Differential Effects of Estrogen and Progestin on Apolipoprotein B100 and B48 Kinetics in Postmenopausal Women

The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B‐containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo‐controlled, randomized, double‐blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4‐week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride‐rich lipoproteins (TRL), intermediate‐density lipoproteins (IDL) and low ‐density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100‐ and apo B48‐containing lipoproteins.     

Orientation and Feeding Responses of the Pollen Beetle, Meligethes aeneus, to Candytuft, Iberis amara

The pollen beetle, Meligethes aeneus, which is an important pest of oilseed rape, Brassica napus, and turnip rape, B. rapa var. campestris, does not oviposit in all species of the Brassicaceae. The relationship between M. aeneus and candytuft, Iberis amara (Brassicacae), was investigated as part of chemical ecological studies into the development of control methods employing non-host-derived repellents. In choice and nonchoice feeding tests, M. aeneus completely rejected I. amara. However, in a field experiment using traps baited with flowering racemes of I. amara and B. napus, M. aeneus was attracted to both species. Gas chromatographic (GC) and GC-electroantennogram (GC-EAG) analyses indicated that the profiles of the floral volatiles of the two species are different. At least 12 compounds among the I. amara floral volatiles were detected by the M. aeneus antenna, and, of these, hexanoic acid, (E)-4,8-dimethyl-1,3,7-nonatriene and alpha-cedrene were not found among B. napus flower volatiles. Since M. aeneus is stimulated by floral volatiles to approach I. amara, but rejects it near, or at, the plant surface, I. amara does not produce repellents that could be used to manipulate M. aeneus. However, it may contain feeding deterrent(s) that could be used in "push-pull" control techniques or in the development of resistant brassicaceous crops.     

Modeling of ultrasonic processing

Curing of fiber‐reinforced thermoset polymer composites requires an elevated temperature to accelerate the crosslinking reaction and also hydrostatic pressure to consolidate the part and suppress the formation of voids. These processing conditions can be provided by autoclaves of appropriate size, but these are expensive and sometimes difficult to schedule. Ultrasonic debulking followed by oven cure is an attractive alternative to autoclave cure. In this technique a movable “horn” driven at ultrasonic frequency is applied to the surface of the uncured part. This generates pressure and at the same time produces heating by viscoelastic dissipation. The part can be debulked to net shape and staged through the action of the ultrasound. There are a large enough number of experimental parameters in ultrasonic debulking and staging to make purely empirical process optimization difficult, and this paper outlines numerical simulation methods useful in understanding and developing the process. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1609–1615, 2004     

Effect of Visual Cues and a Mixture of Isothiocyanates on Trap Capture of Cabbage Seed Weevil, Ceutorhynchus assimilis

The effect of trap design, trap color, and a mixture of isothiocyanates on the capture of Ceutorhynchus assimilis (Paykull) was studied in a series of field experiments. Unbaited yellow water traps, a yellow sticky box trap, and a yellow sticky card trap, mounted vertically, or at 45° to the vertical with the yellow card facing upwards were effective for capturing seed weevils, but a horizontal yellow sticky card trap caught few. White, green, and black traps were unattractive. During migratory periods, trap catch could be enhanced two to four times with a lure consisting of a mixture of allyl, 3-butenyl, 4-pentenyl, and 2-phenylethyl isothiocyanates, but this bait did not attract in a trap with ineffective design. The sticky card trap, mounted at 45° to the vertical and baited with the isothiocyanate mixture, may be useful for monitoring movement of C. assimilis during migratory periods. However, during the colonization phase, lures of either a mixture of isothiocyanates or of allyl isothiocyanate alone were not attractive.     

Controlled dispersion of carbon nanospheres through surface functionalization

The physicochemical properties of cellulose-derived hollow, multiwalled carbon nanospheres (CNS) are investigated. Covalent functionalization with a 12-chain alkylamine and a short-chain di-alcohol is demonstrated. The resulting nanomaterials show increased and reversed solubility compared with the starting CNS and it is shown that the solubility can be tailored according to the choice of surface grafted moiety. Raman spectroscopy reveals similar features to those of other multiwalled carbon nanostructures. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy are used to characterize the CNS at each step in the reaction scheme, and thermogravimetric analysis is used to quantify the grafting. The grafting technique results in functionalization of 0.27% of total carbon atoms, estimated to correspond to about 5% of surface carbons.     

Influence of Visual Cues and Isothiocyanate Lures on Capture of the Pollen Beetle, Meligethes aeneus in Field Traps

The effect of trap design, trap color, and isothiocyanate (NCS) lures on the capture of the pollen beetle, Meligethes aeneus, was studied in field experiments. Unbaited yellow water and adhesive traps were equally attractive. A small sticky card trap with a yellow upper face, mounted at 45° to the vertical, was attractive throughout the year, but horizontal yellow cards were attractive only in spring, and vertical cards only in autumn. Yellow–green and white water traps were less attractive than yellow, while grass green, cream, and black were unattractive. M. aeneus was attracted equally to four alkanyl, three alkenyl, and to 2-phenylethyl isothiocyanate lures, when the release rates were in the range of 5–30 mg/day. Attraction to the most effective unbaited yellow traps was enhanced 1.7–3.3 times with the addition of a lure comprising a mixture of allyl, 3-butenyl, 4-pentenyl, and 2-phenylethyl NCS. Interactions were observed among the visual and odor cues. A yellow sticky card trap, baited with 2-phenylethyl NCS and mounted at 45° to the vertical, may be used throughout the year to monitor M. aeneus.     

实验用纳米纤维的电纺丝装置

近些年来,纳米工艺技术领域取得了飞速发展。纳米纤维已被广泛地应用于许多领域,例如,超细物料的过滤介质、保健与保护织物和生物医学等。     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Insights into the Genetic Variations of Human Cytochrome P450 2C9: Structural Analysis,Characterization and Comparison

Cytochromes P450 (CYP) are one of the major xenobiotic metabolizing enzymes with increasing importance in pharmacogenetics. The CYP2C9 enzyme is responsible for the metabolism of a wide range of clinical drugs. More than sixty genetic variations have been identified in CYP2C9 with many demonstrating reduced activity compared to the wild-type (WT) enzyme. The CYP2C9*8 allele is predominantly found in persons of African ancestry and results in altered clearance of several drug substrates of CYP2C9. The X-ray crystal structure of CYP2C9*8, which represents an amino acid variation from arginine to histidine at position 150 (R150H), was solved in complex with losartan. The overall conformation of the CYP2C9*8-losartan complex was similar to the previously solved complex with wild type (WT) protein, but it differs in the occupancy of losartan. One molecule of losartan was bound in the active site and another on the surface in an identical orientation to that observed in the WT complex. However, unlike the WT structure, the losartan in the access channel was not observed in the *8 complex. Furthermore, isothermal titration calorimetry studies illustrated weaker binding of losartan to *8 compared to WT. Interestingly, the CYP2C9*8 interaction with losartan was not as weak as the CYP2C9*3 variant, which showed up to three-fold weaker average dissociation constant compared to the WT. Taken together, the structural and solution characterization yields insights into the similarities and differences of losartan binding to CYP2C9 variants and provides a useful framework for probing the role of amino acid substitution and substrate dependent activity.