Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1.

The purpose of the present study was to test the hypothesis that the exercise-induced increase in insulin-like growth factor binding protein (IGFBP)-1 is not always linked to a decrease in blood glucose level and to examine whether the decreasing levels of liver glycogen during exercise may be associated with the increase in IGFBP-1. Three groups of rats were submitted to a 70-min treadmill exercise. One group of rats was fed normally, and the two other groups had their food intake restricted by 50% (50% fast) the night before the experiment. One of these two 50% fasted groups of rats was infused (intravenously) with glucose throughout exercise to maintain euglycemia. Exercise in noninfused 50% fasted rats, compared with the normally fed rats, resulted in significantly lower blood glucose (minute 70) and insulin levels, significantly lower liver glycogen content, no change in IGF-I, and significantly higher increases in free fatty acid, glycerol, beta-hydroxybutyrate, and IGFBP-1. Maintenance of euglycemia during exercise in glucose-infused 50% fasted rats reduced to a large extent the decrease in insulin levels but only slightly attenuated the lipid response and the IGFBP-1 response seen in noninfused 50% fasted rats. Comparisons of all individual liver glycogen and IGFBP-1 values revealed that liver glycogen values were highly (P < 0.001) predictive of the IGFBP-1 response during exercise (R = 0.564). The present results indicate that the IGFBP-1 response during exercise is not always linked to a decrease in plasma glucose and suggest that the increase in IGFBP-1 during exercise may be related to the decrease in liver glycogen content.     

Assessing waste collectors' exposure to bioaerosols

Published studies on household wastecollectors' exposure to airborne biologicalagents (bioaerosols) do not indicate highexposures to these agents. However, thesestudies did not consider several factors. Theobjective of this study was to characterize theexposure of waste collectors to bioaerosols andto propose solutions to control exposures tothese agents.Personal exposures of waste collectors tobioaerosols (total bacteria, endotoxins andmolds) were measured for seven types ofcollection during the summer, which representsthe worst conditions. The effect of truckcleaning was also evaluated. Meanconcentrations of bacteria were all in theorder of 10³–10⁴ CFU/m³ of air. Theintervention threshold was exceeded forendotoxins during the collection of compostonce every two weeks in the country. Meanconcentrations varied from 8.5 to 100 endotoxinunits per cubic meter of air (EU/m³). Measuredmean concentrations of molds were between 8,300and 98,170 CFU/m³ of air. Also, the cleaningof an empty garbage truck does not improve thequality of the air. On the other hand, a dirtytruck is not a major source of bioaerosols.The sources of these bioaerosols are leachate,particularly if the waste in the truck is oforganic origin, as well as the garbage pailsthat contain this waste. Unnecessary exposuresto these sources should therefore be avoided. For bioaerosols, stringent personal hygienemeasures remain one of the best means ofprevention.     

Inhibition of the retrograde axonal transport of acetylcholinesterase by the anti-calmodulin agents amitriptyline and desipramine

The possible involvement of calmodulin in mediating the calcium requirement for retrograde axonal transport of acetylcholinesterase was studied in vitro in bullfrog spinal nerves, with the use of the calmodulin inhibitors amitriptyline and desipramine. When nerves were preincubated with 0.2 mM amitriptyline or desipramine for 5 h, and were then ligated and incubated for an additional 17-18 h in drug-containing medium, the accumulation of acetylcholinesterase distal to the ligature was significantly reduced as compared to contralateral control nerves maintained in drug-free medium. The identical degree of transport inhibition observed for both drugs is consistent with their similar anti-calmodulin activity.     

Effects of dietary carbohydrates on mutacin production and activity

Although mutacins (bacteriocins produced by Streptococcus mutans) were shown to be active in vivo, their ecological role in the oral cavity is still controversial. In the present paper, the effect of dietary carbohydrates, one of the ecological parameters which influences oral bacterial populations, on the activity and the production of mutacins from four S. mutans strains (C67-1, Ny257, Ny266 and T8) is described. Results obtained by the deferred antagonism test in solid media and by the mixed cultivation of the mutacinogenic strains with a sensitive indicator strain in liquid batch cultures, indicate that a minimal fermentable sugar concentration is needed for mutacin production. Among all the fermentable carbohydrates tested (fructose, glucose, lactose, mannitol and sucrose), none significantly affected the production and the activity of the four mutacinogenic strains used, in concentrations up to 5%. Although the results do not discount the possibility of mutacin inactivation in vivo, they indicate that they are not affected by dietary carbohydrates.     

A three-dimensional model of an anti-lysozyme antibody

The primary amino acid structure of the lysozyme-binding antibody, HyHEL-10, as determined by amino acid and nucleotide sequencing was utilized to construct a scale model of the Fv (variable region domain of immunoglobulin) using energy-minimized torsional angles of the McPC603 Fv as a prototype template. This model was in turn used as a template for generating a computer-built set of co-ordinates, which were subjected to a total of 600 steps of Adopted Basis Newton-Raphson energy minimizations using the program CHARMM. Only minimal shifts of the backbone (root-mean-square 0.76 A) were required to give an energetically stable structure with a favorable van der Waals' energy. Several notable features were evident from both the scale model and the energy-minimized computer model: (1) the shape of the antibody combining region is that of a very shallow concavity approximately 20 A X 25 A; (2) the concavity is acidic and non-hydrophobic and is bordered by hydrophobic segments; (3) the lower portion of the combining site is dominated by a cluster of tyrosine residues over the L3 and H2 areas; (4) a somatic mutation encoded by the J region of the heavy chain (JH) may contribute significantly to the complementarity of heavy chain H3 to the epitope on hen egg white lysozyme. In addition, the space-filling energy-minimized model revealed that residue 49L, a framework residue, was prominently exposed and accessible in the center of the combining-site concavity. The model suggests that variation in length of complementarity-determining regions may function not only to change directly the shape of the antibody combining site, but may also influence indirectly the nature of the antibody surface by changing the accessibility of residues not usually involved in antigen binding.     

Tyrosine phosphorylation of DEPTOR functions as a molecular switch to activate mTOR signaling

Metabolic dysfunction is a major driver of tumorigenesis. The serine/threonine kinase mechanistic target of rapamycin (mTOR) constitutes a key central regulator of metabolic pathways promoting cancer cell proliferation and survival. mTOR activity is regulated by metabolic sensors as well as by numerous factors comprising the phosphatase and tensin homolog/PI3K/AKT canonical pathway, which are often mutated in cancer. However, some cancers displaying constitutively active mTOR do not carry alterations within this canonical pathway, suggesting alternative modes of mTOR regulation. Since DEPTOR, an endogenous inhibitor of mTOR, was previously found to modulate both mTOR complexes 1 and 2, we investigated the different post-translational modification that could affect its inhibitory function. We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor–dependent manner. Altogether, our work reveals that phosphorylation of Tyr 289 of DEPTOR represents a novel molecular switch involved in the regulation of both mTOR complex 1 and mTOR complex 2.     

Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity.

Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to alpha-motoneuron activity than to motor cortical neuron activity, an idea that has important methodological implications.