bluuebunny/crossref_metadata_2025 huggingface dataset:
Small molecule blockers of the Alzheimer Aβ calcium channel potently protect neurons from Aβ cytotoxicity
Authors: Diaz Juan Carlos , Simakova Olga , Jacobson Kenneth A. , Arispe Nelson , Pollard Harvey B.
Published: February 2009

Alzheimer's disease (AD) is a common, chronic neurodegenerative disease that is thought to be caused by the neurotoxic effect of the Amyloid beta peptides (Aβ). We have hypothesized that the intrinsic Aβ calcium channel activity of the oligomeric Aβ polymer may be responsible for the neurotoxic properties of Aβ, and that Aβ channel blockers may be candidate AD therapeutics. As a consequence of a rational search paradigm based on the model structure of the Aβ channel, we have identified two compounds of interest: MRS2481 and an enatiomeric species, MRS2485. These are amphiphilic pyridinium salts that both potently block the Aβ channel and protect neurons from Aβ toxicity. Both block the Aβ channel with similar potency (≈500 nM) and efficacy (100%). However, we find that inhibition by MRS2481 is easily reversible, whereas inhibition by MRS2485 is virtually irreversible. We suggest that both species deserve consideration as candidates for Alzheimer's disease drug discovery.
The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes
Authors: Mohawk Jennifer A. , Baer Matthew L. , Menaker Michael
Published: February 2009

The “master clock” in the suprachiasmatic nucleus (SCN) of the hypothalamus controls most behavioral, physiological, and molecular circadian rhythms in mammals. However, there are other, still unidentified, circadian oscillators that are able to carry out some SCN functions. Here we show that one of these, the methamphetamine-sensitive circadian oscillator (MASCO), which generates behavioral rhythms in the absence of the SCN, is based on an entirely different molecular mechanism. We tested mice lacking, or with mutations of, genes that form the canonical circadian machinery. In all cases, animals that were arrhythmic as a consequence of genetic defect expressed circadian locomotor rhythms when treated with methamphetamine. These results strongly support the hypothesis that the mechanism generating MASCO does not involve the molecular feedback loops that underlie canonical circadian rhythmicity. The properties of MASCO may provide insight into the evolution of circadian mechanisms. Importantly, MASCO may play a role in addiction to psychostimulants.
The Cluella Study: Optimal Segmentation and Voicing for Oral Blending
Authors: Murray Bruce A. , Brabham Edna G. , Villaume Susan K. , Veal Margo
Published: February 2009

Using a within-subjects design, researchers compared 183 kindergartners' ability to blend words segmented in four different ways. On digitized video, a researcher portraying the fictitious “Cluella” pronounced 40 consonant-vowel-consonant words for participants to blend. She gave 10 words in phoneme segments with a loud schwa added to consonants, 10 in phoneme segments minimizing any schwa voicing, 10 in onset-rime chunks, and 10 in body-coda chunks. Participants were significantly more successful blending body-coda chunks than blending onsetrime chunks. They also were significantly more successful blending phonemes with added schwa than without. We apply these results to suggest procedures for providing optimal scaffolds for helping children learn to identify words.
Evidence for a Proton–Protein Symport Mechanism in the Anthrax Toxin Channel
Authors: Basilio Daniel , Juris Stephen J. , Collier R. John , Finkelstein Alan
Published: February 2009

The toxin produced by Bacillus anthracis, the causative agent of anthrax, is composed of three proteins: a translocase heptameric channel, (PA63)7, formed from protective antigen (PA), which allows the other two proteins, lethal and edema factors (LF and EF), to translocate across a host cell's endosomal membrane, disrupting cellular homeostasis. It has been shown that (PA63)7 incorporated into planar phospholipid bilayer membranes forms a channel capable of transporting LF and EF. Protein translocation through the channel is driven by a proton electrochemical potential gradient on a time scale of seconds. A paradoxical aspect of this is that although LFN (the N-terminal 263 residues of LF), on which most of our experiments were performed, has a net negative charge, it is driven through the channel by a cis-positive voltage. We have explained this by claiming that the (PA63)7 channel strongly disfavors the entry of negatively charged residues on proteins to be translocated, and hence the aspartates and glutamates on LFN enter protonated (i.e., neutralized). Therefore, the translocated species is positively charged. Upon exiting the channel, the protons that were picked up from the cis solution are released into the trans solution, thereby making this a proton–protein symporter. Here, we provide further evidence of such a mechanism by showing that if only one SO3−, which is essentially not titratable, is introduced at most positions in LFN, through the reaction of an introduced cysteine residue at those positions with 2-sulfonato-ethyl-methanethiosulfonate, voltage-driven LFN translocation is drastically inhibited. We also find that a site that disfavors the entry of negatively charged residues into the (PA63)7 channel resides at or near its Φ-clamp, the ring of seven phenylalanines near the channel's entrance.
Winnowing the Chaff of Charlatanism from the Wheat of Science
Authors: Ernst E.
Published: February 2009

Experts and lay people alike can sometimes find it difficult to demarcate the absurd. Here I propose a set of criteria that may be helpful in achieving this in the realm of healthcare: falsifiability, plausibility and some hallmarks of pseudoscience. Applying this method is unlikely to be fool‐proof but it might be a valuable aid in discriminating credible from incredible health claims.
Divergent Paths, United States and France: Capital Markets, the State, and Differentiation in Transportation Systems, 1840–1940
Authors: Cohen Jim
Published: February 2009

Why do the United States and France, both capitalist economies that were dominated by private railways in the 19th and early 20thcenturies, have very different transport systems today? After World War II France developed 200 mph high speed trains, while railways in the United States declined to near irrelevance. This paper argues that cross-national divergence was caused by private and public actions that structured capitalmarkets and controlled planning. In the United States private financial institutions used capital markets to shape rail development. In France, by way of contrast, the state directly intervened in financial markets and controlled planning. Both systems thrived until World War I. But, then, faced with growing competition from cars, buses and trucks and burdened by excessive debt, they declined towards bankruptcy. The Great Depression became a defining moment as a Socialist-dominated government in France nationalized railways while in the United States, President Roosevelt's New Deal failed to enact policies to ensure the competitive viability of rail in relation to motorized transport. Rarely used archival sources provide much of the evidence for this argument.
Characterization of the charge variants of L2 β-lactamase in Stenotrophomonas maltophilia
Authors: Hu Rouh-Mei , Chiang Kai-Hung , Chang Yi-Chih , Yang Tsuey-Ching
Published: February 2009

Stenotrophomonas maltophilia KH has two acid β-lactamases with isoelectric points (pIs) of 4.6 and 5.4, and several basic β-lactamases (pIs >7.0) that produce a ladder-shaped pattern by IEF. An isogenic L2 mutant, KHL2xylE, was constructed by gene replacement. From IEF and native PAGE zymograms of strains KH and KHL2xylE, it was demonstrated that the basic β-lactamases and the acid β-lactamase with pI 5.4 are encoded by the same L2 gene and that the active types of these L2 charge variants were dependent on the buffer pH. The β-lactamase activities of these L2 charge variants in phosphate buffer at pH 7.0 and 8.0 were 1075±29 and 1114±81 U mg−1, respectively. These results indicate that L2 charge variants give S. maltophilia a better chance of adapting and surviving in response to changes in the environment.
Role of Mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease
Authors: Varma-Basil Mandira , Dwivedi Shailendra K. D. , Kumar Krishna , Pathak Rakesh , Rastogi Ritika , Thukral S. S. , Shariff Malini , Vijayan V. K. , Chhabra Sunil K. , Chaudhary Rama
Published: February 2009

Eighty per cent of the cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have an infective aetiology, atypical bacteria including Mycoplasma pneumoniae accounting for 5–10 % of these. However, the importance of association of M. pneumoniae with episodes of AECOPD still remains doubtful. The present study was therefore undertaken to delineate the extent of involvement of M. pneumoniae in patients with AECOPD at a referral hospital in Delhi, India. Sputum samples and throat swabs from a total of 100 AECOPD patients attending the Clinical Research Center of Vallabhbhai Patel Chest Institute, Delhi, were collected during a 2-year period (January 2004–June 2006). The samples were investigated for the presence of aerobic bacterial pathogens and M. pneumoniae. Diagnosis of infection with M. pneumoniae was based on culture, serology, direct detection of M. pneumoniae specific antigen and PCR. Bacterial aetiology could be established in 16 of the 100 samples studied. Pseudomonas spp. were recovered from eight cases, Streptococcus pneumoniae from four and Klebsiella spp. from two cases. Acinetobacter sp. and Moraxella catarrhalis were isolated from one case each. Serological evidence of M. pneumoniae infection and/or detection of M. pneumoniae specific antigen were seen in 16 % of the cases. One case with definite evidence of M. pneumoniae infection also had coinfection with Pseudomonas spp. However, no direct evidence of M. pneumoniae infection was found in our study population as defined by culture isolation or PCR. In conclusion, although the serological prevalence of M. pneumoniae infection in our study population was significantly higher than in the control group, there was no direct evidence of it playing a role in AECOPD.
Multifocal osteomyelitis caused by Candida dubliniensis
Authors: Wellinghausen Nele , Moericke Angelika , Bundschuh Silke , Friedrich Wilhelm , Schulz Ansgar S. , Gatz Susanne A.
Published: February 2009

Candida dubliniensis is an emerging fungal pathogen, especially in immunodeficient patients. We report what is to the best of our knowledge the first case of multifocal osteomyelitis following disseminated infection in a patient after haematopoietic stem cell transplantation. PFGE for typing of C. dubliniensis was developed and the necessity of long-term antifungal therapy is discussed.
Cell-wall thickness: possible mechanism of acriflavine resistance in meticillin-resistant Staphylococcus aureus
Authors: Kawai Mako , Yamada Sakuo , Ishidoshiro Ai , Oyamada Yoshihiro , Ito Hideaki , Yamagishi Jun-ichi
Published: February 2009

Acriflavine resistance in the clinical meticillin-resistant Staphylococcus aureus isolate KT24 was found not to be mediated by multidrug efflux pumps encoded by qacA/B, smr, qacE, qacG, qacH, qacJ or norA. Early uptake and accumulation of ethidium bromide in MRSA KT24 was significantly lower than that in a susceptible strain, although the efflux rates were similar. Therefore, a permeability barrier in MRSA KT24 may be the conceivable mechanism of acriflavine resistance. Interestingly, it was found that MRSA KT24 had a significantly thickened cell wall, and that cell-wall thickness increased gradually during bacterial growth. In contrast, cell size and surface area in MRSA KT24 were not different from those in the susceptible strain. Moreover, MRSA KT24 exposure to sub-MIC concentrations of acriflavine resulted in a thicker cell wall. These results indicate that cell-wall thickness may be responsible for acriflavine resistance in S. aureus.
Assignment of the group A rotavirus NSP4 gene into genotypes using a hemi-nested multiplex PCR assay: a rapid and reproducible assay for strain surveillance studies
Authors: Bányai Krisztián , Bogdán Ágnes , Szücs György , Arista Serenella , De Grazia Simona , Kang Gagandeep , Banerjee Indrani , Iturriza-Gómara Miren , Buonavoglia Canio , Martella Vito
Published: February 2009

The rotavirus non-structural protein NSP4 has been implicated in a number of biological functions during the rotavirus cellular cycle and pathogenesis, and has been addressed as a target for vaccine development. The NSP4 gene has been classified into six genotypes (A–F). A semi-nested triplex PCR was developed for genotyping the major human NSP4 genotypes (A–C), which are common in human rotavirus strains but are also shared among most mammalian rotavirus strains. A total of 192 previously characterized human strains representing numerous G and P type specificities (such as G1P[8], G1P[4], G2P[4], G3P[3], G3P[8], G3P[9], G4P[6], G4P[8], G6P[4], G6P[9], G6P[14], G8P[10], G8P[14], G9P[8], G9P[11], G10P[11], G12P[6] and G12P[8]) were tested for NSP4 specificity by the collaborating laboratories. An additional 35 animal strains, including the reference laboratory strains SA11 (simian, G3P[2]), NCDV (bovine, G6P[1]), K9 and CU-1 (canine, G3P[3]), together with 31 field isolates (canine, G3P[3]; feline, G3P[9]; porcine, G2P[23], G3P[6], G4P[6], G5P[6], G5P[7], G5P[26], G5P[27], G9P[6] and G9P[7]) were also successfully NSP4-typed. Four human G3P[9] strains and one feline G3P[9] strain were found to possess an NSP4 A genotype, instead of NSP4 C, suggesting a reassortment event between heterologous strains. Routine NSP4 genotyping may help to determine the genomic constellation of rotaviruses of man and livestock, and identify interspecies transmission of heterologous strains.
Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukaemia
Authors: Bommer Martin , Hütter Marie-Luise , Stilgenbauer Stephan , de Hoog G. Sybren , de Beer Z. Wilhelm , Wellinghausen Nele
Published: February 2009

We report to our knowledge the first case of human infection withOphiostoma piceae. ThisSporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for identification of rare fungi in the clinical microbiology laboratory.
Peruvian Vibrio cholerae O1 El Tor strains possess a distinct region in the Vibrio seventh pandemic island-II that differentiates them from the prototype seventh pandemic El Tor strains
Authors: Nusrin Suraia , Gil Ana I. , Bhuiyan N. A. , Safa Ashrafus , Asakura Masahiro , Lanata Claudio F. , Hall E. , Miranda H. , Huapaya B. , Vargas G. Carmen , Luna M. A. , Sack D. A. , Yamasaki Shinji , Nair G. Balakrish
Published: February 2009

A collection of environmental and clinical strains of Vibrio cholerae O1 isolated from the beginning of the Latin American epidemic of cholera in 1991 to 2003 from multiple locations in Peru were characterized and compared with V. cholerae O1 El Tor strains of the seventh pandemic from the rest of the world (Asia, Africa, Australia and Europe) using a multilocus virulence gene profiling strategy and DNA sequencing. Peruvian strains differed from El Tor strains from the rest of the world by the failure of PCR to amplify genes VC0512, VC0513, VC0514 and VC0515 in the Vibrio seventh pandemic island-II (VSP-II) gene cluster. Sequencing of the VSP-II gene cluster and its flanking regions in one Peruvian strain (PERU-130) confirmed the PCR results, indicating that the Peruvian strain had low DNA homology (46.6 %) compared to the reference strain N16961 within the VSP-II region encompassing genes VC0511 to VC0515. Based on these differences in VSP-II, and based on the overall similarity between the pulsotypes of the Peruvian strains and the El Tor reference strain N16961, we concluded that the Peruvian, Eurasian and African strains belonged to the same clonal complex, and that the Peruvian strains represented variants that had independently evolved for a relatively short time. Since these ORFs in VSP-II of Peruvian strains are unique and conserved, they could form the basis for tracking the origin of the Peruvian strains and therefore of the Latin American pandemic.
Minimum inhibitory concentration of carbapenems and tigecycline against Salmonella spp.
Authors: Capoor Malini R. , Nair Deepthi , Posti Jitendra , Singhal Smita , Deb Monorama , Aggarwal Pushpa , Pillai Parukutty
Published: February 2009

Antimicrobial resistance in Salmonella spp. is of grave concern, more so in quinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing isolates that cause complicated infections. The MIC of azithromycin, ciprofloxacin, cefixime, cefepime, ceftriaxone, gatifloxacin, imipenem, levofloxacin, meropenem and ofloxacin (E-test strip) and tigecycline and faropenem (agar dilution) against 210 Salmonella spp. was determined. MIC90 (defined as the antimicrobial concentration that inhibited growth of 90 % of the strains) of the carbapenems (imipenem and meropenem) for Salmonella Typhi and Salmonella Paratyphi A was 0.064 μg ml−1. MIC90 of faropenem was 0.25 μg ml−1 for S. Typhi, S. Paratyphi A and Salmonella Typhimurium. The MIC90 of azithromycin for all Salmonella spp. ranged from 8 to 16 μg ml−1. Tigecycline showed an MIC90 of 2 μg ml−1 for S. Typhi, 1 μg ml−1 for S. Paratyphi A and 4 μg ml−1 for S. Typhimurium. We concluded that tigecycline and the carbapenems are likely to have roles in the final stage of treatment of quinolone-resistant and ESBL-producing multidrug-resistant salmonellae.
Detecting heterozygosity in shotgun genome assemblies: Lessons from obligately outcrossing nematodes
Authors: Barrière Antoine , Yang Shiaw-Pyng , Pekarek Elizabeth , Thomas Cristel G. , Haag Eric S. , Ruvinsky Ilya
Published: February 2009

The majority of nematodes are gonochoristic (dioecious) with distinct male and female sexes, but the best-studied species, Caenorhabditis elegans, is a self-fertile hermaphrodite. The sequencing of the genomes of C. elegans and a second hermaphrodite, C. briggsae, was facilitated in part by the low amount of natural heterozygosity, which typifies selfing species. Ongoing genome projects for gonochoristic Caenorhabditis species seek to approximate this condition by intense inbreeding prior to sequencing. Here we show that despite this inbreeding, the heterozygous fraction of the whole genome shotgun assemblies of three gonochoristic Caenorhabditis species, C. brenneri, C. remanei, and C. japonica, is considerable. We first demonstrate experimentally that independently assembled sequence variants in C. remanei and C. brenneri are allelic. We then present gene-based approaches for recognizing heterozygous regions of WGS assemblies. We also develop a simple method for quantifying heterozygosity that can be applied to assemblies lacking gene annotations. Consistently we find that ∼10% and 30% of the C. remanei and C. brenneri genomes, respectively, are represented by two alleles in the assemblies. Heterozygosity is restricted to autosomes and its retention is accompanied by substantial inbreeding depression, suggesting that it is caused by multiple recessive deleterious alleles and not merely by chance. Both the overall amount and chromosomal distribution of heterozygous DNA is highly variable between assemblies of close relatives produced by identical methodologies, and allele frequencies have continued to change after strains were sequenced. Our results highlight the impact of mating systems on genome sequencing projects.
IL‐17 is involved in bone resorption in mouse periapical lesions
Authors: Oseko Fumishige , Yamamoto Toshiro , Akamatsu Yuki , Kanamura Narisato , Iwakura Yoichiro , Imanishi Jiro , Kita Masakazu
Published: February 2009

Periapical lesions are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. Although various immunological studies concerning periapical bone resorption have been reported, the role of cytokines in the formation of periapical lesions remains unclear. In this study, the role of IL‐17A in periapical lesions in mice was investigated. Normal C57BL/6, IFN‐γ−/−, TNF‐α−/−, and IL‐17A−/− mice were subjected to pulp exposure and infected with Prevotella intermedia (ATCC25611) and Porphyromonas gingivalis (ATCC33277) in the mandibular first molar. Periapical lesions were determined by μCT on day 21 after infection, and 3D visual construction was performed using 3D picture quantification software. The expression of IL‐17A mRNA in periapical lesions was determined by the RT‐PCR and real‐time RT‐PCR method. Periapical lesions developed in wild‐type, IFN‐γ−/−, and TNF‐α−/− mice after infection with P. intermedia and P. gingivalis. However, periapical lesions were not observed in IL‐17A−/− mice. The expression of IL‐17A mRNA was significantly induced in periapical lesions of wild‐type mice after infection. These results suggest that IL‐17A, but not IFN‐γ or TNF‐α, plays an important role in the formation of periapical lesions.
Measuring gambling participation
Authors: Rodgers Bryan , Caldwell Tanya , Butterworth Peter
Published: February 2009

There are many parallels between research on gambling and research on alcohol use, but a striking difference is the emphasis in the former area on problem gambling rather than the use of participation measures. We outline five topics that are underdeveloped as a consequence: (i) gambling participation and future problems; (ii) moderate gambling; (iii) separate measurement of exposures and harms; (iv) predictors of participation; and (v) natural history of participation. Challenges to the future development of gambling participation measures are discussed by reference to comparable difficulties in the field of alcohol use and some examples are given as to how progress could be made. Further development of measures will necessarily occur in the context of broader scientific aims. Some recent studies are highlighted that provide hope of gains in this area. We urge further progress to yield conceptually and operationally distinct indices of exposures and harms.
Use of supervised injection facilities and injection risk behaviours among young drug injectors
Authors: Bravo María J. , Royuela Luis , De la Fuente Luis , Brugal María T. , Barrio Gregorio , Domingo‐Salvany Antonia ,   the Itínere Project Group
Published: February 2009

Aims  To study the use of supervised injection facilities (SIFs) as a predictor of safer injecting practices.

Design  Cross‐sectional study conducted with face‐to‐face interview using a structured questionnaire with computer‐assisted personal interviewing. Dried blood spot samples were collected for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) antibody testing.

Setting  All participants were street‐recruited by chain referral methods in Madrid and Barcelona.

Participants  A total of 249 young heroin drug injectors recruited by the ITINERE cohort study in two Spanish cities with SIFs.

Measurements  The main outcome measures were self‐reported injecting behaviours and SIFs attendance.

Results  SIF users were more marginalized socially than non‐users. They were also more often regular injectors (weekly or more versus sporadic) [odds ratio (OR) = 4.9, 95% confidence interval (CI): 2.7–8.8], speedball users (OR = 2.5, 95% CI: 1.5–4.3) and anti‐HCV‐positive (OR = 3.1, 95% CI: 1.4–7.1). In the logistic regression analysis, using SIFs was associated independently with not borrowing used syringes (OR = 3.3, 95% CI: 1.4–7.7). However, no significant association was found between SIF use and not sharing injection equipment indirectly (OR = 1.1, 95% CI: 0.5–2.2).

Conclusions  SIFs attract highly disadvantaged drug injectors who engage none the less in less borrowing of used syringes than non‐users of these facilities. The risks of indirect sharing should be emphasized when counselling SIF attendees.
Disruptiveness, peer experiences and adolescent smoking: a long‐term longitudinal approach
Authors: Otten Roy , Wanner Brigitte , Vitaro Frank , Engels Rutger C. M. E.
Published: February 2009

Aims  This study examined links of peer experiences (i.e. social status and affiliation with disruptive peers) throughout childhood with respect to adolescent smoking trajectories, after controlling for childhood disruptiveness. Specifically, we tested four models regarding links of peer experiences and deviant behaviours.

Design  Prospective community sample.

Participants  A total of 312 children, aged 6.17 years at baseline.

Measurements  Growth parameters of own disruptive behaviour, disruptive behaviour of friends and social status measured at ages 7–12 years as predictors of smoking assessed at ages 13–15 years, while controlling for own disruptive behaviour at age 6 years.

Findings  We found three groups with distinct profiles of smoking. One group displayed hardly any or no smoking at all; a second group showed a trajectory of increased smoking; and a third group that showed high smoking rates initially and increased in smoking intensity over time. Results support the assumption of the selection model that the link between disruptive peers and smoking is spurious and due to shared variances with own early disruptiveness. Moreover, support was found for the popularity–socialization model supporting the assumption that age‐related increases in social status are associated with smoking.

Conclusions  The findings emphasize that early disruptiveness is predictive of later smoking. In addition, it was shown that smoking becomes less deviant over time, in line with group norms. Future prevention programmes should emphasize the need to change these norms.
A taxometric study of alcohol abuse and dependence in a general population sample: evidence of dimensional latent structure and implications for DSM‐V
Authors: Slade Tim , Grove Rachel , Teesson Maree
Published: February 2009

Aims  To explore, with the aid of taxometric analysis, whether alcohol abuse and alcohol dependence are each conceptualized most effectively as single latent dimensions or distinct latent categories.

Design  Data were taken from a nationally representative cross‐sectional epidemiological survey of psychiatric and substance use disorders.

Setting  General population of Australia.

Participants  A subsample of all respondents who had consumed at least 12 drinks in the year prior to the survey and who had consumed at least three drinks on at least one single day (n = 4920 of a possible 10 641).

Measurements  DSM‐IV criteria for alcohol abuse and dependence were assessed with the Composite International Diagnostic Interview, version 2.1. Two independent taxometric procedures, MAXimum EIGenvalue (MAXEIG) and mean above minus below a cut (MAMBAC), together with analysis of simulated dimensional and categorical data sets, were carried out.

Findings  Consistent evidence was found for a single latent dimension underlying the symptoms of alcohol dependence. Less consistent evidence of dimensionality was found for the symptoms of alcohol abuse.

Conclusions  These findings support the growing consensus regarding the need for continuous measures of alcohol use disorders to complement the traditional categorical representations in upcoming versions of the major psychiatric classification systems.
Overweight and perception of overweight as predictors of smokeless tobacco use and of cigarette smoking in a cohort of Swedish adolescents
Authors: Caria Maria Paola , Bellocco Rino , Zambon Antonella , Horton Nicholas J. , Galanti Maria Rosaria
Published: February 2009

Aims  To study the association between measured or perceived overweight in adolescence and subsequent uptake of cigarette smoking and of the Swedish smokeless tobacco ‘snus’ (oral moist snuff).

Design  Population‐based prospective cohort study with 7 years' follow‐up.

Setting  Self‐administered questionnaires and school nurses' visits.

Participants  A total of 2922 children of both sexes and mean age 11.6 years at recruitment, resident in the Stockholm region, Sweden.

Measurements  Tobacco use was self‐reported at baseline and on six subsequent surveys. Subjects' height and weight were measured by school nurses during the first 4 years, self‐reported thereafter. Overweight perception was self‐reported at the age of 15 years.

Findings  Overweight and perception of overweight were not associated with subsequent uptake of either smoking or snus among males. Among females, overweight at baseline was associated with uptake of smoking [adjusted hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.09–1.63], but not of snus. A similar pattern was found with overweight status during follow‐up. Among girls with low‐educated parents, overweight at baseline predicted the uptake of both snus and smoking. Among 15‐year‐old females who never used tobacco perceived overweight was associated with subsequent uptake of smoking (adjusted HR 1.71, 95% CI 1.20–2.46), but not of snus.

Conclusions  In Sweden, adolescent girls with actual or perceived overweight are at increased risk to start smoking, while indications that this increased risk applies to smokeless tobacco (snus) are limited to girls of low socio‐economic status.
How reactions to cigarette packet health warnings influence quitting: findings from the ITC Four‐Country survey
Authors: Borland Ron , Yong Hua‐Hie , Wilson Nick , Fong Geoffrey T. , Hammond David , Cummings K. Michael , Hosking Warwick , McNeill Ann
Published: February 2009

Objectives  To examine prospectively the impact of health warnings on quitting activity.

Design  Five waves (2002–06) of a cohort survey where reactions to health warnings at one survey wave are used to predict cessation activity at the next wave, controlling for country (proxy for warning differences) and other factors. These analyses were replicated on four wave‐to‐wave transitions.

Setting and participants  Smokers from Australia, Canada, the United Kingdom and the United States. Samples were waves 1–2: n = 6525; waves 2–3: n = 5257; waves 3–4: n = 4439; and waves 4–5: n = 3993.

Measures  Warning salience, cognitive responses (thoughts of harm and of quitting), forgoing of cigarettes and avoidance of warnings were examined as predictors of quit attempts, and of quitting success among those who tried (1 month sustained abstinence), replicated across four wave‐to‐wave transitions.

Results  All four responses to warnings were independently predictive of quitting activity in bivariate analyses. In multivariate analyses, both forgoing cigarettes and cognitive responses to the warnings predicted prospectively making quit attempts in all replications. However, avoiding warnings did not add predictive value consistently, and there was no consistent pattern for warning salience. There were no interactions by country. Some, but not all, the effects were mediated by quitting intentions. There were no consistent effects on quit success.

Conclusions  This study adds to the evidence that forgoing cigarettes as a result of noticing warnings and quit‐related cognitive reactions to warnings are consistent prospective predictors of making quit attempts. This work strengthens the evidence base for governments to go beyond the Framework Convention on Tobacco Control to mandate health warnings on tobacco products that stimulate the highest possible levels of these reactions.
Screening for hepatitis B, C and non‐alcoholic fatty liver disease: a survey of community‐based physicians
Authors: KALLMAN J. B. , ARSALLA A. , PARK V. , DHUNGEL S. , BHATIA P. , HADDAD D. , WHEELER A. , YOUNOSSI Z. M.
Published: February 2009

Background  Screening guidelines for hepatitis B (HBV) and hepatitis C viruses (HCV) as well as a position statement for non‐alcoholic fatty liver disease (NAFLD) have been put forth by different sources, but awareness of these guidelines and their impact on the physician practices have not been assessed.

Aim  To assess the attitudes of primary care physicians (PCPs), gastroenterologists (GEs) and hepatologists (HEPs) regarding screening for HBV, HCV and NAFLD.

Design  A survey questionnaire was sent to community‐based PCPs and GEs to assess issues related to HBV, HCV and NAFLD. The same questionnaire was sent to hepatologists (HEPs). The questionnaire contained 10 items related to demographic and practice patterns of these physicians, 35 items related to HBV, 35 items related to HCV and 29 items related to NAFLD.

Results  A total of 214 physicians (103 PCPs, 59 GEs and 52 HEPs) completed the survey. A majority of PCPs, GEs and HEPs agreed on most screening issues for these causes of liver disease. Nevertheless, within group comparison of physicians (guideline aware versus guideline unaware) showed significant differences in accurate response between those who were aware of guidelines and those who were not aware.

Conclusions  A large percentage of PCPs and GEs were unaware of official guidelines for viral hepatitis B and hepatitis C. Those aware of guidelines were more likely to screen appropriately and avoid unnecessary testing. More needs to be done to assess awareness and the impact implementation of guidelines in hepatology.
Genetic evidence for the introgression of Western NR6A1 haplotype into Chinese Licha breed associated with increased vertebral number
Authors: Yang G. , Ren J. , Zhang Z. , Huang L.
Published: February 2009

There is evidence that NR6A1 is a strong candidate for being a causal gene underlying vertebral number in pigs. The Licha Black is one of the leanest Chinese indigenous pig breeds, having an average vertebral number of 21.5. The introgression of Western germplasm into Licha Black, resulting in increased vertebral number, has been assumed but is not confirmed. This study detected allele frequencies of the NR6A1 causative mutation (c.575T>C) in 519 pigs from three Western and seven Chinese breeds including Licha Black, and evaluated the genetic variation in a 650‐kb region containing NR6A1 in the 10 breeds. Allele T for increased vertebral number was fixed in Western breeds. In contrast, this allele was very rare in most of the Chinese native breeds. Notably, the T allele was present in the Licha Black at a rather higher frequency (0.585) and in the Laiwu at lower frequency (0.250). As expected, selection pressure has wiped out the genetic variability in the 650 kb region in Western breeds. Conversely, Chinese indigenous breeds showed a high degree of genetic variability in this region. However, the Licha Black displayed dramatically reduced heterozygosity at the loci proximal to the causative mutation. Moreover, a high proportion (45.9%) of Licha Black pigs and a small number (21%) of Laiwu pigs had the Western NR6A1 haplotype, and the two breeds showed closer relationships with Western commercial breeds than other Chinese breeds in the phylogenic tree. When the results are taken together, this study supports the assumption that the Western NR6A1 haplotypes were introduced into Licha Black and possibly Laiwu and are associated with increased vertebral number.
Linkage disequilibrium in the North American Holstein population
Authors: Kim E.‐S. , Kirkpatrick B. W.
Published: February 2009

Linkage disequilibrium was estimated using 7119 single nucleotide polymorphism markers across the genome and 200 animals from the North American Holstein cattle population. The analysis of maternally inherited haplotypes revealed strong linkage disequilibrium (r2 > 0.8) in genomic regions of ∼50 kb or less. While linkage disequilibrium decays as a function of genomic distance, genomic regions within genes showed greater linkage disequilibrium and greater variation in linkage disequilibrium compared with intergenic regions. Identification of haplotype blocks could characterize the most common haplotypes. Although maximum haplotype block size was over 1 Mb, mean block size was 26–113 kb by various definitions, which was larger than that observed in humans (∼10 kb). Effective population size of the dairy cattle population was estimated from linkage disequilibrium between single nucleotide polymorphism marker pairs in various haplotype ranges. Rapid reduction of effective population size of dairy cattle was inferred from linkage disequilibrium in recent generations. This result implies a loss of genetic diversity because of the high rate of inbreeding and high selection intensity in dairy cattle. The pattern observed in this study indicated linkage disequilibrium in the current dairy cattle population could be exploited to refine mapping resolution. Changes in effective population size during past generations imply a necessity of plans to maintain polymorphism in the Holstein population.
Evaluation of SPATA1‐associated markers for stallion fertility
Authors: Giesecke K. , Hamann H. , Stock K. F. , Woehlke A. , Sieme H. , Distl O.
Published: February 2009

Stallion fertility is an economically important trait because the use of artificial insemination is increasing in the horse industry and superior sires are used more intensely. Molecular genetic markers may be useful as early indicators for a stallion’s fertility and genetic improvement programmes. The testis‐specific SPATA1 protein is involved in shaping the sperm head during spermatogenesis. Thus, the spermatogenesis associated 1 (SPATA1) gene was chosen as candidate for stallion fertility, and we analysed intragenic single nucleotide polymorphisms (SNPs) as genetic markers for the least square means (LSM) of the pregnancy rate per oestrus of stallions and breeding values (BV) for the paternal and embryonic component of the pregnancy rate per oestrus. We sequenced the cDNA of SPATA1 to verify the annotated mRNA sequence. One SPATA1‐associated intronic SNP (BIEC2‐968854) showed a significant association with the embryonic component of BVs of stallions for the pregnancy rate per oestrus. The embryonic component of BVs was positively associated with homozygous C/C stallions. Both the additive and dominance effects were significant with values of −5.8% (P = 0.01) and −6.4% (P = 0.02) for the embryonic component of BVs. For the same SNP, a suggestive association was found for the LSM of the pregnancy rate per oestrus of stallions. Heterozygous stallions had higher pregnancy rates per oestrus than homozygous stallions. The dominance effect was 4.1% with a nominal P‐value of 0.02. The SNP BIEC2‐968854 can change an SP1 binding site and thus we assume that gene regulation may be influenced through this intronic mutation. This is the first report on SPATA1 being associated with the pregnancy rate per oestrus for stallions.
Seasonal variation in the composition of fish assemblages in small Amazonian forest streams: evidence for predictable changes
Authors: ESPÍRITO‐SANTO HELDER MATEUS VIANA , MAGNUSSON WILLIAM ERNEST , ZUANON JANSEN , MENDONÇA FERNANDO PEREIRA , LANDEIRO VICTOR LEMES
Published: February 2009

1. The effects of seasonal inundation on the biology of fishes on floodplains of large Amazonian rivers are well studied. However, the small seasonal changes in headwater streams are generally considered to have little effect on fish assemblages.

2. In this study, we analysed seasonal changes in the species composition and abundance of fish in small Amazonian forest streams. We sampled fish with hand and seine nets in headwater streams in a 10 000 ha terra‐firme forest reserve near Manaus, Brazil. Each stream was surveyed at the end of the 2005 dry season, at the beginning of the 2006 rainy season and at the beginning of the 2006 dry season, by means of a standardized sampling effort.

3. The numbers of individuals and species caught were higher in the dry season, but rarefaction analyses indicated that greater species numbers could have been due simply to the larger number of individuals caught.

4. Between the dry and rainy season, the direction of changes in species composition in multivariate space varied among sites, especially for quantitative (abundance) data. However, the observed variation among sites was the less than expected if the directions of change were random.

5. Fish assemblages in the second dry season were more similar to those in the previous dry season than expected if changes in species composition among seasons were random. This indicates that a general seasonal pattern in fish assemblages can be detected, despite the existence of some erratic site‐specific changes.

6. Most of the species that showed large seasonal variations in density occupy temporary ponds during the rainy season, when much of the valley is inundated and pond networks form adjacent to streams. Short‐duration lateral migrations to these ponds may play an important role in the seasonal fish‐assemblage dynamics in Amazonian headwater streams.

7. Our results contrast with previous studies on small Amazonian streams, which have found little seasonal change in fish assemblages, and highlight the importance of the abundance of common species as an indicator of general fish assemblage structure in biological monitoring programmes.
Seasonal variation in foliar carbon exchange in Pinus radiata and Populus deltoides: respiration acclimates fully to changes in temperature but photosynthesis does not
Authors: OW LAI FERN , WHITEHEAD DAVID , WALCROFT ADRIAN S. , TURNBULL MATTHEW H.
Published: February 2009

We investigated seasonal variation in dark respiration and photosynthesis by measuring gas exchange characteristics on Pinus radiata and Populus deltoides under field conditions each month for 1 year. The field site in the South Island of New Zealand is characterized by large day‐to‐day and seasonal changes in air temperature. The rate of foliar respiration at a base temperature of 10 °C (R10) in both pine and poplar was found to be greater during autumn and winter and displayed a strong downward adjustment in warmer months. The sensitivity of instantaneous leaf respiration to a 10 °C increase in temperature (Q10) was also greater during the winter period. The net effect of this strong acclimation was that the long‐term temperature response of respiration was essentially flat over a wide range of ambient temperatures. Seasonal changes in photosynthesis were sensitive to temperature but largely independent of leaf nitrogen concentration or stomatal conductance. Over the range of day time growth temperatures (5–32 °C), we did not observe strong evidence of photosynthetic acclimation to temperature, and the long‐term responses of photosynthetic parameters to ambient temperature were similar to previously published instantaneous responses. The ratio of foliar respiration to photosynthetic capacity (Rd/Asat) was significantly greater in winter than in spring/summer. This indicates that there is little likelihood that respiration would be stimulated significantly in either of these species with moderate increases in temperature – in fact net carbon uptake was favoured at moderately higher temperatures. Model calculations demonstrate that failing to account for strong thermal acclimation of leaf respiration influences determinations of leaf carbon exchange significantly, especially for the evergreen conifer.
Diagnostic challenges of motility disorders: optimal detection of CD117+ interstitial cells of Cajal
Authors: Garrity Megan M , Gibbons Simon J , Smyrk Thomas C , Vanderwinden Jean Marie , Gomez‐Pinilla Pedro Julian , Nehra Anoop , Borg Matthew , Farrugia Gianrico
Published: February 2009

Aims:  Several gastrointestinal motility diseases are associated with altered numbers of interstitial cells of Cajal (ICC), and testing for alterations in numbers of ICC has been proposed as one way to improve routine diagnosis in motility diseases. However, the protocols currently used to visualize ICC in formalin‐fixed paraffin‐embedded (FFPE) tissue using antibodies to CD117 have not been optimized for studying motility disorders. The aims of this study were therefore to determine the optimal protocol using FFPE tissue, determine normal values for ICC in non‐neoplastic human colon, and compare results with those obtained using immunofluorescence (IF).

Methods and results:  Non‐neoplastic tissue was collected from patients undergoing resection for colonic cancer and fixed for both light (FFPE) and IF testing. Sections were processed for standard immunohistochemistry using different primary antibodies in conjunction with variations in antigen retrieval [ethylenediamine tetraacetricacid (EDTA), citrate], antibody dilution, blocking and detection (Mach2, Mach3, Envision+). Best results were obtained with EDTA retrieval, the DAKO CD117 antibody and Mach3 detection.

Conclusions:  The optimized protocol presented improved CD117 detection in FFPE tissues and showed good concordance with overall localization of CD117‐immunoreactive ICC as detected by IF. As such, this protocol may be more useful than current diagnostic procedures in motility disorders.
Cell cycle alterations and their relationship to proliferation in apocrine adenosis of the breast
Authors: Elayat Ghada , Selim Abdel‐Ghani A , Wells Clive A
Published: February 2009

Aims:  Apocrine adenosis (AA) is generally considered a benign disease of the breast. However, recent studies have suggested a precancerous potential for some of these lesions. The aim was to investigate the status of cell cycle proteins previously reported to be deregulated in breast cancer to identify their possible role in AA.

Methods and results:  The cases were categorized into AA without atypia (NAA) and atypical AA (AAA). Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki67 was determined in 29 NAA and 16 AAA cases. Cyclin D1, p21 and cyclin A were overexpressed in 58.6%, 51.7% and 31.8% of the NAA cases, respectively, whereas 81.3%, 62.5% and 41.7% of the AAA cases showed overexpression of cyclin D1, p21 and cyclin A, respectively. All cases were negative for p16, whereas pRb was expressed in all cases. Furthermore, proliferation in AA (4.5%) was significantly higher than that of normal breast epithelium (1%). There was no statistical significance in the degree of proliferation between the NAA (3.7%) and AAA (4.8%) groups.

Conclusions:  The study indicates that NAA and AAA are biologically similar. A subset of AA defined by increased proliferation and significant cell cycle alterations may be susceptible to oncogenesis.
Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients
Authors: Abeler Vera M , Røyne Odd , Thoresen Steinar , Danielsen Håvard E , Nesland Jahn M , Kristensen Gunnar B
Published: February 2009

Aims:  To determine the frequency and survival of the various types of uterine sarcoma in the total population of Norway and evaluate histopathological prognostic factors in order to identify risk groups.

Methods and results:  Histopathological review of all uterine sarcoma cases reported to the Norwegian Cancer Registry during 1970–2000 was undertaken. Survival dates were provided by The Cancer Registry. Kaplan–Meier survival curves were generated. The log rank test was used for univariate analysis and a Cox proportional hazards regression model for multivariate evaluation of survival. Stage of disease was the most important prognostic factor for all tumour types. Tumour size and the mitotic index (MI) were significant prognostic factors (P < 0.0001) in leiomyosarcomas confined to the uterus and allowed for separation into three risk groups with marked differences in prognosis. The prognosis of endometrial stromal sarcomas confined to the uterus was related to MI (P < 0.0001) and tumour cell necrosis (P < 0.004). Combining these parameters allowed for separation into three risk groups with marked difference in prognosis. In adenosarcomas, tumour cell necrosis was the only significant prognostic factor.

Conclusions:  There are marked differences in survival between uterine sarcoma types. Leiomyosarcomas and endometrial stromal sarcomas can be divided into different groups.