Improved training tolerance by supplementation with α-Keto acids in untrained young adults: a randomized, double blind, placebo-controlled trial

Background

Nutritional supplements designed to increase adenosine 5??-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation.

Methods

Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000?mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5?h (naso-duodenal tube) or 7?h (pellets) post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests.

Results

ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by ~50% after administration via proximal-release pellets (P?=?0.003) and naso-duodenal tube (P?=?0.001), but not after administration via distal-release pellets.

Conclusions

A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability.     

Characterization of l‐polylactide and l‐polylactide–polycaprolactone co‐polymer films for use in cheese‐packaging applications

Impact‐modified and unmodified l ‐polylactide and l ‐polylactide–polycaprolactone co‐polymer films were evaluated for their suitability as materials for cheese packaging. The polymers were in some cases compounded with nanoclays as a possible route to enhanced barrier properties and/or with cyclodextrin complexes designed to provide slow release of encapsulated antimicrobials for control of mould growth on packaged cheeses. The materials demonstrated complete biodegradation under controlled composting conditions and the extruded films had acceptable transparency. Moisture uptake by films and a decrease in polymer molecular weight with time of exposure to high humidity were identified as areas of concern, although the polymer stability experiments were undertaken at 25°C and stability at normal cheese storage temperatures (～4°C) is expected to be better. Nanoclay addition enhanced the thermal stability of the polymer but reduction of oxygen and water vapour permeability to target levels through incorporation of 5% w/w nanoclay was not achieved, possibly in part due to inadequate dispersion of the nanoclays in the chosen polymer matrices. On the positive side, a novel impact‐modified polylactide was developed that overcame problems with brittleness in unmodified l ‐polylactide and l ‐polylactide–polycaprolactone co‐polymer films, and tests indicated that a cyclodextrin‐encapsulated antimicrobial (allyl isothiocyanate) incorporated in l ‐polylactide–polycaprolactone co‐polymer films would be effective in controlling fungi on packaged cheeses. Migration of substances from the l ‐polylactide or l ‐polylactide–polycaprolactone films into cheese is not expected to be a problem. Copyright © 2005 John Wiley & Sons, Ltd.     

User‐Friendly Methylation of Aryl and Vinyl Halides and Pseudohalides with DABAL‐Me3

An extremely technically simple cross‐methylation of aryl and vinyl halides and pseudohalides using an air‐stable adduct of trimethylaluminium with a Pd(0) catalyst supported by commercially available biarylphosphines gives excellent yields of methylated products (mainly >95%). Reactions can be run with either 0.5 mol % catalyst or without requiring the exclusion of atmospheric oxygen or the drying of solvents in some cases. A wide variety of functional groups is tolerated including CN, OH, CO₂R, CHO and NO₂.     

Semi-Automatic Meter Reading

Meter reading in the electric utility Industry has been investigated from many different viewpoints. It is typically concluded that it is difficult to achieve more cost efficiency than the system widely used at present; manual reading at the uers location once a month. This paper will review the development of a new approach to more efficient meter reading.     

The effect of growth atmosphere on the ability of Listeria monocytogenes to survive exposure to acid,proteolytic enzymes and bile salts

Four isolates of Listeria monocytogenes from food, human and environmental sources were grown separately in broth (pH 6.0 at 8 degrees C) under atmospheres of air, 100% N(2), 40% CO(2):60% N(2) or 100% CO(2). Exponential and stationary phase cells were harvested to determine if growth atmosphere and growth phase influenced this pathogen's ability to survive exposure to an acid environment coupled with proteolytic enzymes, and the activity of bile salts. In general, isolates were more resistant to the acid environment than the bile salts environment and stationary phase cells were significantly more resistant to both environments than exponential phase cells. Irrespective of prior growth atmosphere, none of the isolates when in exponential phase remained detectable following full exposure to the acid environment (110 min at 37 degrees C) or the bile environment (3 h at 37 degrees C). With the exception of one isolate grown under the atmosphere of 40% CO(2):60% N(2), all isolates when in stationary phase were detectable following full exposure to the acid environment but death rates varied significantly. Stationary phase cells of all isolates grown under 40% CO(2):60% N(2) and 100% CO(2) were highly susceptible to the bile salts environment: cells were not detectable after a 2-min exposure whereas stationary phase cells grown under air or 100% N(2) were recovered following full exposure to the bile environment. Survival curves were characterised by a population decline of at least 3 log(10)/ml (from an initial level of 7 log(10) CFU/ml) in the first 15 min; thereafter a constant population number of approximately 4 log(10)/ml was maintained over the remaining exposure period. No survival was observed when stationary phase cells of L. monocytogenes FRRB 2538 grown in air and 100% N(2) were subjected to the acid environment followed by immediate exposure to the bile salts environment. The results showed that growth atmosphere and growth phase could influence survival of this pathogen against conditions that imitate the extremes of the most important nonspecific defence mechanisms against microbial infection: the acid environment of the stomach coupled with the activity of proteolytic enzymes, and the activity of bile salts in the small intestine.     

Climate change impact of biochar cook stoves in western Kenyan farm households: system dynamics model analysis

Cook stoves that produce biochar as well as heat for cooking could help mitigate indoor air pollution from cooking fires and could enhance local soils, while their potential reductions in carbon (C) emissions and increases in soil C sequestration could offer access to C market financing. We use system dynamics modeling to (i) investigate the climate change impact of prototype and refined biochar-producing pyrolytic cook stoves and improved combustion cook stoves in comparison to conventional cook stoves; (ii) assess the relative sensitivity of the stoves' climate change impacts to key parameters; and (iii) quantify the effects of different climate change impact accounting decisions. Simulated reductions in mean greenhouse gas (GHG) impact from a traditional, 3-stone cook stove baseline are 3.50 tCO(2)e/household/year for the improved combustion stove and 3.69-4.33 tCO(2)e/household/year for the pyrolytic stoves, of which biochar directly accounts for 26-42%. The magnitude of these reductions is about 2-5 times more sensitive to baseline wood fuel use and the fraction of nonrenewable biomass (fNRB) of off-farm wood that is used as fuel than to soil fertility improvement or stability of biochar. Improved cookstoves with higher wood demand are less sensitive to changes in baseline fuel use and rely on biochar for a greater proportion of their reductions.     

MicroRNA-449a Inhibits Triple Negative Breast Cancer by Disturbing DNA Repair and Chromatid Separation

Chromosomal instability (CIN) can be a driver of tumorigenesis but is also a promising therapeutic target for cancer associated with poor prognosis such as triple negative breast cancer (TNBC). The treatment of TNBC cells with defects in DNA repair genes with poly(ADP-ribose) polymerase inhibitor (PARPi) massively increases CIN, resulting in apoptosis. Here, we identified a previously unknown role of microRNA-449a in CIN. The transfection of TNBC cell lines HCC38, HCC1937 and HCC1395 with microRNA-449a mimics led to induced apoptosis, reduced cell proliferation, and reduced expression of genes in homology directed repair (HDR) in microarray analyses. EME1 was identified as a new target gene by immunoprecipitation and luciferase assays. The reduced expression of EME1 led to an increased frequency of ultrafine bridges, 53BP1 foci, and micronuclei. The induced expression of microRNA-449a elevated CIN beyond tolerable levels and induced apoptosis in TNBC cell lines by two different mechanisms: (I) promoting chromatid mis-segregation by targeting endonuclease EME1 and (II) inhibiting HDR by downregulating key players of the HDR network such as E2F3, BIRC5, BRCA2 and RAD51. The ectopic expression of microRNA-449a enhanced the toxic effect of PARPi in cells with pathogenic germline BRCA1 variants. The newly identified role makes microRNA-449a an interesting therapeutic target for TNBC.