bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced inbreeding depression after species range expansion
Authors: Pujol Benoit , Zhou Shu-Rong , Sanchez Vilas Julia , Pannell John R.
Published: August 2009

Many species expanded their geographic ranges from core “refugium” populations when the global climate warmed after the Pleistocene. The bottlenecks that occur during such range expansions diminish genetic variation in marginal populations, rendering them less responsive to selection. Here, we show that range expansion also strongly depletes inbreeding depression. We compared inbreeding depression among 20 populations across the expanded range of a common European plant, and found that marginal populations had greatly reduced inbreeding depression. Similar patterns were also revealed by multilocus computer simulations. Low inbreeding depression is predicted to ease conditions for the evolution of self-fertilization, and selfing is known to be particularly frequent in marginal populations. Therefore, our findings expose a remarkable aspect of evolution at range margins, where a history of expansion can reverse the direction of selection on the mating system, providing a parsimonious explanation for the high incidence of selfing in marginal populations.
A genome-wide genetic screen for host factors required for hepatitis C virus propagation
Authors: Li Qisheng , Brass Abraham L. , Ng Aylwin , Hu Zongyi , Xavier Ramnik J. , Liang T. Jake , Elledge Stephen J.
Published: August 2009

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and a leading indication for liver transplantation. Current therapy fails in many instances and is associated with significant side effects. HCV encodes only a few proteins and depends heavily on host factors for propagation. Each of these host dependencies is a potential therapeutic target. To find host factors required by HCV, we completed a genome-wide small interfering RNA (siRNA) screen using an infectious HCV cell culture system. We applied a two-part screening protocol to allow identification of host factors involved in the complete viral lifecycle. The candidate genes found included known or previously identified factors, and also implicate many additional host cell proteins in HCV infection. To create a more comprehensive view of HCV and host cell interactions, we performed a bioinformatic meta-analysis that integrates our data with those of previous functional and proteomic studies. The identification of host factors participating in the complete HCV lifecycle will both advance our understanding of HCV pathogenesis and illuminate therapeutic targets.
RETRACTED: Identification of a coronary vascular progenitor cell in the human heart
Authors: Bearzi Claudia , Leri Annarosa , Lo Monaco Francesco , Rota Marcello , Gonzalez Arantxa , Hosoda Toru , Pepe Martino , Qanud Khaled , Ojaimi Caroline , Bardelli Silvana , D'Amario Domenico , D'Alessandro David A. , Michler Robert E. , Dimmeler Stefanie , Zeiher Andreas M. , Urbanek Konrad , Hintze Thomas H. , Kajstura Jan , Anversa Piero
Published: August 2009

Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these cells do not form large conductive coronary arteries that would have important implications in the management of the ischemic heart. In the current study, we determined whether the human heart possesses a class of progenitor cells that regulates the growth of endothelial cells (ECs) and smooth muscle cells (SMCs) and vasculogenesis. The expression of vascular endothelial growth-factor receptor 2 (KDR) was used, together with the stem cell antigen c-kit, to isolate and expand a resident coronary vascular progenitor cell (VPC) from human myocardial samples. Structurally, vascular niches composed of c-kit-KDR-positive VPCs were identified within the walls of coronary vessels. The VPCs were connected by gap junctions to ECs, SMCs, and fibroblasts that operate as supporting cells. In vitro, VPCs were self-renewing and clonogenic and differentiated predominantly into ECs and SMCs and partly into cardiomyocytes. To establish the functional import of VPCs, a critical stenosis was created in immunosuppressed dogs, and tagged human VPCs were injected in proximity to the constricted artery. One month later, there was an increase in coronary blood flow (CBF) distal to the stenotic artery, resulting in functional improvement of the ischemic myocardium. Regenerated large, intermediate, and small human coronary arteries and capillaries were found. In conclusion, the human heart contains a pool of VPCs that can be implemented clinically to form functionally competent coronary vessels and improve CBF in patients with ischemic cardiomyopathy.
Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues
Authors: Ziegler C. G. , Brown J. W. , Schally A. V. , Erler A. , Gebauer L. , Treszl A. , Young L. , Fishman L. M. , Engel J. B. , Willenberg H. S. , Petersenn S. , Eisenhofer G. , Ehrhart-Bornstein M. , Bornstein S. R.
Published: August 2009

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4–71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.
Adversative discourse markers in contrast
Authors: Mortier Liesbeth , Degand Liesbeth
Published: August 2009

This paper deals with the semantics of two discourse markers, viz. French en fait (“in fact”) and Dutch eigenlijk (“actually”), commonly associated with the expression of “opposition” and “reformulation”. A special focus lies on methodological issues in the description of such markers, since their non-propositional meanings seem to require what is called a ‘combined corpus approach’, including written and spoken comparable data as well as translation corpora. It is argued that eigenlijk and en fait are best described as adversatives, at the intersection of “opposition” and “reformulation” which constitute their basic meanings, and from which other meanings such as “causality”, “counterexpectation”, “enhancement” and “attenuation” can be inferred. Evidence from all sets of corpora moreover suggests that it is the semantic underspecification of en fait and (especially) eigenlijk which ultimately accounts for their high level of polysemy.
Applying corpus linguistics to pedagogy
Authors: Flowerdew Lynne
Published: August 2009

This article reviews and discusses four somewhat contentious issues in the application of corpus linguistics to pedagogy, ESP in particular. Corpus linguistic techniques have been criticized on the grounds that they encourage a more bottom-up rather than top-down processing of text in which concordance lines are examined atomistically. One criticism levelled against corpus data is that a corpus presents language out of its original context. For this reason, some corpus linguists have underscored the importance of ‘pedagogic mediation’ to contextualize the data for the students’ own writing environment. Concerns relating to the inductive approach associated with corpus-based pedagogy have also been raised as this approach may not always be the most appropriate one. A final consideration relates to the issue of whether a corpus is always the most appropriate resource to use among the wealth of other resources available.
‘Give’ and take
Authors: Bunting Jacqueline
Published: August 2009

The Sranan verb taigi ‘say to, tell’ is used when a dative object is identified, but in the 18th and 19th centuries taki ‘say, tell, speak, talk’ served this function. This paper explores the early uses of taki alongside variants taki gi and taki na, which paired the optionally ditransitive verb with an optional dative marker. Working from a corpus of Sranan texts spanning the 18th and 19th centuries, I consider the distributions of the three variants and the distinctive uses of gi and na as dative markers to argue for the eventual triumph and contraction of taki gi, looking to the superstrate and substrate languages for potential models. I submit that taki gi was idiomatized and the string syntactically reanalyzed with the result that gi was reinterpreted as an obligatory, rather than optional, dative marker, and that this reanalysis resulted in the decline of taki as an optionally ditransitive verb.
Chinese Pidgin English in Southeastern Australia
Authors: Siegel Jeff
Published: August 2009

More than 38,000 Chinese came to Australia to prospect for gold in the second half of the 19th century. Most of them originated from the Canton region of China (now Guangdong), where Chinese Pidgin English (CPE) was an important trading language. This article describes a recently discovered source that throws light on the nature of CPE used in Australia during that period — a 70 page notebook written in a form of English by a Chinese gold miner, Jong Ah Siug. The article presents some background information about Chinese immigrants in the region where Jong worked (Victoria), and evidence that some CPE was spoken there. It goes on to describe Jong’s notebook and the circumstances that led to him writing it. The main part of the article examines the linguistic features of CPE and other pidgins that are present in the notebook, and discusses other lexical and morphosyntactic features of the text. Some features are typical only of CPE, such as the use of my as the first person pronoun. On the other hand, some features are more characteristic of Australian or Pacific pidgins — for example, the use of belong in possessive constructions. Still other features have not been recorded for any pidgin, such as the use of been as a locative copula. The analysis shows that Jong’s text contains a mixture of features from CPE and other pidgins, as well as features of interlanguage, including some resulting from functional transfer from Jong’s first language, Cantonese.
Developing a depersonalized stance through linguistic means in typologically different languages
Authors: Jisa Harriet , Tolchinsky Liliana
Published: August 2009

Attaining rhetorical competence requires the capacity to use linguistic form to communicate discourse stance as well as discourse content. Languages provide their speakers with a range of options to express content in ways that reveal orientation, generality of reference, and attitude to the propositional content of their message to create a more involved or detached discourse stance. This paper focuses on the linguistic means used by children (9–10-, 12–13-, and 15–16-year olds) and university graduate students in French and Spanish in their attempt to create a detached discourse stance in expository texts. Two types of linguistic means for encoding discourse stance are examined: local devices which call for the manipulation of morphology and the lexicon, and phrase-level devices which require manipulation of argument structure. Our results show (1) that children in both languages are sensitive to the necessity of encoding a depersonalized discourse stance in expository texts early on; (2) that local devices are productive before those involving the rearrangement of argument structure; and (3) that with development and increasing interaction with academic texts the range of devices employed increases. The data reveal that for the phrase-level devices French speakers prefer passive constructions, while Spanish-speakers prefer se-constructions. Our results illustrate how later language development is influenced by language-specific facts and literacy interacting with universally shared communicative needs.
Similarities and differences of Luxembourgish and Romanophone 12 year olds’ spelling strategies in German and in French
Authors: Bodé Sylvie , Serres Joyce , Ugen Sonja
Published: August 2009

The present article examines spelling strategies of children of two different linguistic backgrounds, namely Luxembourgish and Romanophone. In Luxembourg, German literacy skills are acquired from grade 1 on and written French classes begin in grade 3. Luxembourgish is the language of communication, although a high number of Romanophone foreigners speak French in their daily life. In the underlying investigation, Luxembourgish (n = 202) and Romanophone (n = 44) children performed a dictation in German and French. The aim was to see whether a child’s linguistic background influences spelling or whether the relative high transparency of the German writing system eliminates this linguistic difference. In French, both groups performed similarly which proposes no influence of linguistic background on spelling. In German, however, Luxembourgish children obtained higher scores than Romanophones and the latter were more affected by word frequency which suggests that they encounter more difficulties in applying more complex spelling strategies. The more transparent German writing system is not sufficient to erase the linguistic difference between the two groups.
Letter and grapheme perception in English and Dutch
Authors: Bolger Patrick , Borgwaldt Susanne R. , Jakab Emőke
Published: August 2009

In the study of reading, there is a debate about whether letters or graphemes are the primary units of perception. A promising data basis for empirically contributing to this debate can be gained from measuring the perception of single vowel letters compared to vowel digraphs. We used letter detection with masked pseudoword primes on pseudoword targets among skilled native readers in order to test for the existence and time course of vowel digraph effects during reading in deep (English) and shallow (Dutch) orthographies. Selecting these two languages, which are similar in terms of syllabic structure, allowed us to use exactly the same pseudoword stimuli. Results indicate that whereas the Dutch readers show letter effects at short prime durations and digraph effects at longer prime durations, the English readers show only letter effects. These findings are inconsistent with a strong version of the claim that graphemes are perceptual in nature, but consistent with models of reading acquisition and skilled reading that predict that, although letter effects always precede grapheme effects, grapheme activation proceeds faster in relatively shallow orthographies than in relatively deep ones.
The long‐term effects of counselling: The process and mechanisms that contribute to ongoing change from a user perspective
Authors: Perren Sara , Godfrey Mary , Rowland Nancy
Published: August 2009

Aims: This qualitative study aimed to expand the limited evidence base about the long‐term effects of psychological therapies.Method: We conducted in‐depth interviews with 15 people, 1–3 years after primary care counselling, to investigate whether they could identify enduring benefits and the mechanisms that brought about and maintained them. From their narratives, we developed a model of the change process of counselling and mechanisms that were perceived as essential to produce lasting benefit. The model conceptualised movement through distinct phases: engagement; exploration of internal and external worlds; consolidation and negotiated ending. Results: Mechanisms integral to sustained impact were: the active engagement of people during and between sessions to work toward their own solutions; and acquisition through the change process of skills which could be further built on after the counselling ended. These enabled ongoing, dynamic change in the way people conducted their lives and relationships. Conclusion: A key concept in securing long‐term benefit was co‐production, both during counselling and in taking ownership of and using the ‘box of skills’ acquired. Support of the model was reinforced through comparison with the experience of three interviewees who reported no long‐term benefit.
Hand Hygiene with Soap and Water Is Superior to Alcohol Rub and Antiseptic Wipes for Removal ofClostridium difficile
Authors: Oughton Matthew T. , Loo Vivian G. , Dendukuri Nandini , Fenn Susan , Libman Michael D.
Published: August 2009

Objective.

To evaluate common hand hygiene methods for efficacy in removingClostridium difficik.

Design.

Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C.difficile.

Methods.

Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no Intervention. All interventions were evaluated for mean reduction in colony-forming units (CFUs) under 2 contamination protocols: “whole hand” and “palmar surface.” Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations.

Results.

Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log10CFU/mL [95% credible interval (Cri), 1.74-2.54 log10CFU/mL]), cold water with plain soap (1.88 log10CFU/mL [95% Cri, 1.48-2.28 log10CFU/mL), and warm water with antibacterial soap (1.51 log10CFU/mL [95% Cri, 1.12-1.91 logu, CFU/mL]), followed by antiseptic hand wipes (0.57 log10CFU/mL [95% Cri, 0.17-0.96 log10CFU/mL]). Alcohol-based handrub (0.06 log10CFU/mL [95% CrI, -0.34 to 0.45 log10CFU/mL]) was equivalent to no Intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% Cri, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% Cri, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing.

Conclusions.

Handwashing with soap and water showed the greatest efficacy in removingC. difficileand should be performed preferentially over the use of alcohol-based handrubs when contact withC. difficileis suspected or likely.
Chromatin poises miRNA- and protein-coding genes for expression
Authors: Barski Artem , Jothi Raja , Cuddapah Suresh , Cui Kairong , Roh Tae-Young , Schones Dustin E. , Zhao Keji
Published: August 2009

Chromatin modifications have been implicated in the regulation of gene expression. While association of certain modifications with expressed or silent genes has been established, it remains unclear how changes in chromatin environment relate to changes in gene expression. In this article, we used ChIP-seq (chromatin immunoprecipitation with massively parallel sequencing) to analyze the genome-wide changes in chromatin modifications during activation of total human CD4+ T cells by T-cell receptor (TCR) signaling. Surprisingly, we found that the chromatin modification patterns at many induced and silenced genes are relatively stable during the short-term activation of resting T cells. Active chromatin modifications were already in place for a majority of inducible protein-coding genes, even while the genes were silent in resting cells. Similarly, genes that were silenced upon T-cell activation retained positive chromatin modifications even after being silenced. To investigate if these observations are also valid for miRNA-coding genes, we systematically identified promoters for known miRNA genes using epigenetic marks and profiled their expression patterns using deep sequencing. We found that chromatin modifications can poise miRNA-coding genes as well. Our data suggest that miRNA- and protein-coding genes share similar mechanisms of regulation by chromatin modifications, which poise inducible genes for activation in response to environmental stimuli.
A cladistic analysis of the cockroach wasps based on morphological data (Hymenoptera: Ampulicidae)
Authors: Ohl Michael , Spahn Philipp
Published: August 2009

The Ampulicidae are one of the most basal groups within the apoid wasps, the paraphyletic assemblage of wasps previously known as Sphecidae. The morphology and taxonomy of the Ampulicidae are poorly studied, and there is no strict cladistic approach on their phylogeny yet. Here we assemble morphological characters of phylogenetic significance and submit them to parsimony analyses using modern cladistic methods. This produces a well‐resolved and firmly supported phylogenetic hypothesis on the generic relationships within the group. Based on our phylogenetic results a revised classification is provided, subdividing the Ampulicidae into two monophyletic subfamilies, Ampulicinae (Ampulex and Trirogma) and Dolichurinae, the latter comprising two monophyletic tribes, Dolichurini (Dolichurus and Paradolichurus) and Aphelotomini, new tribe (Aphelotoma and Riekefella). Based on the resulting cladogram, the historical biogeography and the fossil record of Ampulicidae are briefly discussed.

© The Willi Hennig Society 2009.
Fluid inclusions as constraints in a three‐dimensional hydro‐thermo‐mechanical model of the Paris basin, France
Authors: Gonçalvès J. , Pagel M. , Violette S. , Guillocheau F. , Robin C.
Published: August 2009

Fluid inclusion homogenization temperatures and three‐dimensional hydro‐thermo‐mechanical modelling were combined to constrain fluid flow, solute and heat transport in the Paris basin, France, focusing on the two main petroleum reservoirs i.e. the Dogger and the Triassic (Keuper) formations. The average homogenization temperatures of two‐phase aqueous inclusions in different samples range from 66 °C to 88 °C in the Dogger calcite cement, from 106 °C to 118 °C in the Keuper dolomite cement and from 89 °C to 126 °C in the Keuper quartz and K‐feldspar cements. The maximum homogenization temperatures for inclusions in the Keuper quartz and K‐feldspar cements were 17–47 °C higher than present‐day temperatures in the boreholes at similar depths. Processes that might explain higher temperatures in the past were examined through numerical simulations and sensitivity tests. A warmer climate in the Late Cretaceous–Early Tertiary resulted in a temperature rise of only 8 °C. Late Cretaceous chalk had a thermal blanketing effect that resulted in simulated temperatures as high as 15–20 °C above the present day ones. An additional 300 m deposition and subsequent erosion of chalk, not taken into account so far, has to be considered to simulate the high palaeo‐temperatures recorded by fluid inclusions in both reservoirs. In view of the simulated thermal history of the basin, in the Keuper, an age of about 85 Ma is consistent with quartz/K‐feldspar temperatures and an age of about 65 Ma is in agreement with the precipitation temperature of the dolomite cement. Our models suggest an age of about 50 Ma for the Dogger calcite cementation.
Genetic caste determination does not impose growth rate costs in Pogonomyrmex harvester ants
Authors: Cahan Sara Helms , Daly Amanda B. , Schwander Tanja , Arthur Woods H.
Published: August 2009

1.
 Caste determination in eusocial insects is the process by which individuals differentiate into reproducer or helper phenotypes.

2.
 Environmental caste determination (ECD) is predicted to be more efficient than genetic caste determination (GCD), yet GCD occurs in several populations of Pogonomyrmex harvester ants.

3.
 We tested whether GCD reduces efficiency by comparing colony growth rates of two GCD lineage pairs (H and J) with two closely related ECD congeners, P. rugosus and P. barbatus, under laboratory conditions over a range of temperatures. In addition, we directly compared metabolic rates of GCD and ECD larvae using flow‐through respirometry.

4.
 Unexpectedly, colonies from GCD lineages grew faster than colonies of P. rugosus across all temperatures, and grew at the same rate as colonies of P. barbatus. Slower colony growth rates of P. rugosus were caused by lower queen fecundity and slower larval development. Variation in developmental rate was not due to differences in larval metabolic rates, which did not differ among taxa.

5.
 These results suggest that GCD in Pogonomyrmex does not impose significant productivity costs during colony growth. Instead, efficiency costs are compensated by other physiological mechanisms which may or may not be directly related to the mode of caste determination.

6.
 Persistence of GCD populations in contact with ECD competitors likely stems from a life‐history trade‐off favouring different taxa across the geographic range of the complex: the slow growing but starvation‐resistant P. rugosus dominates in resource‐poor regions, while faster growing and competitive GCD populations predominate in more mesic habitats.
Expression of matrix metalloproteinases MMP‐2, MMP‐9 and their tissue inhibitors TIMP‐1 and TIMP‐2 in the epithelium and stroma of salivary gland pleomorphic adenomas
Authors: Zhang Xiaojun , Wang Yang , Yamamoto Gou , Tachikawa Tetsuhiko
Published: August 2009

Aims:  The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of normal salivary gland as well as in the mechanisms of tumour invasion and metastasis. The role of MMPs and TIMPs in pleomorphic adenoma has not been elucidated sufficiently. Our aim was to analyse the mRNA and protein expression of MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 in the epithelium and stroma of pleomorphic adenoma and to evaluate their roles.

Methods and results:  In each sample from six patients, cells from the epithelium and stroma were obtained by laser microdissection. The mRNA expression of MMPs and TIMPs was determined by real‐time quantitative reverse transcriptase‐polymerase chain reaction and protein expression was confirmed by immunohistochemistry. Results showed that mRNA expression of MMPs and TIMPs was significantly higher in stroma than in epithelium in most patients. MMPs and TIMPs were immunoreactive mainly in epithelium rather than in stroma.

Conclusions:  Our results provide preliminary evidence that stromal myoepithelium may be the primary source of MMPs and that the stroma has the potential to play a more important role than ductal epithelium in biological behaviour of pleomorphic adenomas. These findings seem worthy of further investigation.
MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients
Authors: Caramori Gaetano , Casolari Paolo , Di Gregorio Carmela , Saetta Marina , Baraldo Simonetta , Boschetto Piera , Ito Kazuhiro , Fabbri Leonardo M , Barnes Peter J , Adcock Ian M , Cavallesco Giorgio , Chung Kian F , Papi Alberto
Published: August 2009

Aims:  Mucus expectoration is a common feature of chronic obstructive pulmonary disease (COPD). MUC5AC and MUC5B, the major mucins, are released predominantly from submucosal glands in the central airways. The aim was to investigate gland size and MUC5AC and MUC5B expression in bronchial rings from smokers with COPD compared with control groups.

Methods and results:  Bronchial rings from 10 non‐smoking subjects, 20 smokers with normal lung function and 20 smokers with COPD were studied. Periodic acid–Schiff (PAS) and Alcian blue histochemistry and MUC5AC and MUC5B immunohistochemistry followed by quantification of the immunoreactive area was performed. The area occupied by MUC5AC+ cells in bronchial submucosal glands was increased in COPD [20% (5.5–31.7%) gland area] compared with smokers with normal lung function [9.5% (2.5–17.5%); P < 0.05] and non‐smoking subjects [2% (0.4–6.2%); P < 0.05]. The area occupied by MUC5AC+ cells in the bronchial surface epithelium was also increased in smokers (with/without COPD) [73.5% (25–92%) epithelial area] compared with non‐smoking subjects [15% (2.7–32%); P < 0.01]. Gland size, PAS, Alcian blue staining and MUC5B expression were not significantly different among groups. MUC5AC expression correlated with the degree of airflow obstruction. MUC5AC and MUC5B expression correlated with pack‐years.

Conclusions:  COPD is associated with increased MUC5AC expression in submucosal glands, indicating that MUC5AC may be involved in the pathophysiology of the disease.
The prognostic value of intraepithelial and stromal innate immune system cells in non‐small cell lung carcinoma
Authors: Al‐Shibli Khalid , Al‐Saad Samer , Donnem Tom , Persson Magnus , Bremnes Roy M , Busund Lill‐Tove
Published: August 2009

Aims:  The major value of prognostic markers in potentially curable non‐small cell lung carcinoma (NSCLC) should be to guide therapy after surgical resection. The prognostic significance of tumour‐infiltrating macrophages, their growth factor, macrophage colony‐stimulating factor (M‐CSF), and its receptor, colony‐stimulating factor‐1 receptor (CSF‐1R), as well as natural killer cells and dendritic cells, is controversial. The aim of this study was to elucidate the prognostic significance of these markers in the epithelial and stromal compartments of NSCLC.

Methods and results:  Tissue microarrays from 335 resected NSCLC, stage I–IIIA were constructed from duplicate cores of epithelial and stromal areas. Immunohistochemistry was used to evaluate epithelial and stromal areas for CD68, M‐CSF, CSF‐1R, CD56 and CD1a. On univariate analysis, increasing numbers of stromal CD1a+ (P = 0.011) and CD56+ cells (P = 0.014) correlated significantly with improved disease‐specific survival (DSS). On multivariate analysis, stromal CD56+ cells were an independent prognostic factor for DSS (hazard ratio = 2.3, confidence interval = 1.1, 5.0, P = 0.031).

Conclusions:  High density of stromal CD56+ cells is an independent factor associated with improved prognosis in resected NSCLC, suggesting that these cells mediate an antitumour immune response in the tumour stroma.
Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas
Authors: Fernandes Raquel C M , Bevilacqua Jose L B , Soares Ibere C , Siqueira Sheila A C , Pires Luis , Hegg Roberto , Carvalho Filomena M
Published: August 2009

Aims:  Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal‐like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with <10% tubular formation, and their correlation with classic prognostic factors.

Methods and results:  One hundred and thirty‐four samples of paraffin‐embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2−; (ii) ER+ and/or PR+ and HER2+; (iii) ER− and/or PR− but HER2+; and (iv) ER−, PR− and HER2− (triple‐negative). The histological features of triple‐negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple‐negative carcinomas. Basal‐CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile.

Conclusions:  Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal‐CK identifies distinct subtypes equivalent to those seen by genetic classification.
Expression profiles of thioredoxin family proteins in human lung cancer tissue: correlation with proliferation and differentiation
Authors: Fernandes Aristi P , Capitanio Arrigo , Selenius Markus , Brodin Ola , Rundlöf Anna‐Klara , Björnstedt Mikael
Published: August 2009

Aims:  Lung cancer is one of the most common causes of cancer lethality worldwide. Despite recent progress, long‐term survival remains poor. The aim of this study was to explore the expression pattern of the thioredoxin superfamily of proteins as potential new diagnostic and/or predictive markers.

Methods and results:  The expression of thioredoxin 1 (Trx1), thioredoxin reductase 1 (TrxR1), the isoforms TrxR1‐v.2,3,5, glutaredoxin 1 (Grx1) and glutaredoxin 2 (Grx2) was examined by immunohistochemistry on paraffin‐embedded sections from 42 cases of non‐small cell lung cancer patients. Additional cases of lung cancer from tissue microarray were examined and the immunoreactivity was compared. All proteins except TrxR1 showed a significant correlation with the degree of differentiation in adenocarcinoma. Trx1 and TrxR1‐v.2,3,5 also showed a significant correlation with differentiation in squamous carcinoma. Furthermore, Grx1 and Grx2 showed a clear inverse correlation with proliferation. The proliferation rate was further analysed in vitro in stably transfected Grx2 overproducing cells, showing that the proliferative effect of Grx2 is strictly dependent on subcellular localization.

Conclusions:  The thioredoxin family of proteins is important for growth and differentiation of lung cancer cells. The correlation with differentiation and proliferation of these enzymes makes them promising predictive/diagnostic markers.
Virtual reality Powerwall versus conventional microscope for viewing pathology slides: an experimental comparison
Authors: Treanor Darren , Jordan‐Owers Naomi , Hodrien John , Wood Jason , Quirke Phil , Ruddle Roy A
Published: August 2009

Aims:  Virtual slides could replace the conventional microscope. However, it can take 60% longer to make a diagnosis with a virtual slide, due to the small display size and inadequate user interface of current systems. The aim was to create and test a virtual reality (VR) microscope using a Powerwall (a high‐resolution array of 28 computer screens) for viewing virtual slides more efficiently.

Methods and results:  A controlled user experiment was performed to compare the Powerwall with the microscope for four types of task: (i) a simple diagnosis, (ii) a decision about a lymph node, (iii) finding small objects, (iv) scoring a tissue microarray. User behaviour was recorded by video and questionnaire. Time taken to perform all four tasks and diagnostic confidence were similar using the Powerwall and conventional microscope.

Conclusions:  After just a few minutes’ familiarization, a VR Powerwall allowed tasks to be performed as quickly and confidently as a microscope. Behavioural data indicated how histopathologists should be trained to make the best use of the large display provided by the VR microscope. Together with the potential for further improvements in the design of the VR microscope, future virtual slide systems could out‐perform conventional microscopes in histopathological diagnosis.
The development of a clinical learning environment scale
Authors: Dunn Sandra V , PhD Paul Burnett
Published: August 2009

Within nursing, there is a strong demand for high‐quality, cost‐effective clinical education experiences that facilitate student learning in the clinical setting The clinical learning environment (CLE) is the interactive network of forces within the clinical setting that influence the students’clinical learning outcomes The identification of factors that characterize CLE could lead to strategies that foster the factors most predictive of desirable student learning outcomes and ameliorate those which may have a negative impact on student outcomes The CLE scale is a 23‐item instrument with five subscales staff–student relationships, nurse manager commitment, patient relationships, interpersonal relationships, and student satisfaction These factors have strong substantive face validity and construct validity, as determined by confirmatory factor analysis Reliability coefficients range from high (0 85) to marginal (0 63) The CLE scale provides the educator with a valid and reliable instrument to evaluate affectively relevant factors in the CLE, direct resources to areas where improvement may be required, and nurture those areas functioning well It will assist in the application of resources in a cost‐effective, efficient, productive manner, and will ensure that the clinical learning experience offers the nursing student the best possible learning outcomes
Observation of three‐dimensional internal structure of steel materials by means of serial sectioning with ultrasonic elliptical vibration cutting
Authors: FUJISAKI K. , YOKOTA H. , NAKATSUCHI H. , YAMAGATA Y. , NISHIKAWA T. , UDAGAWA T. , MAKINOUCHI A.
Published: August 2009

A three‐dimensional (3D) internal structure observation system based on serial sectioning was developed from an ultrasonic elliptical vibration cutting device and an optical microscope combined with a high‐precision positioning device. For bearing steel samples, the cutting device created mirrored surfaces suitable for optical metallography, even for long‐cutting distances during serial sectioning of these ferrous materials. Serial sectioning progressed automatically by means of numerical control. The system was used to observe inclusions in steel materials on a scale of several tens of micrometers. Three specimens containing inclusions were prepared from bearing steels. These inclusions could be detected as two‐dimensional (2D) sectional images with resolution better than 1 μm. A three‐dimensional (3D) model of each inclusion was reconstructed from the 2D serial images. The microscopic 3D models had sharp edges and complicated surfaces.
Structure and function of phage p2 ORF34p2, a new type of single‐stranded DNA binding protein
Authors: Scaltriti Erika , Tegoni Mariella , Rivetti Claudio , Launay Hélène , Masson Jean‐Yves , Magadan Alfonso H. , Tremblay Denise , Moineau Sylvain , Ramoni Roberto , Lichière Julie , Campanacci Valérie , Cambillau Christian , Ortiz‐Lombardía Miguel
Published: August 2009

Lactococcus lactis, a Gram‐positive bacterium widely used by the dairy industry, is subject to infection by a diverse population of virulent phages, predominantly by those of the 936 group, including the siphovirus phage p2. Confronted with the negative impact of phage infection on milk fermentation, the study of the biology of lactococcal provides insight from applied and fundamental perspectives. We decided to characterize the product of the orf34 gene from lactococcus phage p2, which was considered as a candidate single‐stranded DNA binding protein (SSB) due to its localization downstream of a gene coding for a single‐strand annealing protein. Two‐dimensional gel electrophoresis showed that ORF34p2 is expressed in large amounts during the early phases of phage infection, suggesting an important role in this process. Gel‐shift assays, surface plasmon resonance and atomic force microscopy demonstrated that ORF34p2 interacts with single‐strand DNA with nanomolar affinity. We also determined the crystal structure of ORF34p2 and showed that it bears a variation of the typical oligonucleotide/oligosaccharide binding‐fold of SSBs. Finally, we found that ORF34p2 is able to stimulate Escherichia coli RecA‐mediated homologous recombination. The specific structural and biochemical properties that distinguish ORF34p2 from other SSB proteins are discussed.
Chronic allograft nephropathy – a clinical syndrome: early detection and the potential role of proliferation signal inhibitors
Authors: Campistol Josep M. , Boletis Ioannis N. , Dantal Jacques , De Fijter Johan W. , Hertig Alexandre , Neumayer Hans H. , Øyen Ole , Pascual Julio , Pohanka Erich , Ruiz Juan C. , Scolari Maria P. , Stefoni Sergio , Serón Daniel , Sparacino Vito , Arns Wolfgang , Chapman Jeremy R.
Published: August 2009

Abstract:  Chronic allograft nephropathy (CAN) leads to the majority of late graft loss following renal transplantation. Detection of CAN is often too late to permit early intervention and successful management. Most current strategies for managing CAN rely on minimizing or eliminating calcineurin inhibitors (CNIs) once CAN has become established. The proliferation signal inhibitors everolimus and sirolimus have potent immunosuppressive and antiproliferative actions, with the potential to alter the natural history of CAN by reducing CNI exposure whilst avoiding acute rejection. Whilst data will be forthcoming from a number of clinical trials investigating this potential, we discuss early detection of CAN and the rationale for a role for this class of agent.
Gastric bypass and glucose metabolism
Authors: Ukkola O.
Published: August 2009

Roux‐en‐Y gastric bypass leads to a marked improvement of glucose control. The mechanisms are only partly known. Gastrointestinal hormones may play a role. Of these, glucagon‐like peptide 1 and peptide YY have been most consistently associated with the beneficial effects of gastric bypass on glucose metabolism and weight. In this paper, a short review of the topic is presented and a suggestion of the improvement of glucose metabolism is made based on the current published work.
Aspirin sensitivity: acetylsalicylate or excipients
Authors: Hebron B. S. , Hebron H. J.
Published: August 2009

We present three patients who developed urticaria while taking an enteric formulation of aspirin, confirmed on a second exposure. Although hypersensitivity reactions to aspirin, especially in asthmatic patients or those with nasal polyps, are well reported, our patients did not exhibit any underlying history of atopy. Furthermore, two of the patients were able to tolerate a soluble formulation. We review the literature and discuss whether these symptoms might be caused by pharmaceutical excipients, present in very small amounts in the enteric coating, rather than the active ingredient acetylsalicylate. Adverse reactions to excipients are fortunately rare but are occasionally reported.
Age‐related changes in plasma androgen levels and their association with cardiovascular risk factors in male Japanese office workers
Authors: Fukai Shiho , Akishita Masahiro , Miyao Mariko , Ishida Kiyoshi , Toba Kenji , Ouchi Yasuyoshi
Published: August 2009

Aim:  To assess the age‐related change in plasma androgen levels in healthy middle‐aged men and whether any clinical parameters are associated with the hormonal change.

Methods:  The study was comprised of male Japanese office‐workers aged 40–64 years, who had undergone an annual health check‐up in 2002 and 2007 (96 and 76 men, respectively). Body mass index and blood pressure were measured, and serum concentration of lipids, glucose and uric acid in addition to plasma total testosterone, free testosterone and dehydroepiandrosterone sulfate (DHEA‐S) levels were determined in the morning after an overnight fast. The 5‐year hormonal changes and their associations with clinical parameters were analyzed in 33 men who repeated the examination at both check‐ups. The cross‐sectional associations of hormonal levels with clinical parameters were also investigated.

Results:  Age was negatively associated with free testosterone (r = −0.399, P < 0.001 in 2002; r = −0.458, P < 0.001 in 2007) and DHEA‐S (r = −0.233, P = 0.02 in 2002; r = −0.336, P < 0.01 in 2007) but not with total testosterone, while the 5‐year changes of free testosterone and DHEA‐S levels were not significant and showed no associations with major cardiovascular risk factors. Cross‐sectionally, after adjustment for age, linear regression analysis showed a positive association between free testosterone and blood hemoglobin and a negative association between total testosterone and serum uric acid.

Conclusion:  In Japanese middle‐aged men, 5‐year androgen decline is too subtle to detect, and endogenous androgen levels seem to have relatively weak association with cardiovascular risk profiles.
Comprehensive geriatric assessment of elderly highlanders in Qinghai, China II: The association of polycythemia with lifestyle‐related diseases among the three ethnicities
Authors: Okumiya Kiyohito , Sakamoto Ryota , Kimura Yumi , Ishine Masayuki , Kosaka Yasuyuki , Wada Taizo , Wada Chizu , Nakatsuka Masahiro , Ishimoto Yasuko , Hirosaki Mayumi , Kasahara Yoriko , Konno Akiko , Chen Wingling , Fujisawa Michiko , Otsuka Kuniaki , Nakashima Michiro , Wang Hongxin , Dai Qingxiang , Yang Airong , Qiao Haisheng , Gao Jidong , Li Zhanquan , Zhang Yongshou , Ge Ri‐Li , Matsubayashi Kozo
Published: August 2009

Aim:  The objective of this study is to disclose the association of polycythemia with lifestyle‐related diseases (hypertension, obesity and glucose intolerance) among the three ethnicities in Qinghai, China.

Methods:  The subjects were 393 elderly people (247 Han, 97 Tibetan and 49 Mongolian) aged 60 years and more living in Qinghai (3000 m a.s.l.) in China. The associated factors with polycythemia were analyzed in the subjects. Excessive polycythemia was defined as hemoglobin concentration over 20 mg/dL.

Results:  Polycythemia was associated with men, hypoxemia, obesity and high diastolic blood pressure (DBP) in the elderly in Qinghai. Male sex was associated with polycythemia in all ethnicities. Obesity was associated with Han and Tibetan men. Glucose intolerance and activities of daily living were not directly associated with polycythemia after adjustment for sex. There were 7.9% with excessive polycythemia. Independently‐associated factors for excessive polycythemia were male sex, body mass index of 25 or more, SpO2 of less than 85%, DBP of 85 mmHg or more and Han ethnicity (vs Tibetan) by multiple logistic regression.

Conclusion:  There was a close association of polycythemia with diastolic hypertension and obesity in lifestyle‐related diseases in high‐altitude elderly people. Han people had a higher hemoglobin concentration after adjustment of lifestyle‐related diseases compared with Tibetan people. The difference of hemoglobin concentration may be due to Tibetans undergoing a much longer period of adaptation than Han people. Further study is needed to disclose the association between the difference of hypoxic adaptation, lifestyle‐related diseases and chronic mountain sickness for their prevention.