bluuebunny/crossref_metadata_2025 huggingface dataset:
Exceptionally high levels of recombination across the honey bee genome
Authors: Beye Martin , Gattermeier Irene , Hasselmann Martin , Gempe Tanja , Schioett Morten , Baines John F. , Schlipalius David , Mougel Florence , Emore Christine , Rueppell Olav , Sirviö Anu , Guzmán-Novoa Ernesto , Hunt Greg , Solignac Michel , Page Robert E.
Published: October 2006

The first draft of the honey bee genome sequence and improved genetic maps are utilized to analyze a genome displaying 10 times higher levels of recombination (19 cM/Mb) than previously analyzed genomes of higher eukaryotes. The exceptionally high recombination rate is distributed genome-wide, but varies by two orders of magnitude. Analysis of chromosome, sequence, and gene parameters with respect to recombination showed that local recombination rate is associated with distance to the telomere, GC content, and the number of simple repeats as described for low-recombining genomes. Recombination rate does not decrease with chromosome size. On average 5.7 recombination events per chromosome pair per meiosis are found in the honey bee genome. This contrasts with a wide range of taxa that have a uniform recombination frequency of about 1.6 per chromosome pair. The excess of recombination activity does not support a mechanistic role of recombination in stabilizing pairs of homologous chromosome during chromosome pairing. Recombination rate is associated with gene size, suggesting that introns are larger in regions of low recombination and may improve the efficacy of selection in these regions. Very few transposons and no retrotransposons are present in the high-recombining genome. We propose evolutionary explanations for the exceptionally high genome-wide recombination rate.
Assessment may conceal therapeutic benefit: findings from a randomized controlled trial for hazardous drinking
Authors: Kypri Kypros , Langley John D. , Saunders John B. , Cashell‐Smith Martine L.
Published: October 2006

Context  The concept that assessment of a person's health status without subsequent intervention has beneficial effects in itself has stimulated much interest in underlying psychological mechanisms, methodological implications and its public health potential. There have, however, been few experimental studies of assessment effects.

Aim  To test the hypothesis that assessment in itself produces a reduction in hazardous drinking.

Design and setting  Two conditions (group A, leaflet only and group B, leaflet and assessment but no intervention) of a four‐arm randomized controlled trial with enrolment in March–April 2003.

Participants  A total of 975 students (17–29 years) attending a primary health‐care clinic completed a web‐based Alcohol Use Disorders Identification Test (AUDIT) questionnaire. Of 599 who scored ≥ 8576 consented to follow‐up and were included in the full four‐arm trial, of whom 293 (153 women) were assigned to groups A and B.

Intervention  Group A received an information leaflet at baseline. Group B received the information leaflet and 10 minutes of web‐based assessment 4 weeks later.

Measurements  Drinking frequency, typical quantity, heavy episode frequency, personal problems and academic problems.

Findings  Baseline mean AUDIT scores were 15.0 (SD = 5.4) and 14.9 (SD = 5.0) in groups A and B, respectively. Twelve months after baseline, relative to group A, group B reported lower overall consumption (geometric means ratio 0.82, 95% CI: 0.68–0.98), fewer heavy drinking episodes (0.66, 0.47–0.91), fewer problems (0.81, 0.67–0.99) and lower AUDIT scores (beta = −1.63, −0.62 to −2.65).

Conclusions  Brief assessment appeared to reduce hazardous drinking. Controlled trials that rely on assessment may therefore underestimate treatment effects. Limitations include the possibility of measurement artefact due to social desirability bias.
Unusual case presentations associated with the CD45 C77G polymorphism
Authors: Tchilian E Z , Gil J , Navarro M L , Fernandez-Cruz E , Chapel H , Misbah S , Ferry B , Renz H , Schwinzer R , Beverley P C L
Published: October 2006

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.
Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life
Authors: Ponsonby A-L , Dwyer T , Van Der Mei I , Kemp A , Blizzard L , Taylor B , Kilpatrick T , Simmons R
Published: October 2006

Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case–control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0·02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0·04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7·22 (95% CI: 2·52, 20·65). Early life sibling exposure was associated with altered IgG serological responses to Epstein–Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.
ES1, a new lung carcinoma antibody— an immunohistochemical study
Authors: Mai K T , Perkins D G , Zhang J , MacKenzie C R
Published: October 2006

Aims:  To characterize a single domain antibody (sdAb), AFAI, obtained by panning a naive phage display library of single domain antibodies against the non‐small cell lung carcinoma cell line A549. AFAI recognizes a variant form of carcinoembryonic antigen‐related cell adhesion molecule 6 (CEACAM6 or CEA6).

Methods and results:  Various normal tissues and 139 neoplastic lesions from lung and other organs were immunostained with ES1 antibody, a pentameric and highly avid form of AFAI. ES1 was immunoreactive with 34 of 35 non‐squamous large cell lung carcinomas with staining intensities ranging from focal to extensive and from moderate to strong. Importantly, ES1 stained poorly differentiated lung adenocarcinomas and many undifferentiated large cell lung carcinomas that typically show negative immunoreactivity with an antibody specific for thyroid transcription factor‐1. Non‐lung adenocarcinomas showed more focal and weaker immunoreactivity than for lung adenocarcinoma. Other carcinomas showed negative or weak immunoreactivity and normal tissues showed no immunoreactivity.

Conclusions:  Compared with other antibodies used in the clinical evaluation of lung adenocarcinomas, ES1 is more lung carcinoma sensitive, more sensitive in immunostaining of poorly differentiated adenocarcinomas that are usually associated with distant metastasis and less immunoreactive with normal tissues.
Development and design of a ‘ready‐to‐use’ reaction plate for a PCR‐based simultaneous detection of animal species used in foods
Authors: Laube Ines , Zagon Jutta , Spiegelberg Almuth , Butschke Andreas , Kroh Lothar W. , Broll Hermann
Published: October 2006

Different TaqManTM‐polymerase chain reaction systems have been developed, which allow the detection of even minute amounts of beef, pork, lamb, goat, chicken, turkey and duck in processed foods. The species‐specific systems are able to amplify DNA regions with no more than 108 bp in size (exception: duck, 212 bp) located on the single‐copy genes cyclic guanosine monophosphate (cyclic GMP) phosphodiesterase, ryanodine receptor and interleukin‐2 precursor. The parallel detection of the common ingredient ‘meat’ produced from mammals and poultry was based on the amplification of a region of the myostatin gene. The limit of detection was determined to be ten genome copies for each system. The relative SD under repeatability condition was below 30%. In addition, a ‘ready‐to‐use’ reaction plate has been developed, which makes it possible to investigate the presence of the seven animal species in parallel after a single real‐time run.
Use crude olive leaf juice as a natural antioxidant for the stability of sunflower oil during heating
Authors: Farag Radwan S. , Mahmoud Ebtesam A. , Basuny Amany M.
Published: October 2006

Olive leaves (Kronakii cultivar) were obtained from the annual pruning of olive trees and pressed to obtain a crude juice. Aliquots from the concentrated crude olive leaf juice, representing 400, 800, 1600 and 2400 ppm as polyphenols, were added to sunflower oil. Samples of sunflower oil mixed with olive leaf juice were heated intermittently at 180 ± 5 °C for 5 h day−1 and the heating process was repeated for five consecutive days. A control experiment was performed where butylated hydroxyl toluene (BHT) at 200 ppm was added to sunflower oil prior to intermittent heating in order to compare the antioxidant efficiency between the natural polyphenolics of olive leaf juice and synthetic antioxidant BHT. Some physical and chemical constants for the unheated and heated sunflower oil were determined. The data indicate that the addition of olive leaf juice to sunflower oil heated at 180 °C induced remarkable antioxidant activity and at 800 ppm level was superior to that of BHT in increasing sunflower oil stability.
The non‐typeable Haemophilus influenzae Sap transporter provides a mechanism of antimicrobial peptide resistance and SapD‐dependent potassium acquisition
Authors: Mason Kevin M. , Bruggeman Molly E. , Munson Robert S. , Bakaletz Lauren O.
Published: October 2006

We have shown that non‐typeable Haemophilus influenzae (NTHI) resists killing by antimicrobial peptides (APs). A mutant defective in expression of the sap (sensitivity to antimicrobial peptides) gene cluster product SapA is sensitive to killing by APs and is significantly attenuated in its ability to survive in a chinchilla model of otitis media compared with the parent strain. In NTHI, SapA is believed to function as the periplasmic solute binding protein of an ABC transporter. Here, we demonstrated that recombinant chinchilla beta defensin‐1 specifically interacted with recombinant SapA and that AP exposure increased expression of the sap operon. We further demonstrated that the putative Sap transporter ATPase protein, SapD, was required for AP resistance as well as potassium uptake in NTHI strain 86‐028NP. Loss of SapD additionally abrogated NTHI survival in vivo. Complementation of the sapD mutation restored the ability to grow in potassium‐limited medium, resistance to AP‐mediated killing and survival in vivo. Collectively, these data support a mechanism of Sap system‐mediated resistance to APs that depends on Sap‐dependent transport of APs and a Sap‐dependent restoration of potassium homeostasis. Thus, NTHI required a functional Sap system to mediate bacterial survival and pathogenesis in vivo.
A clash to conquer: the malaria parasite liver infection
Authors: Mikolajczak Sebastian A. , Kappe Stefan H. I.
Published: October 2006

All mammalian malaria parasite species have an initial tissue stage in liver cells. The liver stage produces new parasite forms that can enter and live inside red blood cells. Accordingly, the first place of residence provides parasites with a radically different cellular and molecular environment from their subsequent red blood cell home. Liver stages have remained refractory to reveal their secrets, yet the last few years have seen several advances in elucidating their biology. This review looks at the more recent findings concerning the liver stage–host hepatocyte association, some of which may become powerful weapons in the prevention of malaria infection. We also outline areas of liver stage research and technological development that provide promising foci to accelerate a better understanding of this most elusive of the parasites many life cycle stages.
The evolution of endosymbiont density in doubly infected host species
Authors: ENGELSTÄDTER J. , HAMMERSTEIN P. , HURST G. D. D.
Published: October 2006

Multiple infection of individual hosts with several species or strains of maternally inherited endosymbionts is commonly observed in animals, especially insects. Here, we address theoretically the effect of co‐infection on the optimal density of the endosymbionts in doubly infected hosts. Our analysis is based on the observation that a maternally inherited double infection is only stable if doubly infected females produce more doubly infected daughters than singly infected or uninfected females produce daughters. We consider both a general model and a model involving two endosymbionts inducing bidirectional cytoplasmic incompatibility (CI). We demonstrate that the optimal replication rate of endosymbionts in doubly infected hosts can be expected to be similar to or below the optimal replication rate in singly infected hosts. This is in contrast to some theoretical predictions for horizontally transmitted parasites and stems from the two strains of endosymbionts having coupled fitness. We discuss our results with respect to recent empirical results on endosymbiont densities, the evolution of CI‐inducing bacteria and, more generally, the evolution of cooperation through direct fitness benefits.
Analysis of environmental transcriptomes by DNA microarrays
Authors: Parro Víctor , Moreno‐Paz Mercedes , González‐Toril Elena
Published: October 2006

In this work we investigated the correlations between global gene expression patterns and environmental parameters in natural ecosystems. We studied the preferential gene expression of the iron oxidizer bacterium Leptospirillum ferrooxidans to adapt its physiology to changes in the physicochemical parameters in its natural medium. Transcriptome analysis by DNA microarrays can proportionate an instant picture about the preferential gene expression between two different environmental samples. However, this type of analysis is very difficult and complex in natural ecosystems, mainly because of the broad biodiversity and multiple environmental parameters that may affect gene expression. The necessity of high‐quality RNA preparations as well as complicated data analysis are also technological limitations. The low prokaryotic diversity of the extremely acidic and iron‐rich waters of the Tinto River (Spain) ecosystem, where L. ferrooxidans is abundant, allows the opportunity to achieve global gene expression studies and to associate gene function with environmental parameters. We applied a total RNA amplification protocol validated previously for the amplification of the environmental transcriptome (meta‐transcriptome). The meta‐transcriptome of two sites from the Tinto River mainly differing in the salt and oxygen contents were amplified and analysed by a L. ferrooxidans DNA microarray. The results showed a clear preferential induction of genes involved in certain physicochemical parameters like: high salinity (ectAB, otsAB), low oxygen concentration (cydAB), iron uptake (fecA‐exbBD‐tonB), oxidative stress (carotenoid synthesis, oxyR, recG), potassium (kdpBAC) or phosphate concentrations (pstSCAB), etc. We conclude that specific gene expression patterns can be useful indicators for the physiological conditions in a defined ecosystem. Also, the upregulation of certain genes and operons reveals information about the environmental conditions (nutrient limitations, stresses, etc.).
Her kind: Anne Sexton, the Cold War and the idea of the housewife
Authors: POLLARD CLARE
Published: October 2006

As a key figure of the 'Confessional' movement, Anne Sexton's work has often been critically assessed only in relation to her life ‐ her history of mental illness and eventual suicide. This article attempts to place Sexton's poetry back into its historical context, arguing that with American suburbia being viewed as a new 'home front' during the Cold War, the persona of 'Housewife‐poet' that Sexton adopted was highly politically charged. Seizing the language of pop‐culture ‐ from advertising to sci‐fi ‐ Sexton used it to expose the nightmare behind the white picket fence, and deconstruct the carefully constructed propaganda of the American housewife.
Terms of power, today: an essay in political epistemology
Authors: SUVIN DARKO
Published: October 2006

The semantic jungle of 'Force', 'Strength', but mainly of 'Power' and 'Violence', or who rules whom how and why, is examined in view of politics today. Power in class societies is defined as societally significant human agency that involves coercion to enforce (repress and/or promote) given types of asymmetrical relations between people, and Violence as irreversible psychophysical harm or lesion wilfully inflicted by people to other people in pursuit of power. At the end, the 'structural violence' and the 'Fanon‐Gandhi' (liberatory violence vs. non‐violence) problems are briefly envisaged.
On the Credibility of Currency Boards*
Authors: Feuerstein Switgard , Grimm Oliver
Published: October 2006

The paper compares the credibility of currency boards and (standard) pegs. Abandoning a currency board requires a time‐consuming legislative process and an abolition will thus be well‐anticipated. Therefore, a currency board solves the time‐inconsistency problem of monetary policy. However, policy can react to unexpected shocks only with a time lag, thus the threat of large shocks makes the abolition more likely. Currency boards are more credible than standard pegs if the time‐inconsistency problem dominates. In contrast, standard pegs, that can be left at short notice, are more credible if exogenous shocks are highly volatile and constitute the dominant problem.
Trade Union Rights, Democracy, and Exports: a Gravity Model Approach*
Authors: Kucera David , Sarna Ritash
Published: October 2006

The paper uses a gravity trade model to evaluate the effects of trade union rights and democracy on exports for the 1993 to 1999 period for four classifications of manufacturing industries by labor‐intensity. The model includes data for 162 countries and used eight indicators of trade union rights and democracy, including those constructed by the authors. The paper finds robust relationships between stronger trade union rights and higher total manufacturing exports and between stronger democracy and higher total exports, total manufacturing exports, and labor‐intensive manufacturing exports. The paper finds that the relationship between trade union rights and labor‐intensive manufacturing exports is highly sensitive to the classification of labor‐intensive manufacturing industries and to model specification, yielding statistically significant results of opposite sign depending on assumptions.
Bayesian Estimation of Willingness‐to‐pay Where Respondents Mis‐report Their Preferences*
Authors: Balcombe K. , Bailey A. , Chalak A. , Fraser I.
Published: October 2006

We introduce a modified conditional logit model that takes account of uncertainty associated with mis‐reporting in revealed preference experiments estimating willingness‐to‐pay (WTP). Like Hausman et al. [Journal of Econometrics (1988) Vol. 87, pp. 239–269], our model captures the extent and direction of uncertainty by respondents. Using a Bayesian methodology, we apply our model to a choice modelling (CM) data set examining UK consumer preferences for non‐pesticide food. We compare the results of our model with the Hausman model. WTP estimates are produced for different groups of consumers and we find that modified estimates of WTP, that take account of mis‐reporting, are substantially revised downwards. We find a significant proportion of respondents mis‐reporting in favour of the non‐pesticide option. Finally, with this data set, Bayes factors suggest that our model is preferred to the Hausman model.
Predictors of long‐term neurological sequelae of tuberculous meningitis: a multivariate analysis
Authors: Kalita J. , Misra U. K. , Ranjan P.
Published: October 2006

There is paucity of studies on predictors of long‐term sequelae of tuberculous meningitis (TBM). We report the neurological sequelae of TBM at 1 year and their predictors. Patients with TBM who were followed up for 1 year were included. The diagnosis of TBM was based on clinical, cerebrospinal fluid (CSF) and computed tomography (CT) scan findings. Detailed neurological examinations at admission and at 1 year were carried out. All the patients received four‐drug antitubercular therapy. The frequency of sequelae at 1 year were noted and the role of various demographic (age, sex, duration of illness, BCG vaccination), clinical (weakness, seizure, extra central nervous system tuberculosis, Glasgow Coma Scale (GCS) score, cranial nerve palsy, stage, corticosteroid, drug‐induced hepatitis, shunt surgery), and laboratory findings (erythrocyte sedimentation rate (ESR), CSF cell and protein, CT scan evidences of hydrocephalus, basal exudates, infarctions and tuberculoma) at presentation were evaluated employing logistic regression analysis. Sixty‐five patients with TBM were included in this study whose age ranged between 13 and 80 years (mean 33.2), 27 of whom were females. Complete neurological recovery at 1 year occurred in 21.5% patients only although about 50% were independent for activities of daily living. Neurological sequelae were observed in 78.5% patients, which included cognitive impairment in 55%, motor deficit in 40%, optic atrophy in 37% and other cranial nerve palsy in 23%. On logistic regression analysis, focal motor deficit at admission was the most important predictor of neurologic deficits at 1 year. GCS score predicted the cognitive and motor sequelae. Neurological sequelae at year occurred in 78.5% patients with TBM in the form of cognitive impairment, motor deficit and optic atrophy. Sequelae were common in patients who had focal motor deficit and altered sensorium at admission.
Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis
Authors: Mihailova S. M. , Ivanova M. I. , Quin L. M. , Naumova E. J.
Published: October 2006

The occurrence of multiple sclerosis (MS) in subjects clustering to a particular mitochondrial DNA (mtDNA) haplogroup/haplotype or carrying mtDNA mutations associated with Leber's hereditary optic neuropathy (LHON) has suggested that mitochondrial genome may contribute to susceptibility to MS. In the present study, 58 unrelated Bulgarian patients with relapsing remitting form of MS and 104 randomly selected healthy individuals were analysed for the presence of 14 mtDNA polymorphisms determining major European haplogroups as well as three (4216, 14 798, 13 708) secondary LHON mutations. Restriction enzyme analysis used to screen patients and controls for the common haplogroup‐associated polymorphisms showed that each of these changes was present in MS patients at a similar frequency to control subjects. However, 21 of the 58 patients (36.2%) were positive for T4 216C mutation, while only 11.3% of the controls carried this secondary LHON base change (P < 0.01; OR = 4.38). Our finding indicated that 4216C base substitution could be considered as a predisposing marker for MS and supported the hypothesis that particular mtDNA variants could contribute to genetic susceptibility of MS, and merits further investigation.
Increased error‐related negativity (ERN) in childhood anxiety disorders: ERP and source localization
Authors: Ladouceur Cecile D. , Dahl Ronald E. , Birmaher Boris , Axelson David A. , Ryan Neal D.
Published: October 2006

Background:  In this study we used event‐related potentials (ERPs) and source localization analyses to track the time course of neural activity underlying response monitoring in children diagnosed with an anxiety disorder compared to age‐matched low‐risk normal controls.

Methods:  High‐density ERPs were examined following errors on a flanker task from 12 children between 8 and 14 years old diagnosed with an anxiety disorder (ANX) and 13 age‐matched low‐risk normal controls (LRNC).

Results:  Children diagnosed with an anxiety disorder had increased error‐related negativity (ERN) amplitude. The neural generators of the ERN in the ANX group were estimated to be localized in the anterior cingulate cortex (ACC). There were no significant group differences in PE amplitude.

Conclusions:  These data provide evidence for increased ERN amplitude localized to the ACC in children diagnosed with an anxiety disorder, suggesting altered maturational patterns of the ACC circuitry early in the course of this illness.
Childhood onset schizophrenia: cortical brain abnormalities as young adults
Authors: Greenstein Deanna , Lerch Jason , Shaw Philip , Clasen Liv , Giedd Jay , Gochman Peter , Rapoport Judith , Gogtay Nitin
Published: October 2006

Background:  Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset illness.

Methods:  Neuro‐anatomic magnetic resonance scans were obtained prospectively from ages 7 through 26 in 70 children diagnosed with COS and age and sex matched healthy controls. Cortical thickness was measured at 40,962 points across the cerebral hemispheres using a novel, fully automated, validated method. Patterns of patient–control differences in cortical development were compared over a 19‐year period.

Results:  Throughout the age range, the COS group had significantly smaller mean cortical thickness compared to controls. However, the COS brain developmental trajectory appeared to normalize in posterior (parietal) regions, and remained divergent in the anterior regions (frontal and temporal) regions, and the pattern of loss became more like that seen in adults.

Conclusions:  Cortical thickness loss in COS appears to localize with age to prefrontal and temporal regions that are seen for both medication naïve and medicated adult onset patients.
Electrocortical reflections of face and gaze processing in children with pervasive developmental disorder
Authors: Kemner C. , Schuller A‐M. , Van Engeland H.
Published: October 2006

Background:  Children with pervasive developmental disorder (PDD) show behavioral abnormalities in gaze and face processing, but recent studies have indicated that normal activation of face‐specific brain areas in response to faces is possible in this group. It is not clear whether the brain activity related to gaze processing is also normal in children with PDD.

Methods:  Event‐related brain potentials (ERPs) were measured during two spatial attention tasks in which a centrally presented stimulus served as cue for the location of a forthcoming target. In one task faces were used as cues, and in the other arrows. Seventeen children with PDD and 18 age‐ and IQ‐matched control children were tested.

Results:  Face stimuli elicited the same specific ERP activity in both groups. Also, both children with PDD and controls showed shorter reaction times as well as larger amplitudes and shorter latency times of several ERP peaks to congruently cued targets than to incongruently cued targets in both tasks. However, children with PDD showed abnormally small occipital ERPs in response to both face and arrow stimuli.

Conclusions:  The results provide evidence for the capability of normal processing of face and gaze change in children with PDD. The smaller occipital activity might be related to more general abnormalities in perception.
Mitochondrial damage modulates alternative splicing in neuronal cells: implications for neurodegeneration
Authors: Maracchioni Alessia , Totaro Antonio , Angelini Daniela F. , Di Penta Alessandra , Bernardi Giorgio , Carrì Maria Teresa , Achsel Tilmann
Published: October 2006

Mitochondrial damage is linked to many neurodegenerative conditions, such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. These diseases are associated with changes in the splicing pattern of individual mRNAs. Here, we tested the hypothesis that mitochondrial damage modulates alternative splicing, not only of a few mRNAs, but in a general manner. We incubated cultured human neuroblastoma cells with the chemical agent paraquat (a neurotoxin that interferes with mitochondrial function, causing energy deficit and oxidative stress) and analysed the splicing pattern of 13 genes by RT‐PCR. For all mRNAs that are alternatively spliced, we observed a dose‐ and time‐dependent increase of the smaller isoforms. In contrast, splicing of all constitutive splicing exons that we monitored did not change. Using other drugs, we show that the modulation of alternative splicing correlates with ATP depletion, not with oxidative stress. Such drastic changes in alternative splicing are not observed in cell lines of non‐neuronal origin, suggesting a selective susceptibility of neuronal cells to modulation of splicing. As a significant percentage of all mammalian mRNAs undergo alternative splicing, we predict that mitochondrial failure will unbalance a vast number of isoform equilibriums, which would give an important contribution to neurodegeneration.
Fourteen polymorphic microsatellite loci in the field gudgeon, Gnathopogon elongatus elongatus
Authors: KOIZUMI NORIYUKI , TAKAHASHI HIDEAKI , MINEZAWA MITSURU , TAKEMURA TAKESHI , OKUSHIMA SHUJI
Published: October 2006

We isolated and characterized 14 polymorphic microsatellite loci for the field gudgeon, Gnathopogon elongatus elongatus, a popular freshwater species in streams including agricultural canals in Japan. The number of observed alleles for each locus ranged from 9 to 24, and the values of observed and expected heterozygosities ranged from 0.750 to 1.000 and from 0.832 to 0.953, respectively. These microsatellite markers will be useful for studies of population genetic structure and genetic variability of the field gudgeon.
Evaluation of hematological, chemistry and blood gas values in dogs receiving hemoglobin glutamer‐200
Authors: Kerl Marie E. , Langdon Paige F. , Wiedmeyer Charles E. , Branson Keith R.
Published: October 2006

Objective: To evaluate the degree of interference that administration of hemoglobin glutamer‐200 (Hb‐200) caused for complete blood counts (CBC), biochemical profiles, cooximetry, and point of care (POC) testing in healthy dogs.

Design: Prospective, longitudinal experimental study.

Setting: Veterinary medical teaching hospital.

Animals: Six purpose‐bred research hounds.

Interventions: Dogs were administered FDA‐approved hemoglobin‐based oxygen carrier (Hb‐200) intravenously at 7.5 mL/kg over 2 hours. Arterial and venous blood samples were obtained before administration (Time 0) and at 3, 8, 14, 26, 50, 74, 98, 122, and 146 hours following administration.

Measurements and main results: No adverse health effects were observed in any of the dogs. Characteristic mucous membrane, serum, and plasma color changes occurred following administration of Hb‐200. Laboratory values that were significantly lower than baseline included packed cell volume, red blood cell count, hemoglobin, hematocrit, creatinine, cholesterol, alanine aminotransferase, and alkaline phosphatase. Laboratory values that were significantly greater than baseline included mean corpuscular hemoglobin concentration, arterial pH, arterial total carbon dioxide, arterial bicarbonate, amylase, albumin, total protein, globulin, calcium, phosphorous, total bilirubin, carboxyhemoglobin, and methemoglobin. All values returned to baseline by the completion of the 146‐hour monitoring period.

Conclusions: In normal dogs, administration of Hb‐200 resulted in statistically significant changes in multiple laboratory parameters; however, these changes are not likely to be clinically significant in the care of critically ill dogs.
Causes of Impaired Delivery of Hemodialysis Prescription
Authors: Fourtounas Costas , Kopelias Ioannis , Paraskevopoulos Aristides , Dimitriadis George , Agroyannis Basil
Published: October 2006

Abstract:  Urea kinetic modeling (Kt/V) is used to assess adequacy of hemodialysis (HD). However, serial Kt/V measurements may vary with time in the same patient, making the interpretation of the results difficult. The aim of the present study was to find the frequency and the causes that account for these fluctuations of Kt/V. Fifty‐nine patients undergoing chronic HD were included in this prospective study. The results of monthly single pool Kt/V values were analyzed during a 6‐month period. Duration of maintenance HD prior to the study was 4.49 ± 3.6 (±SD) years. Any change of >0.2 from the previous 2‐month average values was defined as abnormal. A total of 354 urea kinetic modeling sessions were recorded during 6 months in 59 patients. Of these, 38 (10.7%) met the criteria for abnormal value. Twenty‐four measurements (6.7%) revealed lower while 14 (3.9%) demonstrated higher Kt/V values. Supervised sampling and conforming to the prescribed dialysis dose were applied for all abnormal measurements a week later. Among the group with lower Kt/V value, nine were due to noncompliance (shorter dialysis), four lower blood flow (Qb), four reversed needles, and one fistula thrombosis. Finally, in six cases no problem could be identified and a repeat measurement failed to document lower values. In the high‐value group, nine cases were expected as there was an effort to increase dialysis dose prescription while five cases were due to false postdialysis sampling (“venous samples”). Overall, 29/354 (8.1%) measurements were in real disagreement with dialysis prescription. Lower‐than‐expected values are quite often due to reduced blood processing (shorter dialysis, lower Qb, and recirculation) and higher values due to inaccurate postdialysis sampling. Any possible pitfall in Kt/V measurements should be investigated before changing dialysis prescription in a stable HD patient.
Collusive Market Sharing and Corruption in Procurement
Authors: Lambert‐Mogiliansky Ariane , Sonin Konstantin
Published: October 2006

This paper investigates links between corruption and collusion in procurement. A first‐price multiple‐object auction is administered by an agent who has legal discretion to allow for a readjustment of (all) submitted offers before the official opening. The agent may be corrupt, that is, willing to “sell” his decision in exchange for a bribe. Our main result shows that the corrupt agent's incentives to extract rents are closely linked with that of a cartel of bidders. First, collusive bidding conveys value to the agent's decision power. Second, self‐interested abuse of discretion to extract rents (corruption) provides a mechanism to enforce collusion. A second result is that package bidding can facilitate collusion. We also find that with corruption, collusion is more likely in auctions where firms are small relative to the market. Our main message to auction designers, competition authorities and criminal courts is that risks of collusion and of corruption must be addressed simultaneously. Some other policy implications for the design of tender procedures are discussed.
To Rebuild Lives: A Longitudinal Study of the Influences of the Holocaust on Relationships Among Three Generations of Women in One Family
Authors: LITVAK‐HIRSCH TAL , BAR‐ON DAN
Published: October 2006

The current article presents an analysis of the life stories of three generations of women within a family headed by a Holocaust survivor. Its uniqueness lies in its double analysis of the stories told by these women, with an interval of 12 years between telling. The first series of interviews were conducted in the early 1990s within the framework of a pioneering study in which, for the first time, three generations in each of 20 families were interviewed and their narratives analyzed. The current analyses are based on the perspective that, through life narratives, it is possible to view the transformations of relationships over time and that these transformations in relationships are central to personal development. We will examine the relationships of the women in these three generations, both with significant others and with each other. We will trace processes of development and changes in these relationships over the 12 years. Finally, we will discuss the social and methodological implications of our study.
Comparison of performance on different host plants between the B biotype and a non‐B biotype of Bemisia tabaci from Zhejiang, China
Authors: Zang Lian‐Sheng , Chen Wei‐Qiang , Liu Shu‐Sheng
Published: October 2006

The capacity of the B biotype of the whitefly, Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae), to invade has often been linked to its presumably wider host range than the non‐B indigenous biotypes. However, there are few experimental studies of the relative performance of the B biotype and non‐B biotypes on different host‐plant species. Here, we compared the performance of the B biotype and an indigenous non‐B biotype (China‐ZHJ‐1) of B. tabaci from Zhejiang, China on five commonly cultivated host plants, each from a different family: cotton, tobacco, cabbage, squash, and kidney bean. We also examined the effect of rearing host plants on the performance of the B biotype. Overall, the performance of the B biotype on the five species of plants was much better than that of the indigenous non‐B population. On tobacco, cabbage, and kidney bean, no individuals of ZHJ‐1 completed development to adulthood, whereas the B biotype developed successfully from egg to adult on all three plants. On squash, the B biotype survived better, developed to adulthood earlier and had a higher fecundity than ZHJ‐1. The two biotypes performed more equally on cotton, but even on this plant the B biotype female adults lived nearly twice as long as that of ZHJ‐1 and may have realized a higher life‐time fecundity. The B biotype also showed a substantial capacity to acclimatize to alternative host plants for improved survival and reproduction, on both highly suitable and marginally suitable host plants. We conclude that the host range of the B biotype of B. tabaci may be much wider than those of some indigenous biotypes, and this advantage of the B biotype over the non‐B biotypes may assist in its invasion and displacement of some indigenous biotypes in the field.
Brain activation measured using functional magnetic resonance imaging during the Tower of London task
Authors: Rasmussen Inge-Andre , Antonsen Ida Kristin , Berntsen Erik Magnus , Xu Jian , Lagopoulos Jim , Håberg Asta Kristine
Published: October 2006

Background:

Individuals with traumatic brain injury (TBI) often suffer from a number of enduring cognitive impairments such as in attention, memory, speed of processing information and dual-task performance.

Objective:

The aim of this study was to assess the patterns of regional brain activation in response to the Tower of London (ToL) task in a group of patients suffering from chronic TBI using functional magnetic resonance imaging (fMRI).

Methods:

fMRI was performed during performance of the ToL planning task in 10 patients suffering from severe TBI and in 10 age- and sex-matched controls using a 3 T magnetic resonance scanner.

Results:

Performance data showed no difference in response accuracy between the TBI group and the healthy control group. Statistical parametric brain maps showed that the TBI group activates larger and additional areas of the cerebral cortex than the healthy control group both for tasks and for a subtraction contrast between the tasks.

Conclusions:

The results of this study are interpreted as a cortical reorganization inside the executive system of vigilance and working memory in patients with TBI. Both parietal and frontal areas are recruited to compensate for damaged brain tissue.
Cutaneous malignant lymphomas: Update 2006
Authors: Burg Günter , Kempf Werner , Cozzio Antonio , Döbbeling Udo , Feit Josef , Golling Philippa , Michaelis Sonja , Schärer Leo , Nestle Frank , Dummer Reinhard
Published: October 2006

Cutaneous lymphomas represent a unique group of lymphomas and are the second most frequent extranodal lymphomas. As with other neoplasias, the pathogenesis is based mainly on a stepwise accumulation of mutations of suppressor genes and oncogenes caused by genetic, environmental or infectious factors. The diagnostic work‐up includes clinical, histological, imaging and hematological investigations and in many cases immunohistochemical and molecular biological analyses.

The current WHO/EORTC classification of cutaneous lymphomas differentiates “mature T‐cell and NK‐cell lymphomas”, “mature B‐cell lymphomas” and “immature hematopoietic malignancies”, their variants and subgroups. It is compatible with the WHO classification for neoplasias of the hematopoietic and lymphoid tissue and respects the organ‐specific peculiarities of primary cutaneous lymphomas.The assignment of the various types of cutaneous lymphomas into prognostic categories (pre‐lymphomatous “abortive” disorders; definite malignant lymphomas of low‐grade malignancy; definite malignant lymphomas of high‐grade malignancy) provides essential information on the biological behavior and allows an appropriate planning of the therapeutic strategy, which may be topical or systemic and aggressive or non‐aggressive. Besides the classical options for therapy, there are new and “experimental” strategies, the efficacy of which has to be studied in clinical trials.
Bacterial β‐peptidyl aminopeptidases with unique substrate specificities for β‐oligopeptides and mixed β,α‐oligopeptides
Authors: Geueke Birgit , Heck Tobias , Limbach Michael , Nesatyy Victor , Seebach Dieter , Kohler Hans‐Peter E.
Published: October 2006

We previously discovered that BapA, a bacterial β‐peptidyl aminopeptidase, is able to hydrolyze two otherwise metabolically inert β‐peptides [Geueke B, Namoto K, Seebach D & Kohler H‐PE (2005) J Bacteriol187, 5910–5917]. Here, we describe the purification and characterization of two distinct bacterial β‐peptidyl aminopeptidases that originated from different environmental isolates. Both bapA genes encode a preprotein with a signal sequence and were flanked by ORFs that code for enzymes with similar predicted functions. To form the active enzymes, which had an (αβ)4 quaternary structure, the preproteins needed to be cleaved into two subunits. The two β‐peptidyl aminopeptidases had 86% amino acid sequence identity, hydrolyzed a variety of β‐peptides and mixed β/α‐peptides, and exhibited unique substrate specificities. The prerequisite for peptides being accepted as substrates was the presence of a β‐amino acid at the N‐terminus; peptide substrates with an N‐terminal α‐amino acid were not hydrolyzed at all. Both enzymes cleaved the peptide bond between the N‐terminal β‐amino acid and the amino acid at the second position of tripeptidic substrates of the general structure H‐βhXaa‐Ile‐βhTyr‐OH according to the following preferences with regard to the side chain of the N‐terminal β‐amino acid: aliphatic and aromatic > OH‐containing > hydrogen, basic and polar. Experiments with the tripeptides H‐d‐βhVal‐Ile‐βhTyr‐OH and H‐βhVal‐Ile‐βhTyr‐OH demonstrated that the two BapA enzymes preferred the peptide with the l‐configuration of the N‐terminal β‐homovaline residue as a substrate.
Crystal structure of the second PDZ domain of SAP97 in complex with a GluR‐A C‐terminal peptide
Authors: von Ossowski Ingemar , Oksanen Esko , von Ossowski Lotta , Cai Chunlin , Sundberg Maria , Goldman Adrian , Keinänen Kari
Published: October 2006

Synaptic targeting of GluR‐A subunit‐containing glutamate receptors involves an interaction with synapse‐associated protein 97 (SAP97). The C‐terminus of GluR‐A, which contains a class I PDZ ligand motif (‐x‐Ser/Thr‐x‐φ‐COOH where φ is an aliphatic amino acid) associates preferentially with the second PDZ domain of SAP97 (SAP97PDZ2). To understand the structural basis of this interaction, we have determined the crystal structures of wild‐type and a SAP97PDZ2 variant in complex with an 18‐mer C‐terminal peptide (residues 890–907) of GluR‐A and of two variant PDZ2 domains in unliganded state at 1.8–2.44 Å resolutions. SAP97PDZ2 folds to a compact globular domain comprising six β‐strands and two α‐helices, a typical architecture for PDZ domains. In the structure of the peptide complex, only the last four C‐terminal residues of the GluR‐A are visible, and align as an antiparallel β‐strand in the binding groove of SAP97PDZ2. The free carboxylate group and the aliphatic side chain of the C‐terminal leucine (Leu907), and the hydroxyl group of Thr905 of the GluR‐A peptide are engaged in essential class I PDZ interactions. Comparison between the free and complexed structures reveals conformational changes which take place upon peptide binding. The βΑ−βΒ loop moves away from the C‐terminal end of αB leading to a slight opening of the binding groove, which may better accommodate the peptide ligand. The two conformational states are stabilized by alternative hydrogen bond and coulombic interactions of Lys324 in βΑ−βΒ loop with Asp396 or Thr394 in βΒ. Results of in vitro binding and immunoprecipitation experiments using a PDZ motif‐destroying L907A mutation as well as the insertion of an extra alanine residue between the C‐terminal Leu907 and the stop codon are also consistent with a ‘classical’ type I PDZ interaction between SAP97 and GluR‐A C‐terminus.
Antidepressant-Induced Inhibition of Genital Vascular Responses is Reversed by Vardenafil in Female Rabbits
Authors: Angulo Javier , Cuevas Pedro , Cuevas Begona , Bischoff Erwin , De Tejada Iñigo Saenz
Published: October 2006

Introduction

Administration of serotonin reuptake inhibitors (SRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) relieves depressive symptoms but may cause sexual dysfunction in women and men.

Aim

The aim of the present study was to evaluate the effects of the phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, on inhibition of genital vascular responses (GVR) induced by SRI or SNRI administration in female rabbits.

Methods

Vaginal and clitoral vasodilatory responses to pelvic nerve electrical stimulation were measured by laser Doppler flow needle probes.

Results

GVR were significantly potentiated by vardenafil even at the low dose of 0.1 mg/kg, in clitoris and vagina (181 ± 22% and 180 ± 31% of control, in vagina and clitoris, respectively, at 8 Hz). The selective SRI, paroxetine (5 mg/kg), significantly inhibited GVR in female rabbits (54 ± 5% and 48 ± 6% of control). GVR were also significantly inhibited by the SNRIs, venlafaxine (5 mg/kg) (57 ± 3% and 32 ± 11%) and duloxetine (1 mg/kg) (40 ± 7% and 28 ± 5%). Treatment with vardenafil (0.1 and 0.3 mg/kg) completely reversed the inhibition of GVR induced by paroxetine, venlafaxine, or duloxetine.

Conclusions

Potentiation of the nitric oxide (NO) pathway by vardenafil improves vascular sexual responses in female rabbits and overcomes the inhibitory effects of acutely administered antidepressants on GVR, irrespective of the underlying pathophysiologic mechanism, i.e., disruption of the NO pathway or enhancement of α-adrenergic mechanisms. PDE5 inhibition may represent a reasonable approach to treat SRI- or SRNI-induced female sexual dysfunction, in particular, arousal disorders.