The use of acetate in the metabolism of penicillium lilacinum thom

Summary The effects of adding sodium acetate to a sucrose-salts medium favorable for fat formation by Penicillium lilacinum on growth and metabolism of the fungus were studied. The presence of acetate suppressed the rate of growth during the early period of incubation, but this effect almost disappeared towards the end of the experiment. The acetate also suppressed the rate of accumulation of the carbohydrates, the nitrogenous compounds, and fats in the mycelial mats, during the logarithmic period of growth. By the end of the incubation period the amounts of these substances in the acetate-fed cultures were not much less than those of the controls. It is suggested that training the fungus on acetate may help it to utilize the acetate for fat synthesis.     

Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression

Background

Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations.

Methodology/Principal Findings

We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data.

Conclusions/Significance

The observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions.     

Prednisolone-Loaded PLGA Microspheres. <Emphasis Type="BoldItalic">In Vitro</Emphasis> Characterization and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Application in Adjuvant-Induced Arthritis in Mice

This study aimed at preparation of a sustained-release steroidal treatment for chronic inflammatory conditions, such as rheumatoid arthritis. To achieve such a goal, biodegradable poly-lactide-co-glycolide prednisolone-loaded microspheres were prepared using o/w emulsion solvent evaporation method. Formulation parameters were adjusted so as to optimize the microsphere characteristics. The prepared microspheres exhibited smooth and intact surfaces, with average size range not exceeding 65 μm. The encapsulation efficiency percent of most microsphere formulations fell within the range of 25–68%. Drug release from these microspheres took place over 4 weeks, with near-to-zero-order patterns. Two successful formulations were chosen for the treatment of unilateral arthritis, induced in mice using Freund's complete adjuvant (FCA). Inflammatory signs of adjuvant arthritis included severe swelling of the FCA-injected limbs, in addition to many histopathological lesions. These included inflammatory cell infiltration, synovial hyperplasia, cartilage, and bone erosion. Parenteral administration of the selected formulae dramatically reduced the swelling of the FCA-injected limbs. In addition, histological examination revealed that the microsphere treatment protocol efficiently protected cartilages and bones of mice, injected with FCA initial and booster doses, from erosion. These results could not be achieved by a single prednisolone dose of 5 mg/kg.     

Synthesis of new pyridothienopyrimidinone and pyridothienotriazolopyrimidine derivatives as pim-1 inhibitors

Three series of 2-arylpyridothieno[3,2-d]pyrimidin-4-ones 3a–j, pyridothienotriazolopyrimidines 6–8 and 4-imino-pyridothieno[3,2-d]pyrimidines 9a,b were prepared to improve the pim-1 inhibitory activity of the previously reported 2-arylpyridothieno[3,2-d]pyrimidin-4-ones. All the test compounds showed highly potent pim-1 inhibition with IC₅₀ in the range of 0.06–1.76?µM. No significant difference was detected between the pim-1 inhibitory activity of the 4-pyrimidinone and the 4-imino (=NH) or the cyclised triazolopyrimidine derivatives. The most active compounds were tested for their cytotoxic activity on MCF7 and HCT116 and showed potent activity on both the cell lines.     

A fluorometric method for measurement of oxygen radical-scavenging activity of water-soluble antioxidants

The relative activities of the antioxidants Trolox, ascorbic acid, uric acid, quercetin, and rutin, and the activities of total antioxidants in serum samples were determined using a fluorometric assay based on the dye 6-carboxyfluoroscein (6C-Fl) as a fluorescent indicator; 2,2'-azobis-2-amidinopropane hydrochloride (AAPH) as a peroxyl radical generator; 6-hydroxy-2,5,7, 8-tetramethyl-1-chroman-2-carboxylic acid (Trolox) as a calibrator; and phosphate buffer (pH 7.0) as a solvent. Incubation of 6C-Fl in 0. 075 M phosphate buffer, in the presence of AAPH at 37 degrees C, resulted in loss of its fluorescence signal at 520 nm with excitation at 495 nm. The antioxidants Trolox, ascorbic acid, and uric acid provided protection of the fluorescence of 6C-Fl, and the relative antioxidant activities, determined by the net protection area under curve technique, were found to be 1:0.4:1, respectively. Trolox and ascorbic acid were used to validate this assay. A linear correlation of the net protection value with the concentration of serum, Trolox, ascorbic acid, and uric acid was demonstrated. Quercetin and rutin were shown to have strong antioxidant activities, nearly 10 times those of vitamin C. This assay is simple, reliable, and suitable for automation to handle many samples and requires few microliters of serum samples.     

Fat synthesis from supplemented beet molasses by penicillium soppi zaleski in still and shaken cultures

Media composed of molasses alone did not support good growth nor high fat formation even when used at high concentrations. Peptone supplement as an external source of nitrogen accelerated both growth and fat formation in still as well as in shake cultures. But shaking mankedly suppressed growth and fat formation in media of molasses alone or molasses and peptone.Addition of corn steep liquor (CSL) to molasses gave rise in still cultures to rapid growth that was further accelerated by shaking. Effect of CSL supplement on fat formation, as measured by fat percentage in dry mycelium, was suppressive in still cultures. In shaken cultures, fat formation was promoted by the lowest concentration only. With higher concentrations of CSL, fat content increased but fat percentage in mycelium decreased.     

Effects of territorial intrusions on eavesdropping neighbors: communication networks in nightingales

Animal communication often occurs in communication networksin which multiple signalers and receivers are within signalingrange of each other. In such networks, individuals can obtaininformation on the quality and motivation of territorial neighborsby eavesdropping on their signaling interactions. In songbirds,extracting information from interactions involving neighborsis thought to be an important factor in the evolution of strategiesof territory defense. In a playback experiment with radio-taggednightingales Luscinia megarhynchos we here demonstrate thatterritorial males use their familiar neighbors' performancein a vocal interaction with an unfamiliar intruder as a standardfor their own response. Males were attracted by a vocal interactionbetween their neighbor and a simulated stranger and intrudedinto the neighbor's territory. The more intensely the neighborhad interacted with playback, the earlier the intrusions weremade, indicating that males eavesdropped on the vocal contestinvolving a neighbor. However, males never intruded when wehad simulated by a second playback that the intruder had retreatedand sang outside the neighbor's territory. These results suggestthat territorial males use their neighbors' singing behavioras an early warning system when territorial integrity is threatened.Simultaneous responses by neighboring males towards unfamiliarrivals are likely to be beneficial to the individuals in maintainingterritorial integrity.     

Reduced scale model qualification of 5-L and 250-ml bioreactors using multivariant visualization and Bayesian inferential methods

A novel method for the qualification of reduced scale models (RSMs) was illustrated using data from both a 250-ml advanced microscale bioreactor (ambr) and a 5-L bioreactor RSM for a 2,000-L manufacturing scale process using a CHO cell line to produce a recombinant monoclonal antibody. The example study showed how the method was used to identify process performance attributes and product quality attributes that capture important aspects of the RSM qualification process. The method uses two novel statistical approaches: multivariate dimension reduction and data visualization techniques, via partial least squares discriminant analysis (PLS-DA), and Bayesian multivariate linear modeling for inferential analysis. Bayesian multivariate linear modeling allows for individual probability distributions of the differences of the mean of each attribute for each scale, as well as joint probability statements on the differences of the means for multiple attributes. Depending on the results of this inferential procedure, PLS-DA is used to identify the process performance outputs at the different scales which have the greatest negative impact on the multivariate Bayesian joint probabilities. Experience with that particular process can then be leveraged to adjust operating conditions to minimize these differences, and then equivalence can be reassessed using the multivariate linear model.