Genetic variation of growth and tree quality traits among 42 diverse genetic origins of Tectona grandis planted under humid tropical conditions in Sabah, East Malaysia

Forty-two different genetic origins of teak (Tectona grandis) comprising 26 open-pollinated families from a clonal seed orchard (CSO) were planted in a replicated trial under 2,500 mm of annual rainfall and no distinct dry season, in 1997, in Sabah, East Malaysia. The trees were measured or scored for various traits at 13, 35, 49, 61, 72, 85, 96, and 106 months after planting. Mortality rate, height (H), diameter at breast height (DBH), volume (V), and fork height (FH) varied strongly among populations and origins. The best population means after 106 months for growth H (21.1 m), DBH (21.1 cm), and V (278 dm³) were for the CSO families. Narrow sense heritabilities for the CSO families increased gradually with age but remained lower after 106 months for DBH (h ² = 0.24) and V (h ² = 0.34) than for H (h ² = 0.51) and FH (h ² = 0.56). Overall, the CSO families were also straighter, less forked, and grew more vertically than the native provenance and seed-derived sources. Such differences did not exist for flowering ability, and at 106 months, the great majority of the trees of the various origins had not yet entered the flowering stage. Overall, at 106 months, the phenotypic correlations between the various quantitative and qualitative traits were weak, except between straightness and bending with values higher than 0.50. These findings confirm the usefulness of CSO for teak improvement and demonstrate the beneficial influence of wet tropical conditions on traits of major economical importance for this species.     

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection

Background

The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.

Methods

A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints.

Results

The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm.

Conclusion

We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00100646","term_id":"NCT00100646"}}NCT00100646     

Identification of Three Novel Genetic Variants in the Melanocortin‐3 Receptor of Obese Children

The melanocortin‐3 receptor (MC3R), a G‐protein‐coupled receptor expressed in the hypothalamus, is a key component of the leptin‐melanocortin pathway that regulates energy homeostasis. It is suggested that an MC3R defect leads to an increased feed efficiency, by which nutrients are partitioned preferentially into fat. In this study, we hypothesized that early‐onset obesity could be induced by mutations in MC3R. To investigate this hypothesis, we screened the entire coding region of the MC3R gene for mutations in obese subjects. A total of 404 overweight and obese children and adolescents, 86 severely obese adults (BMI ≥40 kg/m²), and 150 normal‐weight control adults were included. Besides three synonymous coding variations in the MC3R gene (S69S, L95L, I226I), we were able to identify three novel heterozygous, nonsynonymous, coding mutations (N128S, V211I, L299V) in three unrelated obese children. None of these mutations were found in any of the control subjects. Functional studies assessing localization and signaling properties of the mutant receptors provided proof for impaired function of the L299V mutated receptor, whereas no conclusive evidence for functional impairment of the N128S and V211I mutated receptors could be established. First, these results provide supporting evidence for a role of the MC3R gene in the pathogenesis of obesity in a small subset of patients. Second, they show that caution is called for the interpretation of newly discovered mutations in MC3R.     

The distribution and activity of tachykinin-related peptides in the blood-feeding bug, Rhodnius prolixus

The invertebrate tachykinin-related peptides (TRPs) with the conserved C-terminal sequence FX1GX2Ramide shows sequence similarity to the vertebrate tachykinins after which they are named, and are hypothesized to be ancestrally related. In this study a polyclonal antiserum generated against a locust tachykinin (LomTK I), was used to demonstrate the presence and describe the distribution of LomTK-like immnoreactivity in the CNS and gut of Rhodnius prolixus. Reverse phase high performance liquid chromatography (RP-HPLC) was used in combination with a sensitive radioimmunoassay (RIA) to demonstrate picomolar amounts of immunoreactive material in the CNS, and femptomolar amounts associated with the hindgut. Furthermore, the results from CNS extracts separated by RP-HPLC, suggest that at least two tachykinin isoforms exist in R. prolixus. A hindgut contraction assay was developed to quantify the myotropic effects of selected LomTKs on R. prolixus hindgut contraction. Both LomTK I and II caused an increase in the frequency of hindgut contractions with EC50 values of 3.6x10(-8)M and 3.8x10(-8)M for LomTK I and II, respectively.     

The effects of time and temperature on flow cytometry enumerated live Cryptosporidium parvum oocysts

AIMS: Recoveries of spiked standard suspensions are used to evaluate method performance. For many applications, gamma-irradiated Cryptosporidium oocysts are appropriate. In contrast, methods that determine viability, such as Cryptosporidium cell culture, require the use of live oocysts. Oocyst standards are usually prepared at a flow cytometry laboratory for use at another laboratory, and thus the samples are shipped. The goal of this study was to evaluate the shipping and storage stability of flow cytometry enumerated live oocysts over time at three temperatures: 4 degrees C, room temperature and 37 degrees C. METHODS AND RESULTS: Replicate samples containing 100 live C. parvum oocysts were prepared by flow cytometry and stored at 4 degrees C, room temperature and 37 degrees C. These samples were counted at various time points. Significant oocyst losses were observed after storage for 1 day at 37 degrees C, 7 days at room temperature and 21 days at 4 degrees C. CONCLUSIONS: Live C. parvum oocysts internal standards should be used within 10 days of preparation, and stored and shipped at 4 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: When evaluating method performance with live oocysts, both the storage temperature and time are critical factors for obtaining reliable and accurate results.     

Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury

Ventilator-induced lung injury (VILI) is an inflammatory process that can be attenuated by lung protective ventilation strategies. Our objectives to further investigate the pathogenesis of ALI and VILI and the mechanism of lung protection in these syndromes were: 1) to determine if plasma measurements of soluble TNF receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and mortality in a small single center trial; 2) to test the predictive value of these markers and of TNF-alpha in a larger, broader group of patients with ALI; 3) to test the hypothesis that low tidal volume ventilation (LTVV) would be associated with a decrease in plasma levels of TNF-alpha, sTNFRI, and sTNFRII. In the single center study, sTNFRI and II levels were higher in patients at risk for and with ALI, but they did not predict the development of the syndrome. In the multicenter trial sTNFRI and II were strongly associated with mortality (OR 5.76/1 log10 increment in receptor level; 95% CI 2.63-12.6 and OR 2.58; 95% CI 1.05-6.31, respectively) and morbidity measured as fewer nonpulmonary organ failure-free and ventilator-free days. The LTVV strategy was associated with an attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV is associated with a specific decrease in sTNFRI levels. This suggests that one beneficial effect of LTVV may be to attenuate alveolar epithelial injury.     

Comparison of the backward overhead medicine ball throw to power production in college football players

The purpose of this study was to determine the relationship of the backward overhead medicine ball (BOMB) throw to power production in college football players. Forty National Collegiate Athletic Association Division II college football players were studied at the end of an 8-week off-season conditioning program for power output determined from a countermovement vertical jump on a force plate and for maximal distance in the standing BOMB throw. Although the reliability of the BOMB test was high (interclass correlation coefficient = 0.86), there was a significant learning effect across 3 trials (p < 0.01). Peak and average powers generated during the vertical jump correlated moderately but significantly with the best BOMB throw distance (r = 0.59 and 0.63, respectively). Considering power relative to body mass or lean body mass failed to produce significant correlations with BOMB throw distance (r = 0.27 and 0.28, respectively). Therefore, the BOMB throw may have limited potential as a predictor of total body explosive power in college football players.     

COPS--cis/trans peptide bond conformation prediction of amino acids on the basis of secondary structure information

SUMMARY: COPS predicts for all 20 naturally occurring amino acids whether the peptide bond in a protein is in cis or trans conformation. The algorithm is based only on secondary structure information of amino acid triplets without considering the amino acid sequence information. Conformation parameters are derived from solved 3D structures deposited in the PDB and led to propensities based on modified Chou-Fasman parameters. COPS analyses amino acid triplets taking only their respective secondary structure into consideration and upon application of a set of rules utilizing the conformation parameters, the N-terminal peptide bond conformation of the middle residue is predicted. COPS was tested on a random selection of protein datasets. AVAILABILITY: The COPS program and further information are freely available from the FMP website at http://www.fmp-berlin.de/nmr/cops CONTACT: labudde@fmp-berlin.de.     

Design, synthesis, and evaluation of proline based melanocortin receptor ligands

A series of proline based melanocortin ligands has been developed on the basis of initial piperazine leads by using a more conformationally rigid scaffold. A number of these novel ligands showed significant binding affinity for MC3 and MC4 receptors.