bluuebunny/crossref_metadata_2025 huggingface dataset:
The formation of the Baptistina family by catastrophic disruption: Porous versus non‐porous parent body
Authors: Jutzi Martin , Michel Patrick , Benz Willy , Richardson Derek C.
Published: February 2010

Abstract— In this paper, we present numerical simulations aimed at reproducing the Baptistina family based on its properties estimated by observations. A previous study by Bottke et al. (2007) indicated that this family is probably at the origin of the K/T impactor, is linked to the CM meteorites and was produced by the disruption of a parent body 170 km in size due to the head‐on impact of a projectile 60 km in size at 3 km s−1. This estimate was based on simulations of fragmentation of non‐porous materials, while the family was assumed to be of C taxonomic type, which is generally interpreted as being formed from a porous body. Using both a model of fragmentation of non‐porous materials, and a model that we developed recently for porous ones, we performed numerical simulations of disruptions aimed at reproducing this family and at analyzing the differences in the outcome between those two models.

Our results show that a reasonable match to the estimated size distribution of the real family is produced from the disruption of a porous parent body by the head‐on impact of a projectile 54 km in size at 3 km s−1. Thus, our simulations with a model consistent with the assumed dark type of the family requires a smaller projectile than previously estimated, but the difference remains small enough to not affect the proposed scenario of this family history.

We then find that the break‐up of a porous body leads to different outcomes than the disruption of a non‐porous one. The real properties of the Baptistina family still contain large uncertainties, and it remains possible that its formation did not involve the proposed impact conditions. However, the simulations presented here already show some range of outcomes and once the real properties are better constrained, it will be easy to check whether one of them provides a good match.
The impact origin of Eunomia and Themis families
Authors: Leliwa‐Kopystyński J. , Burcheli M. J. , Włdarczyk I.
Published: February 2010

Abstract— Criteria for finding asteroid families (Zappala et al. 1995) are applied to a large (205,770 member) data set of asteroid orbital elements. The cases of the Eunomia and Themis families are considered as examples. This is combined with the cratering criteria for catastrophic disruption of small bodies in the solar system (Leliwa‐Kopystyński et al. 2008). We find that the Eunomia parent body itself was not catastrophically disrupted in the family‐generating impact event; after impact, the current body contains as much as 70% of its primordial mass. However, by contrast with Eunomia, the present mass of 24 Themis is only about 21% of that of its primordial body. Limits are placed on the sizes of the impactors in both examples, and for the case of Eunomia, the radius of the just sub‐critical crater (which may be present on 15 Eunomia) is predicted as <58 km.
Asteroid photometric and polarimetric phase curves: Joint linear‐exponential modeling
Authors: Muinonen K. , Penttilä A. , Cellino A. , Belskaya I. N. , Delbò M. , Levasseur‐Regourd A. C. , Tedesco E. F.
Published: February 2010

Abstract—We present Markov‐Chain Monte‐Carlo methods (MCMC) for the derivation of empirical model parameters for photometric and polarimetric phase curves of asteroids. Here we model the two phase curves jointly at phase angles ≤25° using a linear‐exponential model, accounting for the opposition effect in disk‐integrated brightness and the negative branch in the degree of linear polarization. We apply the MCMC methods to V‐band phase curves of asteroids 419 Aurelia (taxonomic class F), 24 Themis (C), 1 Ceres (G), 20 Massalia (S), 55 Pandora (M), and 64 Angelina (E). We show that the photometric and polarimetric phase curves can be described using a common nonlinear parameter for the angular widths of the opposition effect and negative‐polarization branch, thus supporting the hypothesis of common physical mechanisms being responsible for the phenomena. Furthermore, incorporating polarimetric observations removes the indeterminacy of the opposition effect for 1 Ceres. We unveil a trend in the interrelation between the enhancement factor of the opposition effect and the angular width: the enhancement factor decreases with decreasing angular width. The minimum polarization and the polarimetric slope at the inversion angle show systematic trends when plotted against the angular width and the normalized photometric slope parameter. Our new approach allows improved analyses of possible similarities and differences among asteroidal surfaces.
Inhibition of serum angiotensin-converting enzyme in rabbits after intravenous administration of enalaprilat-loaded intact erythrocytes
Authors: Hamidi Mehrdad , Tajerzadeh Hosnieh , Dehpour Ahmad-Reza , Ejtemaee-Mehr Shahram
Published: February 2010

Encapsulation of drugs in intact erythrocytes, because of the profound characteristics of these natural microspheres, has gained considerable attention in recent years. In this study, the inhibition time courses of serum angiotensin-converting enzyme (ACE) activity after intravenous administration of enalaprilat encapsulated in intact erythrocytes was evaluated and compared with free drug, in a rabbit model. Three groups of animals each received free drug, drug-loaded erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined in each case using the synthetic substrate hippuryl-histidyl-leucine and quantitation of the hippuric acid released by a developed and validated HPLC method. The serum ACE inhibition profiles in the three groups showed that the encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a considerably longer time and in a more reproducible manner, than the free drug or sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as efficacious slow-release drug carriers for enalaprilat in circulation.
Cimetidine: antioxidant and metal-binding properties
Authors: Lambat Zaynab , Limson Janice L , Daya Santy
Published: February 2010

Cimetidine is one of the most potent H2 receptor antagonists for inhibiting excessive histamine-induced acid secretion and is currently used worldwide to treat peptic ulcers. In this study, levels of free radicals were assessed and the ability of cimetidine to act as an antioxidant was determined using nitroblue-tetrazolium assay and lipid peroxidation assays. Free radical generation in the brain is promoted by the presence of iron, as occurs in the Fenton reaction. The results show that cimetidine reduces the generation of superoxide anion formed in the nitroblue-tetrazolium assay. In addition, cimetidine (1 mm) is able to reduce the iron-induced rise in lipid peroxidation in rat brain homogenates. Electrochemistry, UV/Vis spectroscopy and HPLC experiments show metal-ligand interactions between cimetidine and transition metals. The results imply that cimetidine provides a neuroprotective effect by binding to iron and copper, thus making them unavailable for free radical production.
Modified microplex vector enhances transfection of cells in culture while maintaining tumour-selective gene delivery in-vivo
Authors: Dass Crispin R , Burton Mark A
Published: February 2010

A non-commercial liposome (dimethyl dioctadecyl ammonium bromide: dioleoyl phosphatidyl-ethanolamine) was compared with a commercial variety (Lipofectamine) for transfection of cultured rat adenocarcinoma cells and in an in-vivo kidney tumour model. Transfection of the cells in culture and in tumours in-vivo was variable with both types of liposomes. A high-dose microplex (lipoplex–microsphere) vector enhanced liposome-mediated transfection of cells in culture. When these high-dose microplexes were tested in-vivo, they were better than both microspherical and liposomal delivery modes in terms of transgene expression levels and the tumour-to-normal tissue ratio of gene delivery. Microplexes have been demonstrated to be capable of not only selective delivery of plasmids to solid tumours, but also of increasing transfection in cell culture, a finding that may be used in ex-vivo transfection studies. It is hypothesized that microspheres anchored the combination vector closer to the cultured cells, allowing attached liposomes to gain easier access into cells. In-vivo, microspheres permitted the microplexes to selectively deliver their genetic payload within the tumour tissue, from where the action of cationic liposomes on cellular membranes facilitated increased access of plasmids into the cytosol of target cells.
Characterisation and evaluation of novel surfactant bacterial anti-adherent coatings for endotracheal tubes designed for the prevention of ventilator-associated pneumonia
Authors: Jones David S , McMeel Shauna , Adair Colin G , Gorman Sean P
Published: February 2010

It is accepted that ventilator-associated pneumonia is a frequent cause of morbidity and mortality in intensive care patients. This study describes the physicochemical properties of novel surfactant coatings of the endotracheal tube and the resistance to microbial adherence of surfactant coated endotracheal tube polyvinylchloride (PVC). Organic solutions of surfactants containing a range of ratios of cholesterol and lecithin (0:100, 25:75, 50:50, 75:25, dissolved in dichloromethane) were prepared and coated onto endotracheal tube PVC using a multiple dip-coating process. Using modulated temperature differential scanning calorimetry it was confirmed that the binary surfactant systems existed as physical mixtures. The surface properties of both surfactant-coated and uncoated PVC., following treatment with either pooled human saliva or phosphate-buffered saline (PBS), were characterised using dynamic contact angle analysis. Following treatment with saliva, the contact angles of PVC decreased; however, those of the coated biomaterials were unaffected, indicating different rates and extents of macromolecular adsorption from saliva onto the coated and uncoated PVC. The advancing and receding contact angles of the surfactant-coated PVC were unaffected by sonication, thereby providing evidence of the durability of the coatings. The cell surface hydrophobicity and zeta potentials of isolates of Staphylococcus aureus and Pseudomonas aeruginosa, following treatment with either saliva or PBS, and their adherence to uncoated and surfactant-coated PVC (that had been pre-treated with saliva) were examined. Adherence of S. aureus and Ps. aeruginosa to surfactant-coated PVC at each successive time period (0.5, 1, 2, 4, 8 h) was significantly lower than to uncoated PVC., the extent of the reduction frequently exceeding 90 %. Interestingly, the microbial anti-adherent properties of the coatings were dependent on the lecithin content. Based on the impressive microbial anti-adherence properties and durability of the surfactant coating on PVC following dip coatings, it is proposed that these systems may usefully reduce the incidence of ventilator-associated pneumonia when employed as luminal coatings of the endotracheal tube.
Gene expression of CYP3A4, ABC-transporters (MDR1 and MRP1-MRP5) and hPXR in three different human colon carcinoma cell lines
Authors: Pfrunder Arabelle , Gutmann Heike , Beglinger Christoph , Drewe Jürgen
Published: February 2010

Colon carcinoma cell lines are used widely as screening models for intestinal absorption of drugs. However, the expression of important transport systems and of metabolic enzymes is not completely characterized yet. The expression and inducibility of multidrug resistance gene 1 (MDR1) and cytochrome P450 isoform 3A4 (CYP3A4) was investigated in Caco-2 parental, Caco-2 TC-7 (TC-7) and LS180 cell lines. In the same three cell lines, we investigated the expression of isoforms of the multidrug resistance associated protein family (MRP1–MRP5) and the human pregnane × receptor (hPXR), which may be important for MDR1 and CYP3A4 induction. Cells were treated with rifampicin or 1α, 25-dihydroxycholecalciferol (1,25(OH)2D3) for 72 h and the total RNA was extracted. Afterwards reverse transcription real-time polymerase chain reaction (TaqMan) assay was performed to determine the mRNA expression level. We have shown that in LS180 cells, MDR1 and CYP3A4 were inducible with both inducers. In Caco-2 parental and TC-7 cells, CYP3A4 was only inducible with 1,25(OH)2D3. Furthermore, differences were shown in gene expression of several transport proteins (MDR1 and MRP1–MRP5) and CYP3A4 in different human colon carcinoma derived cell lines. hPXR mRNA was expressed in all three cell lines but the amount of mRNA detected was significantly higher in LS180 cells than in Caco-2 and TC-7 cells. We concluded that LS180 cells were a suitable model to study MDR1 and CYP3A4 induction, but for drug transport studies Caco-2 parental and TC-7 cells would be preferred as the more physiological model.
Efficacy of repifermin (keratinocyte growth factor-2) against abnormalities in gastrointestinal mucosal transport in a murine model of colitis
Authors: Meerveld B Greenwood-Van , Venkova K , Connolly K
Published: February 2010

Human keratinocyte growth factor-2 (KGF-2) is a member of the fibroblast growth factor family that promotes healing of experimental small intestinal ulceration and colitis. The aim of this study was to determine whether repifermin, a truncated form of recombinant human KGF-2, reverses abnormalities in colonic mucosal transport in a murine model of dextran sulfate sodium (DSS)-induced colitis. Male Swiss-Webster mice were given 4% DSS in drinking water for 7 days and then normal drinking water for 3 days. Repifermin (5 mg kg−1, i.p.) or vehicle was administered daily for 7 days starting on Day 4 of DSS exposure. On Day 10, net ion transport was measured electrophysiologically in colonic mucosal sheets. Repifermin significantly reduced DSS-induced colonic inflammation measured by tissue myeloperoxidase activity. Concurrently, in colonic tissue taken from mice treated with repifermin, there was a normalization of basal potential difference and short circuit current, and an improvement in the secretory responses to stimulation of muscarinic and ganglionic cholinoceptors. In control mice, repifermin did not interact directly with colonic epithelial cells or intramural neurones to induce immediate changes in net electrogenic transport. The results suggest that repifermin therapy may improve the mucosal electrogenic transport that is impaired during colitis.
Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human β3-adrenoceptor
Authors: Ahmed Maruf , Hanaoka Yoko , Nagatomo Takafumi , Kiso Tatsuya , Kakita Takao , Kurose Hitoshi , Nagao Taku
Published: February 2010

β3-Adrenoceptor is the predominant β-adrenoceptor in adipocytes and has drawn much attention during the investigation for anti-obesity and antidiabetes therapeutics. Thirteen new compounds have been evaluated for their potencies and efficacies as β3-adrenoceptor agonists on human β3- adrenoceptor expressed in COS-7 and Chinese hamster ovary (CHO) cells using radio ligand binding assay and cyclic AMP (cAMP) accumulation assay. Phenoxypropanolamine derivatives, SWR-0334NA (([E)-[4-[5-[(3-phenoxy-2-hydroxypropyl)amino]-2-pentene−3-yl] phenoxy]acetic acid sodium salt), SWR-0335SA ((E)-[4-[5-[(3-phenoxy-2-hydroxypropyl)amino]-2-pentene−3-yl] phenoxy] acetic acid ethanedioic acid), SWR-0342SA (S-(Z)-[4-[[1-[2-[(2-hydroxy−3-phenoxypropyl)]amino]ethyl]-1-pro-penyl]phenoxy] acetic acid ethanedioic acid), SWR-0348SA-SITA ((E)-[4-[5-[(3-phenoxy-2-hydroxy-propyl)amino]-2-hexene−3-yl] phenoxy]acetic acid ethanedioic acid) and SWR-0361SA ((E)-N-methyl-[4-[5-[(3-phenoxy-2-hydroxypropyl)amino]-2-pentene−3-yl]phenoxy]acetoamide ethanedioic acid) showed higher agonistic activity for the β3-adrenoceptor. Among the compounds tested, SWR-0334NA exhibited full agonist activity (%Emax = 100.26) despite its lower binding affinity (pK1 = 6.11). Compounds SWR-0338SA((E)-[4-[5-[(2-phenyl-2-hydroxyethyl)amino]-2-pentene−3-yl]phenoxy]acetic acid ethanedioic acid), SWR-0339SA (S-(E)-[4-[5-[(3-phenoxy-2-hydroxypropyl)amino]-2-pentene−3-yl] phenoxy] acetic acid ethanedioic acid), SWR-0345HA ((E)-2-methyl−3-[4-[2-(2-phenyl-2-hydroxyethyl-amino)ethoxy] phenyl]-2-propenoic acid ethyl ester hydrochloride), SWR-0358SA ((E)-(2-methoxy-ethyl)-[4-[5-[(3-phenoxy-2-hydroxypropyl) amino]-2-pentene−3-yl]phenoxy]acetoamide ethanedioic acid) and SWR-0362SA ((E)-1-[[[4-[5-[(3-phenoxy-2-hydroxypropyl)amino]-2-pentene −3-yl]phenoxy]-acetyl]carbonyl]piperidine ethanedioic acid) had moderate agonistic activity and were phenethylamine and phenoxypropanolamine derivatives. Compounds SWR-0065HA ([4-[2-[3-[[(3,4-dihydro-4-oxo-[1,2,4]-triazino(4,5-a)indol)-lyl]oxy]-2-hydroxypropylamino]ethoxy]phenyl]acetic acid methyl ester hydrochloride), SWR-0098NA ((E)-[4-[3-[(2-phenyl-2-hydroxyethyl)amino]-1-butenyl] phenoxy]-acetic acid sodium salt) and SWR-0302HA ([4-[[4-[2-(3-chlorophenoxy-2-hydroxypropyl)amino]-E-2-butenyl]oxy]phenoxy]acetic acid hydrochloride) had very low binding affinity towards β3-adreno-ceptors and they did not induce cAMP accumulation. We concluded that compounds SWR-0334NA, SWR-0335SA, SWR-0342SA, SWR-0348SA-SITA and SWR-0361SA were potential agonists of human β3- adrenoceptor. Further investigation on their selectivity towards β3-adrenoceptor could be useful for the exploration of the physiological properties of the β3-adrenoceptor.
Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts
Authors: Yao Kozo , Ina Yasuhiro , Sonoda Rie , Nagashima Ken , Ohmori Kenji , Ohno Tetsuji
Published: February 2010

We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H2O2)-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H2O2 (600 μmol L−1) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H2O2 exposure. Benidipine at 1 nmol L−1 and nifedipine at 10 nmol L−1 decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L−1) significantly reduced the H2O2-induced myocardial damage. Nifedipine (10 nmol L−1) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H2O2. The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.
Behavioural evidence of agonist-like effect of isoteoline at 5-HT1B serotonergic receptors in mice
Authors: Zhelyazkova-Savova Maria D , Zhelyazkov Delcho K
Published: February 2010

Isoteoline is a compound of aporphine structure derived from the alkaloid glaucine. Previous studies with isoteoline have shown antagonistic activity at 5-HT2C serotonergic receptors. We have investigated whether isoteoline interacts with 5-HT1B receptors. An isolation-induced social behavioural deficit test in mice was used as a model of stimulation of these receptors. The deficit in the behaviour of isolated mice in this experimental procedure was reported to be sensitive to 5-HT1B-receptor stimulation, since agonists at these receptors are capable of reversing it. In our study, we used N-(3-trifluoromethylphenyl) piperazine (TFMPP) (2 mg kg−1) as a reference agonist at these receptor sites. TFMPP completely restored the normal behaviour of the isolated mice. Its effect was prevented by propranolol (4 mg kg−1), a β-adrenergic receptor antagonist with a high affinity for 5-HT1B receptors, which was inactive by itself. When isoteoline was given before TFMPP, it did not prevent the effect of the latter. Given alone at doses of 0.25, 1, 4 or 8 mg kg−1, isoteoline showed an effect of its own to normalize the behaviour of isolated mice. The effect of isoteoline (1 mg kg−1, i.p.) was antagonized by pretreatment with propranolol, indicating that it was mediated through stimulation of 5-HT1B receptors. Repeated treatment with isoteoline (1 mg kg−1, 2 × 3 days, i.p.) produced tolerance to its effect and significantly attenuated the effect of TFMPP, when animals were tested 16 h after the last injection. In conclusion, the results provided functional evidence of agonist-like activity of isoteoline at the 5-HT1B receptors.
Preformulation stability of Spantide II, a promising topical anti-inflammatory agent for the treatment of psoriasis and contact dermatitis
Authors: Kikwai Loice , Babu R J , Kanikkannan Narayanasamy , Singh Mandip
Published: February 2010

Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin-1 receptor (NKR-1) and blocks inflammation associated with substance P. The anti-inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N-methyl-2-pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high-performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40°C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable α-helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine–proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate–ethanol, ethanol–water, ethanol and N-methyl-2-pyrrolidone. The results of this study indicate that ethyl oleate–ethanol (1:1) and ethanol–water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II.
The mechanisms underlying the anti-aging activity of the Chinese prescription Kangen-karyu in hydrogen peroxide-induced human fibroblasts
Authors: Satoh Akiko , Yokozawa Takako , Kim Young Ae , Cho Eun Ju , Okamoto Takuya , Sei Yasuo
Published: February 2010

Our previous study showed that Kangen-karyu extract protected against cellular senescence by reducing oxidative damage through the inhibition of reactive oxygen species generation and regulation of the antioxidative status. Although these findings suggest that Kangen-karyu could delay the aging process, the mechanisms responsible for protection against aging have rarely been elucidated. Therefore, this study was focussed on the mechanisms responsible for the anti-aging activity of Kangen-karyu extract using hydrogen peroxide (H2O2)-induced human diploid fibroblasts, a well-established experimental model of cellular aging. Kangen-karyu extract exerted a protective effect against the morphological changes induced by H2O2 treatment and inhibited senescence-associated β-galactosidase activity. In addition, the beneficial effects of Kangen-karyu extract on cell viability and lifespan indicated that Kangen-karyu extract could delay the cellular aging process. The observation that Kangen-karyu extract prevented nuclear factor kappa B (NF-κB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-κB modulation and prevention of H2O2-induced overexpression of haem oxygenase-1 protein. Moreover, pretreatment with Kangen-karyu extract reduced overexpression of bax protein and prevented the mitochondrial membrane potential decline, suggesting that Kangen-karyu extract may protect mitochondria from mitochondrial oxidative stress and dysfunction. These findings indicate that Kangen-karyu is a promising potential anti-aging agent that may delay, or normalize, the aging process by virtue of its protective activity against oxidative stress-related conditions.
Novel selective cytotoxicity of wild sarsaparilla rhizome extract
Authors: Huang Y G , Li Q Z , Ivanochko G , Wang R
Published: February 2010

Among six fractions, including total extract and fractions of hexane, ethyl acetate, butanol, water and boiling water extracted and separated from wild sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in eliminating four different human cancer cell lines with cellular viability less than 6.8%. HRW exhibited the highest potency against human leukaemia cells with an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 ± 0.3 μg mL−1, which was 17.6-fold smaller than that against normal human umbilical vein endothelial cells (IC50, 58.0 ± 1.5 μg mL−1). For its rich natural resources, simple extraction procedure and high yield (3.2%), HRW has the potential to be developed as a selective anti-cancer nutraceutical or pharmaceutical natural health product with low side effects and high economical return.
The inhibition of paw oedema formation caused by the oil of Copaifera multijuga Hayne and its fractions
Authors: Veiga Valdir F , Zunino Luciano , Patitucci Maria Lúcia , Pinto Angelo C , Calixto João B
Published: February 2010

Two oils exuded from a Copaifera multijuga Hayne tree (Leguminosae-Caesalpinoideae), collected from the same plant, but in different periods of the year, and the hexanic, dichloromethanic and methanolic fractions of one of these oils were analysed by high-resolution gas chromatography (HRGC) and HRGC coupled with mass spectrometry (HRGC-MS). In addition, the in-vivo preliminary anti-oedematogenic actions of the oil and some fractions of it were assessed against carrageenan- and bradykinin-induced oedema formation in the rat paw. Twenty-seven sesquiterpenes and six diterpenes were identified, β-caryophyllene, α-copaene and copalic acid being the main components. The dichloromethanic and methanolic fractions obtained from C. multijuga oil given by the intraperitoneal route caused a significant inhibition of paw oedema caused by carrageenan with inhibition of 49 ± 13% and 64 ± 9 %, respectively. Likewise, dexamethasone (the positive control drug) also greatly inhibited carrageenan-induced paw oedema formation (60 ± 4% at 2 h). The hexanic fraction also significantly inhibited (50 ± 6%) the paw oedema formation caused by bradykinin. These results suggest the presence of still non-identified active terpene compounds in the oil of C. multijuga that exhibit anti-oedematogenic properties. Of note, the yield of these compounds and the pharmacological actions of the oil, exhibited great seasonal variations, a relevant aspect that should be carefully observed for the correct medicinal use of this plant by the population.
Patterns of Diversity in Marine Phytoplankton
Authors: Barton Andrew D. , Dutkiewicz Stephanie , Flierl Glenn , Bragg Jason , Follows Michael J.
Published: February 2010

Diversity Gradients

Latitudinal gradients in species abundance, with relatively few occurring at the poles and many at the equator, are well known for macroorganisms. It is a matter of controversy, fueled by a lack of observational data, whether such gradients also occur among microorganisms.

Barton
et al.

(p.
1509
, published online 25 February) have built on a global marine circulation model to predict the dynamics of phytoplankton populations. In silico, they obtain patterns of latitudinal gradation for plankton that are interspersed with hotspots of amplified diversity, which point to plausible natural explanations for the phenomenon that can be tested in the future by systematic metagenomic surveys.
Unicellular Cyanobacterial Distributions Broaden the Oceanic N
2
Fixation Domain
Authors: Moisander Pia H. , Beinart Roxanne A. , Hewson Ian , White Angelicque E. , Johnson Kenneth S. , Carlson Craig A. , Montoya Joseph P. , Zehr Jonathan P.
Published: February 2010

Oceanic Nitrogen Fixation

Nitrogen fixation in the oceans is important in sustaining global marine productivity and balances carbon dioxide export to the deep ocean. It was previously believed that marine nitrogen fixation was due to a single genus of filamentous cyanobacteria,
Trichodesmium
. The recent discovery of unicellular open-ocean cyanobacteria has raised the question of how they contribute to global ocean nitrogen fixation and how they compare in distribution and activity to
Trichodesmium
. Using data collected from the southwest Pacific Ocean,

Moisander
et al.

(p.
1512
, published online 25 February) show that the unicellular nitrogen-fixing cyanobacteria (UCYN-A and
Crocosphaera watsonii
) have distinct ecophysiologies and distinct oceanic distributions from each other, and from
Trichodesmium
. These data can be incorporated into models to retune estimates of the global rates of oceanic nitrogen fixation and carbon sequestration.
β2-Adrenergic Receptor Redistribution in Heart Failure Changes cAMP Compartmentation
Authors: Nikolaev Viacheslav O. , Moshkov Alexey , Lyon Alexander R. , Miragoli Michele , Novak Pavel , Paur Helen , Lohse Martin J. , Korchev Yuri E. , Harding Sian E. , Gorelik Julia
Published: February 2010

Heart Cell Signaling in 3D

A healthy heart relies on the proper transduction of cellular signals through the β1- and β2-adrenergic receptors (βARs), which are located on the surface of the heart's muscle cells (cardiomyocytes). The surface of these cells resembles a highly organized series of hills and valleys and it has been unclear whether this topography plays a role in the βAR signaling events that are critical to cell function.Nikolaevet al.(p.1653, published online 25 February; see Perspective byDorn) monitored the cyclic adenosine monophosphate (cAMP) signals generated by the βARs in living cardiomyocytes. In cells from healthy rats and from rats with heart failure, the β1ARs were localized across the entire cell surface. In contrast, the spatial localization of the β2ARs differed in healthy and failing cells. In healthy cardiomyocytes, the β2ARs resided exclusively within surface invaginations called transverse tubules, thereby producing spatially confined cAMP signals, whereas in failing cardiomyocytes, the β2ARs redistributed to other cell surface areas, thereby producing diffuse cAMP signals. Thus, changes in the spatial localization of β2AR-induced cAMP signaling may contribute to heart failure.
Arco Limited: Launch and Closure of a Ready Mix Cement Plant
Authors: Parikh Margie
Published: February 2010

Arco Limited was a Projects and Infrastructure-sector conglomerate. Some of its key officials believed that entering the Ready Mix Cement (RMC) could be beneficial for Arco and planned entry into the manufacturing of RMC through its subsidiary, EG Ltd. (EGL). A feasibility report was ordered in 2004 on the basis of preliminary market leads which included detailed survey reports. Kolkata was identified as one of the locations for the business where high growth potential was sensed. Projections were made for demand and cost components. Government-prescribed formalities associated with starting the business were identified. Two alternate locations for Kolkata were identified and one of these two was recommended. Cement was one critical component for the business but the company did not have its own source of cement. One strategic option recommended was to tie up with one of the cement companies on back end. Alternatively, since the conversion of potential demand into orders depended upon construction projects, a tie up with a construction company on the front end could also be possible. There was a delay of a year in commissioning the plant and thereafter a number of factors caused the projections to be revised. The senior General Manager rejected and returned the revisions in the estimates apparently because of the managerial failure to foresee the market realities. After a few months' operations and losses, EGL closed down the RMC operations and rented it out because "it was actually a stupid decision." This case deals with challenges in decision making in uncertain environments.
Effect of in-water oxygen prebreathing at different depths on decompression-induced bubble formation and platelet activation
Authors: Bosco Gerardo , Yang Zhong-jin , Di Tano Guglielmo , Camporesi Enrico M. , Faralli Fabio , Savini Fabio , Landolfi Angelo , Doria Christian , Fanò Giorgio
Published: February 2010

Effect of in-water oxygen prebreathing at different depths on decompression-induced bubble formation and platelet activation in scuba divers was evaluated. Six volunteers participated in four diving protocols, with 2 wk of recovery between dives. On dive 1, before diving, all divers breathed normally for 20 min at the surface of the sea (Air). On dive 2, before diving, all divers breathed 100% oxygen for 20 min at the surface of the sea [normobaric oxygenation (NBO)]. On dive 3, before diving, all divers breathed 100% O2 for 20 min at 6 m of seawater [msw; hyperbaric oxygenation (HBO) 1.6 atmospheres absolute (ATA)]. On dive 4, before diving, all divers breathed 100% O2 for 20 min at 12 msw (HBO 2.2 ATA). Then they dove to 30 msw (4 ATA) for 20 min breathing air from scuba. After each dive, blood samples were collected as soon as the divers surfaced. Bubbles were measured at 20 and 50 min after decompression and converted to bubble count estimate (BCE) and numeric bubble grade (NBG). BCE and NBG were significantly lower in NBO than in Air [0.142 ± 0.034 vs. 0.191 ± 0.066 ( P < 0.05) and 1.61 ± 0.25 vs. 1.89 ± 0.31 ( P < 0.05), respectively] at 20 min, but not at 50 min. HBO at 1.6 ATA and 2.2 ATA has a similar significant effect of reducing BCE and NBG. BCE was 0.067 ± 0.026 and 0.040 ± 0.018 at 20 min and 0.030 ± 0.022 and 0.020 ± 0.020 at 50 min. NBG was 1.11 ± 0.17 and 0.92 ± 0.16 at 20 min and 0.83 ± 0.18 and 0.75 ± 0.16 at 50 min. Prebreathing NBO and HBO significantly alleviated decompression-induced platelet activation. Activation of CD62p was 3.0 ± 0.4, 13.5 ± 1.3, 10.7 ± 0.9, 4.5 ± 0.7, and 7.6 ± 0.8% for baseline, Air, NBO, HBO at 1.6 ATA, and HBO at 2.2 ATA, respectively. The data show that prebreathing oxygen, more effective with HBO than NBO, decreases air bubbles and platelet activation and, therefore, may be beneficial in reducing the development of decompression sickness.
Exercise training prevents the exaggerated exercise pressor reflex in rats with chronic heart failure
Authors: Wang Han-Jun , Pan Yan-Xia , Wang Wei-Zhong , Gao Lie , Zimmerman Matthew C. , Zucker Irving H. , Wang Wei
Published: February 2010

An exaggerated exercise pressor reflex (EPR) occurs in the chronic heart failure (CHF) state, which contributes to exercise intolerance and excessive sympathoexcitation during exercise. Exercise training (ExT) improves abnormal cardiovascular reflexes in CHF. Whether ExT can normalize the exaggerated EPR function remains to be determined. This study was designed to investigate the effects of ExT on the EPR and on the mechanical or metabolic components of this reflex in sham-operated and CHF rats. The EPR was activated by static contraction induced by electrical stimulation of L4/L5 ventral roots. The afferent fibers associated with the mechanoreflex and metaboreflex were activated by passive stretch and hindlimb arterial injection of capsaicin (0.1 and 1 μg/kg, 0.2 ml), respectively. Heart rate, blood pressure, and sympathoexcitatory responses during the activation of these reflexes were compared in sham + sedentary (Sed), sham + ExT, CHF + Sed, and CHF + ExT rats. Compared with sham + Sed rats, CHF + Sed rats exhibited exaggerated heart rate and pressor and sympathoexcitatory responses to either static contraction or passive stretch, whereas the cardiovascular responses to injection of capsaicin were blunted. Eight to ten weeks of ExT normalized the exaggerated responses induced by static contraction or passive stretch and partially improved the blunted responses due to intra-arterial capsaicin in CHF rats. ExT had no significant effect on the EPR and mechanoreflex and metaboreflex functions in sham rats. These findings suggest a potential therapeutic role for ExT in minimizing arterial pressure and sympathetic outflow following activation of the EPR in the CHF state.
ABCA1 Gene Variants Regulate Postprandial Lipid Metabolism in Healthy Men
Authors: Delgado-Lista Javier , Perez-Martinez Pablo , Perez-Jimenez Francisco , Garcia-Rios Antonio , Fuentes Francisco , Marin Carmen , Gómez-Luna Purificación , Camargo Antonio , Parnell Laurence D. , Ordovas Jose Maria , Lopez-Miranda Jose
Published: February 2010

Objective—

Genetic variants of
ABCA1
, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high-density lipoproteins and apolipoprotein A1; however, results from different studies have been inconsistent.

Methods and Results—

To further characterize the effects of
ABCA1
variants in human postprandial lipid metabolism, we studied the influence of 3 single nucleotide polymorphisms (i27943 [rs2575875]; i48168 [rs4149272]; R219K [rs2230806]) in the postprandial lipemia of 88 normolipidemic young men who were given a fatty meal. For i27943 and i48168 single nucleotide polymorphisms, fasting and postprandial values of apolipoprotein A1 were higher and postprandial lipemia was much lower in homozygotes for the major alleles, total triglycerides in plasma, and large triglyceride-rich lipoprotein triglycerides. These persons also showed a higher apolipoprotein A1/apolipoprotein B ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher high-density lipoproteins and lower postprandial apolipoprotein B.

Conclusion—

Our work shows that major allele homozygotes for
ABCA1
single nucleotide polymorphisms i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism.
Acadesine Inhibits Tissue Factor Induction and Thrombus Formation by Activating the Phosphoinositide 3-Kinase/Akt Signaling Pathway
Authors: Zhang Weiyu , Wang Jianguo , Wang Huan , Tang Rong , Belcher John D. , Viollet Benoit , Geng Jian-Guo , Zhang Chunxiang , Wu Chaodong , Slungaard Arne , Zhu Chuhong , Huo Yuqing
Published: February 2010

Objective—

Acadesine, an adenosine-regulating agent and activator of AMP-activated protein kinase, has been shown to possess antiinflammatory activity. This study investigated whether and how acadesine inhibits tissue factor (TF) expression and thrombus formation.

Methods and Results—

Human umbilical vein endothelial cells and human peripheral blood monocytes were stimulated with lipopolysaccharide to induce TF expression. Pretreatment with acadesine dramatically suppressed the clotting activity and expression of TF (protein and mRNA). These inhibitory effects of acadesine were unchanged for endothelial cells treated with ZM241385 (a specific adenosine A
2A
receptor antagonist) or AMP-activated protein kinase inhibitor compound C, and in macrophages lacking adenosine A
2A
receptor or α1–AMP-activated protein kinase. In endothelial cells and macrophages, acadesine activated the phosphoinositide 3-kinase/Akt signaling pathway, reduced the activity of mitogen-activated protein kinases, and consequently suppressed TF expression by inhibiting the activator protein-1 and NF-κB pathways. In mice, acadesine suppressed lipopolysaccharide-mediated increases in blood coagulation, decreased TF expression in atherosclerotic lesions, and reduced deep vein thrombus formation.

Conclusion—

Acadesine inhibits TF expression and thrombus formation by activating the phosphoinositide 3-kinase/Akt pathway. This novel finding implicates acadesine as a potentially useful treatment for many disorders associated with thrombotic pathology, such as angina pain, deep vein thrombosis, and sepsis.
Oxidized Phospholipids Regulate Expression of ATF4 and VEGF in Endothelial Cells via NRF2-Dependent Mechanism: Novel Point of Convergence Between Electrophilic and Unfolded Protein Stress Pathways
Authors: Afonyushkin Taras , Oskolkova Olga V. , Philippova Maria , Resink Therese J. , Erne Paul , Binder Bernd R. , Bochkov Valery N.
Published: February 2010

Objective—

The ATF4 arm of the unfolded protein response is increasingly recognized for its relevance to pathology, and in particular to angiogenic reactions. Oxidized phospholipids (OxPLs), known to accumulate in atherosclerotic vessels, were shown to upregulate vascular endothelial growth factor (VEGF) and induce angiogenesis via an ATF4-dependent mechanism. In this study, we analyzed the mechanism of ATF4 upregulation by OxPLs and more specifically the involvement of NRF2, the major transcriptional mediator of electrophilic stress response.

Methods and Results—

Using reverse transcription/real-time polymerase chain reaction and Western blotting, we found that OxPLs induced upregulation of ATF4 mRNA and protein in several types of endothelial cells and that these effects were suppressed by short interfering RNA (siRNA) against NRF2. Electrophilic (iso)prostaglandins and oxidized low-density lipoprotein, similarly to OxPLs, elevated ATF4 mRNA levels in an NRF2-dependent mode. Chromatin immunoprecipitation revealed OxPL-dependent binding of NRF2 to a putative antioxidant response element site in the
ATF4
gene promoter. Knockdown of NRF2 inhibited OxPL-induced elevation of VEGF mRNA and endothelial cell sprout formation.

Conclusion—

Our data characterize NRF2 as a positive regulator of ATF4 and identify a novel cross-talk between electrophilic and unfolded protein responses, which may play a role in stress-induced angiogenesis.
TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish
Authors: Yu Peng-chun , Gu Shan-ye , Bu Ji-wen , Du Jiu-lin
Published: February 2010

Rationale
:

Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development.

Objective
:

To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development.

Methods and Results
:

Knockdown of zebrafish
trpc1
by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide–resistant form of zebrafish
trpc1
mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell–autonomous. In vivo time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a–induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase.

Conclusions
:

These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.
Id3 Is a Novel Atheroprotective Factor Containing a Functionally Significant Single-Nucleotide Polymorphism Associated With Intima–Media Thickness in Humans
Authors: Doran Amanda C. , Lehtinen Allison B. , Meller Nahum , Lipinski Michael J. , Slayton R. Parker , Oldham Stephanie N. , Skaflen Marcus D. , Yeboah Joseph , Rich Stephen S. , Bowden Donald W. , McNamara Coleen A.
Published: February 2010

Rationale
:

The gene encoding the helix–loop–helix transcription factor Id3 (inhibitor of differentiation-3) is located within atherosclerosis susceptibility loci of both mice and humans, yet its influence on atherosclerosis is not known.

Objective
:

The present study sought to determine whether polymorphisms in the
ID3
gene were associated with indices of atherosclerosis in humans and if loss of Id3 function modulated atherogenesis in mice.

Methods and Results
:

Six tagging single-nucleotide polymorphisms (SNPs) (tagSNPs) in the human
ID3
gene were assessed in participants of the Diabetes Heart Study. One tagSNP, rs11574, was independently associated with carotid intima–media thickness (IMT). The human
ID3
variant at rs11574 results in an alanine to threonine substitution in the C terminus. To determine the effect of this polymorphism on the basic function of Id3, site-directed mutagenesis of the human
ID3
gene at rs11574 was performed. Results demonstrated a significant reduction in coimmunoprecipitation of the known E-protein partner, E12, with Id3 when it contains the sequence encoded by the risk allele (Id3105T). Further, Id3105T had an attenuated ability to modulate E12-mediated transcriptional activation compared to Id3 containing the ancestral allele (Id3105A). Microarray analysis of vascular smooth muscle cells from WT and
Id3
−/−
mice revealed significant modulation of multiple gene pathways implicated in atherogenesis. Moreover,
Id3
−/−
ApoE
−/−
mice developed significantly more atherosclerosis in response to 32 weeks of Chow or Western diet feeding than
Id3
+/+
ApoE
−/−
mice.

Conclusions
:

Taken together, results provide novel evidence that Id3 is an atheroprotective factor and link a common SNP in the human
ID3
gene to loss of Id3 function and increased IMT.