Metalloendoprotease inhibitors which block the differentiation of L6 myoblasts inhibit insulin degradation by the endogenous insulin-degrading enzyme

The cultured myoblasts of the rat skeletal muscle cell line L6 proliferate till confluency and then fuse to form myotubes and express a number of muscle-specific proteins. We had shown that this differentiation process is blocked by specific metalloendoprotease inhibitors. We now demonstrate that metabolizing L6 myoblasts and their cell extracts degrade insulin to acid-soluble fragments by a non-lysosomal pathway. About 90% of the insulin-degrading activity residues in the cytoplasm and is due to a 110-kDa enzyme known as the insulin-degrading enzyme. The same metalloendoprotease inhibitors that block the differentiation of L6 myoblasts also inhibit insulin degradation by the metabolizing L6 cells, their cell extracts, and the insulin-degrading enzyme immunoprecipitated from the cytosolic extracts by a monoclonal antibody. These results suggest that the insulin-degrading enzyme is the metalloendoprotease whose activity is required for the initiation of the morphological and biochemical differentiation of L6 myoblasts.     

Molecular dynamics simulation of the graphene–water interface: comparing water models

In this work, different water models (i.e. SPC/E, TIP3P, TIP4P/2005, TIP5P, SPC/Fw, TIP4P/2005f and SWM4_DP) are implemented to simulate water on neutral, negatively charged and positively charged graphene. In all cases ambient conditions are considered. Structural and dynamical properties for water are calculated to quantify the differences among various water models. The results show that SPC/E, TIP4P/2005, SPC/Fw, TIP4P/2005f and SWM4_DP water models yield a similar structure for interfacial water on graphene, whether it is neutral, negatively charged or positively charged. TIP5P is the model whose predictions for the structure of the interface deviate the most from those of the other models. Although qualitatively the results are for the most part similar, a large quantitative variation is observed among the dynamical properties predicted when various water models are implemented. Although experimental data are not available to discriminate the most/least accurate of the model predictions, our results could be useful for comparing results for interfacial water obtained implementing different models. Such critical comparison will benefit practical applications such as the development of energy-storage and water-desalination devices (e.g. electric double-layer capacitors), among others.     

A preliminary report on a bacteriological assay for compound 1080 (sodium monofluoroacetate)

A new, inexpensive, simple and rapid bioassay for sodium monofluoroacetate (compound 1080) was developed using bacteria. Two 1080-sensitive isolates ( Bacillus sp. DHW and Acinetobacter sp. DHW) from local aquatic environments were tested on different agar media using the disc diffusion technique. Both bacteria exhibited zones of growth inhibition surrounding the 1080 discs that were linearly proportional to the concentrations (log₁₀) of 1080. Preliminary studies indicate that this technique can be used for assaying 1080 in environmental and biological samples.     

The Binaural Masking-Level Difference of Mandarin Tone Detection and the Binaural Intelligibility-Level Difference of Mandarin Tone Recognition in the Presence of Speech-Spectrum Noise

Binaural hearing involves using information relating to the differences between the signals that arrive at the two ears, and it can make it easier to detect and recognize signals in a noisy environment. This phenomenon of binaural hearing is quantified in laboratory studies as the binaural masking-level difference (BMLD). Mandarin is one of the most commonly used languages, but there are no publication values of BMLD or BILD based on Mandarin tones. Therefore, this study investigated the BMLD and BILD of Mandarin tones. The BMLDs of Mandarin tone detection were measured based on the detection threshold differences for the four tones of the voiced vowels /i/ (i.e., /i1/, /i2/, /i3/, and /i4/) and /u/ (i.e., /u1/, /u2/, /u3/, and /u4/) in the presence of speech-spectrum noise when presented interaurally in phase (S₀N₀) and interaurally in antiphase (S_πN₀). The BILDs of Mandarin tone recognition in speech-spectrum noise were determined as the differences in the target-to-masker ratio (TMR) required for 50% correct tone recognitions between the S₀N₀ and S_πN₀ conditions. The detection thresholds for the four tones of /i/ and /u/ differed significantly (p<0.001) between the S₀N₀ and S_πN₀ conditions. The average detection thresholds of Mandarin tones were all lower in the S_πN₀ condition than in the S₀N₀ condition, and the BMLDs ranged from 7.3 to 11.5 dB. The TMR for 50% correct Mandarin tone recognitions differed significantly (p<0.001) between the S₀N₀ and S_πN₀ conditions, at –13.4 and –18.0 dB, respectively, with a mean BILD of 4.6 dB. The study showed that the thresholds of Mandarin tone detection and recognition in the presence of speech-spectrum noise are improved when phase inversion is applied to the target speech. The average BILDs of Mandarin tones are smaller than the average BMLDs of Mandarin tones.     

Preclinical Assessment of Adjunctive tPA and DNase for Peritoneal Dialysis Associated Peritonitis

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.     

Differential Gene Expression in the Liver of the African Lungfish,Protopterus annectens,after 6 Months of Aestivation in Air or 1 Day of Arousal from 6 Months of Aestivation

The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver of P. annectens.     

Lipids of Angiostrongylus cantonensis (Nematoda: Metastrongyloidea): a comparison between young adults and gravid worms

1. All major classes of lipids were found in the young adults in brain (22 days post-infection) and gravid Angiostrongylus cantonensis in lung of rats (34 days post-infection) comprising approximately 60% of phospholipids, 30% of neutral lipids and the rest, glycolipids. 2. The relative composition of phospholipids were quite similar between worms from the two different habitats, with phosphatidylcholine predominating. The glycolipid profiles were also similar. 3. More neutral lipids in the worms from brain existed as cholesterol and cholesterol esters than those from the lung. More than 20% of the fatty acids in these lipids of the brain were found as C10-C14 acids while oleic acid was the main component in the lung worm.