bluuebunny/crossref_metadata_2025 huggingface dataset:
Faecal DNA and calprotectin as biomarkers of acute intestinal toxicity in patients undergoing pelvic radiotherapy
Authors: VARELA E. , ANTOLÍN M. , GUARNER F. , VERGES R. , GIRALT J. , MALAGELADA J.‐R.
Published: April 2009

Background  Acute intestinal toxicity is a frequent complication that may lead to interruption of treatment in patients undergoing pelvic radiotherapy. Reliable, non‐invasive biological markers to evidence their severity are not yet available.

Aim  To test faecal DNA and calprotectin as potential biomarkers of intestinal toxicity caused by pelvic radiotherapy.

Methods  Patients were categorized according to the location of the cancer as nonrectal (n = 25) and rectal (n = 27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy) and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA. Intestinal toxicity was scored according to the Common Toxicity Criteria.

Results  In the nonrectal group, acute diarrhoea toxicity was present in 80% of patients, faecal DNA increased 10‐fold during radiotherapy (1.5 × 103 copies/mg dry weight, 9.5 × 102–8.8 × 103 at w0, median and interquartile range vs. 1.3 × 104, 1.9 × 103–3.9 × 104 at w5, P < 0.01), but was not recovered at w7 (3.4 × 103, 1.5 × 103–4.1 × 104) and calprotectin doubled during treatment at w3 and w5. No significant changes in faecal markers were found in the rectal group.

Conclusion  Faecal excretion of human DNA and calprotectin increased during pelvic radiotherapy treatment, and may be a good objective biomarker of intestinal damage in nonrectal cancer patients.
Meta‐analysis: longitudinal studies of serum vitamin D and colorectal cancer risk
Authors: YIN L. , GRANDI N. , RAUM E. , HAUG U. , ARNDT V. , BRENNER H.
Published: April 2009

Background  In 1980, Garland hypothesized that lower levels of vitamin D resulting from much weaker UV‐B radiation at higher latitudes may account for the striking geographical pattern of cancer mortality. Further research has been conducted over the past 20 years.

Aim  To perform a systematic review and meta‐analysis of longitudinal studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and the risk of colorectal cancer (CRC).

Methods  Relevant studies published until September 2008 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross‐referencing. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/mL. Summary odds ratios (ORs) were calculated using meta‐analysis methods.

Results  Overall, eight original articles reporting on the association between serum 25(OH) D and CRC risk were included. In meta‐analyses, summary ORs (95% confidence intervals) for the incidence of CRC, colon cancer and rectal cancer associated with an increase of 25(OH)D by 20 ng/mL were 0.57 (0.43–0.76), 0.78 (0.54–1.13) and 0.41 (0.11–1.49). No indication for publication bias was found.

Conclusions  Our results support suggestions that serum 25(OH)D is inversely related to CRC risk.
Meta‐analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis
Authors: GISBERT J. P. , LINARES P. M. , MCNICHOLL A. G. , MATÉ J. , GOMOLLÓN F.
Published: April 2009

Background  Debate exists regarding to whether thiopurine therapy is as effective in ulcerative colitis (UC) as it is in Crohn's disease.

Aim  To review systematically the efficacy of azathioprine (AZA) and mercaptopurine (MP) in UC, and to conduct a meta‐analysis of randomized clinical trials evaluating the efficacy of AZA/MP for the induction or maintenance of UC clinical remission.

Methods  Selection of studies: Evaluating AZA/MP for induction and/or maintenance of clinical remission of UC. Randomized‐controlled‐trials comparing AZA/MP with placebo/5‐aminosalicylates were included in the meta‐analysis. Search strategy: Electronic and manual. Study quality: Independently assessed by two reviewers. Data synthesis: By ‘intention‐to‐treat’.

Results  Thirty noncontrolled studies (1632 patients) were included in the systematic review. Mean efficacy of AZA/MP was 65% for induction and 76% for maintenance of the remission. Seven controlled studies were included in the meta‐analysis. (i) Induction of remission: four studies (89 AZA/MP‐treated patients) showed mean efficacy of 73% vs. 64% in controls (OR = 1.59; 95% CI = 0.59–4.29). (ii) Maintenance of remission: six studies (124 AZA/MP‐treated patients) showed mean efficacy of 60% vs. 37% in controls (OR = 2.56; 95% CI = 1.51–4.34). When only studies comparing AZA/MP vs. placebo were considered, OR was 2.59 (95% CI = 1.26–5.3), absolute risk reduction was 23% and number‐needed‐to‐treat (NNT) to prevent one recurrence was 5.

Conclusion  Thiopurine drugs (AZA/MP) are more effective than placebo for the prevention of relapse in UC, with an NNT of 5 and an absolute risk reduction of 23%.
Beta2‐microglobulin is a better predictor of treatment‐free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate
Authors: Delgado Julio , Pratt Guy , Phillips Neil , Briones Javier , Fegan Chris , Nomdedeu Josep , Pepper Chris , Aventin Anna , Ayats Ramon , Brunet Salut , Martino Rodrigo , Valcarcel David , Milligan Donald , Sierra Jorge
Published: April 2009

Even in the era of newer and sophisticated prognostic markers, beta2‐microglobulin (B2M) remains a simple but very powerful predictor of treatment‐free survival (TFS) and overall survival (OS) in patients with chronic lymphocytic leukaemia (CLL). However, B2M levels are heavily influenced by the patient’s glomerular filtration rate (GFR) and this study aimed to evaluate whether GFR‐adjusted B2M (GFR‐B2M) had improved prognostic value compared to unadjusted B2M in a cohort of over 450 consecutive CLL patients from two separate institutions. Multivariate analysis identified a significantly shorter TFS in patients who were ZAP‐70 + (P < 0·001), with increased GFR‐B2M (P < 0·001), and del(11q) or del(17p) as detected by fluorescence in situ hybridization (FISH; P < 0·001). When OS was evaluated by multivariate analysis, age 65 years or older (P < 0·001) and poor risk FISH abnormalities (P < 0·001) had a confirmed adverse prognostic impact, but the predictive value of GFR‐B2M was lost in the validation analysis. In all survival models, B2M did not attain independent significance unless GFR‐B2M was eliminated from the analysis. In conclusion, GFR‐B2M is a better predictor of TFS than unadjusted B2M in CLL patients.
Serine protease activity of Per a 10 augments allergen‐induced airway inflammation in a mouse model
Authors: Sudha V. T. , Arora N. , Singh B. P.
Published: April 2009

Background We recently reported an immunodominant serine protease allergen (Per a 10) fromPeriplaneta americana.This study investigates the role of its proteolytic activity in driving the immune responses towards self and other allergens.

Materials and methods Groups of Balb/c mice were sensitized intraperitoneally and subcutaneously with proteolytically active Per a 10 or inactivated Per a 10 (using aminoethyl benzenesulfonyl fluoride hydrochloride) or whole bodyP. americanaextract and subsequently challenged intranasally with the respective antigens. Mice were also sensitized and challenged with ovalbumin (OVA) alone or co‐administered with active or inactive Per a 10. The immune‐inflammatory responses were measured by airway hyperresponsiveness (AHR) and cellular infiltration of lungs i.e. eosinophil counts, eosinophil peroxidase (EPO) activity, myeloperoxidase activity (MPO), lung histopathology, serum levels of specific‐antibodies and levels of Th1/Th2 interleukins in bronchoalveolar lavage fluid (BALF) and in spleen cells culture supernatant.

Results Mice challenged with active Per a 10/P. americanaextract showed a significant airway inflammation demonstrated by enhanced AHR and increased cellular infiltration of lungs as evidenced by high eosinophil counts, EPO activity, IL‐4 and IL‐5 in BALF. Active Per a 10 also induced a significant proliferation of spleen cells, increased secretion of IL‐4 and IL‐5 in the spleen cells culture supernatant and systemic production of specific‐IgE and IgG1. However, exposure with inactive Per a 10 elicited a low cellular infiltration and systemic antibody production. Exposure to OVA with active Per a 10 demonstrated a significantly high cellular infiltration and production of OVA‐specific IgE and IgG1, than exposure to OVA alone or with inactive Per a 10.

Conclusions Proteolytic activity of Per a 10 plays an important role in driving the allergic immune response by providing an adjuvant effect, towards self and other potential allergens present in the same microenvironment.
Nutrient allocations and metabolism in two collembolans with contrasting reproduction and growth strategies
Authors: Larsen Thomas , Ventura Marc , Damgaard Christian , Hobbie Erik A. , Krogh Paul Henning
Published: April 2009

Physiological mechanisms such as allocation and release of nutrients are keys to understanding an animal's adaptation to a particular habitat. This study investigated how two detrivores with contrasting life‐history traits allocated carbon (C) and nitrogen (N) to growth, reproduction and metabolism. As model organisms we used the collembolans, Proisotoma minuta (Tullberg 1871) and Protaphorura fimata (Gisin 1952).

To estimate allocations of C and N in tissue, we changed the isotopic composition of the animal's yeast diets when they became sexually mature and followed isotope turnover in tissue, growth and reproduction for 28 days. In addition, we measured the composition of C, N and phosphorus (P) to gain complementary information on the stoichiometry underlying life‐history traits and nutrient allocation.

For P. minuta, the smallest and most fecund of the two species, the tissue turnover of C and N were 13% and 11% day−1, respectively. For P. fimata, the equivalent rates were 5% and 4% d−1, respectively. Protaphorura fimata had the lowest metabolic rate relative to total body mass but the highest metabolic rates relative to reproductive investment. Adult P. fimata retained approximately 17% of the nutrient reserves acquired while a juvenile and adult P. minuta about 11%. N and P contents of total tissue were significantly higher in P. minuta than in P. fimata, suggesting that tissue turnover was correlated with high protein‐N and RNA‐P.

Our results suggest that the lower metabolism and nutritional requirements by P. fimata than P. minuta is an adaptation to the generally low availability and quality of food in its natural habitat.

The methodological approach we implemented tracking mass balance, isotope turnover and elemental composition is promising for linking nutrient budgets and life‐history traits in small invertebrates such as Collembola.
Nuclear localization and pro‐apoptotic signaling of YAP2 require intact PDZ‐binding motif
Authors: Oka Tsutomu , Sudol Marius
Published: April 2009

The Hippo signaling pathway regulates the intrinsic size of organs by controlling two opposing processes, proliferation and apoptosis. The nuclear effector of this pathway is Yes kinase‐associated protein (YAP) which is a WW domain‐containing transcriptional co‐activator. In addition to WW domains, YAP2 has a Post‐synaptic density, Discs large, Zonula occludens‐1 (PDZ)‐binding motif that is located at its COOH terminus. To determine whether the localization of YAP2 in cells is PDZ‐binding motif dependent, we generated a delta C mutant of YAP2 lacking the five most COOH terminal amino acids, ‐FLTWL, which constitute a well‐conserved PDZ‐binding motif. We report here that the PDZ‐binding motif is necessary for YAP2 localization in the nucleus, for the stabilization of p73, and for promoting apoptosis of HEK293 cells maintained at low concentration of serum. We suggest that an unknown PDZ domain‐containing protein (or proteins) functions as a shuttle, facilitating YAP2 translocation from the cytoplasm to the nucleus. Since the Hippo pathway acts as a tumor suppressor pathway, the PDZ complex of YAP represents a potential target of cancer therapy.
GAK, a regulator of clathrin‐mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus
Authors: Sato Jun , Shimizu Hiroyuki , Kasama Takashi , Yabuta Norikazu , Nojima Hiroshi
Published: April 2009

The ubiquitously expressed Cyclin G‐associated kinase (GAK) regulates clathrin‐mediated membrane trafficking in the cytoplasm. However, the association of GAK with a nuclear protein Cyclin G1 that is unrelated to membrane trafficking suggests an unidentified role of GAK in the nucleus. Indeed, we report here that GAK localizes in both cytoplasm and nucleus by immunostaining, ectopic expression of GFP‐GAK and pull‐down assays using dissected GAK fragments. GAK forms complexes not only with cyclin G1 but also with other nuclear proteins such as p53, clathrin heavy chain (CHC) and protein phosphatase 2A (PP2A) B′α1. Moreover, CHC associates with GAK via a different domain depending on whether it is in the cytoplasm or nucleus. Immunostaining revealed that about 20~30% of B′α1, cyclin G1 and p53 complex with nuclear GAK. CHC also displayed dots in the nucleus and almost all nuclear CHC signals colocalized with GAK. These observations together suggest an important function of GAK in the nucleus.
Selfish prion of Rnq1 mutant in yeast
Authors: Kurahashi Hiroshi , Shibata Shoichiro , Ishiwata Masao , Nakamura Yoshikazu
Published: April 2009

[PIN+] is a prion form of Rnq1 in Saccharomyces cerevisiae and is necessary for the de novo induction of a second prion, [PSI+]. We previously isolated a truncated form of Rnq1, named Rnq1Δ100, as a [PSI+]‐eliminating factor in S. cerevisiae. Rnq1Δ100 deletes the N‐terminal non‐prion domain of Rnq1, and eliminates [PSI+] in [PIN+] yeast. Here we found that [PIN+] is transmissible to Rnq1Δ100 in the absence of full‐length Rnq1, forming a novel prion variant [RNQ1Δ100+]. [RNQ1Δ100+] has similar [PIN+] properties as it stimulates the de novo induction of [PSI+] and is eliminated by the null hsp104Δ mutation, but not by Hsp104 overproduction. In contrast, [RNQ1Δ100+] inherits the inhibitory activity and hampers the maintenance of [PSI+] though less efficiently than [PIN+] made of Rnq1–Rnq1Δ100 co‐aggregates. Interestingly, [RNQ1Δ100+] prion was eliminated by de novo [PSI+] induction. Thus, the [RNQ1Δ100+] prion demonstrates selfish activity to eliminate a heterologous prion in S. cerevisiae, showing the first instance of a selfish prion variant in living organisms.
Impacts of climate change on the seasonal distribution of migratory caribou
Authors: SHARMA SAPNA , COUTURIER SERGE , CÔTÉ STEEVE D.
Published: April 2009

Arctic ecosystems are especially vulnerable to global climate change as temperature and precipitation regimes are altered. An ecologically and socially highly important northern terrestrial species that may be impacted by climate change is the caribou, Rangifer tarandus. We predicted the current and potential future occurrence of two migratory herds of caribou [Rivière George herd (RG) and Rivière‐aux‐Feuilles (RAF) herd] under a Canadian General Circulation Model climate change scenario, across all seasons in the Québec–Labrador peninsula, using climatic and habitat predictor variables. Argos satellite‐tracking collars have been deployed on 213 caribou between 1988 and 2003 with locations recorded every 4–5 days. In addition, we assembled a database of climate (temperature, precipitation, snowfall, timing and length of growing season) and habitat data obtained from the SPOT VEGETATION satellite sensor. Logistic regression models indicated that both climatic and physical habitat variables were significant predictors of current migratory caribou occurrence. Migratory caribou appeared to prefer regions with higher snowfall and lichen availability in the fall and winter. In the summer, caribou preferred cooler areas likely corresponding to a lower prevalence of insects, and they avoided disturbed and recently burnt areas. Climate change projections using climate data predicted an increased range for the RAF herd and decreased range for the RG herd during 2040–2069, limiting the herds to northeastern regions of the Québec–Labrador peninsula. Direct and indirect consequences of climate change on these migratory caribou herds possibly include alteration in habitat use, migration patterns, foraging behaviour, and demography, in addition to social and economic stress to arctic and subarctic native human populations.
Critical periods for impact of climate warming on early seedling establishment in subarctic tundra
Authors: SHEVTSOVA ANNA , GRAAE BENTE JESSEN , JOCHUM TILL , MILBAU ANN , KOCKELBERGH FRED , BEYENS LOUIS , NIJS IVAN
Published: April 2009

Climate warming is expected to shift bioclimatic zones and plant species distribution. Yet, few studies have explored whether seedling establishment is a possible bottleneck for future migration and population resilience. We test how warming affects the early stages of seedling establishment in 10 plant species in subarctic tundra. To zoom into the life phases where the effects of warming actually take place, we used a novel approach of breaking down the whole‐season warming effect into full factorial combination of early‐, mid‐, and late‐season warming periods. Seeds were sown in containers placed under field conditions in subarctic heath and were exposed to 3 °C elevation of surface temperature and 30% addition of summer precipitation relative to ambient. Heating was achieved with Free Air Temperature Increase systems. Whole‐season heating reduced germination and establishment, significantly in four out of 10 species. The whole‐season warming effect originated from additive effects of individual periods, although some of the periods had disproportionally stronger influence. Early‐germinating species were susceptible to warming; the critical phases were early summer for germination and mid summer for seedling survival. Graminoids, which emerged later, were less susceptible although some negative effects during late summer were observed. Some species with intermediate germination time were affected by all periods of warming. Addition of water generally could not mitigate the negative effects of whole‐season heating, but at individual species level both strengthening and amelioration of these negative effects were observed. We conclude that summer warming is likely to constrain seedling recruitment in open micro sites, which is a common seed regeneration niche in tundra ecosystem. Importantly, we described both significant temporal and species‐specific variation in the sensitivity of seedling establishment to warming which needs to be taken into consideration when modelling population dynamics and vegetation transitions in a warmer climate.
Identification and isolation of cDNA clones encoding the abundant secreted proteins in the saliva proteome of Culicoides nubeculosus
Authors: Russell C. L. , Heesom K. J. , Arthur C. J. , Helps C. R. , Mellor P. S. , Day M. J. , Torsteinsdottir S. , Björnsdóttir T. S. , Wilson A. D.
Published: April 2009

Culicoides spp. are vectors of several infectious diseases of veterinary importance and a major cause of allergy in horses and other livestock. Their saliva contains a number of proteins which enable blood feeding, enhance disease transmission and act as allergens. We report the construction of a novel cDNA library from Culicoides nubeculosus linked to the analysis of abundant salivary gland proteins by mass spectrometry. Fifty‐four novel proteins sequences are described including those of the enzymes maltase, hyaluronidase and two serine proteases demonstrated to be present in Culicoides salivary glands, as well as several members of the D7 family and protease inhibitors with putative anticoagulant activity. In addition, several families of abundant proteins with unknown function were identified including some of the major candidate allergens that cause insect bite hypersensitivity in horses.
Peer teaching pilot programme for caries prevention in underprivileged and migrant populations
Authors: REINHARDT CLAUS H. , LÖPKER NADINE , NOACK MICHAEL J. , ROSEN EVELYNE , KLEIN KLAUS
Published: April 2009

Background.  Focused caries prevention programmes for migrant children often fail because there is an important barrier of linguistic and cultural diversity.

Aim.  The aim of this study was to evaluate whether a tailored peer teaching approach can improve oral health behaviours of underprivileged and/or multinational migrant first graders.

Design.  Two fourth grade classes (30 children, mean age 9.6) and two first grade classes (38 children, mean age 6.6) with high migrant background participated. The fourth graders took part in a preparatory course of oral health and developed a concept for tutoring first graders in oral health concepts as well as the Fones toothbrushing method. Later then, the fourth graders instructed the first graders during two lessons. Toothbrushing of each first grader was filmed before and 7 days after instruction. Toothbrushing time, method, and systematic were evaluated.

Results.  After instruction, circular toothbrushing movements and systematic toothbrushing were observed significantly more often (P = 0.0001); toothbrushing time did not change.

Conclusions.  This pilot study shows that tutoring by older peers of similar origin resulted in significant changes towards better oral health in underprivileged and/or multinational migrant first graders. Authentic role models could be provided, and communication and cultural barriers circumvented.
Spatial–temporal analysis of species range expansion: the case of the mountain pine beetle,Dendroctonus ponderosae
Authors: Robertson Colin , Nelson Trisalyn A. , Jelinski Dennis E. , Wulder Michael A. , Boots Barry
Published: April 2009

Aim The spatial extent of western Canada’s current epidemic of mountain pine beetle,Dendroctonus ponderosaeHopkins (Coleoptera: Curculionidae, Scolytinae), is increasing. The roles of the various dispersal processes acting as drivers of range expansion are poorly understood for most species. The aim of this paper is to characterize the movement patterns of the mountain pine beetle in areas where range expansion is occurring, in order to describe the fine‐scale spatial dynamics of processes associated with mountain pine beetle range expansion.

Location Three regions of Canada’s Rocky Mountains: Kicking Horse Pass, Yellowhead Pass and Pine Pass.

Methods Data on locations of mountain pine beetle‐attacked trees of predominantly lodgepole pine (Pinus contortavar.latifolia) were obtained from annual fixed‐wing aircraft surveys of forest health and helicopter‐based GPS surveys of mountain pine beetle‐damaged areas in British Columbia and Alberta. The annual (1999–2005) spatial extents of outbreak ranges were delineated from these data. Spatial analysis was conducted using the spatial–temporal analysis of moving polygons (STAMP), a recently developed pattern‐based approach.

Results We found that distant dispersal patterns (spot infestations) were most often associated with marginal increases in the areal size of mountain pine beetle range polygons. When the mountain pine beetle range size increased rapidly relative to the years examined, local dispersal patterns (adjacent infestation) were more common. In Pine Pass, long‐range dispersal (> 2 km) markedly extended the north‐east border of the mountain pine beetle range. In Yellowhead Pass and Kicking Horse Pass, the extension of the range occurred incrementally via ground‐based spread.

Main conclusions Dispersal of mountain pine beetle varies with geography as well as with host and beetle population dynamics. Although colonization is mediated by habitat connectivity, during periods of low overall habitat expansion, dispersal to new distant locations is common, whereas during periods of rapid invasion, locally connected spread is the dominant mode of dispersal. The propensity for long‐range transport to establish new beetle populations, and thus to be considered a driver of range expansion, is likely to be determined by regional weather patterns, and influenced by local topography. We conclude that STAMP appears to be a useful approach for examining changes in biogeograpical ranges, with the potential to reveal both fine‐ and large‐scale patterns.
Genetic diversity and phylogeographic analysis of Pinus leiophylla: a post‐glacial range expansion
Authors: Rodríguez‐Banderas Abril , Vargas‐Mendoza Carlos F. , Buonamici Anna , Vendramin Giovanni G.
Published: April 2009

Aim  Mexico is a centre of diversity for species of the genus Pinus, most of which have restricted geographical distributions. An exception is Pinus leiophylla Schiede and Deppe, which is widely distributed throughout most of Mexico’s mountainous regions. We attempt to reconstruct the phylogeographic history of this species, in order to determine if its current broad distribution is associated with major events of environmental change that occurred during the Quaternary.

Location  Coniferous forests in Sierra Madre Occidental, Eje Volcánico Transversal and Sierra Montañosa del Norte de Oaxaca, Mexico.

Methods  A total of 323 individuals of both P. leiophylla var. leiophylla and P. leiophylla var. chihuahuana sampled from 22 populations were screened for variation at six paternally inherited chloroplast DNA microsatellite markers (cpSSR). In addition to haplotypic diversity estimates and neutrality tests, the following clustering methods were employed: principal components analysis (PCA), analysis of molecular variance (AMOVA), spatial analysis of molecular variance (SAMOVA), haplotype network and a technique similar to Croizat’s panbiogeographical method of individual and generalized tracks.

Results  The combination of mutations at the six microsatellites yielded a total of 92 different haplotypes. The percentage of shared haplotypes between varieties (P. leiophylla var. leiophylla and P. leiophylla var. chihuahuana) was only 2.2%. The average haplotypic diversity for the species was H = 0.760. PCA and SAMOVA indicate the presence of four main genetic clusters. The estimated divergence time between the two most frequent haplotypes was between 75,000 and 110,000 years. Significantly large negative Fs values suggest that most of the sampled populations are currently expanding. Individual and generalized tracks identified three potential zones that may have harboured ancestral populations of P. leiophylla and from which the expansion of this species started, as well as two secondary contact zones between the two varieties.

Main conclusions  The results indicate that one of the three potential areas hypothesized to have harboured ancestral populations of P. leiophylla may be related to the origin of P. leiophylla var. chihuahuana, while the other two may be related to the origin of P. leiophylla var. leiophylla. The current broad distribution of P. leiophylla is probably associated with its strong colonization ability.
Nodavirus provokes subclinical encephalitis and retinochoroiditis in adult farmed Atlantic cod, Gadus morhua L
Authors: Gjessing M C , Kvellestad A , Ottesen K , Falk K
Published: April 2009

Viral nervous necrosis (VNN) caused by betanodavirus affects many species of farmed marine fish, in particular juveniles. Apparently healthy, normally feeding, adult farmed Atlantic cod, Gadus morhua, were sampled in a farm 14 months after an outbreak of VNN with clinical signs. Following necropsy, brain and eye tissues were examined by histology, immunohistochemistry and polymerase chain reaction (PCR). Nodavirus‐provoked cell death and inflammation was detected in eye and brain, particularly in the retina and cerebellum and differed from that previously described in Atlantic cod during clinical stages of VNN. Virus was detected both by PCR and immunohistochemistry. This is, to the best of our knowledge, the first description of pathological changes associated with chronic subclinical nodavirus infection in Atlantic cod. Our observations suggest that severe infection and pathological changes may go undetected if investigations are restricted to clinical examination and macroscopic evaluation at necropsy.
Development of an RPD CAD system with finite element stress analysis
Authors: KIBI M. , ONO T. , DONG J. , MITTA K. , GONDA T. , MAEDA Y.
Published: April 2009

Summary  The structural design of removable partial dentures (RPDs) is critical for preventing distortion of the prosthesis, protecting abutment teeth and residual ridges as well as for high masticatory performance. The aim of this study was to clarify the feasibility and utility of a computer‐aided designing (CAD) system with finite element analysis (FEA) for molar teeth arrangement in unilateral distal extension base RPDs. The shapes of artificial teeth and residual ridge were measured and converted into point group data. Solid models were created from surface‐modelled point group data in a 3D surface CAD format. An occlusal rim was created on the residual ridge mucosa and the occlusal rim ‐ residual ridge mucosa model with FEA function was created. Stress distribution on the residual ridge mucosa was compared by changing the loading point. The artificial teeth were then arranged in locations with the lowest amount of stress. After building an artificial teeth – saddle – residual ridge mucosa model, stress distribution in the residual ridge mucosa was re‐evaluated by simulating occlusal force. On the occlusal rim ‐ residual ridge mucosa model, stress was reduced when the loading point was located around the buccal shelf where functional cusps of artificial teeth were charted. It was confirmed that stress distribution in the residual ridge mucosa was equalized on the artificial teeth – saddle – residual ridge mucosa model. This system might be clinically useful tool for designing RPDs if FEA‐guided designing of retainers and connectors can be added.
Hardening trumps acclimation in improving cold tolerance of Drosophila melanogaster larvae
Authors: RAJAMOHAN ARUN , SINCLAIR BRENT J.
Published: April 2009

Abstract Chill‐susceptible insects are able to improve their survival of acute cold exposure over both the short term (i.e. hardening at a relatively severe temperature) and longer term (i.e. acclimation responses at milder temperatures over a longer time frame). However, the mechanistic overlap of these responses is not clear. Four larval stages of four different strains of Drosophila melanogaster are used to test whether low temperature acclimation (10 °C for 48 h) improves the acute cold tolerance (LT90, ∼2 h) of larvae, and whether acclimated larvae still show hardening responses after brief exposures to nonlethal cold or heat, or a combination of the two. Acclimation results in increased cold tolerance in three of four strains, with variation among instars. However, if acclimation is followed by hardening pre‐treatments, there is no improvement in acute cold survival. It is concluded that short‐term thermal responses (e.g. hardening) may be of more ecological relevance to short‐lived life stages such as larvae, and that the mechanisms of low temperature hardening and acclimation in D. melanogaster may be antagonistic, rather than complementary.
Escape of the yolk sac: a hypothesis to explain the embryogenesis of gastroschisis
Authors: Stevenson RE , Rogers RC , Chandler JC , Gauderer MWL , Hunter AGW
Published: April 2009

Gastroschisis is a significant birth defect that in many countries has shown an increased prevalence in recent decades, and the change has affected primarily younger mothers. Despite numerous epidemiological studies no other consistent associated risk factor has been identified. In this paper we review the five main theories related to the pathogenesis of this malformation and outline the reasons why we think none fully explains the embryogenesis of gastroschisis. We briefly present some clinical observations we have made that we consider germane to the pathogenesis and outline a hypothesis that we think can account for the origins of this malformation. Our proposal is that the determining defect in gastroschisis is failure of the yolk sac and related vitelline structures to be incorporated into the umbilical stalk. Otherwise, ventral closure of the lateral abdominal walls occurs normally, thus orphaning the vitelline duct and yolk sac outside both the main body stalk and the abdominal wall. Thus, in addition to the umbilicus, the abdominal wall has a separate perforation through which the midpoint of the gut is attached to the exteriorized vitelline structures. This connection through the ventral wall prevents normal egress of the gut into the umbilical cord during the second month of development and acts as the egress point for the gut resulting in gastroschisis.
Germ line MLH1 and MSH2 mutations in Taiwanese Lynch syndrome families: characterization of a founder genomic mutation in the MLH1 gene
Authors: Tang R , Hsiung C , Wang J‐Y , Lai C‐H , Chien H‐T , Chiu L‐L , Liu C‐T , Chen H‐H , Wang H‐M , Chen S‐X , Hsieh L‐L ,   the TCOG HNPCC Consortium
Published: April 2009

This multicenter study evaluated the mutation spectrum and frequencies of the MLH1 and MSH2 genes and determined the occurrence of large genomic deletions in 93 unrelated Taiwanese families that fulfilled the Amsterdam criteria II by denaturing high‐performance liquid chromatography analysis, DNA sequencing for aberrant chromatograms, and multiplex ligation‐dependent probe amplification analysis. In total, 38 pathogenic mutations (10 large deletions and 28 point mutations or small deletion/insertions) in the MSH2 or MLH1 gene were identified in 61 of the 93 families (66%). Three of the 10 large deletions and 14 of the 28 point mutations or small insertions/deletions have not been reported elsewhere. Three mutations in the MLH1 gene, the MLH1c.1846_1848delAAG (5 families), deletion exons 11–15 (4 unrelated families), and MLH1c.793C>T (13 unrelated families), accounted for 35% of all cases with pathogenic mutations. Haplotype analysis indicated that mutant c.793C>T alleles were derived from two distinct common founders that might be inherited from a single ancestor of presumably Chinese origin. As a mutation detection strategy for Taiwanese Lynch syndrome patients, we recommend that diagnosis starts with screening for large genomic deletions and continues by screening for common mutations in exons 10 and 16 of the MLH1 gene prior to searching for small mutations in the remaining exons.
Safety and tolerability of cidofovir in high‐risk pediatric patients
Authors: Bhadri V.A. , Lee‐Horn L. , Shaw P.J.
Published: April 2009

Abstract: Adenovirus (ADV) infection is a serious complication after hematopoietic stem cell transplantation with significant morbidity and mortality. Cidofovir has emerged as the primary therapy for ADV infection, but its use has been limited by concerns of nephrotoxicity. We report the safety and tolerability of 234 cidofovir infusions in 23 patients at a single institution, and demonstrate evidence of acceptable nephrotoxicity despite concomitant use of other nephrotoxic agents. Three patients suffered adverse events, two related to the hydration regimen associated with cidofovir administration. We conclude that cidofovir is a safe and mostly well tolerated drug in a high‐risk pediatric population.
The three‐way stopcock may be a weak component of total intravenous anaesthesia
Authors: ZECHA‐STALLINGER A. , SCHMÖLZ W. , WENZEL V.
Published: April 2009

Background: An intravenous line is needed to administer anaesthesia, particularly when total intravenous anaesthesia (TIVA) is performed. A disadvantage of TIVA is that the intravenous concentration of anaesthetics cannot be easily measured compared with volatile anaesthetics. If a three‐way stopcock is accidentally unscrewed, TIVA drugs cannot reach the patient's veins, thus resulting in inadequate anaesthesia levels, possibly resulting in awareness. We therefore measured the required torque to open five different brands of three‐way stopcocks in an attempt to make an intravenous‐line including all elements safer.

Methods: The torque required to open one, two or three three‐way stopcocks being connected in a perpendicular manner was measured with a biaxial servo hydraulic material testing machine.

Results: The force required to open three‐way stopcocks connected with an intravenous catheter ranged in five different stopcock models from 5.03±0.75 to 2.21±0.51 N respectively; with two three‐way stopcocks from 2.68±0.42 to 1.31±0.59 N, respectively, and with three three‐way stopcocks from 1.29±0.27 to 0.82±0.05 N, respectively.

Conclusion: Turning a three‐way stopcock to become loose with possibly leaking drugs requires minimal amounts of force and decreases significantly if not connected in‐line.
Attraction of Flatworms at Various Hunger Levels Toward Cues from an Odonate Predator
Authors: Collins Andrea M. , Gerald Gary W.
Published: April 2009

Different hunger levels can modify a prey’s antipredator behavior in the presence or absence of food. Satiated animals often forego foraging if a predator is nearby, whereas starved animals may risk a predator encounter to search for food. This study evaluated the influence of nutritional state on the behavior of the flatworm Dugesia dorotocephala in the presence of food, predator, and crushed conspecific cues. We found that flatworms are attracted to cues originating from a food source, crushed conspecifics, and a predator (dragonfly larva) compared with control cues. Among the different hunger level treatment groups, levels of satiation had no influence on activity levels but significantly influenced time spent close to and distance from the cue source. Flatworm movement toward predator cues emitted from dragonfly larvae is contrary to our expectations. These results suggest either a unique case of chemical mimicry from the dragonfly larvae or an inherent attraction of planarians to odonate predators that allows them to scavenge the remains of other odonate prey items.
Inter‐Population Variation in Hoarding Behaviour in Degus,Octodon degus
Authors: Quispe René , Villavicencio Camila P. , Cortés Arturo , Vásquez Rodrigo A.
Published: April 2009

Although foraging comprises a set of behaviours that typically vary with resource availability and/or climatic conditions, few studies have analysed how foraging, particularly food hoarding, varies across populations inhabiting different habitats. We carried out an inter‐population study on foraging behaviour with the caviomorph rodentOctodon deguscollected from two geographically separated populations in central Chile, with contrasting climates. One population was located in a mountainous zone (at 2600 m elevation) characterized by a high‐altitude climate. The other population was from a low‐altitude Mediterranean climate zone (450 m elevation). Under laboratory conditions, we measured population‐specific differences in food consumption and hoarding by recording food utilization. We also assessed whether acclimation played a role in behavioural differences, by using two different sets of animals that had been in captivity for (1) 2 wk or (2) 6 mo, under common conditions. The results showed variation in food hoarding between populations. Individuals from the low‐altitude population exclusively displayed scatter hoarding behaviour. In contrast, high‐altitude animals carried out larder hoarding combined with scatter hoarding (37.4% and 62.6% respectively). There was no intra‐population variation between degus with different acclimation periods under captivity, thus inter‐population differences in larder hoarding were maintained despite 6 mo of acclimation to a common environment. The geographic variation observed suggests that larder hoarding is favoured under harsher environmental conditions. We discuss some probable causes for this variation. The lack of effect of acclimation suggests that inter‐population differences in larder hoarding might be the result of local adaptation or, less likely, it corresponds to an ontogenetically acquired irreversible behaviour.
Marmoset (Callithrix geoffroyi) Food‐Associated Calls are Functionally Referential
Authors: Kitzmann Carolyn D. , Caine Nancy G.
Published: April 2009

Signals that are functionally referential provide listeners with information about a signaler’s external environment, such as the presence of a nearby predator. Just as alarm calls may signal the presence of a predator, food‐associated calls may signal the presence of food. To date, however, the only conclusive evidence that conspecifics perceive information about food from food‐associated calls comes from a single species, the domestic chicken. Geoffroy’s marmosets, small, arboreal New World primates, often emit food‐associated calls when finding or consuming food. We presented playbacks of food calls and control sounds to two groups of naturalistically housed marmosets and observed the frequency of food‐related behaviors (FRBs) during the 20‐min post‐playback period. Relative to the control playbacks, food call playbacks elicited an increase in the frequency of two FRBs (foraging and feeding), lasting throughout the post‐playback observations. Moreover, the effect of food call playbacks was robust, occurring without regard to the type of food eliciting the food calls, the rate of food calling, or whether the signaler was a member of the receiver’s group. To our knowledge, this research is the first to demonstrate that the food‐associated calls of a primate species, like the food‐associated calls of domestic chickens, meet the perception criterion for functionally referential communication. The results are discussed in light of the affective and cognitive mechanisms that may underlie the responses of receivers to hearing food‐associated calls given by marmoset conspecifics.
Agonistic Behaviour and Sexual Conflict in Atypical Reproductive Groups: The Case of Bearded VultureGypaetus barbatusPolyandrous Trios
Authors: Bertran Joan , Margalida Antoni , Arroyo Beatriz E.
Published: April 2009

Social behaviour in species forced to form atypical breeding coalitions is poorly documented. The saturation of optimum territories in the Bearded vultureGypaetus barbatuspopulation in the Pyrenees has led floating males to settle in already occupied territories, thereby forming polyandrous trios. We examined the patterns of intrasexual aggression in five trios (nine reproductive events in total) during courtship. Alpha males initiated 82% of agonistic encounters that were mainly aimed at preventing or disrupting copulations. During the fertile period in recently formed groups, intrasexual aggression had a negative influence on the frequency of heterosexual copulations, which may be a contributing factor to the lower productivity of polyandrous trios. Females rejected a higher proportion of beta male‐ than alpha male‐initiated copulations, and rejected copulations with both alpha and beta males more often when the other male was present close by. These results indicate that alpha males cannot effectively prevent all copulation attempts by beta males and that females avoid harassment by minimizing sexual activity when both males are present. Aggression between males decreased with time, occurring less often in established than in recent trios, despite the fact that the frequency of heterosexual copulations – the cause of conflicts – was similar. The frequency of homosexual interactions tended to increase in established trios, suggesting that this behaviour may help to regulate aggression within these groups, although no significant relationship between homosexual interactions and aggression was found. In summary, reproductive conflicts in trios seem to be unavoidable, although they tend to decrease if the group is maintained. This suggests that, for birds in these groups, the maintenance of a quality territory is more important than solving sexual conflicts.
Spatial Neophilia and Spatial Neophobia in Resident and Migratory Warblers (Sylvia)
Authors: Mettke‐Hofmann Claudia , Lorentzen Sandy , Schlicht Emmi , Schneider Janine , Werner Franziska
Published: April 2009

Residents and migrants use their environment very differently – the former remain in a given habitat throughout the year, whereas the latter are repeatedly confronted with unfamiliar environments. The difference in ecology may influence decision‐making processes whether, when and to which extent to explore an unfamiliar environment. We have investigated spatial neophobia and spatial neophilia – two important novelty reactions that may underlie decision‐making – in two closely related warbler species, the resident Sardinian warbler and the migratory garden warbler. Individuals of both species could access an unfamiliar room from a familiar cage. We assessed the conflict between the motivation to enter the novel room (spatial neophilia) and the motivation to avoid it (spatial neophobia) as the frequency and duration of perching on the dowel in the cage, which led to the unfamiliar room before entering it. Furthermore, we measured the latency to enter the novel room and compared the number of individuals of each species entering the room. The combination of the parameters measured allowed assessing the degree of both neophobia and neophilia. Finally, the time spent on each branch in the novel room was taken as a measure for spatial exploration. The migrants perched less often and spent less time on the dowel leading to the room, and entered the novel room quicker than the residents. Additionally, more migrants than residents entered the room. The migrants’ decision to enter the novel room can best be explained with a combination of low spatial neophobia coupled with high spatial neophilia, whereas the residents’ decision‐making is best explained with high spatial neophobia coupled with high spatial neophilia. The differences in neophobia support the migrant‐neophobia hypothesis. When in the room, the migrants spent less time on each branch than the residents, possibly indicating that the former collect less spatial information than the latter.
Wild Female Olive Baboons Adapt their Grunt Vocalizations to Environmental Conditions
Authors: Ey Elodie , Rahn Charlotte , Hammerschmidt Kurt , Fischer Julia
Published: April 2009

Sound propagates differently and visibility varies according to the habitat type. Animals should therefore adapt the acoustic structure and the usage of their vocal signals to the environment. In the present study, we examined the influence of the habitat on the vocal behaviour of wild olive baboons (Papio hamadryas anubis) in two populations: one living in Gashaka‐Gumti National Park, Nigeria, and the other in Budongo Forest, Uganda. We investigated whether female baboons modified the acoustic structure of their grunts and their rate of grunting when they wandered between closed and open habitat types. As an adaptation to the environmental conditions, baboons might utter calls with a longer duration, a lower fundamental frequency and/or energy concentrated in lower frequencies in a closed habitat like forest than in an open habitat. Baboons should also grunt more frequently in the closed habitat. Analyses showed that in both populations grunts uttered in forest were significantly longer than in open habitat. Additionally, baboons from Uganda showed a significantly higher grunt rate in forest than in open habitat. These results revealed a certain degree of plasticity in vocal production and call usage with regard to the habitat type. However, results in Nigeria suggested that, besides habitat structure, other proximate factors like the context of calling and the proximity between group members could also have an influence on the actual communication patterns.