OLIGOAGARS ELICIT A PHYSIOLOGICAL RESPONSE IN GRACILARIA CONFERTA (RHODOPHYTA)

Gracilaria conferta (Schousboe ex Montagne) J. et G. Feldmann responded with an oxidative burst and rapid increases in respiration and halogenating activity when agar, agarose, or the agarose degradation products neoagarotetraose and neoagarohexaose were added to the growth medium. In contrast, carrageenan, oligocarrageenans, neoagarobiose, l-galactose, d-galactose, and several other mono- and oligosaccharides did not have any effect. Sixfold increases in respiration were observed 3 min after addition of neoagarohexaose. The response could only be induced in species of the genera Gracilaria and Gracilariopsis. Neoagarohexaose also elicited a release of hydrogen peroxide in less than 15 min, resulting in an immediate increase in algal brominating activity. Bleached thallus tips appeared a few hours after the addition of neoagarohexaose. This effect was dependent on the release of hydrogen peroxide and exposure to light. Exposure to light and oligosaccharide elicitors increased the production of reactive oxygen species, which reached destructive concentrations when both mechanisms were simultaneously active. Concentrations of 0.1 to 3.3 μM agarose or agars were sufficient to trigger an increase in respiration, an oxidative burst response, and tip bleaching. However, higher concentrations of neoagarohexaose and neoagarotetraose were necessary to elicit the responses, indicating that the alga is more sensitive to oligoagars with degrees of biose-polymerization > 3. The extremely short reaction time and high specificity indicate that intermediates of agar degradation are recognized by Gracilaria as messengers when microbial degradation of its cell wall occurs. The physiological responses may represent the early stages of algal defense mechanisms involved in repression of pathogen ingress.     

Increased demand for NAD+ relative to ATP drives aerobic glycolysis

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Azide-resistant mutants in Acinetobacter calcoaceticus A2 are defective in protein secretion

Abstract Azide, an inhibitor of ATPase, and a specific inhibitor of protein export was used in order to select for protein secretion mutants in Acinetobacter calcoaceticus A2. Two such mutants were isolated that were azide-resistant and defective in the general protein transport system. The mutation also conferred additional phenotypic changes, including an inability to grow on minimal media or at 40°C. The existence of protein secretion mutants with a selectable phenotype may be useful for the genetic study of protein export.     

Attenuation of DNA-protein interactions associated with intrinsic, sequence-dependent DNA curvature.

Inherently curved DNA segments, associated with short runs of adenines, have been identified in many gene regulatory regions, yet their physiological significance remains unknown. The observations reported in this study indicate that intrinsically bent nucleic acid fragments are characterized by substantially attenuated affinities toward DNA-binding proteins involved in structural functions, such as H1 histone and protamine, as well as toward various DNA-modifying enzymes including ligases and exo- and endonucleases. Two mechanisms might be responsible for the altered binding properties. According to the first mechanism, the attenuated binding affinities and the bending represent two independent consequences of the unique structural parameters exhibited by A-tracts. Indeed, analysis of the degradation products obtained upon exposure of the curved sequences to various chemical nucleases points toward the narrowing of the DNA minor groove, a conformational modulation known to characterize A-tracts and to run along the axially-bent motifs, as a potential determinant of the observed binding attenuation. Alternatively, the conformational constraints which result from the stable bending might act to modulate the strength of DNA-protein interactions. Although the factor directly responsible for the altered binding affinities revealed by the bent sequences cannot as yet be conclusively resolved, it is proposed that a reiteration of this specific factor, being either an A-tract or a bend, in phase with the DNA helical repeat acts to amplify the modulation of the binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomic Deregulation of the E2F/Rb Pathway Leads to Activation of the Oncogene EZH2 in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm with extremely poor clinical outcomes and no approved targeted treatments. To elucidate the mechanisms responsible for driving the SCLC phenotype in hopes of revealing novel therapeutic targets, we studied copy number and methylation profiles of SCLC. We found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96% of the SCLC samples investigated and was strongly associated with increased expression of EZH2, an oncogene and core member of the polycomb repressive complex 2 (PRC2). Through its catalytic role in the PRC2 complex, EZH2 normally functions to epigenetically silence genes during development, however, it aberrantly silences genes in human cancers. We provide evidence to support that EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in vitro, and is associated with aberrant methylation profiles of PRC2 target genes indicative of a “stem-cell like” hypermethylator profile in SCLC tumours. Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a potential therapeutic target in clinical disease.     

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.     

Oxytocin and vasopressin in the rodent hippocampus

The role of the hippocampus in social memory and behavior is under intense investigation. Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. Oxt‐ and Avp‐expressing fibers are abundant in the hippocampus and receptors for both peptides are seen throughout the different subfields, suggesting that Oxt and Avp modulate hippocampal‐dependent processes. In this review, we first focus on the anatomical sources of Oxt and Avp input to the hippocampus and consider the distribution of their corresponding receptors in different hippocampal subfields and neuronal populations. We next discuss the behavioral outcomes related to social memory seen with perturbation of hippocampal Oxt and Avp signaling. Finally, we review Oxt and Avp modulatory mechanisms in the hippocampus that may underlie the behavioral roles for both peptides.