The effects of amino acid supplementation on muscular performance during resistance training overreaching

The purpose of this study was to examine the effects of amino acid supplementation on muscular strength, power, and high-intensity endurance during short-term resistance training overreaching. Seventeen resistance-trained men were randomly assigned to either an amino acid (AA) or placebo (P) group and underwent 4 weeks of total-body resistance training consisting of two 2-week phases of overreaching (phase 1: 3 x 8-12 repetitions maximum [RM], 8 exercises; phase 2: 5 x 3-5 RM, 5 exercises). Muscle strength, power, and high-intensity endurance were determined before (T1) and at the end of each training week (T2-T5). One repetition maximum squat and bench press decreased at T2 in P (5.2 and 3.4 kg, respectively) but not in AA, and significant increases in 1 RM squat and bench press were observed at T3-T5 in both groups. A decrease in the ballistic bench press peak power was observed at T3 in P but not AA. The fatigue index during the 20-repetition jump squat assessment did not change in the P group at T3 and T5 (fatigue index = 18.6 and 18.3%, respectively) whereas a trend for reduction was observed in the AA group (p = 0.06) at T3 (12.8%) but not T5 (15.2%; p = 0.12). These results indicate that the initial impact of high-volume resistance training overreaching reduces muscle strength and power, and it appears that these reductions are attenuated with amino acid supplementation. In addition, an initial high-volume, moderate-intensity phase of overreaching followed by a higher intensity, moderate-volume phase appears to be very effective for enhancing muscle strength in resistance-trained men.     

Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme

We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.     

Drugs for the control of parasitic diseases: current status and development in schistosomiasis

The morbidity caused by schistosomiasis has been controlled in China, Egypt and the Philippines mainly by the widespread use of the safe and efficacious drug praziquantel (PZQ), and by oxamniquin and PZQ in Brazil. To date, there is no evidence of development of clinically relevant resistance. Thanks to the commitment of national governments at the World Health Assembly in 2001, and the emergence of significant funding for control, it is predicted that there will soon be more widespread use of PZQ in sub-Saharan Africa, where morbidity due to schistosomiasis is most prevalent. There are currently no available alternative drugs to PZQ (with the possible exception of oxamniquin), although perhaps PZQ analogues could be developed. Artemether, used to control malaria, is effective against immature schistosomes, but is less effective against adult worms. The efficacy of myrrh, recently marketed as an antischistosomacide in Egypt, has not been independently confirmed.     

Photochemical transformations and bacterial utilization of high-molecular-weight dissolved organic carbon in a southern Louisiana tidal stream (Bayou Trepagnier)

UVirradiation of dissolved organic carbon (DOC) in the laboratory can producesmall, labile organic compounds utilizable by microbes, but few studies haveattempted to document this process in situ. ¹³Cnuclear magnetic resonance (NMR) was used to examine the bulk chemicalcomposition of natural and laboratory-irradiated high-molecular-weight DOC(HMW-DOC) from shaded (150 mol m^–2s^–1 average light in surface water) and open (1500mol m^–2 s^–1) field sitesoverone and a half years. ¹³C NMR revealed only small differences incarbon functional groups between laboratory irradiated and non-irradiatedHMW-DOC. However, bacterial protein productivity per cell (BPP) was enhanced innaturally irradiated samples of HMW-DOC in a field mesocosm experiment (p <0.05), suggesting that bacterial growth was enhanced by photochemicalproductionof labile DOC substrates. Absorbance characteristics such as spectral slope,absorbance at 350 nm, and the absorbance ratio 250nm/365 nm revealed that HMW-DOC was photoreactive,yetno differences in these values were found between samples irradiated with andwithout UV-B. In experiments conducted with simulated solar radiation in thelaboratory and with natural light in the field mesocosm experiment, UV-A(320–400 nm) and photosynthetically active radiation (PAR;400–700 nm) were more effective than UV-B (280–320nm) in HMW-DOC photolysis.     

Psychophysical study of image orientation perception

The experiment reported here investigates the perception of orientation of color photographic images. A collection of 1000 images (mix of professional photos and consumer snapshots) was used in this study. Each image was examined by at least five observers and shown at varying resolutions. At each resolution, observers were asked to indicate the image orientation, the level of confidence, and the cues they used to make the decision. The results show that for typical images, accuracy is close to 98% when using all available semantic cues from high-resolution images, and 84% when using only low-level vision features and coarse semantics from thumbnails. The accuracy by human observers suggests an upper bound for the performance of an automatic system. In addition, the use of a large, carefully chosen image set that spans the 'photo space' (in terms of occasions and subject matter) and extensive interaction with the human observers reveals cues used by humans at various image resolutions: sky and people are the most useful and reliable among a number of important semantic cues.     

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

Platelets roll and adhere in venules exposed to ischemia-reperfusion (I/R). This platelet-endothelial adhesion may influence leukocyte trafficking because platelet depletion decreases I/R-induced leukocyte emigration. The objectives of this study were 1) to assess the time course of platelet adhesion in the small bowel after I/R and 2) to determine the roles of endothelial and/or platelet P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) in this adhesion. The adhesion of fluorescently labeled platelets was monitored by intravital microscopy in postcapillary venules exposed to 45 min of ischemia and up to 8 h of reperfusion. Peak platelet adhesion was observed at 4 h of reperfusion. To assess the contributions of platelet and endothelial cell P-selectin, platelets from P-selectin-deficient and wild-type mice were infused into wild-type and P-selectin-deficient mice, respectively. Platelets deficient in P-selectin exhibited low levels of adhesion comparable to that in sham-treated animals. In the absence of endothelial P-selectin, platelet adhesion was reduced by 65%. Treatment with a blocking antibody against PSGL-1 reduced adhesion by 57%. These results indicate that I/R induces a time-dependent platelet-endothelial adhesion response in postcapillary venules via a mechanism that involves PSGL-1 and both platelet and endothelial P-selectin, with platelet P-selectin playing a greater role.     

Increased insulin-like growth factor-I gene expression precedes left ventricular cardiomyocyte hypertrophy in a rapidly-hypertrophying rat model system

Chronic pressure overload leads to an increase in the size, i.e. hypertrophy, of cardiomyocytes in the heart. However, the molecular mechanisms underlying this hypertrophy are not understood. Insulin-like growth factor-I (IGF-I) synthesized locally in the heart is known to be associated with the hypertrophic process. So far, however, cardiac IGF-I gene expression in the widely used rat model system has only been shown to be increased when the hypertrophy induced by pressure-overload was already established. Therefore, the question of whether IGF-I serves as an initiating or early-enhancing factor for the cardiac hypertrophy remains unanswered. Here, cardiac hypertension and hypertrophy were rapidly induced in the rat by complete constriction of the abdominal aorta between the origins of the renal arteries. Carotid arterial systolic blood pressure remained unchanged in sham rats but increased rapidly in the pressure-overloaded constricted rats with a sustained hypertension established by 3 days. Hypertrophy of left ventricular (LV) cardiomyocytes in constricted rats also occurred by 3 days. However, this hypertrophy was preceded by increases in LV IGF-I mRNA and protein which occurred within 1 day. These results support the hypothesis that cardiac-synthesized IGF-I is an initiating or early-enhancing factor for hypertrophy of LV cardiomyocytes.     

The Mre11 complex is required for ATM activation and the G2/M checkpoint

The maintenance of genome integrity requires a rapid and specific response to many types of DNA damage. The conserved and related PI3-like protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate signal transduction pathways in response to genomic insults, such as DNA double-strand breaks (DSBs). It is unclear which proteins recognize DSBs and activate these pathways, but the Mre11/Rad50/NBS1 complex has been suggested to act as a damage sensor. Here we show that infection with an adenovirus lacking the E4 region also induces a cellular DNA damage response, with activation of ATM and ATR. Wild-type virus blocks this signaling through degradation of the Mre11 complex by the viral E1b55K/E4orf6 proteins. Using these viral proteins, we show that the Mre11 complex is required for both ATM activation and the ATM-dependent G(2)/M checkpoint in response to DSBs. These results demonstrate that the Mre11 complex can function as a damage sensor upstream of ATM/ATR signaling in mammalian cells.