the wild.     

Role of zinc in regulating the levels of hepatic elements following nickel toxicity in rats

This study was designed to determine the protective effects of zinc on the hepatotoxicity induced by nickel in rats. Female Sprague-Dawley (SD) rats received either nickel sulfate alone in the dose of 800 mg/L nickel in drinking water, zinc sulfate alone in the dose of 227 mg/L zinc in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. The effects of different treatments were studied on activities of rat liver marker enzymes like alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferases (AST) and on the status of essential elements in rat liver. The study revealed a significant increase in the activities of enzymes ALP and ALT in rats subjected to nickel treatment. Interestingly, zinc supplementation to rats treated with nickel brought back the raised activities of these enzymes to within normal limits. Further, the levels of elements in liver that include zinc, copper, selenium, and potassium were found to be significantly suppressed following nickel treatment, whereas the levels of iron and sulfur were elevated. However, zinc treatment alone did not cause any appreciable change in the concentration of these elements. To the contrary, when zinc was given to nickel-treated rats, the concentrations of zinc, copper, potassium, and phosphorus were not significantly different from that of normal controls, whereas the levels of iron, selenium, and sulfur were improved in comparison to nickel-treated rats but were not within the normal limits. The present study concludes that zinc has the ability to maintain the levels of hepatic elements and has bearing in regulating the liver functions by maintaining the activities of marker enzymes in conditions of nickel toxicity.