bluuebunny/crossref_metadata_2025 huggingface dataset:
ROLE OF GLUTAMATE DEHYDROGENASE AND GLUTAMINE SYNTHETASE IN CHLORELLA VULGARIS DURING ASSIMILATION OF AMMONIUM WHEN JOINTLY IMMOBILIZED WITH THE MICROALGAE‐GROWTH‐PROMOTING BACTERIUM AZOSPIRILLUM BRASILENSE1
Authors: De‐Bashan Luz E. , Magallon Paola , Antoun Hani , Bashan Yoav
Published: September 2008

Enzymatic activities of glutamate dehydrogenase (GDH) and glutamine synthetase (GS) participating in the nitrogen metabolism and related ammonium absorption were assayed after the microalga Chlorella vulgaris Beij. was jointly immobilized with the microalgae‐growth‐promoting bacterium Azospirillum brasilense. At initial concentrations of 3, 6, and 10 mg · L−1 NH4+, joint immobilization enhances growth of C. vulgaris but does not affect ammonium absorption capacity of the microalga. However, at 8 mg · L−1 NH4+, joint immobilization enhanced ammonium absorption by the microalga without affecting the growth of the microalgal population. Correlations between absorption of ammonium per cell and per culture showed direct (negative and positive) linear correlations between these parameters and microalga populations at 3, 6, and 10 mg · L−1 NH4+, but not at 8 mg · L−1 NH4+, where the highest absorption of ammonium occurred. In all cultures, immobilized and jointly immobilized, having the four initial ammonium concentrations, enzymatic activities of Chlorella are affected by A. brasilense. Regardless of the initial concentration of ammonium, GS activity in C. vulgaris was always higher when jointly immobilized and determined on a per‐cell basis. When jointly immobilized, only at an initial concentration of 8 mg · L−1 NH4+ was GDH activity per cell higher.
PLASTID DYNAMICS DURING SURVIVAL OF DINOPHYSIS CAUDATA WITHOUT ITS CILIATE PREY1
Authors: Park Myung Gil , Park Jong Soo , Kim Miran , Yih Wonho
Published: September 2008

To survive, the marine dinoflagellate Dinophysis caudata Saville‐Kent must feed on the plastidic ciliate Myrionecta rubra (=Mesodinium rubrum), itself a consumer of cryptophytes. Whether D. caudata has its own permanent chloroplasts or retains plastids from its ciliate prey, however, remains unresolved. Further, how long D. caudata plastids (or kleptoplastids) persist and remain photosynthetically active in the absence of prey remains unknown. We addressed those issues here, using the first established culture of D. caudata. Phylogenetic analyses of the plastid 16S rRNA and psbA gene sequences directly from the three organisms (D. caudata, M. rubra, and a cryptophyte) revealed that the sequences of both genes from the three organisms are almost identical to each other, supporting that the plastids of D. caudata are kleptoplastids. A 3‐month starvation experiment revealed that D. caudata can remain photosynthetically active for ∼2 months when not supplied with prey. D. caudata cells starved for more than 2 months continued to keep the plastid 16S rRNA gene but lost the photosynthesis‐related genes (i.e., psaA and psbA genes). When the prey was available again, however, D. caudata cells starved for more than 2 months were able to reacquire plastids and slowly resumed photosynthetic activity. Taken all together, the results indicate that the nature of the relationship between D. caudata and its plastids is not that of permanent cellular acquisitions. D. caudata is an intriguing protist that would represent an interesting evolutionary adaptation with regard to photosynthesis as well as help us to better understand plastid evolution in eukaryotes.
GROWTH AND CARBON CONTENT OF THREE DIFFERENT‐SIZED DIAZOTROPHIC CYANOBACTERIA OBSERVED IN THE SUBTROPICAL NORTH PACIFIC1
Authors: Goebel Nicole L. , Edwards Christopher A. , Carter Brandon J. , Achilles Katherine M. , Zehr Jonathan P.
Published: September 2008

To develop tools for modeling diazotrophic growth in the open ocean, we determined the maximum growth rate and carbon content for three diazotrophic cyanobacteria commonly observed at Station ALOHA (A Long‐term Oligotrophic Habitat Assessment) in the subtropical North Pacific: filamentous nonheterocyst‐forming Trichodesmium and unicellular Groups A and B. Growth‐irradiance responses of Trichodesmium erythraeum Ehrenb. strain IMS101 and Crocosphaera watsonii J. Waterbury strain WH8501 were measured in the laboratory. No significant differences were detected between their fitted parameters (±CI) for maximum growth rate (0.51 ± 0.09 vs. 0.49 ± 0.17 d−1), half‐light saturation (73 ± 29 vs. 66 ± 37 μmol quanta · m−2 · s−1), and photoinhibition (0 and 0.00043 ± 0.00087 [μmol quanta · m−2 · s−1]−1). Maximum growth rates and carbon contents of Trichodesmium and Crocosphaera cultures conformed to published allometric relationships, demonstrating that these relationships apply to oceanic diazotrophic microorganisms. This agreement promoted the use of allometric models to approximate unknown parameters of maximum growth rate (0.77 d−1) and carbon content (480 fg C · μm−3) for the uncultivated, unicellular Group A cyanobacteria. The size of Group A was characterized from samples from the North Pacific Ocean using fluorescence‐activated cell sorting and real‐time quantitative PCR techniques. Knowledge of growth and carbon content properties of these organisms facilitates the incorporation of different types of cyanobacteria in modeling efforts aimed at assessing the relative importance of filamentous and unicellular diazotrophs to carbon and nitrogen cycling in the open ocean.
EARLY DEVELOPMENT PATTERN OF THE BROWN ALGAECTOCARPUS SILICULOSUS(ECTOCARPALES, PHAEOPHYCEAE) SPOROPHYTE1
Authors: Le Bail Aude , Billoud Bernard , Maisonneuve Carole , Peters Akira F. , Mark Cock J. , Charrier Bénédicte
Published: September 2008

The distant phylogenetic position of brown macroalgae from the other multicellular phyla offers the opportunity to study novel and alternative developmental processes involved in the establishment of multicellularity. At present, however, very little information is available about developmental patterning in this group.Ectocarpus siliculosus(Dillwyn) Lyngb. has uniseriate filaments and displays one of the simplest architectures in the Phaeophyceae. The aim of this study was to decipher the morphogenetic steps that lead to the development of theEctocarpussporophyte. We carried out a detailed morphometric study of the events that occurred between gamete germination and the 100‐cell stage. This analysis was performed on two ecologically distant isolates to assess plasticity in developmental patterning within this species. Cell sizes were measured in both isolates, allowing the definition of two main cell types based on their shape (round and elongated). On average, the filament is composed of about 40% round cells, which are present in the central region of the filament, but different combinations of the two cell types within filaments were observed and quantified. Young sporophytes grew apically, with elongated cells progressively differentiating into round cells. Secondary filaments emerged preferentially on round cells, primarily from the older central cells. Statistical analyses showed that the pattern of branching was regulated to ensure a stereotyped architecture. This description of the developmental patterning during the growth of theE. siliculosussporophyte will serve as a base for more detailed studies of development, in this species and in brown algae in general.
DETECTION OF DIATOM XANTHOPHYLL CYCLE USING SPECTRAL REFLECTANCE1
Authors: Jesus Bruno , Mouget Jean‐Luc , Perkins Rupert G.
Published: September 2008

Analysis of reflectance spectra was used to monitor the conversion of diadinoxanthin (DD) into diatoxanthin (DT) in two benthic diatom species, Amphora coffeaeformis (C. Agardh) Kütz. and Cylindrotheca closterium (Ehrenb.) J. C. Lewin et Reiman, cultured at high light (HL, 400 μmol · m−2 · s−1 PAR) and low light (LL, 25 μmol · m−2 · s−1 PAR). Cultures were exposed to saturating light for 32 min. HL cultures of both species showed higher (DT + DD) content, whereas LL cultures exhibited higher chl a and fucoxanthin content. DD to DT conversion, measured by HPLC, occurred mainly in the first 2 min (LL) or 5 min (HL) after exposure to saturating light. Nonphotochemical quenching (NPQ), measured by PAM fluorescence, showed the same pattern as DT/(DD + DT), resulting in a linear relationship between these parameters. Addition of dithiothreitol (DTT) blocked the conversion of DD into DT and significantly reduced NPQ induction. Reflectance spectra showed no obvious change after light exposure. However, second derivative spectra (δδ) showed a shift in reflectance from 487 to 508 nm, which was not present for DTT‐treated samples. Changes in δδ487 were strongly correlated with changes in DD (r = 0.76), while changes in δδ508 were strongly correlated with changes in DT (r = 0.94). The best index to estimate DD to DT conversion was δδ508/δδ630 (r = 0.87). This index was very sensitive to minute changes that occurred immediately after exposure to light and was species insensitive. Good relationships were observed between indices for xanthophyll cycle activation (DD to DT conversion and NPQ induction) and the second derivative spectra. With further in situ validation, this index may prove to be highly useful for investigation into aquatic global photoregulation mechanisms in diatom‐dominated samples.
Dilated Left Atrium and Pulmonary Veins in Patients with Calcified Coronary Artery: A Potential Contributor to the Genesis of Atrial Fibrillation
Authors: PAN NAN‐HUNG , TSAO HSUAN‐MING , CHANG NEN‐CHUNG , LEE CHIH‐MING , CHEN YI‐JEN , CHEN SHIH‐ANN
Published: September 2008

Introduction: Coronary artery disease (CAD) is an important etiology of atrial fibrillation (AF). Coronary artery calcification is a marker of coronary atherosclerosis and coronary events. The purpose of this study was to investigate whether larger left atrium (LA) and pulmonary veins (PVs) were seen by multidetector computed tomography (MDCT) scans in those patients with higher coronary calcium scores.

Methods and Results: A total of 166 patients undergoing MDCT for general check‐up (n = 128, 77%) or suspected CAD (n = 38, 23%) were enrolled and divided into a control (calcium score = 0, n = 60), medium calcium score (calcium score = 100∼400, n = 47), and high calcium score (calcium score >400, n = 59) groups. Diameters and areas of the LA, left atrial appendage (LAA), and PVs were measured by MDCT. The high calcium score group had significantly larger PVs diameters, LAA orifice area (1.9 ± 1.4 cm2, 0.9 ± 0.5 cm2, 0.8 ± 0.4 cm2, P < 0.005), LA anterior‐posterior distance (32.2 ± 6.8 mm, 30.4 ± 6.5 mm, 27.3 ± 6.0 mm, P < 0.05), and transverse distance (52.6 ± 7.3 mm, 50.2 ± 9 mm, 49.5 ± 4.6 mm, P < 0.05) than the medium calcium score and control groups. Six (3.6%) patients with paroxysmal AF had higher calcium scores and larger diameters of LA, LAA, and PVs than those (96.4%) without paroxysmal AF. Two patients in the high calcium score group had calcified PVs localized to the right upper and left upper PVs. The incidence of calcified PVs was 1.2% for the total patients and 3.3% for the high calcium score patients.

Conclusion: In the presence of high calcium scores in this patient population, the LA, LAA, and PVs were enlarged.
To Replace or Not to Replace: A Systematic Approach to Respond to Device Advisories
Authors: PRIORI SILVIA G. , AURICCHIO ANGELO , NISAM SEAH , YONG PATRICK
Published: September 2008

Aim:The decision of whether and when to replace a device in response to an “advisory” letter requires careful consideration, because device replacement carries related risks and is influenced by the clinical characteristics of the patient.

Methods and Results:The risk/benefit of device replacement depends on four parameters: expected annual sudden cardiac death rate; residual device life; difference in failure rate between the device listed on the advisory letter and the replacement device; and the replacement procedure mortality risk. Using these four factors, we have developed an equation that provides the “number needed to replace” (NNR) to save one life. Per our model, patients implanted with a device with a failure rate approaching 1% and a probability of requiring device intervention ≥25% per year—in particular, pacemaker‐dependent patients—have an NNR <250. Pacemaker‐dependent patients, with devices having three or more years longevity, but with device failure rates ≥0.5%, have an NNR <100. Patients with arrhythmic risk ≤2.5% per year and those with devices having failure rates <0.1% have a high NNR and stand more risk to be harmed than benefited from device replacement.

Conclusions:Pacemaker‐dependent patients and those with high arrhythmic risk (≥25% annually) when having “advisory” devices with high failure rate (≥1%) have an NNR <250 and, hence, could be considered for device replacement. Conversely, patients with arrhythmic risk ≤2.5% per year and those with devices having failure rates ≤0.1% have a high NNR or even risk of “harm” from device replacement. In all the intermediate cases, the NNR will quantify the benefit/risk ratio of replacement, thus helping physicians and patients decide on the preferred approach. The NNR methodology proposed here is also applicable to advisory notices issued to leads, but the high morbidity associated with lead replacement will generally rule out interventions to replace leads.
Cost Comparison of Ablation Versus Antiarrhythmic Drugs As First‐Line Therapy for Atrial Fibrillation: An Economic Evaluation of the RAAFT Pilot Study
Authors: KHAYKIN YAARIV , WANG XIAOYIN , NATALE ANDREA , WAZNI OUSSAMA M. , SKANES ALLAN C. , HUMPHRIES KARIN H. , KERR CHARLES R. , VERMA ATUL , MORILLO CARLOS A.
Published: September 2008

Introduction:
Radiofrequency ablation (RFA) has become an accepted therapy for atrial fibrillation (AF). The objective of this study was to perform an economic evaluation of RFA versus antiarrhythmic drug therapy (AAD) as first‐line treatment of symptomatic paroxysmal AF.

Methods:
To estimate and compare the costs of RFA versus AAD, a decision analytic model was developed using data on AF recurrence, hospitalization rates, AAD use, and treatment crossover rates derived directly from the Randomized Trial of RFA versus AAD as First‐Line Treatment of Symptomatic Atrial Fibrillation (RAAFT). Resource utilization was modeled to reflect Canadian clinical practice in AF management. Unit costs of healthcare interactions were based on available Canadian government resources and published literature. Costs were assessed based on intention‐to‐treat. Total expected costs were computed to include initial treatment, hospital stay, physician fees, diagnostic tests, and outpatient visits. Sensitivity analyses were performed to account for the uncertainties. The study was conducted from the third party payer's perspective and costs are reported in 2005 Canadian dollars with 3% discount rate used in the analysis.

Results:
During the 2‐month blanking period following therapy selection, total average costs for RFA and AAD were $10,465 and $2,556, respectively; at 1‐year follow‐up, these were $12,823 and $6,053; and total 2‐year cumulative total average costs were $15,303 and $14,392. Sensitivity analyses did not alter the results, suggesting the model is robust.

Conclusions:
RFA as first‐line treatment strategy in patients with symptomatic paroxysmal AF was cost neutral 2 years after the initial procedure compared to AAD.
Right Ventricular Pressure Changes During Induced Ventricular Tachycardias Predict Clinical Symptoms of Cerebral Hypoperfusion: Implications for a Reduction of Unnecessary, Painful ICD Shocks
Authors: PETRUCCI ETTORE , BRAGA SIMONA SARZI , BALIAN VRUYR , PEDRETTI ROBERTO F.E.
Published: September 2008

Right Ventricular Pressure and VTs Tolerance. Background: ICD shocks occurring in conscious patients (as in the case of well‐tolerated arrhythmias, electromagnetic interference, or oversensing) have a deleterious impact on the quality of life. We evaluated if a hemodynamic parameter, calculated from the right ventricular pressure (RVP) or systemic arterial pressure (AP) signals, could predict early clinical symptoms of cerebral hypoperfusion during induced ventricular tachycardias (VTs).

Methods and results:
We analyzed 42 tolerated (no symptoms) and 30 untolerated (syncope or severe symptoms within 30 seconds from the onset) VTs, induced during electrophysiological study. The cycle length (CL) and the hemodynamic data (mean AP and RVP, arterial pulse pressure and RV pulse pressure, and maximum AP and RVP dP/dT) were automatically sampled in two VT epochs: the “detection” window, from beat 24 to 32, and the “preintervention” window, immediately before the first therapeutic attempt. Although the CL and all the hemodynamic parameters (expressed as % change versus pre‐VT values) were significantly lower in untolerated versus tolerated VTs both at detection and preintervention (with the exception of the mean RVP which progressively increased in both groups), ROC analysis demonstrated that only the preintervention RV pulse pressure showed no overlap between groups, providing 100% sensitivity and positive predictive value.

Conclusions:
The reduction of the RV pulse pressure is a better predictor of early cerebral symptoms than CL or other hemodynamic indexes during induced VTs. Since long‐term RVP monitoring is feasible, this parameter could be incorporated into ICDs decisional path, in the perspective of reducing unnecessary, painful shocks. (J Cardiovasc Electrophysiol, Vol. 20, pp. 299‐306, March 2009)
Major Mango Polyphenols and Their Potential Significance to Human Health
Authors: Masibo Martin , He Qian
Published: September 2008

ABSTRACT:  The mango is a rich source of various polyphenolic compounds. The major polyphenols in the mango in terms of antioxidative capacity and/or quantity are: mangiferin, catechins, quercetin, kaempferol, rhamnetin, anthocyanins, gallic and ellagic acids, propyl and methyl gallate, benzoic acid, and protocatechuic acid. The nutraceutical and pharmaceutical significance of mangiferin, which is a special polyphenol in the mango has been extensively demonstrated and continues to attract much attention especially in its potential to combat degenerative diseases like heart diseases and cancer. The amounts of the different polyphenolic compounds in the mango vary from part to part (pulp, peel, seed, bark, leaf, and flower) with most polyphenols being found in all the parts. Mango polyphenols, like other polyphenolic compounds, work mainly as antioxidants, a property that enables them to protect human cells against damage due to oxidative stress leading to lipid peroxidation, DNA damage, and many degenerative diseases. Use of pure isolated compounds has been found to be less effective than the use of crude mixtures from the particular mango part suggesting that synergism of the various mango polyphenols is important for maximum antioxidative activity. In this article, we review the major mango polyphenols, looking at their proposed antioxidative activity, estimated amounts in the different parts, their structures, suggested modes of action, and related significance to human health, with great emphasis on mangiferin.
Bioactivity of Flavonoids on Insulin‐Secreting Cells
Authors: Pinent Montserrat , Castell Anna , Baiges Isabel , Montagut Gemma , Arola Lluís , Ardévol Anna
Published: September 2008

ABSTRACT:  Flavonoids are usually found in fruits and other plant organs and therefore widely consumed. They are antioxidants, anti‐inflammatory, anticarcinogenic, and protective against coronary disease and metabolic disorders. These beneficial effects make them good candidates for the development of new functional foods with potential protective/preventive properties against several diseases. We must consider that this fact could lead to a higher intake of some of these flavonoids. Most of the studies concerning their beneficial effects showed peripheral activity of these molecules, but there is no clear information about their central effects on a key organ on metabolic control: the endocrine pancreas. The pancreas has an endocrine function of major importance to regulate nutrient metabolism, such as control of glucose homeostasis via insulin and glucagon secretion. Its importance in whole body nutrient equilibrium is highlighted by the fact that several pathologies, such as type 1 and/or 2 diabetes, are related at some point to a pancreatic cell deregulation. In this review, we compile the most relevant results concerning the effects of flavonoids on several aspects of pancreatic functionality. Studies using animals with drug‐induced diabetes support the hypothesis that flavonoids can ameliorate this pathogenesis. The great diversity of flavonoid structures makes it difficult to establish common effects in the pancreas. Published data suggest that there might be direct effects of flavonoids on insulin secretion, as well as on prevention of beta‐cell apoptosis, and they could even act via modulation of proliferation. The mechanisms of action involve mainly their antioxidant properties, but other pathways might also take place.
Self‐Propagating High‐Temperature Synthesis of Ti3SiC2: II. Kinetics of Ultra‐High‐Speed Reactions from In Situ Neutron Diffraction
Authors: Riley Daniel P. , Kisi Erich H. , Hansen Thomas C.
Published: September 2008

In situ neutron diffraction data at 0.9‐s time resolution during the self‐propagating high‐temperature synthesis of Ti3SiC2 from stoichiometric 3Ti+SiC+C mixtures have been further analyzed to give the phase quantities during all five stages of the identified reaction [(i) preheating, (ii) α→β phase transformation in Ti, (iii) preignition reactions, (iv) intermediate phase formation, and (v) rapid nucleation and growth of Ti3SiC2]. The phase quantities thus determined have been used, in conjunction with temperatures estimated from lattice parameters and thermal expansion data, to determine the kinetic parameters for the nucleation and growth stage using a nonisothermal form of the Avrami kinetic equation. The analysis gave an Avrami exponent, n, close to 3 in agreement with nucleation and the observed two‐dimensional growth of Ti3SiC2 crystals. An activation energy of ∼45 kJ/mol was also estimated.
High‐Temperature Oxidation at 1900°C of ZrB2–xSiC Ultrahigh‐Temperature Ceramic Composites
Authors: Han Wen‐Bo , Hu Ping , Zhang Xing‐Hong , Han Jie‐Cai , Meng Song‐He
Published: September 2008

Oxidation of ZrB2‐based ultrahigh‐temperature ceramic composites containing 10, 20, and 30 vol% SiC was performed at 1900°C for 1 h in air. ZrB2–20 vol% SiC exhibited the highest oxidation resistance at this temperature and formed a dense coherent oxide scale after oxidation, whereas a strong degradation was observed for both ZrB2–10 vol% SiC and ZrB2–30 vol% SiC. In addition, cracks and spallation in the oxide scale were also detected for the latter materials. The oxidation behaviors of ZrB2–SiC composites were investigated. The effect of SiC content was analyzed and oxidation models were proposed to describe the observed microstructures.
Synthesis of Zirconia Nanoparticles in a Continuous‐Flow Microwave Reactor
Authors: Bondioli Federica , Bonamartini Corradi Anna , Ferrari Anna Maria , Leonelli Cristina
Published: September 2008

Monodispersed zirconia colloidal spherical nanoparticles were synthesized from the hydrolysis and condensation of tetra‐n‐propylzirconate by using a continuous microwave synthesis process. The flow rate was varied from 50 to 100 mL/min in order to establish the optimum conditions required to obtain unagglomerated zirconia nanopowders. The results were compared with those obtained in batch systems. In particular as the flow rate is decreased from 100 to 50 mL/min the particle became spherical with a mean particle size of about 100 nm.
The Ethical Assignment of Authorship in Scientific Publications: Issues and Guidelines
Authors: Feeser V. Ramana , Simon Jeremy R.
Published: September 2008

Properly assigning authorship of academic papers is often an ethical challenge. Through a hypothetical case study, the authors examine some of the potential ethical issues involved in determining who should and should not be listed as an author: the problems of honorary authorship, coerced authorship, and ghost authorship, as well as the question of how to order authors. Guidelines for avoiding and negotiating these issues are also discussed.
Vers un respect durable de la législation: résultats des modèles d'inspection du travail au Brésil
Authors: PIRES Roberto
Published: September 2008

Peut‐on concilier les droits des travailleurs et la protection sociale avec la compétitivité et la productivité des entreprises? Se démarquant de la doctrine en vogue, qui prône la déréglementation et la «flexibilisation» de la protection du travail, l'auteur analyse le débat sur les styles réglementaires et suggère que les différentes pratiques d'inspection du travail influent sur les résultats obtenus dans le respect de la législation. Son enquê te permet de constater que les inspecteurs du travail brésiliens ont su élaborer des solutions assurant un respect durable de la réglementation sans nuire à la productivité des entreprises, en utilisant des méthodes faisant appel à la fois aux sanctions et à la pédagogie.
Corticotropin‐releasing factor decreases IL‐18 in the monocyte‐derived dendritic cell
Authors: Lee Hee Jung , Kwon Yeon Sook , Park Chang Ook , Oh Sang Ho , Lee Ju Hee , Wu Wen Hao , Chang Nam Soo , Lee Min‐Geol , Lee Kwang Hoon
Published: September 2008

Abstract:  Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin‐releasing factor (CRF), which activates the hypothalamo‐pituitary‐adrenal (HPA) axis under stress, also has pro‐inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte‐derived DC (MoDC) of atopic dermatitis patients and non‐atopic healthy controls. In this study, mRNAs for CRF‐R1α and 1β, as well as the CRF‐R1 protein, were detected in MoDCs. CRF‐R2α (but not R2β or R2γ) mRNA and the CRF‐R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL‐18 in both atopic dermatitis patients and non‐atopic healthy controls. However, CRF did not alter the expression of IL‐6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs.
Epilysin (MMP‐28) – structure, expression and potential functions
Authors: Illman Sara A. , Lohi Jouko , Keski‐Oja Jorma
Published: September 2008

Abstract:  Epilysin (MMP‐28) is the newest member of the matrix metalloproteinase (MMP) family of extracellular proteases. Together the MMPs can degrade almost all components of the extracellular matrix (ECM). MMPs also regulate cell behaviour by releasing growth factors and biologically active peptides from the ECM by modulating cell surface receptors and adhesion molecules and by regulating the activity of mediators of the inflammatory pathways. Epilysin differs from most other MMPs as it is expressed in a number of normal tissues, suggestive of functions in tissue homeostasis. The epilysin homologue in Xenopus laevis (XMMP‐28) is expressed in neural tissues, where it cleaves the neural cell adhesion molecule. Enhanced expression of epilysin has been observed in basal keratinocytes during wound healing and in different forms of cancer. There are, however, also reports on the downregulation of epilysin in malignant cells. The roles of epilysin in cancer seem to vary based on tumor type and stage of the disease. Importantly, epilysin can induce stable epithelial to mesenchymal transition (EMT) when overexpressed in epithelial lung carcinoma cells. Transforming growth factor β (TGF‐β) is a crucial mediator of this process, which was characterized by the loss of E‐cadherin and increased cell migration and invasion. Current results suggest a plausible interaction between epilysin and TGF‐β also under physiological circumstances, where epilysin activity may not induce EMT but, instead, trigger less permanent changes in TGF‐β signalling and cell motility.
Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene
Authors: Shimomura Yutaka , Garzon Maria C. , Kristal Leonard , Shapiro Lawrence , Christiano Angela M.
Published: September 2008

Abstract:  During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein‐coupled receptor, underlie autosomal recessive woolly hair (WH)/hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifestations of P2RY5 mutations have not completely been elucidated because of limited information to date. In this study, we ascertained a consanguineous family of Iranian origin with an affected girl showing sparse and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair density at birth, but progressed with age to develop hypotrichosis. Direct sequencing analysis resulted in the identification of a novel homozygous mutation in the P2RY5 gene of the patient, which results in a non‐conservative amino acid change, G146R, at the protein level. Our findings extend the mutation spectrum of P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in humans.
Astaxanthin, canthaxanthin and β‐carotene differently affect UVA‐induced oxidative damage and expression of oxidative stress‐responsive enzymes
Authors: Camera Emanuela , Mastrofrancesco Arianna , Fabbri Claudia , Daubrawa Felicitas , Picardo Mauro , Sies Helmut , Stahl Wilhelm
Published: September 2008

Abstract:  Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms underlying photoprotective effects of carotenoids, here we compared the modulation of UVA‐related injury by carotenoids. Human dermal fibroblasts (HDF) were exposed to moderate doses of UVA, which stimulated apoptosis, increased levels of reactive oxygen species and thiobarbituric acid reactive substances, decreased antioxidant enzymes activities, promoted membrane perturbation, and induced the expression of heme oxygenase‐1 (HO‐1). The carotenoids astaxanthin (AX), canthaxanthin (CX) and β‐carotene (βC) were delivered to HDF 24 h before exposure to UVA. Astaxanthin exhibited a pronounced photoprotective effect and counteracted all of the above‐mentioned UVA‐induced alterations to a significant extent. β‐Carotene only partially prevented the UVA‐induced decline of catalase and superoxide dismutase activities, but it increased membrane damage and stimulated HO‐1 expression. Moreover, βC dose‐dependently induced caspase‐3 activity following UVA exposure. In contrast, CX had no effect on oxidative damage, except for HO‐1 expression, which was augmented. Uptake of AX by fibroblasts was higher than that of the other two carotenoids. The photostability of the three compounds in fibroblasts was AX > CX >> βC. The data indicate that the oxo‐carotenoid AX has a superior preventive effect towards photo‐oxidative changes in cell culture.
Vasculitis of small blood vessels – some riddles about IgA and about the complexity of transmigration
Authors: Sunderkötter Cord
Published: September 2008

Abstract:  Research on leukocytoclastic vasculitis (LcV) provides insights into mechanisms of antibody‐mediated immune responses as well as into the complex process of neutrophil transmigration. Clinical observations on immune complex vasculitis have revealed that adult patients with IgA containing immune complexes [Henoch–Schoenlein purpura (HSP)] have a higher rate of severe complications than children with HSP or adult patients with IgG or IgM containing immune complexes. This has direct impact on classification and management of vasculitis and warrants further studies on pathophysiology of IgA and on aberrant glycosylation of IgA1 associated with renal involvement.

In order to dissect the pathomechanisms specific for LcV, we have been comparing different mouse models of LcV with a non‐vasculitic, acute inflammation (i.e. irritant contact dermatitis). We found that one characteristic constellation in the vasculitis models encompasses interference with both normal transmigration and activation of neutrophils. Toxic products released by activated neutrophils have the potential to damage endothelial cells. However, one still needs to reveal how exactly they exert such damaging effects during diapedesis in vivo, considering the short contacts between neutrophils and endothelial cells.

This review shows that research on LcV is embedded in an exciting context revealing special features of transmigration and antibody‐mediated immune responses.
Role for nectin‐1 in herpes simplex virus 1 entry and spread in human retinal pigment epithelial cells
Authors: Tiwari Vaibhav , Oh Myung‐Jin , Kovacs Maria , Shukla Shripaad Y. , Valyi‐Nagy Tibor , Shukla Deepak
Published: September 2008

Herpes simplex virus 1 (HSV‐1) demonstrates a unique ability to infect a variety of host cell types. Retinal pigment epithelial (RPE) cells form the outermost layer of the retina and provide a potential target for viral invasion and permanent vision impairment. Here we examine the initial cellular and molecular mechanisms that facilitate HSV‐1 invasion of human RPE cells. High‐resolution confocal microscopy demonstrated initial interaction of green fluorescent protein (GFP)‐tagged virions with filopodia‐like structures present on cell surfaces. Unidirectional movement of the virions on filopodia to the cell body was detected by live cell imaging of RPE cells, which demonstrated susceptibility to pH‐dependent HSV‐1 entry and replication. Use of RT‐PCR indicated expression of nectin‐1, herpes virus entry mediator (HVEM) and 3‐O‐sulfotransferase‐3 (as a surrogate marker for 3‐O‐sulfated heparan sulfate). HVEM and nectin‐1 expression was subsequently verified by flow cytometry. Nectin‐1 expression in murine retinal tissue was also demonstrated by immunohistochemistry. Antibodies against nectin‐1, but not HVEM, were able to block HSV‐1 infection. Similar blocking effects were seen with a small interfering RNA construct specifically directed against nectin‐1, which also blocked RPE cell fusion with HSV‐1 glycoprotein‐expressing Chinese hamster ovary (CHO‐K1) cells. Anti‐nectin‐1 antibodies and F‐actin depolymerizers were also successful in blocking the cytoskeletal changes that occur upon HSV‐1 entry into cells. Our findings shed new light on the cellular and molecular mechanisms that help the virus to enter the cells of the inner eye.
Antimicrobial effects of H4‐(86–100), histogranin and related compounds – possible involvement of DNA gyrase
Authors: Lemaire Simon , Trinh Thuy‐Tiên , Le Hoang‐Thanh , Tang Shun‐Chii , Hincke Maxwell , Wellman‐Labadie Olivier , Ziai Sophie
Published: September 2008

Histone‐derived antimicrobial peptides have been identified in various organisms from plants to humans. The rat histone H4 mRNA variants, H4‐v.1 and rat histogranin (HNr) mRNAs, were recently reported to be involved in the synthesis of H4‐(86–100) and its related peptide HNr, respectively. Herein, the two peptides were investigated for putative antimicrobial activity and found to inhibit growth of Gram‐negative (Escherichia coli, Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis, Staphylococcus aureus) bacteria. Their inhibitory potencies in E. coli (LD50: 3.48 and 4.34 μg·mL−1) are comparable to that of the antimicrobial peptide LL‐37 (LD50: 4.10 μg·mL−1). The antimicrobial activities of H4‐(86–100) and HNr depend upon the integrity of the molecules, as precursors [H4‐(84–102), pro‐HNr] and fragments [bovine histogranin (HNb)‐(1–13), HNb‐(3–13), H4‐(89–102) or OGP] are at least five times less potent than the parent peptides. Among various HN‐like compounds, cyclo‐(‐Gly‐pCl‐Phe‐Tyr‐d‐Arg) (compound 3) and N‐5‐guanidino pentanamide‐(2R)‐yl‐2‐N‐(p‐hydroxyphenylacetyl)‐4‐(p‐chlorobenzoyl)‐phenylene diamine (compound 8) display antimicrobial activities comparable to that of HNr. Interestingly, the antimicrobial activities of H4‐(86–100), HNr and compound 3, like those of quinolone antibiotics acting as DNA gyrase poisons, are potentiated by ATP (1 mm) and coumermycin A1 (a DNA gyrase‐linked ATPase inhibitor) and blocked by 2,4‐dinitrophenol (DNP, an uncoupler of oxidative phosphorylation) and fluoroacetic acid (a metabolic poison). Finally, in vitro experiments indicate that H4‐(86–100), HNr, compound 3 and compound 8, but not HNb‐(1–13) or HNb‐(3–13), inhibit DNA gyrase‐mediated supercoiling of pBR322 DNA. These data indicate that the naturally occurring H4‐(86–100) and HNr display antimicrobial effects that involve a modulation of ATP‐dependent DNA gyrase.
Calmodulin binds to maize lipid transfer protein and modulates its lipids binding ability
Authors: Li Cuifeng , Xie Wanqin , Bai Wenyan , Li Zhenpeng , Zhao Yulong , Liu Hua
Published: September 2008

Although plant non‐specific lipid transfer proteins (ns‐LTPs) are characterized by their ability to bind and transfer a broad range of hydrophobic ligands in vitro, their biological functions in vivo remain unclear. Recently, it has been proposed that ns‐LTPs may play a key role in plant defense mechanisms, particularly during the induction of systemic acquired resistance, however, very little is known about the regulation in this process. We report that the binding of maize non‐specific lipid transfer protein (Zm‐LTP) to calmodulin (CaM) is in a calcium‐independent manner. To better understand the interaction mechanism between Zm‐LTP and CaM, the CaM‐binding site of Zm‐LTP was mapped to the region of amino acids 46–60. Point mutations indicate that four amino acid residues, R46, R47, K54 and R58, in this region are crucial for binding. Furthermore, we tested the effects of CaM on the lipid‐binding activity of Zm‐LTP in the presence of Ca2+, EGTA, N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulfonamide and trifluoperazine respectively. We also investigated the structural features of CaM‐binding motifs in LTPs from different species and strong differences were observed. Taken together, our results suggest that the interaction with CaM could be a common feature of plant LTPs. The identification and characterization of CaM‐binding domain of LTPs should provide new insights into the mechanism by which the physiological functions of LTPs are regulated.
Distinct Influence of Atypical 1,4‐Dihydropyridine Compounds in Azidothymidine‐Induced Neuro‐ and Cardiotoxicity in Mice Ex Vivo
Authors: Pupure Jolanta , Isajevs Sergejs , Gordjushina Valentina , Taivans Immanuels , Rumaks Juris , Svirskis Simons , Kratovska Aina , Dzirkale Zane , Pilipenko Jelena , Duburs Gunars , Klusa Vija
Published: September 2008

Abstract:  This study demonstrates the effective protection by compounds of atypical 1,4‐dihydropyridine (DHP) series cerebrocrast, glutapyrone and tauropyrone against neuro‐ and cardiotoxicity caused by the model compound azidothymidine, a well‐known mitochondria‐compromising anti‐HIV drug. In previous in vitro experiments, we have demonstrated distinct effects of these DHP compounds to influence mitochondrial functioning. In the present in vivo experiments, DHP compounds were administered intraperitoneally in mice daily for 2 weeks, per se and in combinations with azidothymidine at doses: azidothymidine 50 mg/kg; cerebrocrast 0.1 mg/kg; glutapyrone 1 mg/kg; and tauropyrone 1 mg/kg. At the end of the experiment, mice were killed, heart and brain tissues were removed and examined ex vivo histopathologically and immunohistochemically. NF‐κBp65 and caspase‐3 were used as the markers indicating inflammatory and apoptotic events, respectively. Cerebrocrast (dicyclic structure) was the most potent DHP, which effectively reduced azidothymidine‐induced overexpression of NF‐κBp65 and caspase‐3 in mouse myocardium and brain cortex. Glutapyrone per se increased the number of caspase‐3‐positive cells in the brain, whereas it reduced NF‐κBp65 and caspase‐3 expression in cardiac tissue caused by azidothymidine. Tauropyrone showed dual action: per se it increased caspase‐3 in the brain and NF‐κBp65 expression in the heart, but it considerably reduced these activations in azidothymidine‐treated mice. This study provides the first demonstration of a distinct pharmacological action for atypical DHP compounds in cardiac and brain tissues. The dicyclic structure of cerebrocrast is considered beneficial for neuro‐ and cardioprotection at least in part via mitochondrial targeting and consequent regulation of inflammatory and apoptotic processes.
Meta‐Analysis of the Effect of MDR1 C3435T Polymorphism on Cyclosporine Pharmacokinetics
Authors: Jiang Zhi‐Ping , Wang Yi‐Ren , Xu Ping , Liu Rong‐Rong , Zhao Xie‐Lan , Chen Fang‐Ping
Published: September 2008

Abstract: The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of cyclosporine; thus, the aim was to conduct a meta‐analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. A literature search was conducted to locate the relevant papers by using the PubMed electronic source from 1997 and onwards. The pharmacokinetic parameters, including AUC0–4, AUC0–12, AUC0‐inf, Cmax, CL/F and trough concentration (C0), were extracted and a meta‐analysis was performed by using Stata version 9.1. A total of 14 papers concerning 1036 individuals were included in the meta‐analysis. The overall results showed no major influence of SNP C3435T on the pharmacokinetic parameters, including AUC0–4, AUC0‐inf, CL/F, Cmaxand C0, although AUC0–12was lower in subjects with CC genotype. A subanalysis by ethnic population showed that C0was lower in Caucasian individuals harbouring CC genotype. In conclusion, our meta‐analysis of available studies has thus far failed to demonstrate a definitive correlation between the SNP C3435T inMDR1gene and alterations in P‐glycoprotein function that can result in altered pharmacokinetics of cyclosporine, although it was indicated in this meta‐analysis that the carrier of CC genotype of the SNP C3435T of MDR1 had lower cyclosporine exposure presented as AUC0–12than those with at least one T allele. There seems to be ethnic differences in the relationship between the SNP C3435T of MDR1 and cyclosporine pharmacokinetics.
Cardioprotective Effects of Nigella sativa Oil on Cyclosporine A‐Induced Cardiotoxicity in Rats
Authors: Ebru Uz , Burak Uz , Yusuf Selcoki , Reyhan Bayrak , Arif Kaya , Faruk Turgut H. , Emin Mete , Aydın Karanfil , Lhan Atilla İ , Semsettin Sahin , Kemal Erdemli
Published: September 2008

Abstract:  Cyclosporine A is a well‐known immunosuppressor agent universally used in allotransplantation. However, it has been demonstrated that this drug produces side‐effects in several organs, particularly in the kidney and in the heart. Nigella sativa oil has long been used in folk medicine for a wide range of illnesses. One of the potential properties of N. sativa oil is the ability of one or more of its constituents to reduce toxicity due to its antioxidant activities. The antioxidant effects of N. sativa oil have been examined using different hepatic and kidney toxicity in in vivo murine models. The aim of this study was to evaluate the effects of N. sativa oil in the antioxidant enzyme status and myocardium of cyclosporine‐A‐treated rats. This study included 24 male Wistar albino young healthy rats (8–12 weeks) weighing 150–200 g. The control group received sunflower oil (21 days, 2 ml/kg/day, orally) without any treatment. The second group received only N. sativa oil (21 days, 2 ml/kg, orally) (N. sativa oil group). The animals in the third group received only cyclosporine A (21 days, 25 mg/kg, orally) (cyclosporine A group). The animals in the fourth group were treated with cyclosporine A (21 days, 25 mg/kg, orally) and starting one day before cyclosporine A administration were treated with N. sativa oil (21 days, 2 ml/kg, orally) (cyclosporine A +N. sativa oil group). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) activities in the heart tissues were significantly reduced in the cyclosporine A group compared to control values. Nigella sativa oil treatment caused an increase in the activities of SOD, CAT and GSH‐Px compared to the control group. Malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were increased in the cyclosporine A‐treated group in comparison with the control and N. sativa groups. Co‐administration of N. sativa oil and cyclosporine A abrogated the cyclosporine A‐induced MDA, N. sativa oil and PC increase compared to the cyclosporine A group. The results of our study show that pre‐treatment with N. sativa oil reduced the subsequent cyclosporine A injury in rat heart, demonstrated by normalized cardiac histopathology, decrease in lipid peroxidation, improvement in antioxidant enzyme status and cellular protein oxidation.
Anti‐Inflammatory and Analgesic Activities of the Aqueous Extract of Acacia karroo Stem Bark in Experimental Animals
Authors: Adedapo Adeolu A. , Sofidiya Margaret O. , Masika Patrick J. , Afolayan Anthony J.
Published: September 2008

Abstract:  The aqueous extract of the stem bark of Acacia karroo Hayne was investigated for its anti‐inflammatory and analgesic activities in animal models. The extract at 100 and 200 mg/kg reduced significantly the formation of oedema induced by carrageenan and histamine. In the acetic acid‐induced writhing model, the extract showed a good analgesic effect characterized by a significant reduction in the number of writhes with two doses (100 and 200 mg/kg) used when compared to the untreated control group. In the tail immersion test, the extract at the doses used (100 and 200 mg/kg) increased reaction time to pain after 30 min. of oral administration of the extract. Indomethacin at 10 mg/kg served as reference drug in all these tests. The results gave a scientific basis to the traditional uses of Acacia karroo mainly for wound poultices, eye treatments and cold remedies.
Analyses of CYP2C in Porcine Microsomes
Authors: Skaanild Mette T. , Friis Christian
Published: September 2008

Abstract: The cytochrome P450 2C (CYP2C) subfamily in human beings includes four different isoenzymes that metabolize different substrates although with some cross reactivity. Some of these substrates (e.g. diclofenac and tolbutamide), have been investigated in porcine microsomes, but without identifying the specific CYP catalysing the reactions. The objective of this study was therefore to test some CYP2C substrates and identify the porcine CYP2C responsible for the reaction. Three substrates, paclitaxel, tolbutamide and omeprazole, were chosen, as they are metabolized by three different CYP2C isoenzymes in human beings. Microsomes, isolated from 20 different pigs, 12 conventional, and 8 minipigs, were incubated with these compounds, and correlations between the metabolism rates of these three substrates were found indicating that the reactions are catalysed by the same enzyme. Male minipigs tend to have higher average activity than female minipigs, which is in contrast to the gender‐dependent expression seen for other CYP isoenzymes. The metabolic activities correlated with the protein level determined in Western blotting, using anti‐human CYP2C9, indicating that this enzyme is responsible for the reaction. The expression of the CYP2C enzymes was analysed by real‐time polymerase chain reaction, using a primer set that could amplify CYP2C8, CYP2C9 and CYP2C19. The melting curves (peaks) revealed that all three genes were present, showing very different expression levels in the various types of pigs. The area of one of the peaks, however, correlated with the CYP2C9‐like enzyme concentration, suggesting that this peak represents CYP2C9. Among paclitaxel, tolbutamide and omeprazole, omeprazole is the best probe of CYP2C9‐like enzyme in the pig.