The effect of wood-derived inhibitors on 2, 3-butanediol production by Klebsiella pneumoniae

Four potential inhibitors, hydroxymethylfurfural, furfural, syringaldehyde and vanillin, were assayed over a range of concentrations and times to simulate the amounts that might be expected to accumulate when the hydrolyzed water-soluble fraction from steam-treated aspenwood was added in a fed-batch mode to K. pneumoniae. Combinations of the individual materials resulted in a cumulative inhibitory effect. Prolonged incubation could alleviate some of the inhibition.     

Efficacy of Selective PDE4D Negative Allosteric Modulators in the Object Retrieval Task in Female Cynomolgus Monkeys (Macaca fascicularis)

Cyclic adenosine monophosphate (cAMP) signalling plays an important role in synaptic plasticity and information processing in the hippocampal and basal ganglia systems. The augmentation of cAMP signalling through the selective inhibition of phosphodiesterases represents a viable strategy to treat disorders associated with dysfunction of these circuits. The phosphodiesterase (PDE) type 4 inhibitor rolipram has shown significant pro-cognitive effects in neurological disease models, both in rodents and primates. However, competitive non-isoform selective PDE4 inhibitors have a low therapeutic index which has stalled their clinical development. Here, we demonstrate the pro-cognitive effects of selective negative allosteric modulators (NAMs) of PDE4D, D159687 and D159797 in female Cynomolgous macaques, in the object retrieval detour task. The efficacy displayed by these NAMs in a primate cognitive task which engages the corticostriatal circuitry, together with their suitable pharmacokinetic properties and safety profiles, suggests that clinical development of these allosteric modulators should be considered for the treatment of a variety of brain disorders associated with cognitive decline.     

Respiration in relation to ion uptake in the crayfish Austropotamobius pallipes (Lereboullet).

1. O2 uptake was determined for periods of 23-46 h in salt-depleted crayfish held in deionized water (DW) or Na-free media at 10 degrees C. These media were replaced by artificial lakewater media (ALW) containing 0-2-0-6 mM Na and O2 uptake was again determined for periods of 24-66 h. 2. During net ion uptake in ALW the metabolic rate was either elevated or depressed. Standard metabolism in ALW altered by amounts equivalent to 0-1 - 15-5% (mean 6-4 (15) +/- 4-4% S. D.) of the metabolic rate measured during salt-depletion. On three occasions the metabolic rate was elevated by 22-0 - 66-7%, but some of this increase may have been due to locomotor activity. 3. The calculated values for thermodynamic work involved in ion transport were 0-056 - 0-268 J/10 g. h at 10 degrees C, or 1-5 - 7-2% of the mean standard metabolic rate. Most of the observed changes in metabolic rate lie within the limits of experimental error (ca. +/- 7%). Hence the energetic cost of ion transport is too small for direct measurement in intact crayfish.     

A chemotaxonomic appraisal of the distribution of lipomannans within the genus Micrococcus

Abstract Bactericidal effects of polylysine on different bacterial species were measured. Marked differences in sensitivity were observed. Based on the concentration of polylysine required to reduce cell viability by 50%, Mycobacterium smegmatis and Mycobacterium tuberculosis were found to be the most sensitive and Escherichia coli the most resistant. In addition, two Gram-positive organisms, Staphylococcus epidermidis and Streptococcus salivarius exhibited significant differences in sensitivity which suggests that the relationship between sensitivity towards polylysine and bacterial cell type is not necessarily a function of the overall cell envelope structure. The high sensitivity of mycobacteria suggests the possible use of polylysine. or a conjugate of polylysine and another agent in anti-mycobacterial drug design.     

An inositol containing lipomannan from Propionibacterium freudenreichii

Abstract A lipoglycan has been extracted from cells of Propionibacterium freudenreichii by the standard procedures used to isolate lipoteichoic acids from Gram-positive bacteria. The polymer was purified by chromatography and shown to contain mannose, inositol, glycerol, fatty acids and phosphate. The presence of the components of phosphatidylinositol suggests the lipoglycan may be a mannan anchored to the membrane by a covalently linked phosphatidylinositol although alternative structures cannot be excluded.     

Different requirements for proteolytic processing of bone morphogenetic protein 5/6/7/8 ligands in Drosophila melanogaster

Bone morphogenetic proteins (BMPs) are synthesized as proproteins that undergo proteolytic processing by furin/subtilisin proprotein convertases to release the active ligand. Here we study processing of BMP5/6/7/8 proteins, including the Drosophila orthologs Glass Bottom Boat (Gbb) and Screw (Scw) and human BMP7. Gbb and Scw have three functional furin/subtilisin proprotein convertase cleavage sites; two between the prodomain and ligand domain, which we call the Main and Shadow sites, and one within the prodomain, which we call the Pro site. In Gbb each site can be cleaved independently, although efficient cleavage at the Shadow site requires cleavage at the Main site, and remarkably, none of the sites is essential for Gbb function. Rather, Gbb must be processed at either the Pro or Main site to produce a functional ligand. Like Gbb, the Pro and Main sites in Scw can be cleaved independently, but cleavage at the Shadow site is dependent on cleavage at the Main site. However, both Pro and Main sites are essential for Scw function. Thus, Gbb and Scw have different processing requirements. The BMP7 ligand rescues gbb mutants in Drosophila, but full-length BMP7 cannot, showing that functional differences in the prodomain limit the BMP7 activity in flies. Furthermore, unlike Gbb, cleavage-resistant BMP7, although non-functional in rescue assays, activates the downstream signaling cascade and thus retains some functionality. Our data show that cleavage requirements evolve rapidly, supporting the notion that changes in post-translational processing are used to create functional diversity between BMPs within and between species.     

Studies on the effectiveness of coroplast sticky traps for sampling stable flies (Diptera: Muscidae), including a comparison to Alsynite

Stable flies, Stomoxys calcitrans (L.) (Diptera: Muscidae), are a blood-feeding pest of cattle worldwide. A new trapping material, Coroplast, was compared with Alsynite sticky traps based on the number, sex, and parity of stable flies caught. Coroplast sticky traps caught more stable flies than Alsynite (trap catches of 2384 versus 753 on 15 traps), with this increase attributed to catching more males (1531 versus 532) and nulliparous females (817 versus 175); parous catches were similar (36 versus 46). The spectral reflectance of Alsynite and Coroplast sticky traps is reported. We also examine Coroplast traps in detail with respect to trap color. Although clean sheets of Alsynite had a higher solar reflectance than Coroplast (90 versus 82% at 450 nm), Coroplast with debris had a higher reflectance than debris-covered Alsynite (62 versus 30% at 450 nm). White Coroplast was most effective, followed by closely by gray. Black and blue were the least effective trapping colors.