bluuebunny/crossref_metadata_2025 huggingface dataset:
Cylindrical inclusion protein of potato virus A is associated with a subpopulation of particles isolated from infected plants
Authors: Gabrenaite-Verkhovskaya Rasa , Andreev Igor A. , Kalinina Natalia O. , Torrance Lesley , Taliansky Michael E. , Mäkinen Kristiina
Published: February 2008

Potato virus A (PVA) particles were purified by centrifugation through a 30 % sucrose cushion and the pellet (P1) was resuspended and sedimented through a 5–40 % sucrose gradient. The gradient separation resulted in two different virus particle populations: a virus fraction (F) that formed a band in the gradient and one that formed a pellet (P2) at the bottom of the gradient. All three preparations contained infectious particles that retained their integrity when visualized by electron microscopy (EM). Western blotting of the P1 particles revealed that the viral RNA helicase, cylindrical inclusion protein (CI), co-purified with virus particles. This result was confirmed with co-immunoprecipitation experiments. CI was detected in P2 particle preparations, whereas F particles were devoid of detectable amounts of CI. ATPase activity was detected in all three preparations with the greatest amount in P2. Results from immunogold-labelling EM experiments suggested that a fraction of the CI present in the preparations was localized to one end of the virion. Atomic force microscopy (AFM) studies showed that P1 and P2 contained intact particles, some of which had a protruding tip structure at one end, whilst F virions were less stable and mostly appeared as beaded structures under the conditions of AFM. The RNA of the particles in F was translated five to ten times more efficiently than RNA from P2 particles when these preparations were subjected to translation in wheat-germ extracts. The results are discussed in the context of a model for CI-mediated functions.
Mutational analysis of a principal neutralization domain of visna/maedi virus envelope glycoprotein
Authors: Haflidadóttir Benedikta S. , Matthíasdóttir Sigrídur , Agnarsdóttir Gudrún , Torsteinsdóttir Sigurbjorg , Pétursson Gudmundur , Andrésson Ólafur S. , Andrésdóttir Valgerdur
Published: February 2008

We have shown previously that a type-specific neutralization domain is located within a 39 aa sequence in the fourth variable domain of gp135 in visna/maedi virus. We now show that neutralizing antibodies detected early in infection are directed to this epitope, suggesting an immunodominant nature of this domain. Ten antigenic variants were previously analysed for mutations in this region, and all but one were found to be mutated. To assess the importance of these mutations in replication and neutralization, we reconstructed several of the mutations in an infectious molecular clone and tested the resulting viruses for neutralization phenotype and replication. Mutation of a conserved cysteine was shown to alter the neutralization epitope, whilst the replication kinetics in macrophages were unchanged. Mutations modulating potential glycosylation sites were found in seven of the ten antigenic variants. A frequently occurring mutation, removing a potential glycosylation site, had no effect on its own on the neutralization phenotype of the virus. However, adding an extra potential glycosylation site in the region resulted in antigenic escape. The results indicate that the conserved cysteine plays a role in the structure of the epitope and that glycosylation may shield the principal neutralization site.
Positively selected sites on the surface glycoprotein (G) of infectious hematopoietic necrosis virus
Authors: LaPatra Scott E. , Evilia Caryn , Winston Vern
Published: February 2008

Mutations in the surface glycoprotein (G) of infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that causes significant losses in hatcheries raising salmonid fish, were studied. A 303 nt segment (mid-G region) of this protein from 88 Idaho isolates of IHNV was sequenced. Evidence of positive selection at individual codon sites was estimated by using a Bayesian method (MrBayes). A software algorithm (CPHmodels) was used to construct a three-dimensional (3D) representation of the IHNV protein. The software identified structural homologies between the IHNV G protein and the surface glycoprotein of vesicular stomatitis virus (VSV) and used the VSV structure as a template for predicting the IHNV structure. The amino acids predicted to be under positive selection were mapped onto the proposed IHNV 3D structure and appeared at sites on the surface of the protein where antigen–antibody interaction should be possible. The sites identified as being under positive selection on the IHNV protein corresponded to those reported by others as active sites of mutation for IHNV, and also as antigenic sites on VSV. Knowledge of the sites where genetic variation is positively selected enables a better understanding of the interaction of the virus with its host, and with the host immune system. This information could be used to develop strategies for vaccine development for IHNV, as well as for other viruses.
Recombinant simian varicella viruses expressing respiratory syncytial virus antigens are immunogenic
Authors: Ward Toby M. , Traina-Dorge Vicki , Davis Kara A. , Gray Wayne L.
Published: February 2008

Recombinant simian varicella viruses (rSVVs) were engineered to express respiratory syncytial virus (RSV) antigens. The RSV surface glycoprotein G and second matrix protein M2 (22k) genes were cloned into the SVV genome, and recombinant viruses were characterized in vitro and in vivo. rSVVs were also engineered to express the membrane-anchored or secreted forms of the RSV-G protein as well as an RSV G lacking its chemokine mimicry motif (CX3C), which may have different effects on priming the host immune response. The RSV genes were efficiently expressed in rSVV/RSV-infected Vero cells as RSV-G and -M2 transcripts were detected by RT-PCR, and RSV antigens were detected by immunofluorescence and immunoblot assays. The rSVVs replicated efficiently in Vero cell culture. Rhesus macaques immunized with rSVV/RSV-G and rSVV/RSV-M2 vaccines produced antibody responses to SVV and RSV antigens. The results demonstrate that recombinant varicella viruses are suitable vectors for the expression of RSV antigens and may represent a novel vaccine strategy for immunization against both pathogens.
Climate change affects breeding of reed warblers Acrocephalus scirpaceus
Authors: Halupka Lucyna , Dyrcz Andrzej , Borowiec Marta
Published: February 2008

Between 1970 and 2006 reed warblers Acrocephalus scirpaceus started breeding progressively earlier; both the initiation of breeding (the earliest first egg dates) and peak of breeding (median first egg dates) advanced. Median first egg dates correlated significantly with increasing May–July mean temperatures. However, in contrast to other studies showing the advancement in laying dates, the end of the season did not shift. As a result, the breeding season is now longer increasing re‐nesting opportunities. Individuals are able to re‐nest 4–5 times, which might have important implications for the species. It was also found that in warmer seasons the population suffered fewer nest losses. Both factors, higher re‐nesting potential and a trend toward fewer losses, should lead to increased fitness of individuals in the studied population.
Mixed mating strategies in cooperatively breeding apostlebirds Struthidea cinerea
Authors: Woxvold Iain A. , Mulder Raoul A.
Published: February 2008

In cooperatively breeding apostlebirds Struthidea cinerea philopatry by both sexes is coupled with low levels of dispersal, resulting in large groups (up to 17 birds) that may include multiple males and females of varying age and relatedness. We investigated mating patterns within 18 groups of apostlebirds using a set of six polymorphic microsatellite loci. Apostlebirds appear to adopt flexible and context‐dependent mating strategies, with both monogamy and polygamy detected in separate groups. Most groups (11/18, 17/26 group‐seasons) were putatively monogamous, with a single pair matching all typed offspring. Despite the potential for inbreeding, members of breeding pairs were less closely related than other potential within‐group mating combinations. Polygamy was inferred in four groups (four group‐seasons) from the presence of more than four alleles at one locus among offspring within a brood. Pairwise relatedness was lower among adults in polygamous groups than those in groups that included a monogamous breeding pair. There was no conclusive evidence of extra‐group paternity or egg dumping.
Occurrence and life history correlates of vocal duetting in North American passerines
Authors: Benedict Lauryn
Published: February 2008

Vocal duetting, where two birds produce temporally coordinated vocalizations, has been reported in a taxonomically and geographically diverse set of avian species. Researchers have suggested a number of potential correlates of duetting, including long term monogamy, year‐round territory defense and sexual plumage monomorphism. Because the majority of duetting species are tropical, they have been the focus of the most comprehensive studies to date. There is, therefore, a real need for data regarding avian duets in temperate species. I used the recently completed Birds of North America species reports to examine the frequency, evolutionary origins and potential life history correlates of duetting behavior in North American passerines. “Duetting” behavior was reported in 7% of species from 12 avian families, likely representing 17 separate evolutionary origins. Duetting species showed apparent long term monogamy and year‐round territoriality at frequencies more than double those of non‐duetting passerines: 65% of duetting species were long term monogamous, compared to 27% of non‐duetting species, and 50% of duetting species defended the same territory throughout the year, compared with only 11% of non‐duetting species. Duetting and non‐duetting species showed statistically indistinguishable frequencies of sexual plumage monomorphism. Comparative analyses of duetting species and their sister taxa revealed that the shift to duetting is accompanied by a gain of long term monogamy and year‐round territoriality more often than it is associated with a loss of those traits. This study provides intriguing summary evidence that selective factors promoting duetting may be associated with a sedentary, monogamous lifestyle, and may operate similarly across taxonomic groups. Furthermore, vocal duetting may be considerably more common among temperate‐zone species than previously recognized.
Respiratory protection during high‐fidelity simulated resuscitation of casualties contaminated with chemical warfare agents*
Authors: Schumacher J. , Runte J. , Brinker A. , Prior K. , Heringlake M. , Eichler W.
Published: February 2008

Emergency room personnel are threatened by secondary poisoning when treating victims affected by chemical warfare agents. Therefore, resuscitation skills practised with respiratory protection equipment in place require evaluation. We investigated the influence of wearing air‐purifying respirators on the simulated resuscitation of chemical warfare agent casualties. We studied 22 anaesthetic trainees in a simulated resuscitation scenario requiring five set tasks, either unprotected, wearing a binocular visor respirator or a panoramic visor respirator in a randomised, crossover study. Treatment times did not differ between the three groups, with mean (SD) times to complete the tasks being 122 (8) s without a mask, 126 (7) s when wearing the panoramic visor mask and 129 (8) s when wearing the binocular respirator mask. All anaesthetists preferred the panoramic visor in terms of visual orientation but 88% of them rated the binocular mask as being more comfortable. Modern respirators have a negligible effect on simulated resuscitation scenarios for victims affected by chemical warfare agents. Panoramic visor respirators allow better visual orientation for anaesthetists during simulated resuscitation.
Cigarette smoking and the haemodynamic response to tracheal intubation
Authors: Cuvas O. , Er A. , Ikeda O. C. , Dikmen B. , Basar H.
Published: February 2008

This study investigated the effects of smoking and gender on the haemodynamic response after tracheal intubation. Patients were assigned to one of four groups: female non‐smokers, female smokers, male non‐smokers and male smokers. After tracheal intubation, the highest mean (SD) increase in heart rate (30 (18) %) and rate–pressure product (40 (29) %) was seen in male smokers. The increases in heart rate and rate–pressure product in male smokers were significantly greater than those in female non‐smokers, p < 0.05. The increase in rate–pressure product was significantly greater in male smokers than in male non‐smokers, p = 0.022.
Pulmonary elimination rate of inhaled 99mTc‐sestamibi radioaerosol is delayed in healthy cigarette smokers
Authors: Ruparelia Prina , Cheow Heok K. , Evans John W. , Banney Leith , Shankar Sonal , Szczepura Katherine R. , Swift Anna E. , Ballinger James R. , Hartman Neil G. , Chilvers Edwin R. , Peters A. Michael
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Very little is known about the physiology of P‐glycoprotein (P‐gp) expression in the lungs.

• Ex vivo evidence based on resected lung tissue suggests that pulmonary P‐gp is upregulated by cigarette smoke, but there are no in vivo studies to date.

WHAT THIS STUDY ADDS

• The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled 99mTc‐sestamibi, a P‐gp substrate, provides for the first time a potential method for quantifying functional pulmonary P‐gp expression that may inform about drug therapy by inhalation as well as provide a non‐invasive, quantitative, human biomarker for assessing P‐gp modulators.

AIM To explore inhaled technetium‐99m‐labelled hexakis‐methoxy‐isobutyl isonitrile (99mTc‐sestamibi) for quantifying pulmonary P‐glycoprotein (P‐gp) expression.

METHODS The elimination rate from the lungs of 99mTc‐sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease.

RESULTS 99mTc‐sestamibi elimination rates [% min−1 (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated.

CONCLUSION Cigarette smoke upregulates lung P‐gp. 99mTc‐sestamibi elimination in normal smokers could be used to test new P‐gp modulators. The findings also have implications for inhaled drug delivery.
First trimester adipocytokine concentrations and risk of developing gestational diabetes later in pregnancy
Authors: Lain Kristine Y. , Daftary Ashi R. , Ness Roberta B. , Roberts James M.
Published: February 2008

Objective  Adipocytokines are important regulators of insulin resistance. The aim of this study was to compare maternal adipocytokines in early pregnancy among women diagnosed with and without gestational diabetes (GDM) months later.

Design  A nested case‐control study.

Patients  Adiponectin, resistin and interleukin‐6 (IL‐6) were measured in 59 nulliparous women (30 women with GDM and 29 controls) in plasma obtained in early pregnancy. Patients underwent routine testing for GDM in late pregnancy.

Measurements  Adiponectin was measured using radioimmunoassay. Resistin and IL‐6 were measured by ELISA. Statistical analysis included Student's t‐test, logistic regression and Pearson's correlation.

Results  Groups were not different by baseline descriptors or obstetric outcomes. Mean gestational age at sampling was 9·3 ± 2·6 weeks. Adiponectin was lower (P < 0·001) in women who later developed GDM compared to controls (4·3 ± 0·4 vs. 6·9 ± 0·6 µg/ml). Adiponectin was negatively associated with the development of GDM (P = 0·002; OR: 0·70, 95% CI: 0·56, 0·88) and the association persisted in multivariable analysis controlling for confounders (P = 0·01; OR: 0·69, 95% CI: 0·52, 0·92). Women with first trimester adiponectin concentrations < 25th% were 10 times more likely to be diagnosed with GDM (OR 10·2; 95% CI 1·3, 78·7). Early adiponectin concentrations negatively correlated with BMI (P = 0·01; r = –0·32) and subsequent 50 g glucose challenge (P = 0·03; r =–0·29). Mean resistin and IL‐6 concentrations were not different between the two groups.

Conclusions  Women with GDM have evidence of altered adipocyte function as measured by adiponectin early in pregnancy, months before the clinical diagnosis of GDM is traditionally made.
Ovariectomy increases vascular calcification via the OPG/RANKL cytokine signalling pathway
Authors: Choi B. G. , Vilahur G. , Cardoso L. , Fritton J. C. , Ibanez B. , Zafar M. U. , Yadegar D. , Speidl W. S. , Schaffler M. B. , Fuster V. , Badimon J. J.
Published: February 2008

Background  Observational studies suggest a strong relationship between menopause and vascular calcification. Receptor activator of nuclear factor‐κΒ ligand (RANKL) and osteoprotegerin (OPG) are critical regulators of bone remodelling and modulate vascular calcification. We assessed the hypothesis that ovariectomy increases vascular calcification via the OPG/RANKL axis.

Materials and methods  Age‐matched sexually mature rabbits were randomized to ovariectomy (OVX, n = 12) or sham procedure (SHAM, n = 12). One month post‐procedure, atherosclerosis was induced by 15 months 0·2%‐cholesterol diet and endothelial balloon denudations (at months 1 and 3). Aortic atherosclerosis was assessed in vivo by magnetic resonance imaging (MRI) at months 9 and 15. At sacrifice, aortas were harvested for ex vivo microcomputed tomography (µCT) and molecular analysis of the vascular tissue.

Results  Vascular calcification density and calcific particle number were significantly greater in OVX than SHAM (8·4 ± 2·8 vs. 1·9 ± 0·6 mg cm−3, P = 0·042, and 94 ± 26 vs. 33 ± 7 particles cm−3, P = 0·046, respectively). Calcification morphology, as assessed by the arc angle subtended by the largest calcific particle, showed no difference between groups (OVX 33 ± 7° vs. SHAM 33 ± 5°, P = 0·99). By Western blot analysis, OVX increased the vascular OPG:RANKL ratio by 66%, P = 0·029, primarily by decreasing RANKL (P = 0·019). At month 9, MRI demonstrated no difference in atheroma volume between OVX and SHAM, and no significant change was seen by the end of the study.

Conclusions  In contrast to bone, vascular OPG:RANKL ratio increased in response to ovariectomy with a corresponding fourfold increase in arterial calcification. This diametrical organ‐specific response may explain the comorbid association of osteoporosis with calcifying atherosclerosis in post‐menopausal women.
Redox potential distribution inferred from self‐potential measurements associated with the corrosion of a burden metallic body
Authors: Castermant J. , Mendonça C.A. , Revil A. , Trolard F. , Bourrié G. , Linde N.
Published: February 2008

Negative self‐potential anomalies can be generated at the ground surface by ore bodies and ground water contaminated with organic compounds. These anomalies are connected to the distribution of the redox potential of the ground water. To study the relationship between redox and self‐potential anomalies, a controlled sandbox experiment was performed. We used a metallic iron bar inserted in the left‐hand side of a thin Plexiglas sandbox filled with a calibrated sand infiltrated by an electrolyte. The self‐potential signals were measured at the surface of the tank (at different time lapses) using a pair of non‐polarizing electrodes. The self‐potential, the redox potential, and the pH were also measured inside the tank on a regular grid at the end of the experiment. The self‐potential distribution sampled after six weeks presents a strong negative anomaly in the vicinity of the top part of the iron bar with a peak amplitude of −82 mV. The resulting distributions of the pH, redox, and self‐potentials were interpreted in terms of a geobattery model combined with a description of the electrochemical mechanisms and reactions occurring at the surface of the iron bar. The corrosion of iron yields the formation of a resistive crust of fougerite at the surface of the bar. The corrosion modifies both the pH and the redox potential in the vicinity of the iron bar. The distribution of the self‐potential is solved with Poisson's equation with a source term given by the divergence of a source current density at the surface of the bar. In turn, this current density is related to the distribution of the redox potential and electrical resistivity in the vicinity of the iron bar. A least‐squares inversion method of the self‐potential data, using a 2D finite difference simulation of the forward problem, was developed to retrieve the distribution of the redox potential.
Species persistence in northerly glacial refugia of Europe: a matter of chance or biogeographical traits?
Authors: Bhagwat Shonil A. , Willis Katherine J.
Published: February 2008

Aim  The southern European peninsulas (Iberian, Italian and Balkan) are considered to have been refugia for many European species of plants and animals during the climatic extremes of the Pleistocene ice ages. A number of recent studies (fossil and genetic), however, have provided evidence for full‐glacial survival of some species beyond these peninsulas. Here we explore the biogeographical traits of these species, and ask whether they possessed certain characteristics that enabled them to persist in more northerly refugia.

Location  Europe.

Methods  Fossil and genetic evidence for refugial localities of species that survived in Europe during the last full‐glacial was obtained from the literature (totalling 90 species: 34 woody plants and 56 vertebrates). Forty‐seven of these species (23 woody plants and 24 vertebrates) had fossil evidence, whereas the remaining 43 species (11 woody plants and 32 vertebrates) had only genetic evidence. All species were scored according to their present geographical distribution, habitat preference and life‐history traits. The species were classified on the basis of these traits using hierarchical cluster analysis. Analysis of similarities was used to examine differences in vertebrate and woody plant species groups that survived only in southerly refugia and those that also persisted in more northerly locations. Non‐metric multi‐dimensional scaling was used to examine patterns observed between and within groups.

Results  Results from our analysis of species with fossil and genetic evidence for survival in refugia reveal that species that survived only in southerly refugia were large‐seeded trees or thermophilous vertebrates. In contrast, species that had a full‐glacial distribution, including more northerly locations, were wind‐dispersed, habitat‐generalist trees with the ability to reproduce vegetatively, and habitat‐generalist mammals with present‐day northerly distributions.

Main conclusions  Analysis of the geographical distribution, habitat preference and life‐history traits of the species studied suggests that underlying biogeographical traits may have determined their response to Pleistocene glaciation. The traits most commonly found in present populations with a northerly distribution in Europe enabled the same species to exist much farther north than the southern European peninsulas during the full‐glacial. It is possible that many of these species are now in restricted populations, within the ‘warm‐stage’ refugia of the current interglacial. The northerly full‐glacial survival of a number of woody plants and vertebrate species has significant implications for understanding migration rates of these species in response to climate change. It also has important implications for understanding current patterns of genetic diversity of European species. We suggest that both fossil and genetic evidence should be used to identify and prioritize for conservation of refugial localities in southern and northern Europe.
Catching fairies and the public representation of biogeography
Authors: Ladle Richard J.
Published: February 2008

Biogeography is a vibrant academic discipline that plays an important role in framing and directing debates on some of the most important environmental issues of our time, such as the impacts of climate change on biodiversity, biotic homogenization and the effectiveness of global conservation policy. Despite this, biogeography suffers from a low public profile and may consequently be poorly understood by the public. Here I review the representation of the term biogeography, and a selection of biogeographers in the public sphere (newspapers, websites, blogs) and the academic sphere (journals and reports) to understand more fully the public perception of the discipline. As anticipated, the survey suggests that the term ‘biogeography’ has little public currency, and that the public still largely associate the subject area with either eminent Victorians such as A.R. Wallace or modern greats such as E.O. Wilson. I conclude by discussing the potential consequences of the virtual absence of biogeography from public discourse for education and professional biogeographers.
Timing of implant placement relative to tooth extraction
Authors: SCHROPP L. , ISIDOR F.
Published: February 2008

Summary  In recent years, immediate or early implant placement after tooth extraction has becoming more common. The present review focuses on the clinical outcome of immediate or early implant placement. Only limited knowledge exists about most of the factors with particular significance for this treatment mode. Randomized controlled clinical studies comparing the various treatment protocols are scarce. With the background in the existing literature some conclusions can be drawn with caution. Survival rates for implants placed immediately, early, delayed, or late seem to be similar in the short perspective and amounts to approximately 95%. Successful immediate implant placement may be possible in all regions of the jaws, although replacement of molars is more challenging. Chronic infection is not an absolute contraindication for immediate implant placement. It is controversial whether immediate placement of implants may preserve the alveolar bone. Small gaps between implant surface and socket wall have a potential for spontaneous healing. No consensus exists on the need for bone augmentation in these situations. With the limited information available it may be stated that a good prognosis can be obtained following immediate/early functional or non‐functional loading of immediately placed implants. However, higher risk of failures seems to exist compared with a delayed, conventional approach. It is advocated that this treatment modality should be restricted to skilled well‐trained teams. Data on the aesthetic outcomes following immediate/early implant placement are inconclusive, but this treatment can offer high patient satisfaction with the aesthetic and functional outcomes.
Longevity of teeth and implants – a systematic review
Authors: TOMASI C. , WENNSTRÖM J. L. , BERGLUNDH T.
Published: February 2008

Summary  The objective of this systematic review was to describe the incidence of tooth and implant loss reported in long‐term studies.

Prospective longitudinal studies reporting on teeth or implants survival with a follow‐up period of at least 10 years were considered. Papers were excluded if the drop out rate exceeded 30% or if <70% of the initial subject sample was examined at 10 years of follow‐up.

Seventy publications on teeth were identified as potentially relevant for the focussed question. The analysis of the abstracts yielded 37 studies eligible for full‐text analysis. The inclusion criteria were met in 11 of the publications that included in all 3015 subjects. The initial search on implant studies generated 52 publications that possibly could be included. Following the evaluation of the abstracts and full‐text analysis nine publications were found to fulfil the inclusion criteria. The nine studies included 476 subjects.

The incidence of tooth loss among subjects with a follow‐up period of 10–30 years varied from 1.3% to 5% in the majority of studies, while in two epidemiological studies on rural Chinese populations the incidences of tooth loss were 14% and 20%. The percentage of implants reported as lost during the follow‐up period varied between 1% and 18%.

In clinically well‐maintained patients, the loss rate at teeth was lower than that at implant. Bone level changes appeared to be small at teeth as well as at implants in well‐maintained patients. Comparisons of the longevity at teeth and dental implants are difficult due to heterogeneity among the studies.
Medico‐legal assessment of disability in narcolepsy: an interobserver reliability study
Authors: INGRAVALLO FRANCESCA , VIGNATELLI LUCA , BRINI MARTINA , BRUGALETTA CONCETTA , FRANCESCHINI CHRISTIAN , LUGARESI FEDERICA , MANCA MARIA C. , GARBARINO SERGIO , MONTAGNA PASQUALE , CICOGNANI ALBERTO , PLAZZI GIUSEPPE
Published: February 2008

Impairment because of narcolepsy strongly limits job performance, but there are no standard criteria to assess disability in people with narcolepsy and a scale of disease severity is still lacking. We explored: (1) the interobserver reliability among Italian Medical Commissions making disability and handicap benefit decisions for people with narcolepsy, searching for correlations between the recognized disability degree and patients’ features; (2) the willingness to report patients to the driving licence authority and (3) possible sources of variance in judgement. Fifteen narcoleptic patients were examined by four Medical Commissions in simulated sessions. Raw agreement and interobserver reliability among Commissions were calculated for disability and handicap benefit decisions and for driving licence decisions. Levels of judgement differed on percentage of disability (P < 0.001), severity of handicap (P = 0.0007) and the need to inform the driving licence authority (P = 0.032). Interobserver reliability ranged from Kappa = −0.10 to 0.35 for disability benefit decision and from Kappa = −0.26 to 0.36 for handicap benefit decision. The raw agreement on driving licence decision ranged from 73% to 100% (Kappa not calculable). Spearman’s correlation between percentages of disability and patients’ features showed correlations with age, daytime naps, sleepiness, cataplexy and quality of life. This first interobserver reliability study on social benefit decisions for narcolepsy shows the difficulty of reaching an agreement in this field, mainly because of variance in interpretation of the assessment criteria. The minimum set of indicators of disease severity correlating with patients’ self assessments encourages a disability classification of narcolepsy.
A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder
Authors: FERRI RAFFAELE , MANCONI MAURO , PLAZZI GIUSEPPE , BRUNI OLIVIERO , VANDI STEFANO , MONTAGNA PASQUALE , FERINI‐STRAMBI LUIGI , ZUCCONI MARCO
Published: February 2008

The aim of this study was to evaluate quantitatively the amplitude of the submentalis muscle EMG activity during sleep in controls and in patients with idiopathic REM sleep behavior disorder (RBD) or with RBD and multiple system atrophy (MSA). We recruited 21 patients with idiopathic RBD, 10 with MSA, 10 age‐matched and 24 young normal controls. The average amplitude of the rectified submentalis muscle EMG signal was used for the assessment of atonia and a Sleep Atonia Index was developed; moreover, also chin muscle activations were detected and their duration and interval analyzed. The Sleep Atonia Index was able to distinguish clearly REM from NREM sleep in normal controls with values very close to 1 in young normal subjects and only slightly (but significantly) lower in old controls. Idiopathic RBD patients showed a further significant decrease of this index; MSA patients showed the lowest values of REM Sleep Atonia Index, which were very well distinguishable from those of normal controls and of idiopathic RBD patients. The distribution of the duration of chin activations was monomodal in all groups, with idiopathic RBD patients showing the highest levels. This study is a really quantitative attempt to provide practical indices for the objective evaluation of EMG atonia during REM sleep and of EMG activations. Our proposed Sleep Atonia Index can have a practical application in the clinical evaluations of patients and represents an additional useful parameters to be used in conjunction with the other criteria for the diagnosis of this sleep motor disorder.
Thermal antinociception after dexmedetomidine administration in cats: a dose‐finding study
Authors: SLINGSBY L. S. , TAYLOR P. M.
Published: February 2008

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups (n = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 μg/kg; positive and negative controls were administered buprenorphine (20 μg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey’s tests (P < 0.05). Only dexmedetomidine at 40 μg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 μg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose‐dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.
DrRRA: a novel response regulator essential for the extreme radioresistance of Deinococcus radiodurans
Authors: Wang Liangyan , Xu Guangzhi , Chen Huan , Zhao Ye , Xu Nan , Tian Bing , Hua Yuejin
Published: February 2008

Two‐component systems are predominant signal transduction pathways in prokaryotes, and also exist in many archaea as well as some eukaryotes. A typical TCS consists of a histidine kinase and a cognate response regulator. In this study, a novel gene encoding a response regulator (we designate it drRRA) is identified to be essential for the extreme radioresistance of Deinococcus radiodurans. DrRRA null mutant (we designate it MR) is sensitive to gamma‐radiation compared with the wild‐type strain. Transcriptional assays show that numerous genes are changed in their transcriptional levels in MR at exponential growth phase under normal or gamma‐radiation condition. Most of them are related to stress response and DNA repair. Antioxidant activity assays exhibit that both superoxide dismutases and catalases are decreased in the mutant, whereas Western blotting assays show that RecA and PprA are also reduced in MR, verifying the microarray and quantitative real‐time PCR data. Furthermore, pulsed‐field gel electrophoresis assay demonstrates that deletion of drRRA results in the delay of genome restitution. These data support the hypothesis that DrRRA contributes to the extreme radioresistance of D. radiodurans through its regulatory role in multiple pathways such as antioxidation and DNA repair pathways.
Expression of BRI2 mRNA and protein in normal human brain and familial British dementia: its relevance to the pathogenesis of disease
Authors: Lashley T. , Revesz T. , Plant G. , Bandopadhyay R. , Lees A. J. , Frangione B. , Wood N. W. , De Silva R. , Ghiso J. , Rostagno A. , Holton J. L.
Published: February 2008

Introduction: Two different disease‐specific mutations in the BRI2 gene, situated on chromosome 13, have been identified as giving rise to familial British dementia (FBD) and familial Danish dementia (FDD). Each mutation results in extension of the open reading frame generating the disease‐specific precursor proteins which are cleaved by furin‐like proteolysis releasing the amyloidogenic C‐terminal peptides ABri and ADan in FBD and FDD, respectively. Material and methods: To understand the mechanism of the formation of amyloid lesions in FBD, we studied the origin of the precursor proteins and furin in the human brain. We used control brains, cases of sporadic Alzheimer's disease (AD), variant AD with cotton wool plaques and FBD to study BRI2 mRNA expression using in situ hybridization. Furin and BRI2 protein expression was investigated using Western blotting and immunohistochemistry. Results: BRI2 mRNA and BRI2 protein are widely expressed primarily by neurones and glia and are deposited in the amyloid lesions in FBD. They were, however, not expressed by cerebrovascular components. Furin expression showed a similar pattern except that it was also present in cerebrovascular smooth muscle cells. Conclusions: These findings suggest that neurones and glia and are a major source of BRI2 protein and that in FBD, the mutated precursor protein may undergo furin cleavage within neurones to produce the amyloid peptide ABri. The failure to demonstrate BRI2 in blood vessels under the conditions tested suggests that vascular amyloid peptide production does not contribute significantly to cerebral amyloid angiopathy (CAA) in FBD and FDD, lending indirect support to the drainage hypothesis of CAA.
Heterogeneity of gas exchange rates over the leaf surface in tobacco: an effect of hydraulic architecture?
Authors: NARDINI ANDREA , GORTAN EMMANUELLE , RAMANI MATTEO , SALLEO SEBASTIANO
Published: February 2008

Spatial heterogeneity of gas exchange rates in the leaves of Nicotiana tabacum L. (tobacco) was investigated. Leaf conductance to water vapour was higher (by about 18%) at the apical regions of leaves than at the basal ones. Local, small‐scale measurements of pressure–volume (PV) parameters and water status (performed with a dewpoint hygrometer) revealed that bulk leaf water potential, osmotic potential, turgor pressure and bulk modulus of elasticity were not significantly different in the leaf apex or base. Hydraulic measurements showed that the apical regions of the leaf blade were about 30% more conductive than the basal regions. Such differences were explained by analogous differences in terms of venation patterns. In fact, vein density turned out to be higher (by about 13%) near the leaf apex with respect to the leaf base. On the contrary, stomatal density was the same both in the apical and basal leaf portions. Our data suggest that spatial stomatal heterogeneity may arise from heterogenous distribution of local hydraulic resistances and would be addressed to maintaining local water potential above critical values, possibly triggering vein cavitation.
Microbiological diversity of generalized aggressive periodontitis by 16S rRNA clonal analysis
Authors: Faveri M. , Mayer M. P. A. , Feres M. , De Figueiredo L. C. , Dewhirst F. E. , Paster B. J.
Published: February 2008

Background/aim:  The purpose of this study was to determine the bacterial diversity in the subgingival plaque of subjects with generalized aggressive periodontitis by using culture‐independent molecular methods based on 16S ribosomal DNA cloning.

Methods:  Samples from 10 subjects with generalized aggressive periodontitis were selected. DNA was extracted and the 16S rRNA gene was amplified with the universal primer pairs 9F and 1525R. Amplified genes were cloned, sequenced, and identified by comparison with known 16S rRNA sequences.

Results:  One hundred and ten species were identified from 10 subjects and 1007 clones were sequenced. Of these, 70 species were most prevalent. Fifty‐seven percent of the clone (40 taxa) sequences represented phylotypes for which no cultivated isolates have been reported. Several species of Selenomonas and Streptococcus were found at high prevalence and proportion in all subjects. Overall, 50% of the clone libraries were formed by these two genera. Selenomonas sputigena, the species most commonly detected, was found in nine of 10 subjects. Other species of Selenomonas were often present at high levels, including S. noxia, Selenomonas sp. EW084, Selenomonas sp. EW076, Selenomonas FT050, Selenomonas sp. P2PA_80, and Selenomonas sp. strain GAA14. The classical putative periodontal pathogens, such as, Aggregatibacter actinomycetemcomitans, was below the limit of detection and was not detected.

Conclusion:  These data suggest that other species, notably species of Selenomonas, may be associated with disease in generalized aggressive periodontitis subjects.
Differential utilization of nuclear factor‐κB signaling pathways for gingival epithelial cell responses to oral commensal and pathogenic bacteria
Authors: Chung W. O. , Dale B. A.
Published: February 2008

Introduction:  Human β‐defensin‐2 (hBD‐2) is an antimicrobial peptide, induced by bacterial stimuli and inflammation, that plays a role in mucosal and skin innate immune defense. The nuclear factor‐κB (NF‐κB) transcription factor family is important in innate and adaptive immune responses to bacteria and proinflammatory cytokines. NF‐κB operates via the traditional IKKβ signaling, as well as an alternative pathway utilizing IKKα signaling, which is important in keratinocyte differentiation. Our previous studies showed that pathogenic, but not commensal, bacteria used NF‐κB signaling in hBD‐2 induction. The objective of this study was to understand which arm of the NF‐κB pathway is involved in gingival epithelial cell responses to pathogenic bacteria, including hBD‐2 induction.

Methods:  Cultured oral epithelial cells were transfected with synthetic small interfering RNAs (siRNAs) specific for various steps in each pathway, namely IKKβ, TRAF6 and MyD88 in the canonical, and IKKα and TRAF3 in the alternative pathway, and subsequently stimulated with various oral bacteria.

Results:  The hBD‐2 induction level was reduced to 21–61% in cells in which the alternative NF‐κB pathway was blocked and subsequently stimulated with pathogenic bacteria, while cells in which the canonical pathway was blocked showed reduction to 78–99%. Cells stimulated with commensals showed little change in hBD‐2 induction level regardless of the siRNA used. Microarray analysis showed that oral epithelia differentially regulated numerous innate immune markers in response to pathogens and commensals.

Conclusion:  Our data suggest a role for the IKKα/TRAF3 pathway in NF‐κB activation by pathogenic bacteria, while commensal bacteria do not utilize either NF‐κB pathway, for hBD‐2 induction.
Aggregatibacter actinomycetemcomitans serotype f O‐polysaccharide mediates coaggregation with Fusobacterium nucleatum
Authors: Rupani D. , Izano E. A. , Schreiner H. C. , Fine D. H. , Kaplan J. B.
Published: February 2008

Background/aims:  Intergeneric bacterial coaggregation may play an important role in plaque development.

Methods:  In this study we investigated the coaggregation reaction between two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum.

Results:  Previous studies showed that A. actinomycetemcomitans serotype b strains coaggregate with F. nucleatum strain PK1594, and that A. actinomycetemcomitans serotype b O‐polysaccharide (O‐PS) is the receptor responsible for coaggregation between A. actinomycetemcomitans and F. nucleatum. A. actinomycetemcomitans serotype f O‐PS has been shown to be structurally and antigenically related to serotype b O‐PS. In the present study we show that A. actinomycetemcomitans strain CU1060N, a serotype f strain, also coaggregated with F. nucleatum PK1594. Like coaggregation between serotype b strains and F. nucleatum, coaggregation between CU1060N and F. nucleatum was inhibited by galactose. An O‐PS mutant of CU1060N failed to coaggregate with F. nucleatum.

Conclusion:  We concluded that A. actinomycetemcomitans serotype f O‐PS, like serotype b O‐PS, mediates coaggregation between A. actinomycetemcomitans and fusobacteria.
Demographics and response to therapeutic plasma exchange in pediatric renal transplantation for focal glomerulosclerosis: A single center experience
Authors: Mahesh Shefali , Del Rio Marcela , Feuerstein Dianne , Greenstein Stuart , Schechner Richard , Tellis Vivian , Kaskel Frederick
Published: February 2008

Abstract:  Recurrence of FSGS following renal transplantation in pediatric patients is reported as 20–57%. Records of 37 pediatric patients transplanted for FSGS between 1990 and 2005 at a single center were reviewed. Recurrence of disease was assessed by nephrotic range proteinuria and/or FSGS on biopsy. Response to TPE was defined as urine protein to creatinine ratio <0.2. Forty‐nine percent of patients were African American, 38% were Caucasian. Fifty‐four percent received kidneys from deceased donors and 46% from live donors. Seven patients received preemptive TPE prior to transplantation. Two of these seven patients recurred in the transplanted kidney (28%). Recurrent FSGS occurred in 16 of 37 patients (46%), all of whom received TPE. Recurrence occurred within one month in 12 of 37 patients (32%); eight remitted with TPE (67%). Four of 12 patients failed to respond to TPE. Four of 37 patients (14%) recurred more than one month after transplantation and underwent TPE; three‐fourths of patients remitted (75%). Twenty‐one of 37 patients (54%) did not recur. One and five yr graft survivals were 84% and 67%, respectively. Median graft survival was 6.7 yr (5.2–10.3). Despite recurrence, FSGS patients can achieve sustained graft function.
Age‐Related Immunohistochemical and Ultrastructural Changes in Rat Oculomotor Nerve
Authors: Bahcelioglu M. , Elmas C. , Kurkcuoglu A. , Calguner E. , Erdogan D. , Kadıoglu D. , Gözil R.
Published: February 2008

During ageing process, multiple changes occur on nervous tissue composed of cells and extracellular matrix. Changes on nervous tissues are usually known as degenerative changes on axon structure and connective tissue covering the nerve such as a decrease in the number of fibre or general structural changes. For this purpose, we have studied age‐dependent ultrastructural changes in the rat oculomotor nerve with electron microscopy and also demonstrated collagen structure of the neural sheaths with immunohistochemical techniques. This study was conducted in Gazi University Faculty of Medicine, Department of Anatomy with a total of nine Wistar albino rats. We observed strong collagen type I immunoreactivity in endoneurium and slight to moderate reactivity in fibroblast cytoplasm in 3‐month‐ and 12‐month‐old groups and mild reactivity in 24‐month‐old group. Collagen type IV immunoreactivity was stronger in endoneurium and perineurium in the 3‐month‐ and 12‐month‐old groups compared with collagen type I and fibroblast cytoplasm showed a very strong reactivity. On the other hand, in the 24‐month‐old group, there was slight reactivity in endoneurium and a strong reactivity in perineurium. NGF staining showed moderate to strong reactivity on Schwann cells of the 3‐month‐old group. The immunoreactivity decreased in the 12‐month‐ and 24‐month‐old groups. In the 3‐month‐old rat group, Schwann cell cytoplasm, mitochondrial structure and neurofilaments were normal. In the 12‐month‐old group, there were no changes in organelle distribution, mitochondrial structure and neurofilaments, but there was an increase in the connective tissue. An inconsiderable number of degenerated myelinated nerves were observed. We detected an important decrease in the collagen type I immunoreactivity, which could suggest that the endoneurium, perineurium and epineurium are less resistant to the age‐related collagen loss and that the peripheral nerve is protected by a weaker barrier in the old group. The collagen type IV immunoreactivity was significantly decreased with age. NGF synthesis decreases with age because of Schwann cell structural degeneration or for different reasons. Thus, this could explain the diminished capacity of regeneration and damage of the myelination of the peripheral nerve.