3-desoxyhex-2-enono-1,4-lactone aus D-hexofuran(osid)- urono-6,3-lactonen

The yield of 2-O-benzyl-3-deoxy-L-threo-hex-2-enono-1,4-lactone by reaction of 5-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranurono-6,3-lactone with sodium borohydride was improved by variation of the aprotic dipolar solvent and temperature. The general validity of this elimination—reduction reaction was ascertained by conversion of eleven other D-hexofuran(osid)urono-6,3-lactones into various 3-deoxy-hex-2-enono-1,4-lactones by treatment with sodium borohydride in hexamethyl phosphoric triamide.     

Relationship between set, development and activities of growth regulators in tomato fruits

The actions of plant regulators in set and development of fruitsare well known. However, the presence and function of endogenoushormones in parthenocarpic fruits have still not been sufficientlyinvestigated. A comparison between seeded and seedless fruitsmakes it possible to obtain a more accurate understanding ofsome relationships between growth regulators and stages of fruitdevelopment. Endogenous auxin and gibberellin activity levelsand some growth parameters (fresh and dry weight, cell numberand cell volume, DNA content) have been determined in tomatofruits (Lycopersicon esculentum Mill.) of the cultivar Venturaand of its isogenic parthenocarpic mutant. In both genotypes,auxin and gibberellin are present in the first week after anthesis,though at different concentrations and with different patterns.These two activities are involved in fruit setting. The simultaneousoccurrence of maximum auxin concentration and of the beginningof cell enlargement, in both genotypes, shows that the activitypresent at this time starts fruit development and possibly determinesthe size of the fruits. High auxin activity is observed only in seeded fruits 20–40days after anthesis, and it is probably synthesized by seeds.Gibberellin activity is present, corresponding to the changein fruit development from the mature green to pink stages. (Received February 16, 1978; )     

The high‐molecular‐weight kininogen Domain 5 is an intrinsically unstructured protein and its interaction with ferritin is metal mediated

High‐molecular‐weight kininogen domain 5 (HK5) is an angiogenic modulator that is capable of inhibiting endothelial cell proliferation, migration, adhesion, and tube formation. Ferritin can bind to a histidine–glycine–lysine‐rich region within HK5 and block its antiangiogenic effects. However, the molecular intricacies of this interaction are not well understood. Analysis of the structure of HK5 using circular dichroism and nuclear magnetic resonance [¹H, ¹⁵N]‐heteronuclear single quantum coherence determined that HK5 is an intrinsically unstructured protein, consistent with secondary structure predictions. Equilibrium binding studies using fluorescence anisotropy were used to study the interaction between ferritin and HK5. The interaction between the two proteins is mediated by metal ions such as Co²⁺, Cd²⁺, and Fe²⁺. This metal‐mediated interaction works independently of the loaded ferrihydrite core of ferritin and is demonstrated to be a surface interaction. Ferritin H and L bind to HK5 with similar affinity in the presence of metals. The ferritin interaction with HK5 is the first biological function shown to occur on the surface of ferritin using its surface‐bound metals.     

DPP6 Domains Responsible for Its Localization and Function

Dipeptidyl peptidase-like protein 6 (DPP6) is an auxiliary subunit of the Kv4 family of voltage-gated K⁺ channels known to enhance channel surface expression and potently accelerate their kinetics. DPP6 is a single transmembrane protein, which is structurally remarkable for its large extracellular domain. Included in this domain is a cysteine-rich motif, the function of which is unknown. Here we show that this cysteine-rich domain of DPP6 is required for its export from the ER and expression on the cell surface. Disulfide bridges formed at C349/C356 and C465/C468 of the cysteine-rich domain are necessary for the enhancement of Kv4.2 channel surface expression but not its interaction with Kv4.2 subunits. The short intracellular N-terminal and transmembrane domains of DPP6 associates with and accelerates the recovery from inactivation of Kv4.2, but the entire extracellular domain is necessary to enhance Kv4.2 surface expression and stabilization. Our findings show that the cysteine-rich domain of DPP6 plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER.     

A smart device inertial-sensing method for gait analysis

The purpose of this study was to establish and cross-validate a method for analyzing gait patterns determined by the center of mass (COM) through inertial sensors embedded in smart devices. The method employed an extended Kalman filter in conjunction with a quaternion rotation matrix approach to transform accelerations from the object onto the global frame. Derived by double integration, peak-to-trough changes in vertical COM position captured by a motion capture system, inertial measurement unit, and smart device were compared in terms of averaged and individual steps. The inter-rater reliability and levels of agreement for systems were discerned through intraclass correlation coefficients (ICC) and Bland–Altman plots. ICCs corresponding to inter-rater reliability were good-to-excellent for position data (ICCs,.80–.95) and acceleration data (ICCs,.54–.81). Levels of agreements were moderate for position data (LOA, 3.1–19.3%) and poor for acceleration data (LOA, 6.8%–17.8%). The Bland–Altman plots, however, revealed a small systematic error, in which peak-to-trough changes in vertical COM position were underestimated by 2.2 mm; the Kalman filter?s accuracy requires further investigation to minimize this oversight. More importantly, however, the study?s preliminary results indicate that the smart device allows for reliable COM measurements, opening up a cost-effective, user-friendly, and popular solution for remotely monitoring movement. The long-term impact of the smart device method on patient rehabilitation and therapy cannot be underestimated: not only could healthcare expenditures be curbed (smart devices being more affordable than today‘s motion sensors), but a more refined grasp of individual functioning, activity, and participation within everyday life could be attained.     

Transfusion medicine and safety

Advances in safety of blood transfusion in clinical practice principally relate to preventing transfusion-transmitted infections (TTI). Epidemiological studies of TTI have resulted in the development, standardization, and implementation of an expanding array of immunoassays employed worldwide in routine screening of blood donated by voluntary blood donors. Exclusion of infected blood and their donors has remarkably reduced the risk of transmitting HBV, HCV, HIV-1/2, and HTLV-I/II infections. Nucleic acid tests (NAT) using enzymatic amplification of viral gene sequences have augmented the risk reduction in “window period” infections that are undetectable by the serological tests. Improved viral safety of transfusion therapy has led us to recognize the risk of bacterial contamination, especially in platelet concentrates stored optimally at room temperature. Besides the current effort devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. The clinical effectiveness of the foregoing measures, international harmonization/standardization of practices and procedures, and continued hemovigilance portend safest possible safety in the clinical practice of blood transfusion.     

Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation

Recent studies have suggested that Rap1 and Rap2 small GTP-binding proteins are both expressed in human red blood cells (RBCs). In this work, we carefully examined the expression of Rap proteins in leukocytes- and platelets-depleted RBCs, whose purity was established on the basis of the selective expression of the beta2 subunit of the Na+/K+ -ATPase, as verified according to the recently proposed "beta-profiling test" [J.F. Hoffman, A. Wickrema, O. Potapova, M. Milanick, D.R. Yingst, Na pump isoforms in human erythroid progenitor cells and mature erythrocytes, Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 14572-14577]. In pure RBCs preparations, Rap2, but not Rap1 was detected immunologically. RT-PCR analysis of mRNA extracted from highly purified reticulocytes confirmed the expression of Rap2b, but not Rap2a, Rap2c, Rap1a or Rap1b. In RBCs, Rap2 was membrane-associated and was rapidly activated upon treatment with Ca2+/Ca2+ -ionophore. In addition, Rap2 segregated and was selectively enriched into microvesicles released by Ca2+ -activated RBCs, suggesting a possible role for this GTPase in membrane shedding.     

Comparison of HIV-1 Genotypic Resistance Test Interpretation Systems in Predicting Virological Outcomes Over Time

Background

Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford''s HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

Methodology/Principal Findings

Included were 3763 treatment-change episodes (TCEs) for which a HIV-1 genotype was available at the time of changing treatment with at least one follow-up viral load measurement. Genotypic susceptibility scores for the active regimens were calculated using scores defined by each interpretation system. Using logistic regression, we determined the association between the genotypic susceptibility score and proportion of TCEs having an undetectable viral load (<50 copies/ml) at 12 (8–16) weeks (2152 TCEs), 24 (16–32) weeks (2570 TCEs), and 48 (44–52) weeks (1083 TCEs). The Area under the ROC curve was calculated using a 10-fold cross-validation to compare the different interpretation systems regarding the sensitivity and specificity for predicting undetectable viral load. The mean genotypic susceptibility score of the systems was slightly smaller for HIVdb, with 1.92±1.17, compared to Rega and ANRS, with 2.22±1.09 and 2.23±1.05, respectively. However, similar odds ratio''s were found for the association between each-unit increase in genotypic susceptibility score and undetectable viral load at week 12; 1.6 [95% confidence interval 1.5–1.7] for HIVdb, 1.7 [1.5–1.8] for ANRS, and 1.7 [1.9–1.6] for Rega. Odds ratio''s increased over time, but remained comparable (odds ratio''s ranging between 1.9–2.1 at 24 weeks and 1.9–2.2 at 48 weeks). The Area under the curve of the ROC did not differ between the systems at all time points; p = 0.60 at week 12, p = 0.71 at week 24, and p = 0.97 at week 48.

Conclusions/Significance

Three commonly used HIV drug resistance interpretation systems ANRS, Rega and HIVdb predict virological response at 12, 24, and 48 weeks, after change of treatment to the same extent.     

Indole-3-acetic acid and rice coleoptile elongation under anoxia

To investigate the presence of a possible synergistic effect of IAA and anaerobiosis on rice coleoptile elongation, excised coleoptiles grown in aerobic and anaerobic conditions were tested and compared with intact seedling aerial parts for response to exogenous IAA and for levels of endogenous IAA. Excised coleoptiles were fed with³H-IAA to study aerobic and anaerobic IAA metabolism. Our results can be summarized as follows. (1) IAA and anaerobiosis have no synergistic effect on rice coleoptile elongation. (2) This behavior is due not to an inhibition of IAA uptake but probably to a reduced and different IAA metabolism in coleoptile grown in the absence of oxygen. (3) In anaerobic rice coleoptiles, the conversion to inactive conjugate (IAA-Asp) could be adopted as means of detoxification in the case of abnormally high and unutilized IAA levels. (4) The increase in IAA level found in coleoptiles of intact seedlings during anaerobic treatment could be due, as in the roots, to a translocation from the endosperm, in which the hormone is contained in a great quantity.