Chrotacumines E and F,Two New Chromone‐Alkaloid Analogs from Dysoxylum acutangulum (Meliaceae) Leaves

A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F ( 1 and 2 , resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D‐NMR. Both of these alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100 μg/ml, respectively.     

Gender Disparities in the Presentation,Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2)

Background

Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients.

Methodology/Principal Findings

Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008–2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities.

Conclusions/Significance

Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.     

Role of AKAP79/150 Protein in β1-Adrenergic Receptor Trafficking and Signaling in Mammalian Cells

Protein kinase A-anchoring proteins (AKAPs) participate in the formation of macromolecular signaling complexes that include protein kinases, ion channels, effector enzymes, and G-protein-coupled receptors. We examined the role of AKAP79/150 (AKAP5) in trafficking and signaling of the β₁-adrenergic receptor (β₁-AR). shRNA-mediated down-regulation of AKAP5 in HEK-293 cells inhibited the recycling of the β₁-AR. Recycling of the β₁-AR in AKAP5 knockdown cells was rescued by shRNA-resistant AKAP5. However, truncated mutants of AKAP5 with deletions in the domains involved in membrane targeting or in binding to calcineurin or PKA failed to restore the recycling of the β₁-AR, indicating that full-length AKAP5 was required. Furthermore, recycling of the β₁-AR in rat neonatal cardiac myocytes was dependent on targeting the AKAP5-PKA complex to the C-terminal tail of the β₁-AR. To analyze the role of AKAP5 more directly, recycling of the β₁-AR was determined in ventricular myocytes from AKAP5^−/− mice. In AKAP5^−/− myocytes, the agonist-internalized β₁-AR did not recycle, except when full-length AKAP5 was reintroduced. These data indicate that AKAP5 exerted specific and profound effects on β₁-AR recycling in mammalian cells. Biochemical or real time FRET-based imaging of cyclic AMP revealed that deletion of AKAP5 sensitized the cardiac β₁-AR signaling pathway to isoproterenol. Moreover, isoproterenol-mediated increase in contraction rate, surface area, or expression of β-myosin heavy chains was significantly greater in AKAP5^−/− myocytes than in AKAP5^+/+ myocytes. These results indicate a significant role for the AKAP5 scaffold in signaling and trafficking of the β₁-AR in cardiac myocytes and mammalian cells.     

Persistence to Unrewarding Feeding Locations by Honeybee Foragers (Apis mellifera): the Effects of Experience,Resource Profitability and Season

Honeybee foragers that find a profitable food source quickly establish spatiotemporal memories, which allow them to return to this foraging site on subsequent days. The aim of this study was to investigate how the previous experience of honeybee foragers at a feeding location affects their persistence at that location once food is no longer available. We hypothesised that persistence would be greater to locations that were more rewarding (closer to the hive, higher concentration of sucrose solution), for which a bee had greater prior experience (0.5‐h vs. 2‐h training access), and at times of the year of lower nectar availability in the environment. We studied individually marked worker bees from four colonies trained to sucrose‐solution feeders. Our results support most of these predictions. Persistence, measured both in duration and number of visits, was greater to locations that previously offered sucrose solution of higher concentration (2 m vs. 1 m ) or were closer to the hive (20 m vs. 450 m). Persistence was also greater in bees that had longer access at the feeder before the syrup was terminated (2 h vs. 0.5 h). However, contrary to our prediction, persistence was not higher in the season of the lowest nectar availability in the environment in the study year. In summary, honeybees show considerable persistence at foraging sites that ceased providing rewards. The decision to abandon a foraging site depends on the profitability the forager experienced when the foraging site was still rewarding.     

Auswirkungen von abgestufter pflanzenschutzmittel‐intensität und unkrautbesatz auf laufkäferzönosen (coleoptera; carabidae) während einer fruchtfolgerotation unter den spezifischen Bedingungen des mitteldeutschen trockengebietes*

Die Untersuchungen fanden von 1991 bis 1995 auf einem 43 ha großen Schlag in Obhausen (Querfurter Platte) statt. Zielstellung der Untersuchungen war es, Auswirkungen abgestufter Pflanzenschutzintensitäten auf Laufkäfer zu erfassen. Dazu wurden auf dem Feld 6 Parzellen von 72 × 200 m Größe angelegt, von denen zwei als pflanzenschutzmittelfreie Kontrollflächen dienten. Auf zwei weiteren Teilstücken erfolgten intensive chemische Pflanzenschutzmaßnahmen. In den anderen beiden Varianten wurden im Sinne eines integrierten Pflanzenschutzes unter Beachtung von Schadschwellenwerten (Unkräuter, pilzliche und tierische Schaderreger) gezielte Pflanzenschutzmaßnahmen praktiziert. Zur Erfassung der Laufkäfer dienten Bodenfallen. Die Fruchtfolge begann 1991 mit Wintergerste, die aber wegen Trockenheit umgebrochen werden mußte. Die Intensitätsabstufungen des Pflanzenschutzmitteleinsatzes erfolgten ab 1992 im Mais und 1993 sowie 1994 in Winterweizen. Letztes Fruchtfolgeglied war 1995 Winterroggen, bei dem alle Parzellen wieder konventionell bewirtschaftet wurden. Im Mais kam es in den unbehandelten Kontrollen zu einer starken Verunkrautung. In diesen Parzellen erreichte die Fangsumme der Laufkäfer den 2,5 fachen Wert gegenüber den anderen Prüfgliedern. In den darauffolgenden Jahren, in den Winterweizenbeständen, lagen die höchsten Fangsummen wiederum in den Kontrollen vor, doch fielen die Differenzen zu den anderen Prüfgliedern nicht so groß aus. Die wenigsten Laufkäfer wurden in den Intensiv‐Varianten erfaßt. Die Bewirtschaftung nach dem Schadschwellenprinzip erbrachte wesentlich höhere Fangsummen. Während der Intensitätsabstufung besiedelten die Arten Calosoma auropunc‐tatum, Harpalus affinis, Pseudoophonus rufipes, Harpalus distinguendus, Poecilus punctulatus, Harpalus tardus sowie Harpalus zabroides überwiegend die Kontrollparzellen. Bei den abschließenden Untersuchungen im Winterroggen 1995 traf dies nur noch für Harpalus affinis zu. Ob für das Überwiegen dieser Arten in den Kontrollen der starke Unkrautbesatz im Jahre 1992 bzw. nachfolgend der Vorrat an Diasporen oder der völlige Verzicht auf Pflanzenschutzmittel ausschlaggebend war, konnte nicht eindeutig geklärt werden. Entgegen allen Erwartungen lag im Winterroggen die höchste Fangsumme der Laufkäfer in den ehemals intensiv behandelten Parzellen vor.

Ein Verzicht auf Pflanzenschutzmittel geht oft mit nicht mehr tolerierbaren Ertragsverlusten einher, wie z.B. im Mais 1992. Bei einem Einsatz von Pflanzenschutzmitteln nach Schadschwellenwerten entsprechend den Prinzipien eines integrierten Pflanzenschutzes sind langfristig keine negativen Effekte auf den Naturhaushalt zu erwarten.     

Sex- and age-dependent DNA methylation at the 17q12-q21 locus associated with childhood asthma

Chromosomal region 17q12-q21 is one of the best-replicated genome-wide association study (GWAS) hits and associated with childhood-onset asthma. However, the mechanism by which the genetic association is restricted to childhood-onset disease is unclear. During childhood, more boys than girls develop asthma. Therefore, we tested the hypothesis that the 17q12-q21 genetic association was sex-specific. Indeed, a TDT test showed that in the Saguenay-Lac-Saint-Jean familial collection, the 17q12-q21 association was significant among male, but not among female asthmatic subjects. We next hypothesized that the bias in the genetic association resulted from sex-specific and/or age-dependent DNA methylation at regulatory regions and determined the methylation profiles of five 17q12-q21 gene promoters using the bisulfite sequencing methylation assay. We identified a single regulatory region within the zona pellucida binding protein 2 (ZPBP2) gene, which showed statistically significant differences between males and females with respect to DNA methylation. DNA methylation also varied with age and was higher in adult males compared to boys. We have recently identified two functionally important polymorphisms, both within the ZPBP2 gene that influence expression levels of neighboring genes. Combined with the results of the present work, these data converge pointing to the same 5 kb region within the ZPBP2 gene as a critical region for both gene expression regulation and predisposition to asthma. Our data show that sex- and age-dependent DNA methylation may act as a modifier of genetic effects and influence the results of genetic association studies.     

The phase diagram of the Lennard-Jones fluid using temperature dependent interaction parameters

The forces of interaction between argon atoms can be described by the Lennard-Jones potential model. It is hypothesised that the use of temperature dependent interaction parameters, instead of using temperature independent interaction parameters, may lead to improvement in the prediction of the vapour–liquid coexistence curve. Published second virial coefficient data were used to fit a simple two-parameter temperature dependent model for the collision diameter and well depth. Vapour–liquid coexistence curve for argon was simulated in the NVT Gibbs ensemble Monte Carlo technique. The simulations were carried out using each of the temperature independent and temperature dependent parameters in the temperature range: 110–148 K. The critical temperature and density were determined using the Ising-scaling model. The results using temperature dependent parameters produce, overall, a more accurate phase diagram compared to the diagram generated using temperature independent interaction parameters. The root mean square deviation is reduced by 42.1% using temperature dependent interaction parameters. Also, there was no significant difference between the results obtained using temperature dependent interaction parameters and the highly accurate and computationally demanding phase diagrams based on three body contributions.     

Preparation and immunogenicity of conjugate based on hydrazine-treated lipopolysaccharide antigen of Vibrio cholerae O139

A glycoconjugate construct was based on attachment of V. cholerae O139 hydrazine-treated lipopolysaccharide (LPS) to carboxylated bovine serum albumin (CBSA) via its amino group. The immunological properties of the glycoconjugate were tested using BALB/c mice, injected subcutaneously without any adjuvant three times at 2?weeks interval. The immunogenicity of the conjugate was estimated by enzyme-linked immunosorbent assay, testing of anti-LPS IgG, IgM, and IgA antibodies. The conjugate elicited a statistically significant increase of LPS-specific IgG levels in mice (p?<?0.001). The specific anti-LPS IgG and IgA response after the second booster dose was significantly higher compared with reference and unconjugated detoxified LPS response. Antibodies elicited by the dLPS–CBSA conjugate were vibriocidal.