Sensory gating in bilayer amorphous carbon memristors.

Multi-state amorphous carbon-based memory devices have been developed that exhibit both bipolar and unipolar resistive switching behaviour. These modes of operation were implemented independently to access multiple resistance states, enabling higher memory density than conventional binary non-volatile memory technologies. The switching characteristics have been further utilised to study synaptic computational functions that could be implemented in artificial neural networks. Notably, paired-pulse inhibition (PPI) is observed at bio-realistic timescales (<100 ms). Devices displaying this rich synaptic behaviour could function as robust stand-alone synapse-inspired memory or be applied as filters for specialised neuromorphic circuits and sensors.

Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains postoperatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. METHODS: Mice with NCC-specific deletion of Ednrb were used to measure the neuronal density and neurotransmitter expression in ganglia. KEY RESULTS: At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared with het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nNOS and VIP is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. CONCLUSIONS & INFERENCES: We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.

Inhibition of cell death results in hyperganglionosis: implications for enteric nervous system development.

The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells (NCC) that delaminate from the neural tube and undergo extensive migration and proliferation in order to colonize the entire length of the gut and differentiate into many millions of neurons and glial cells. Although apoptotic programmed cell death is an essential physiological process during development of the majority of the vertebrate nervous system, apoptosis within early ENS development has not been comprehensively investigated. The aim of this study was to determine the presence and extent of apoptosis within the vagal NCC population that gives rise to most of the ENS in the chick embryo. We demonstrated that apoptotic cells, as shown by terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling and active caspase-3 immunoreactivity, are present within an electroporated green fluorescent protein (GFP) and human natural killer-1 (HNK-1) immunopositive NCC population migrating from the vagal region of the neural tube to the developing foregut. Inhibition of caspase activity in vagal NCC, by electroporation with a dominant-negative form of caspase-9, increased the number of vagal NCC available for ENS formation, as shown by 3-dimensional reconstruction of serial GFP or HNK-1 labelled sections, and resulted in hyperganglionosis within the proximal foregut, as shown by NADPH-diaphorase whole gut staining. These findings suggest that apoptotic cell death may be a normal process within the precursor pool of pre-enteric NCC that migrates to the gut, and as such it may play a role in the control of ENS formation.

Myocardial contractility in premature neonates with and without patent ductus arteriosus.

Controversy exists as to whether a hemodynamically significant left-to-right shunt due to a patent ductus arteriosus (PDA) affects ventricular contractility. Load-dependent indices such as ejection fraction and shortening fraction have traditionally been used to assess contractility, but the relationship between the rate-corrected velocity of fiber shortening (MVCFc) and wall stress may be more suitable, as it is a preload-independent, afterload-adjusted method of assessing ventricular contractility. Age-related differences have been established for these variables in normal adults and children and it has been recommended for use in the premature neonate. The study was performed to assess left ventricular contractility in premature neonates with a significant left-to-right shunt due to a PDA. Using echocardiography, we measured the relationship of MVCFc to stress at peak systole (SPS) in two groups of premature infants. Group 1 consisted of 15 controls (680-1495 g, 25-32 weeks' gestation), and Group 2 of 15 neonates with hemodynamically significant PDA (840-1635 g, 26-33 weeks' gestation). In both groups, MVCFc was linearly and inversely related to SPS ( p < 0.001). The regression equations were as follows: Group 1, MVCFc = -0.0153SPS + 1.70 ( R(2) = 0.68); and Group 2, MVCF = - 0.019SPS + 1.89 ( R(2) = 0.76). There was no significant difference in the relationship between the two groups, but their slopes were significantly steeper and had a higher Y-intercept than the relationship we previously reported for older children. This preliminary study establishes the normal MVCFc/SPS relationship in the premature neonate (25-33 weeks' gestation) and suggests that premature infants function at a higher resting contractile state than older children. A hemodynamically significant PDA has no effect on contractility. These data will be useful in assessing left ventricular contractility in premature neonates with other types of ventricular loading and noncardiac stress.

Misexpression of noggin leads to septal defects in the outflow tract of the chick heart.

BMP-2 and BMP-4 are known to be involved in the early events which specify the cardiac lineage. Their later patterns of expression in the developing mouse and chick heart, in the myocardium overlying the atrioventricular canal (AV) and outflow tract (OFT) cushions, also suggest that they may play a role in valvoseptal development. In this study, we have used a recombinant retrovirus expressing noggin to inhibit the function of BMP-2/4 in the developing chick heart. This procedure resulted in abnormal development of the OFT and the ventricular septum. A spectrum of abnormalities was seen ranging from common arterial trunk to double outlet right ventricle. In hearts infected with noggin virus, where the neural crest cells have been labelled, the results show that BMP-2/4 function is required for the migration of neural crest cells into the developing OFT to form the aortopulmonary septum. Prior to septation, misexpression of noggin also leads to a decrease in the number of proliferating mesenchymal cells within the proximal cushions of the outflow tract. These results suggest that BMP-2/4 function may mediate several key events during cardiac development.

Biosynthesis of the hemi- and monoterpene moieties of isoprenyl phenyl ethers from the liverwort Trichocolea tomentella.

The incorporation of 13C labelled glucose into trichocolein, deoxytomentellin, trans-phytol and stigmasterol has been studied in axenic cultures of the liverwort Trichocolea tomentella. Quantitative 13C NMR spectroscopic analysis of the resulting labelling patterns showed that the isoprene units of the hemi- and monoterpenoid moieties and the diterpene phytol are derived from the methylerythritol phosphate pathway, whereas the isoprene units of stigmasterol are built up via the mevalonic acid pathway. These results indicate the involvement of both IPP biosynthetic pathways in different cellular compartments. A new, hydroperoxy geranyl phenyl ether derivative is also described.

Conservation of early odontogenic signaling pathways in Aves.

Teeth have been missing from birds (Aves) for at least 60 million years. However, in the chick oral cavity a rudiment forms that resembles the lamina stage of the mammalian molar tooth germ. We have addressed the molecular basis for this secondary loss of tooth formation in Aves by analyzing in chick embryos the status of molecular pathways known to regulate mouse tooth development. Similar to the mouse dental lamina, expression of Fgf8, Pitx2, Barx1, and Pax9 defines a potential chick odontogenic region. However, the expression of three molecules involved in tooth initiation, Bmp4, Msx1, and Msx2, are absent from the presumptive chick dental lamina. In chick mandibles, exogenous bone morphogenetic protein (BMP) induces Msx expression and together with fibroblast growth factor promotes the development of Sonic hedgehog expressing epithelial structures. Distinct epithelial appendages also were induced when chick mandibular epithelium was recombined with a tissue source of BMPs and fibroblast growth factors, chick skin mesenchyme. These results show that, although latent, the early signaling pathways involved in odontogenesis remain inducible in Aves and suggest that loss of odontogenic Bmp4 expression may be responsible for the early arrest of tooth development in living birds.

Expression of chick Barx-1 and its differential regulation by FGF-8 and BMP signaling in the maxillary primordia.

The vertebrate face develops from a series of primordia surrounding the primitive mouth and is thought to be patterned by the differential expression of homeobox-containing genes. Here we describe the isolation of the chick homologue of the homeobox-containing gene, Barx-1, and show its expression in the developing facial primordia, stomach, and appendicular skeleton. In the maxillary primordia, mesenchymal expression of Barx-1 is complementary to that of Msx-1, which correlate with overlying epithelial expression of Fgf-8 and Bmp-4, respectively. We show that epithelial signals are required to maintain Barx-1 expression and that FGF-8 can substitute for the epithelium. By contrast, BMPs reduce Barx-1 expression and can antagonize FGF-8 signaling. This suggests that in vivo, FGF-8/BMP signaling may regulate Barx-1 gene expression. This provides evidence that the differential expression of FGF-8 and BMPs may determine homeobox-containing gene expression and hence patterning of the facial primordia.

Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia.

The facial primordia initially consist of buds of undifferentiated mesenchyme, which give rise to a variety of tissues including cartilage, muscle and nerve. These must be arranged in a precise spatial order for correct function. The signals that control facial outgrowth and patterning are largely unknown. The bone morphogenetic proteins Bmp-2 and Bmp-4 are expressed in discrete regions at the distal tips of the early facial primordia suggesting possible roles for BMP-2 and BMP-4 during chick facial development. We show that expression of Bmp-4 and Bmp-2 is correlated with the expression of Msx-1 and Msx-2 and that ectopic application of BMP-2 and BMP-4 can activate Msx-1 and Msx-2 gene expression in the developing facial primordia. We correlate this activation of gene expression with changes in skeletal development. For example, activation of Msx-1 gene expression across the distal tip of the mandibular primordium is associated with an extension of Fgf-4 expression in the epithelium and bifurcation of Meckel's cartilage. In the maxillary primordium, extension of the normal domain of Msx-1 gene expression is correlated with extended epithelial expression of shh and bifurcation of the palatine bone. We also show that application of BMP-2 can increase cell proliferation of the mandibular primordia. Our data suggest that BMP-2 and BMP-4 are part of a signalling cascade that controls outgrowth and patterning of the facial primordia.

Coiled-birefringent-fiber polarizers.

Experimental results are presented that illustrate the excellent reproducibility and thermal stability of fiber polarizers made by coiling highly birefringent bow-tie fibers. The effective extinction ratio of the polarizer when used in a fiber-optic gyroscope is shown to be 62 dB.

Birefringence and polarization mode-dispersion in spun single-mode fibers.

A theoretical and experimental analysis of the polarization properties of twisted single-mode fibers is presented. It is shown that whereas a conventionally twisted fiber possesses considerable optical rotation, a fiber which has a permanent twist imparted by spinning the preform during fiber drawing exhibits almost no polarization anisotropy. It is thus possible to virtually eliminate the commonly observed fiber linear birefringence. As a consequence, fibers made in this way are ideally suited for use in the Faraday-effect current transducer. It is further shown that a permanent twist of a few turns/meter effectively eliminates polarization mode-dispersion. The technique therefore appears attractive for enhancing the bandwidth of very long unrepeatered telecommunication links.

Induction of the mycelial form of Candida albicans by hydrolysates of peptides from seminal plasma.

Previous work led to the separation from seminal plasma of a peptide fraction which promoted a high rate of germination of blastospores of Candida albicans. It has now been shown that an acid hydrolysate of this material is also highly active. A minimal amino-acid mixture consisting of aspartic acid, lysine, histidine, threonine, proline and beta-alanine gave 90% germination in 4 h with 17 out of 28 strains examined. Glucose and inorganic phosphate were also required. Phosphate was not required for the activity of the original peptide fraction.

Changes in the cell surface of the dimorphic forms of Candida albicans by treatment with hydrolytic enzymes.

The release of acid phosphatase and polysaccharide-peptide complexes by hydrolytic enzymes from the surface of the blastospore and mycelial forms of Candida albicans has been examined in cells from 4 h and 18 h cultures and the results correlated with the appearance of the treated cells in the electron microscope. Treatment with dithiothreitol was necessary for the degradative action of the enzymes to occur. Material released by all the treatments used had a similar qualitative composition, but the proportions of mannan, glucan, peptide and acid phosphatase varied with different treatments and with the type of cell examined. I,3-beta-Glucanase was required for major changes in the cell wall to be effected, but a significant amount of material was released with a chitinase preparation containing some protease activity. Protoplasts were obtained from all types of cell using Cytophaga lytic enzyme L1 which had I,3-beta-glucanase and protease activity, but the purified I,3-beta-glucanase and protease prepared from Streptomyces violaceus cultures required the presence of a chitinase before protoplasts were released. The bonding association between the major components which comprise the cell wall, and the spatial distribution of these macromolecules, varies appreciably between the two dimorphic forms and with the age of the culture.