bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure‐Strength Properties in Ceramics: II, Fatigue Relations
Authors: COOK ROBERT F. , LAWN BRIAN R. , FAIRBANKS CAROLYN J.
Published: June 2006

The study of crack‐size effects in aluminas and other selected ceramics in Part I is here extended to dynamic fatigue properties. Controlled flaws are used to measure the fatigue response in the large‐crack (indentation‐controlled) and small‐crack (microstructure‐controlled) regions. It is demonstrated that the “microstructural driving forces” responsible for the R‐curve behavior are readily accommodated into existing indentation fracture theories of fatigue strengths. The modified theory provides well‐defined solutions for the strengths in terms of stressing rate and indentation load. Two load‐invariant quantities, relating to the exponent and coefficient in an assumed power‐law crack velocity function, are sufficient to define the entire data set for a given material, at all stressing rates and loads. This is demonstrated graphically by reducing such data sets onto universal fatigue diagrams. The data for sapphire do not coincide with those for the poly crystalline aluminas, suggesting again that it is the grain‐boundary structure which holds the key to the fracture properties in the latter. From the standpoint of reliability, the study emphasizes the need to account for microstructural effects when extrapolating to the domain of naturally occurring flaws. In this context, the adjustable quantities obtained from the dynamic fatigue data fits emerge as appropriate design parameters.
EGFR point mutation in non‐small cell lung cancer is occasionally accompanied by a second mutation or amplification
Authors: Yokoyama Toshihiko , Kondo Masashi , Goto Yasuhiro , Fukui Takayuki , Yoshioka Hiromu , Yokoi Kohei , Osada Hirotaka , Imaizumi Kazuyoshi , Hasegawa Yoshinori , Shimokata Kaoru , Sekido Yoshitaka
Published: June 2006

Activating mutations of EGFR are found frequently in a subgroup of patients with non‐small cell lung cancer (NSCLC) and are highly correlated with the response to gefitinib and erlotinib. In the present study, we searched for mutations of EGFR, HER2 and KRAS in 264 resected primary NSCLC from Japanese patients and determined whether there is a correlation between genetic alterations of these genes and clinicopathological factors, together with 85 tumors that we reported previously. EGFR mutations were found in 102 of the total 349 tumors, and seven tumors had two missense mutations. Reverse transcription–polymerase chain reaction of EGFR and subsequent subcloning analyses identified that the double mutations occurred in the same allele. Furthermore, in 202 NSCLC analyzed by Southern blotting, we identified 11 tumors with gene amplification of EGFR, with eight tumors containing a mutation in EGFR. Sequence analysis detected only weak or no signals of the wild‐type allele in the eight tumors, strongly suggesting that the mutated allele was amplified selectively. These findings indicate that a dual genetic change of EGFR can occur in the same allele either with a possible second‐hit mutation or with amplification, which may imply a more selective growth advantage in a cancer cell. Meanwhile, HER2 mutations and amplifications were found in six of 349 tumors and three of 202 tumors, respectively, and KRAS mutations in 21 of 349 tumors. Mutations of the EGFR and HER2 genes were more frequently found in female never or light‐smoking patients with adenocarcinoma, and there were no tumors that had two or more mutations simultaneously among EGFR, HER2 and KRAS. The current study further demonstrates that a double genetic event in EGFR can occasionally occur in lung cancer, thus providing new clues for understanding the involvement of epidermal growth factor receptor signaling cascades in the pathogenesis of NSCLC. (Cancer Sci 2006; 97: 753–759)
Overuse of institutional care for children in Europe
Authors: Reading Richard
Published: June 2006

.
 
Browne K.,
Hamilton‐Giachritsis C.,
Johnson R. &
Ostergren M.
(
2006
)

,
332
,
485
–
487
.
Risk and protective factors for meningococcal disease in adolescents: matched cohort study
Authors: Reading Richard
Published: June 2006

.
 
Tully J.,
Viner R.M.,
Coen P.G.,
Stuart J.M.,
Zambon M.,
Peckham C.,
Booth C.,
Klein N.,
Kaczmarski E. &
Booy R.
(
2006
)

,
332
,
445
–
450
.

Objective  To examine biological and social risk factors for meningococcal disease in adolescents.

Design  Prospective, population‐based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner.

Setting  Six contiguous regions of England, which represent some 65% of the country’s population.

Participants  Fifteen‐to‐nineteen‐year‐olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls.

Methods  Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression.

Results  A total of 144 case–control pairs were recruited [74 male (51%); median age 17.6 years]. In total, 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4–5.9), intimate kissing with multiple partners (3.7, 1.7–8.1), being a university student (3.4, 1.2–10) and preterm birth (3.7, 1.0–13.5). Religious observance (0.09, 0.02–0.6) and meningococcal vaccination (0.12, 0.04–0.4) were associated with protection.

Conclusions  Activities and events increasing risk for meningococcal disease in adolescence are different from those in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.
Reproducibility of jaw movements in patients with craniomandibular disorders
Authors: STIESCH‐SCHOLZ M. , DEMLING A. , ROSSBACH A.
Published: June 2006

summary  It has never been investigated, if mandibular movements of patients with craniomandibular disorders (CMD) result in a lower reproducibility of dynamic functional parameters which are used for the individual articulator setting. The aim of the present study was to compare the reproducibility of electronically registered functional parameters in patients with CMD and in a control group. Dynamic functional parameters were recorded in 30 patients and 30 volunteers with a computerized ultrasound system (ARCUSdigma). The whole registration was performed three times during one session and three times at a second session 1 week later. The horizontal condylar inclination in the patient group gave a standard deviation of 2·17° ± 0·95°, indicating poorer reproducibility than in the volunteer group, for which the standard deviation was 1·37° ± 0·42°. The reproducibility of measurements of the Bennett angle was also poorer in the patient group than in the volunteer group, with standard deviations of 1·70° ± 0·62° and 1·22° ± 0·40°, respectively. The standard deviations calculated for determination of incisal inclination during laterotrusion was 3·02° ± 1·49° for patients and 2·30° ± 1·17° for volunteers. The standard deviations for incisal inclination during protrusion was 2·02° ± 0·95° for patients and 2·06° ± 1·82° for volunteers. The reproducibility of measurement of horizontal condylar inclination, Bennett angle and incisal inclination during laterotrusion therefore showed significantly lower reproducibility in the patient group than in the volunteer group (P < 0·05). The overall reproducibility of the measurements was nevertheless good in both groups, with standard deviations under 3·1°, so that an individual setting of an articulator seems useful even in patients with CMD.
Multiple paternity in wild‐caughtDrosophila mojavensis
Authors: GOOD JEFFREY M. , ROSS CHARLES L. , MARKOW THERESE A.
Published: June 2006

Female remating frequency and sperm allocation patterns can strongly influence levels of sperm competition and reproductive success in natural populations. In the laboratory,Drosophila mojavensismales transfer very few sperm per copulation and females remate often, suggesting multiple paternity should be common in nature. Here, we examine female sperm loads, incidence of multiple paternity, and sperm utilization by genotyping progeny from 20 wild‐caught females at four highly polymorphic microsatellite loci. Based on indirect paternity analyses of 814 flies, we found evidence for high levels of multiple paternity coupled with relatively low reproductive output, consistent with the high levels of female remating predicted in this sperm‐limited species. Overall, we found little evidence for last ‐ male sperm precedence though some temporal variation in sperm utilization was observed, consistent with laboratory findings.
Multiple nuclear gene sequences identify phylogenetic species boundaries in the rapidly radiating clade of Mexican ambystomatid salamanders
Authors: WEISROCK DAVID W. , SHAFFER H. BRADLEY , STORZ BRIAN L. , STORZ SHONNA R. , VOSS S. RANDAL
Published: June 2006

Delimiting the boundaries of species involved in radiations is critical to understanding the tempo and mode of lineage formation. Single locus gene trees may or may not reflect the underlying pattern of population divergence and lineage formation, yet they constitute the vast majority of the empirical data in species radiations. In this study we make use of an expressed sequence tag (EST) database to perform nuclear (nDNA) and mitochondrial (mtDNA) genealogical tests of species boundaries inAmbystoma ordinarium, a member of an adaptive radiation of metamorphic and paedomorphic salamanders (theAmbystoma tigrinumcomplex) that have diversified across terrestrial and aquatic environments. Gene tree comparisons demonstrate extensive nonmonophyly in the mtDNA genealogy ofA. ordinarium, while seven of eight independent nuclear loci resolve the species as monophyletic or nearly so, and diagnose it as a well‐resolved genealogical species. A differential introgression hypothesis is supported by the observation that westernA. ordinariumlocalities contain mtDNA haplotypes that are identical or minimally diverged from haplotypes sampled from a nearby paedomorphic species,Ambystoma dumerilii, while most nDNA trees place these species in distant phylogenetic positions. These results provide a strong example of how historical introgression can lead to radical differences between gene trees and species histories, even among currently allopatric species with divergent life history adaptations and morphologies. They also demonstrate how EST‐based nuclear resources can be used to more fully resolve the phylogenetic history of species radiations.
‘Sax‐sess’— genetics of primary succession in a pioneer species on two parallel glacier forelands
Authors: RAFFL C. , SCHÖNSWETTER P. , ERSCHBAMER B.
Published: June 2006

The primary succession on glacier forelands is characterized by a sequence of early and late successional species, but whether there is also a chronosequence at the intraspecific, genetic level is a matter of debate. Two opposing hypotheses differ in their prediction of genetic diversity in colonizing populations due to founder effects and postcolonization gene immigration. The development of genetic diversity in the pioneer Saxifraga aizoides was investigated along a successional gradient on two parallel glacier forelands, in order to test whether populations from older successional stages were less genetically diverse than populations from younger successional stages, and to locate the sources of the propagules that originally colonized new glacier foreland. Genetic diversity was determined with amplified fragment length polymorphisms, and potential sources of colonizing propagules were assessed via assignment tests. Our results indicate considerable postcolonization gene flow among populations on glacier forelands, since population differentiation was low and genetic diversity within populations was significantly higher. Molecular diversity and differentiation of populations did not develop linearly. Dispersal events within the glacier foreland, from the adjacent valley slopes, and from parallel glacier valleys were identified. In summary, it seems that the colonization of glacier forelands in the European Alps is highly dynamic and stochastic.
Patterns of genetic connectivity among anchialine habitats: a case study of the endemic Hawaiian shrimpHalocaridina rubraon the island of Hawaii
Authors: SANTOS SCOTT R.
Published: June 2006

Anchialine habitats, landlocked bodies of mixohaline water that fluctuate with the tides but have no surface connection to the sea, are known from around the world. Many anchialine organisms have widespread distributions and it has been hypothesized that high levels of gene flow and low levels of genetic differentiation are characteristic of populations from these habitats. However, the generality of this hypothesis requires further assessment, particularly in light of the significant negative impact these habitats and their biota have experienced from anthropogenic causes. This study investigated the population structure and demography of an endemic Hawaiian anchialine species, the atyid shrimpHalocaridina rubra, using mitochondrial cytochromecoxidase subunit I (COI) gene sequences. A survey of 305 individuals from 16 populations collected on the island of Hawaii revealed 135 haplotypes. These haplotypes belonged to one of two divergent (2.7–4.9%) lineages; notably, no haplotypes were shared between the two coasts of the island. Along each coast, strong subdivision and little to no gene flow occurs between populations separated by > 30 km. The population structure and demography ofH. rubraon Hawaii are influenced by regional hydrology, geology, volcanism and two distinct colonization events of the island. Thus,H. rubraon Hawaii demonstrates that populations of endemic anchialine organisms may exhibit significant levels of genetic structure and restricted levels of gene flow over limited geographic scales. This report brings novel insight into the biology of anchialine organisms and has important implications for the future management of these habitats and their biota.
Recombination and selection shape the molecular diversity pattern of nitrogen‐fixing Sinorhizobium sp. associated to Medicago
Authors: BAILLY XAVIER , OLIVIERI ISABELLE , DE MITA STÉPHANE , CLEYET‐MAREL JEAN‐CLAUDE , BÉNA GILLES
Published: June 2006

We investigate the genetic structure and molecular selection pattern of a sympatric population of Sinorhizobium meliloti and Sinorhizobium medicae. These bacteria fix nitrogen in association with plants of the genus Medicago. A set of 116 isolates were obtained from a soil sample, from root nodules of three groups of plants representing among‐species, within‐species and intraline diversity in the Medicago genus. Bacteria were characterized by sequencing at seven loci evenly distributed along the genome of both Sinorhizobium species, covering the chromosome and the two megaplasmids. We first test whether the diversity of host plants influence the bacterial diversity recovered. Using the same data set, we then analyse the selective pattern at each locus. There was no relationship between the diversity of Medicago plants that were used for sampling and the diversity of their symbionts. However, we found evidence of selection within each of the two main symbiotic regions, located on the two different megaplasmids. Purifying selection or a selective sweep was found to occur in the nod genomic region, which includes genes involved in nodulation specificity, whereas balancing selection was detected in the exo region, close to genes involved in exopolysaccharide production. Such pattern likely reflects the interaction between host plants and bacterial symbionts, with a possible conflict of interest between plants and cheater bacterial genotypes. Recombination appears to occur preferentially within and among loci located on megaplasmids, rather than within the chromosome. Thus, recombination may play an important role in resolving this conflict by allowing different selection patterns at different loci.
Community‐based study to assess the efficacy of DEC plus ALB against DEC alone on bancroftian filarial infection in endemic areas in Tamil Nadu, south India
Authors: Rajendran R. , Sunish I. P. , Mani T. R. , Munirathinam A. , Arunachalam N. , Satyanarayana K. , Dash A. P.
Published: June 2006

As part of the Global Programme for Elimination of Lymphatic Filariasis (GPELF), India is implementing mass drug administration (MDA) with annual single dose of diethylcarbamazine (DEC) with and without albendazole (ALB). The impact of MDAs on filarial infections and soil‐transmitted helminth (STH) infections was assessed during a 3‐year period in two communities, one with DEC + ALB and the other with DEC alone. Prior to each MDA (during 2001, 2002 and 2003), filarial indices (microfilaraemia and antigenaemia) were assessed from blood samples of 450–650 persons aged 2–25 years and STH infections in stool samples (Kato–Katz method) from 325 to 500 children aged 9–10 years. Mosquitoes resting indoors were collected to determine the filarial infection status. The microfilaraemia prevalence decreased significantly (P < 0.05) in both arms, with the highest decline in the DEC + ALB arm (72%vs. 51%). Decline in micrefilaria intensity was also higher in the DEC + ALB arm (81.4%vs. 48.5%). In this arm alone, the antigenaemia prevalence was reduced significantly (62%; P < 0.001). The reduction in STH prevalence was lower in the DEC alone arm (6.5%; NS) than in the DEC + ALB arm (70.9%; P < 0.001). Also, the egg reduction in DEC alone arm was only half that of DEC + ALB arm (49%vs. 97%). Our community‐based follow‐up study showed higher and sustained benefits with regard to filarial and STH infections for the two‐drug arm over the DEC alone arm. The trends suggest that at least 10 MDAs may be necessary to achieve the goal of elimination.
Cutaneous metastasis to the chest wall from prostate cancer
Authors: Wu Jashin J. , Huang David B. , Pang Katie R. , Tyring Stephen K.
Published: June 2006

Prostate cancer is the most common malignancy in men in the United States. However, skin metastasis from prostate carcinoma is extremely uncommon. Here, we present a 75‐year‐old Caucasian man with a history of metastatic prostate cancer developing multiple subcutaneous, erythematous nodules over the left anterior chest over a 3‐month period. A fine needle aspiration of a subcutaneous nodule showed neoplastic cells consistent with metastatic prostate cancer. This case represents only the fourth reported case of cutaneous metastasis from prostate cancer to the chest wall and the ninth case outside the inguinal area.
Pyoderma gangrenosum occurring near an arteriovenous dialysis shunt
Authors: Sangiray Hayri , Nguyen Josephine C. , Turiansky George W. , Norwood Christopher
Published: June 2006

Abtract

Pyoderma gangrenosum (PG) is an uncommon cutaneous disease of unknown etiology. In 50 percent of affected patients, PG is associated with systemic disease including inflammatory bowel disease, arthritis, and hematologic malignancies.1 Diagnosis of PG is based on clinical presentation, histopathology and on the exclusion of other diseases that can produce clinically similar lesions, e.g. infection, vasculitis, malignancy, collagen vascular diseases, diabetes, and trauma. Four variants of PG have been described: ulcerative, pustular, bullous, and vegetative.2 We report a woman with renal failure who developed PG in the absence of any obvious triggering trauma in a distinctive unilateral crop just distal to an arteriovenous dialysis shunt.
L’encadrement sectoriel de l’expression citoyenne: innovation sociale dans la democratie locale
Authors: Bratosin Stefan
Published: June 2006

Résumé**:  L’article restitue les résultats d’une recherche herméneutique sur le Conseil Communal de Concertation de la Ville de Lille, recherche alimentée par les données recueilles lors des entretiens avec les acteurs, par l’analyse des documents issus de l’activité du Conseil et par l’observation directe lors de différents types de réunions participant du fonctionnement du Conseil. Dans ce cadre, l’encadrement sectoriel de l’expression citoyenne est présenté, d’une part, comme une innovation sociale issue de la rencontre incontournable entre le besoin d’agir au nom d’un idéal appréhendé comme démocratie participative et le besoin d’exercer un contrôle supplémentaire sur la gestion urbaine par l’attachement aux traditions de la démocratie représentative et, d’autre part, comme une innovation sociale à but pédagogique visant l’éducation à la démocratie.
HLA‐C molecular characterization of a Lebanese population and genetic structure of 39 populations from Europe to India–Pakistan
Authors: Buhler S. , Megarbane A. , Lefranc G. , Tiercy J.‐M. , Sanchez‐Mazas A.
Published: June 2006

Lebanon is located at a continental crossroad between Europe, Africa, and Asia. This region has been the center of wide‐scale movements of populations as well as the theater of genetic and cultural trade off among neighboring populations. In this study, HLA‐C alleles were characterized by a PCR‐SSOP (sequence‐specific oligonucleotide probes) hybridization protocol in a sample of 97 Lebanese. A total of 23 alleles were identified with four predominant, Cw*0401, Cw*0602, Cw*0701/06, and Cw*1203, accounting for almost 60% of HLA‐C allele frequencies. We included the Lebanese data into a broad analysis of the HLA‐C genetic structure of a large set of populations located in Europe, the Middle East, and the Indian subcontinent. Our results indicate that Lebanese exhibit an intermediate genetic profile among the populations from the Middle East, which constitute a rather homogeneous genetic group. In Europe, a high correlation coefficient is found between genetic and geographic distances. In this continent, we also identified a significant genetic frontier following a north‐east to south‐west axis. This frontier cuts through the Alps and the Pyrenees, thus separating the north‐western European populations from those located in the eastern and Mediterranean areas. Finally, the populations from India – Pakistan are very heterogeneous, particularly the Dravidians. Their differentiation has probably been caused by rapid genetic drift under complex influences of cultural, linguistic, and/or religious barriers. Overall, the results show that the HLA‐C genetic patterns of these three geographic regions, i.e., the Middle East, Europe, and India – Pakistan, have been shaped by very different genetic histories.
Do the leukotriene receptor antagonists work in children with grass pollen‐induced allergic rhinitis?
Authors: Keskin Ozlem , Alyamac Evrim , Tuncer Ayfer , Dogan Cahit , Adalioglu Gonul , Sekerel Bulent Enis
Published: June 2006

Although cysteinyl‐leukotriene receptor antagonists were recently approved for use in allergic rhinitis (AR), there has been no study to date investigating their application in children. The aim was to evaluate whether montelukast provides any benefit in nasal allergen challenge‐induced symptoms in children, and whether it could improve the control provided by an antihistamine during pollen season. Two randomized studies, one a double‐blind, placebo‐controlled, nasal allergen challenge study and one an open‐label, cross‐over, parallel‐group clinical study, were performed in 18 (11.7 ± 0.7 years) and 32 children (10.5 ± 0.5 years), respectively, with grass pollen allergy. In the first study, the effect of a single dose of montelukast and its combination with loratadine were compared with placebo on nasal responses induced by allergen challenge. In the second study, the additive effect of montelukast to loratadine was tested in an open‐label cross‐over clinical study. In the challenge study, early‐phase and late‐phase nasal reactions peaked at 15 min and 4 h after the challenge respectively. During the early phase, combination improved total nasal symptoms (p = 0.004) during the first hour and sneezing (p = 0.012) at 15 min compared with placebo group. During the late phase, montelukast (p = 0.017) and combination (p = 0.011) caused less nasal obstruction at 4 h and combination caused less sneezing at 6 h (p = 0.015). In the clinical trial, montelukast provided protection on seasonal increase in pulmonary symptoms [0 (0, 14) vs. 6.5 (0, 27.7); p = 0.016] and on the decrease in FEF25−75 [−0.09 (−0.34, 0.17) vs. −0.28 (−0.66, 0.02); p = 0.002]. However, there was no improvement in nasal symptoms and flows. Although we showed protection against nasal challenge‐induced congestion with montelukast, we were not able to show the same in the clinical study possibly because of low pollen counts and mildness of the symptoms of the patients with AR. However, montelukast provided better control of pulmonary symptoms and protection from seasonal decrease in lung function, indicating its potential therapeutic benefit in children with AR.
Morphological and functional characterization of a pancreatic β‐cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride)
Authors: Stadlbauer V. , Stiegler P. B. , Schaffellner S. , Hauser O. , Halwachs G. , Iberer F. , Tscheliessnigg K. H. , Lackner C.
Published: June 2006

Abstract:  Background:  Late diabetic complications cannot be prevented totally by current antidiabetic strategies. Therefore, new therapeutic concepts of insulin replacement such as pancreas transplantation are evolving. Due to the shortage of human donor organs, transplantation of microencapsulated xenogeneic pancreatic islet cells has attracted considerable attention. Sodium cellulose sulfate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC) is a material with favorable biogenic properties that has been used for microencapsulation of various cell types. However, there are no data on the suitability of NaCS/PDADMAC for microencapsulation of pancreatic β‐cells.

Material and methods:  Cell growth and viability of NaCS/PDADMAC‐microencapsulated HIT‐T15 cells, an immortalized hamster pancreatic β‐cell line, were assessed using a dimethylthiazol‐diphenyltetrazoliumbromide (MTT)‐based cell growth determination kit and apoptosis was detected by antibodies against activated caspase 3. Glucose‐dependent insulin secretion was assessed with ELISA and the uptake of glucose was measured using fluorescence‐labeled glucose.

Results:  Statistical analysis revealed no differences in glucose‐dependent cell proliferation, insulin secretion and glucose uptake between non‐microencapsulated and microencapsulated HIT‐T15 cells. Stimulation of HIT‐T15 cells with glucose (100 mg/ml) resulted in a biphasic insulin secretion response.

Conclusion:  Microencapsulation of HIT‐T15 cells in NaCS/PDADMAC does not influence cell proliferation, insulin secretion and glucose uptake. Our results indicate that NaCS/PDADMAC is well suited for microencapsulation of pancreatic β‐cells.
Human NK cells can lyse porcine endothelial cells independent of their expression of Galα(1,3)‐Gal and killing is enhanced by activation of either effector or target cells
Authors: Horvath‐Arcidiacono Judith A. , Porter Cynthia M. , Bloom Eda T.
Published: June 2006

Abstract:  Background:  Xenotransplantation of pig organs may provide an approach to alleviate the severe shortage of human organs. Natural antibodies against Galα(1,3)‐Gal (αGal) epitopes cause hyperacute rejection of pig organs in primates. However, evidence for the role of αGal in the natural killer (NK) cell‐mediated xenoresponse has been contradictory.

Methods:  We investigated the recognition of αGal by human NK cells using endo‐β‐galactosidase C, an enzyme that cleaves αGal, and endothelial cells (EC) from α1,3‐galactosyltransferase null pigs that do not synthesize αGal. Endo‐β‐galactosidase C treatment variably reduced the susceptibility of porcine EC to lysis by fresh human NK cells.

Results:  Removal of αGal from porcine EC using endo‐β‐galactosidase C, produced variable results, i.e. cytotoxicity was decreased in half of the human NK cell donors tested. The two EC strains from αGal−/− pigs were marginally, and not significantly, less susceptible to lysis by naïve human NK cells compared with αGal‐expressing cells obtained from animals from the same herd, but these differences were not statistically significant (P > 0.10). Treatment of porcine EC with recombinant human tumor necrosis factor (TNF)‐α, which is known to activate porcine EC, enhanced the susceptibility of all target cells to lysis by fresh human NK cells. Surface expression of MHC or adhesion molecules on αGal−/− cells, compared with wild type cells, showed no consistent difference in either MHC or adhesion molecules CD106 (VCAM‐1), CD31 (PECAM) or CD62E (E‐selectin), either with or without TNF‐α stimulation, that could explain the differential susceptibility to lysis. Strikingly, all αGal−/− and wild type EC exhibited similar susceptibility to human NK cells that had been cultured for 5 days with or without interleukin‐2.

Conclusions:  These findings demonstrate that human NK cells can kill porcine targets in the absence of αGal, and donor variability plays a major role in whether αGal has a role in determining susceptibility of porcine EC to lysis. Moreover, susceptibility to lysis of αGal null EC is enhanced to the level of wild type EC by activation of either effector or target cells. Elimination of αGal alone from source pigs will be insufficient to circumvent the NK cell mediated destruction of porcine EC.
Genetic architecture of traits associated with serpentine adaptation of Silene vulgaris
Authors: Bratteler M. , Lexer C. , Widmer A.
Published: June 2006

Serpentine soils provide a difficult substrate for plant colonization and growth and therefore represent an ideal system for studying the genetics of habitat adaptation and the evolution of plant-ecotypes. Using an F2 mapping population derived from an intraspecific cross between a serpentine and a nonserpentine ecotype of Silene vulgaris, the genetic architecture of seven morphological, physiological and life-history traits was explored. A quantitative trait locus (QTL) analysis identified 23 QTLs, 15 of which were classified as major QTLs. The observed genetic architecture suggests that traits potentially involved in habitat adaptation are controlled by few genes of major effect and have evolved under consistent directional selection. Several linkage groups harboured overlapping QTLs for different traits, which can be due to either pleiotropy or linkage. The potential roles of these factors and of the time available for habitat adaptation and ecological speciation on serpentine are discussed.
Protein sequences of linked genes are highly conserved in two bacterial species
Authors: Theodosiou T. , Iliopoulos I.
Published: June 2006

It has been shown that proteins encoded by linked genes have similar rates of evolution and that clusters of essential genes are found in regions with low recombination rates. We show here that proteins encoded by linked genes in two closely related bacterial species, namely Escherichia coli K12 and Salmonella typhimurium LT2, evolve more slowly when compared with proteins encoded by genes that are not linked as assessed by protein sequence similarity. The proteins encoded by the identified linked genes share an average sequence identity of 82.5% compared with a 46.5% identity of proteins encoded by genes that are not linked.
Runx3 controls growth and differentiation of gastric epithelial cells in mammals
Authors: Fukamachi Hiroshi
Published: June 2006

Runx3 is a transcription factor expressed by gastric epithelial cells. In the Runx3−/– mouse, gastric epithelia exhibited hyperplasia, and epithelial apoptosis was suppressed. By analyzing growth of the epithelial cells in primary culture, we found that Runx3−/– gastric epithelial cells are less sensitive to the growth‐inhibitory and apoptosis‐inducing activities of TGF‐β, suggesting that Runx3 is a major growth regulator of gastric epithelial cells by regulating their response to TGF‐β. We also found that Runx3 plays an important role in the control of gastric epithelial differentiation. When subcutaneously implanted into nude mice, Runx3−/– gastric epithelial cells formed tumors in which some cells differentiated into intestinal‐type cells. Clonal analysis showed that gastric epithelial cells transdifferentiate into intestinal‐type cells in the tumor. Considering that gastric epithelial differentiation is very stable, and that intestinal‐type cells never differentiate in the mouse stomach, it is remarkable that gastric epithelial cells transdifferentiate into intestinal‐type cells. We conclude that Runx3 is deeply involved in the control of both growth and differentiation of gastric epithelial cells. The role of Runx3 in the specification of gastric epithelial cells is discussed.
EFFECT OF NITRIC OXIDE ON THE HYPOGLYCAEMIC PHASE OF ENDOTOXAEMIA
Authors: Engin Atilla , Zemheri Mahmut , Bukan Neslihan , Memiş Leyla
Published: June 2006

Background:  Depletion of liver glycogen stores and subsequent hypoglycaemia is one of the unresolved features in endotoxaemia. The aim of this study was to elucidate the effect of L‐arginine treatment on the glucose requirement and impending liver damage during the hypoglycaemic period of endotoxaemia.

Methods:  Sixty‐three of 98 male Wistar rats were assigned equally to one of three groups and received saline as control, L‐arginine as selective nitric oxide donor or NG‐nitro‐L‐arginine methyl ester for non‐selective inhibition of nitric oxide production 1 h before endotoxin injection. At 2, 4 and 6 h following endotoxin, blood and liver samples were collected. Plasma nitrite plus nitrate, glucose, insulin and glucagon concentrations and total liver‐reduced glutathione were measured. Hepatocellular glycogen content and liver damage were assessed simultaneously by histological quantification. An additional seven rats were allocated to each group and subjected to i.v. glucose tolerance test during the hypoglycaemic period.

Results:  Increased levels of endogenousglutathione (P = 0.003) and excess nitric oxide (P = 0.002) apparently protected the liver from endotoxin‐induced injury by preserving the optimum glucose consumption rate, insulin/glucagon ratio and liver glycogen in L‐arginine‐plus‐endotoxin‐treated group. Furthermore, expected hypoglycaemic period was not observed in these animals.

Conclusion:  Exogenous L‐arginine prevented the excessive liver glycogen release without inhibiting glucose consumption while decreasing hepatic injury during the expected hypoglycaemic phase of endotoxaemia.
Usefulness of carotid parameters measured by ultrasonography as a marker of atherothrombotic infarction and lacunar infarction in high‐risk elderly people
Authors: Watanabe Kentaro , Suzuki Tatsuya , Nakano Hiroshi , Oba Kenzo
Published: June 2006

Aim:  Many studies have reported that carotid parameters measured by ultrasonography are predictors for cerebral infarction. The aim of this study was to investigate by a cross‐sectional study whether those carotid parameters are markers for atherothrombotic infarction (AI) and lacunar infarction (LI) in elderly people having cardiovascular risk factors.

Methods:  We studied 314 patients aged 65 years or older who had controlled cardiovascular diseases and assessed carotid arteries by ultrasonography. The subjects were categorized into control, AI and LI groups. Clinical characteristics (biochemical analysis, body mass index, systolic/diastolic blood pressure, smoking habits, hypertension, diabetes mellitus and statin therapy) and carotid parameters (maximum intima‐media thickness [Max‐IMT], plaque score [PLQ‐S] and maximum pulsatility index [Max‐PI]) were compared among the three groups.

Results:  PLQ‐S, Max‐PI, frequency of PLQ‐S ≥ 10 mm and frequency of Max‐PI ≥ 2.0 were significantly higher in the AI group than in the control group. There were no significant differences between the control and LI groups concerning carotid parameters. Multivariate logistic regression analysis showed that there were significant correlations between AI and PLQ‐S ≥ 10 mm (odds ratio 2.980; P = 0.011), AI and Max‐PI ≥ 2.0 (odds ratio 2.458; P = 0.038), but there were no significant correlations between those carotid parameters and LI.

Conclusions:  This study suggests that in high‐risk elderly people, PLQ‐S and PI are better markers for AI than IMT, but those carotid parameters do not correlate with LI.
Successful treatment using cyclosporine A plus corticosteroid therapy in an elderly patient with severe idiopathic interstitial pneumonia
Authors: Kikawada Masayuki , Kimura Akihiro , Watanabe Daisuke , Nakai Toshiki , Koyama Shunichi , Kanetaka Hidekazu , Hanyu Haruo , Iwamoto Toshihiko
Published: June 2006

An 81‐year‐old woman was referred to our hospital due to acute progressive respiratory failure. Her chest X‐ray film showed bilateral interstitial changes and computed tomography revealed a diffuse ground‐glass appearance. Histological examination of transbronchial lung biopsy specimens did not provide a final diagnosis. The patient was diagnosed as having idiopathic interstitial pneumonia (IIP) and was treated with corticosteroid therapy. The chest X‐ray appearance improved temporarily after corticosteroid therapy, but the interstitial changes did not resolve and subsequently became worse again, so administration of cyclosporine A was added. After commencement of cyclosporine A, corticosteroid therapy could be gradually tapered over 10 months. This case suggests that a combination of steroid therapy with cyclosporine A is effective for severe IIP of unknown pathological diagnosis.
Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease
Authors: Galati Salvatore , Mazzone Paolo , Fedele Ernesto , Pisani Antonio , Peppe Antonella , Pierantozzi Mariangela , Brusa Livia , Tropepi Domenicantonio , Moschella Vincenzo , Raiteri Maurizio , Stanzione Paolo , Bernardi Giorgio , Stefani Alessandro
Published: June 2006

To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN‐DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92–3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear‐cut increase in cyclic guanosine 3',5'‐monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus‐synchronized activation of the STN target, SNr. Our findings suggest that, during STN‐DBS, a critical change towards a high‐frequency oscillatory discharge occurs.
Testosterone and photoperiod interact to affect spatial learning and memory in adult male white‐footed mice (Peromyscus leucopus)
Authors: Pyter Leah M. , Trainor Brian C. , Nelson Randy J.
Published: June 2006

Gonadal hormones affect spatial learning and memory in mammals and circulating gonadal hormone concentrations fluctuate by season. Most nontropical rodents are spring/summer breeders and males display higher testosterone concentrations during the breeding season compared with the nonbreeding season (fall/winter). Seasonal patterns of testosterone concentration (as well as many other seasonal modifications of physiology, morphology, and behaviour) are induced by manipulation of photoperiod (day length; i.e. short or long days) in the laboratory. Coincident with reducing testosterone concentration, short days also impair spatial learning and memory performance in male white‐footed mice (Peromyscus leucopus) compared with long days. We hypothesized that short‐day‐induced reduction of testosterone concentrations inhibits spatial learning and memory performance compared with long days. Adult male white‐footed mice were maintained in long (16 h light/day) or short (8 h light/day) days for 14 weeks following sham‐castration, castration plus saline implant, or castration plus testosterone implant treatment. Spatial learning and memory was assessed using a water maze, and photoperiod‐evoked changes in gene expression of sex steroid receptors within the hippocampus were also examined. Castrated, short‐day mice with testosterone replacement displayed enhanced water maze performance compared with other short‐day mice, but no differences among testosterone treatments were observed in long‐day mice. Photoperiod did not affect hippocampal androgen, oestrogen α, or oestrogen β receptor gene expression. These results suggest that photoperiod modulates the effects of testosterone on spatial learning performance by mechanisms indirect of the hippocampus.
Selective prefrontal serotonin depletion impairs acquisition of a detour‐reaching task
Authors: Walker S.C. , Mikheenko Y.P. , Argyle L.D. , Robbins T.W. , Roberts A.C.
Published: June 2006

We have recently shown that serotonin in the primate orbitofrontal cortex (OFC) contributes to the flexible control of behaviour. 5,7‐dihydroxytryptamine‐induced 5‐HT depletions of OFC impair performance on a serial reversal discrimination task [Clarke et al. (2004)Science, 304, 878–880]. The deficit is characterized by perseverative responding to the previously rewarded stimulus, a deficit similar to that seen following lesions of the intrinsic neurones of the OFC [Dias et al. (1996)Nature, 380, 69–72]. The effect is neurochemically selective as dopaminergic lesions of the OFC, induced by 6‐hydroxydopamine, have no effect [Clarke et al. (2006)Cerebral Cortex]. In order to test for the generality of the effect of serotonin on orbitofrontal processing and, in particular, its effects on flexible behaviour, the present study investigated the effects of serotonin depletions of OFC on performance of another task dependent upon an intact OFC, the detour‐reaching task [Wallis et al. (2001)European Journal of Neuroscience, 13, 1797–1808]. Successful performance of this task requires inhibition of the animal's prepotent response tendency to reach directly along its line of sight to the reward. Compared with sham‐operated controls, we found that lesioned monkeys made significantly more barrier reaches directly along their line of sight to the visible reward during task acquisition. This finding provides further support for the role of prefrontal serotonin in inhibitory control processes specifically in tasks sensitive to OFC dysfunction.
Early midline interactions are important in mouse optic chiasm formation but are not critical in man: a significant distinction between man and mouse
Authors: Neveu Magella M. , Holder Graham E. , Ragge Nicola K. , Sloper John J. , Collin J. Richard O. , Jeffery Glen
Published: June 2006

The optic chiasm is one of the most popular models for studying axon guidance. Here axons make a key binary decision either to cross the midline to innervate the contralateral hemisphere or to remain uncrossed. In rodents, midline interactions between axons from the two eyes are critical for normal development, as early removal of one eye systematically disrupts hemispheric projections from the remaining eye, increasing the crossed projection at the expense of the uncrossed. This is similar to the abnormal decussation pattern seen in albinos. This pattern is markedly different in marsupials where early eye removal has no impact on projections from the remaining eye. These differences are related to the location of the uncrossed projection through the chiasm. In rodents these axons approach the midline whereas in marsupials they remain segregated laterally. We provide anatomical evidence in man suggesting that, unlike in rodents, uncrossed axons are confined laterally and do not mix in each hemi‐chiasm, which is a pattern similar to that found in marsupials. Further, we demonstrate electrophysiologically, using visual cortical evoked potentials, that the failure of one eye to develop in man has no impact on the hemispheric projections from the remaining eye. These data demonstrate that the mechanisms regulating chiasmal development in man differ from those in rodents but may be similar to those in marsupials. We suggest that mouse models of the organization and development of the optic chiasm are not common to placental mammals in general.
An endogenous inhibitor of calcium/calmodulin‐dependent kinase II is up‐regulated during consolidation of fear memory
Authors: Lepicard Eve M. , Mizuno Keiko , Antunes‐Martins Ana , Von Hertzen Laura S. J. , Giese K. Peter
Published: June 2006

CaMKIINα and CaMKIINβ are endogenous inhibitors of the abundant synaptic protein, calcium/calmodulin‐dependent protein kinase II (CaMKII). CaMKII exerts a prominent function in memory formation and the endogenous inhibitors might be important regulators of CaMKII activity during this process. Here we investigated whether or not CaMKIINα and CaMKIINβ gene expressions are regulated in the mouse hippocampus and amygdala after background contextual fear conditioning. Quantitative real‐time PCR revealed that the hippocampal expression of CaMKIINα mRNA was up‐regulated 30 and 60 min after conditioning. In contrast, CaMKIINβ mRNA expression did not change. The up‐regulation of CaMKIINα expression was specific for the fear memory because the context alone and a shock control did not induce any variation of transcription level. Quantification of in situ hybridization signals showed that CaMKIINα expression increased in hippocampal area CA1, in the dentate gyrus (DG) and in the lateral amygdala (LA) 30 min after training. Our findings show an up‐regulation in the expression of the endogenous inhibitor gene CaMKIINα during consolidation of fear memory. The early onset and the amplitude of the up‐regulation are similar to those of immediate‐early genes. Taken together, our results suggest that the CaMKIINα inhibitor has a physiological role in controlling CaMKII activity from an early stage of memory consolidation.