Effects of L-carnitine administration on VO2max and the aerobic-anaerobic threshold in normoxia and acute hypoxia

Seven healthy young male adults were subjected to a total of 56 tests to ascertain the effects of L-carnitine (L-C) and a placebo (P) on ventilation, O2 intake (VO2), CO2 output, heart rate, blood pressure and serum lactic acid, non-esterified fatty acid, glycerol and glucose during strenuous and aerobic/anaerobic threshold-level treadmill exercise. The tests were made in conditions of normoxia (O2 = 20.9%) and hypoxia (O2 = 13.0%, equivalent to 3,500 m above sea level). The only clear difference was in the respiratory quotient (RQ = 0.883, SD 0.025 vs 0.904, SD 0.035) after L-C and P administration respectively (P less than 0.01), under normal oxygenation and 0.861, SD 0.052 following L-C vs 0.926, SD 0.040 after P (P less than 0.01) in acute hypoxia at VO2 levels around the anaerobic threshold. The lower RQ values of the L-C-treated subjects during hypoxia indicate a lower rate of carbohydrate transformation.     

New Chinchillid Rodents (Hystricognathi: Caviomorpha) from Northern Chile and Bolivia Fill a 17-Million-Year Gap in the Pan-Chinchilline Fossil Record

Journal of Mammalian Evolution - The fossil record of chinchillid rodents (Hystricomorpha: Caviomorpha) begins in the early Miocene. However, nearly all remains have thus far been limited to the...     

Accuracy of single-plane fluoroscopy in determining relative position and orientation of total knee replacement components

The accuracy of estimating the relative pose between knee replacement components, in terms of clinical motion, is important in the study of knee joint kinematics. The objective of this study was to determine the accuracy of the single-plane fluoroscopy method in calculating the relative pose between the femoral component and the tibial component, along knee motion axes, while the components were in motion relative to one another. The kinematics of total knee replacement components were determined in vitro using two simultaneous methods: single-plane fluoroscopic shape matching and an optoelectronic motion tracking system. The largest mean differences in relative pose between the two methods for any testing condition were 2.1°, 0.3°, and 1.1° in extension, abduction, and internal rotation respectively, and 1.3, 0.9, and 1.9 mm in anterior, distal, and lateral translations, respectively. For the optimized position of the components during dynamic trials, the limits of agreement, between which 95% of differences can be expected to fall, were -2.9 to 4.5° in flexion, -0.9 to 1.5° in abduction, -2.4 to 2.1° in external rotation, -2.0 to 3.9 mm in anterior-posterior translation, -2.2 to 0.4mm in distal-proximal translation and -7.2 to 8.6mm in medial-lateral translation. These mean accuracy values and limits of agreement can be used to determine whether the shape-matching approach using single-plane fluoroscopic images is sufficiently accurate for an intended motion tracking application.     

Processed kaolin as an alternative insecticide against the European pear sucker, Cacopsylla pyri (L.)

Abstract:  Application of processed kaolin particle film (Surround^® WP; Engelhard Corporation, Iselin, NJ, USA) repels insects without lethal effects; hence side effects on beneficial arthropods are low. Processed kaolin may be an alternative to broad-spectrum insecticides used against European pear sucker, Cacopsylla pyri (L.), in organic and conventional pear production. A small-plot field trial was conducted in spring 2003 to assess this hypothesis. Multiple applications of processed kaolin during the first flying period of C. pyri significantly reduced the number of nymphs compared to the untreated control. Processed kaolin protected pear trees at least as good as the standard organic insecticide rotenone. Since the effects on the summer population could not be assessed in this small-plot trial due to the high mobility of the adult C. pyri , a large-plot trial was conducted in 2004. Thereby, the processed kaolin showed a very high efficacy and the population of C. pyri was kept under a damaging level over the whole season. At the end of June the population density of C. pyri in the processed kaolin treated area was lower than in the IPM treated plot. In conclusion, kaolin shows promise as an alternative control for C. pyri in organic and IPM orchards.     

1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors

In a search for novel DPP-IV inhibitors, 2-aminobenzo[a]quinolizines were identified as submicromolar HTS hits. Due to the difficult synthetic access to this compound class, 1,3-disubstituted 4-aminopiperidines were used as model compounds for optimization. The developed synthetic methodology and the SAR could be transferred to the 2-aminobenzo[a]quinolizine series, leading to highly active DPP-IV inhibitors.     

Mechanisms of HsSAS-6 assembly promoting centriole formation in human cells

SAS-6 proteins are thought to impart the ninefold symmetry of centrioles, but the mechanisms by which their assembly occurs within cells remain elusive. In this paper, we provide evidence that the N-terminal, coiled-coil, and C-terminal domains of HsSAS-6 are each required for procentriole formation in human cells. Moreover, the coiled coil is necessary and sufficient to mediate HsSAS-6 centrosomal targeting. High-resolution imaging reveals that GFP-tagged HsSAS-6 variants localize in a torus around the base of the parental centriole before S phase, perhaps indicative of an initial loading platform. Moreover, fluorescence recovery after photobleaching analysis demonstrates that HsSAS-6 is immobilized progressively at centrosomes during cell cycle progression. Using fluorescence correlation spectroscopy and three-dimensional stochastic optical reconstruction microscopy, we uncover that HsSAS-6 is present in the cytoplasm primarily as a homodimer and that its oligomerization into a ninefold symmetrical ring occurs at centrioles. Together, our findings lead us to propose a mechanism whereby HsSAS-6 homodimers are targeted to centrosomes where the local environment and high concentration of HsSAS-6 promote oligomerization, thus initiating procentriole formation.     

Short-term load bearing capacity of osteochondral autografts implanted by the mosaicplasty technique: an in vitro porcine model

Articular surface congruency and graft stability are considered essential factors in the success of osteochondral grafting; however, quantitative measures of short-term load bearing capacity of grafts implanted by the mosaicplasty technique have not been reported. The purpose of this study was to develop a live tissue in vitro model to examine short-term fixation strength of mosaicplasty autografts immediately after and 1 week following graft implantation. Cylindrical osteochondral autografts were implanted in vitro by the mosaicplasty technique on five pairs of porcine femoral condyles within one and a half hours of animal sacrifice. Immediately following the surgical procedure, graft push-in and pull-out strength tests as well as indentation tests to determine modulus of the surrounding cancellous bone were performed on half of the specimens from the distal femurs of each animal. The remaining specimens, matched for location in the contralateral leg, were incubated in culture medium for 7 days prior to performing the same set of mechanical tests. Averaged push-in and pull-out graft fixation strength decreased 44% from 135.7 to 75.5N over the 7-day period, while no change in modulus was detected in the surrounding cancellous bone. These in vitro results demonstrate a substantial deterioration of short-term fixation strength of mosaicplasty grafts from the immediate post-operative state. Such a reduction in short-term graft load bearing capacity may pose a threat to the surgically established articular surface congruency and blood vessels formed during the early stages of the healing response.     

Modification of different IgG1 antibodies via glutamine and lysine using bacterial and human tissue transglutaminase

The modification of proteins by chemical methods is well-established, however usually difficult to control. In this paper, we describe the posttranslational modification of different IgGs via the Lys or Gln side chains catalyzed by bacterial and human tissue transglutaminase (BTGase and TG2). For proof of concept, different IgG1s (commercial bovine IgG1, and L1CAM targeting chCE7 and chCE7 aglycosylated) were enzymatically functionalization with different fluorescent TGase substrates based on the CY3 analogue Dy547. The optimal reaction conditions were determined in order to assess the two enzymes. The efficiency of the enzymatic method was also compared with a standard chemical method employing a reactive NHS ester of Dy547. Three new TGase substrates were synthesized for this study including Lys-substrate 1 useful for BTGase and TG2 and two Gln-substrates tailor-made for BTGase (substrate 2) and TG2 (substrate 3). Of the two TGases tested, BTGase incorporated Lys-substrate 1 more efficiently than TG2. On the other hand, both enzymes reacted equally efficiently with the corresponding Gln-substrates 2 and 3. Reproducible labeling could be achieved in a broad concentration "window" of the substrates (up to 400 microM) without the risk of overlabeling of chCE7 or chCE7 aglycosylated. The biological activities of the functionalized antibodies were unaltered as shown by in vitro antigen affinity measurements and cell internalization experiments using confocal laser scanning microscopy. A maximum label-to-protein ratio of approximately 1 was achieved with chCE7 aglycosylated and substrate 1 using BTGase. It is important to recognize that the enzymatic activity of TGases enables the stable functionalization of proteins via the side chains of Gln, which is not possible by any chemical method available today. In addition, we could prove that the enzymatic modification of all antibodies occurred selectively at the heavy chain whereas the chemical method led to labeling of both the heavy and the light chains.