bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway
Authors: Fritsche‐Guenther Raphaela , Noske Aurelia , Ungethüm Ute , Kuban Ralf‐Jürgen , Schlag Peter M. , Tunn Per‐Ulf , Karle Janine , Krenn Veit , Dietel Manfred , Sers Christine 
Published: December 2010

Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway Aims:  In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.Methods and results:  Osteosarcoma samples were characterized using genome‐wide microarrays: increased expression of the EphA2 receptor and its ligand EFNA1 was detected. In addition, increased expression of EFNB1, EFNB3 and EphA3 was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and de novo expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further in vitro investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phoshorylation, receptor degradation and downstream mitogen‐activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.Conclusion:  Upregulation and de novo expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.
Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma
Authors: Xu Jing Da , Furuya Tomoko , Cao Xi Xi , Liu Xiao Li , Li Qing Quan , Wang Wen Juan , Xu Jia Wen , Xu Zu De , Sasaki Kohsuke , Liu Xiu Ping 
Published: December 2010

Xu J D, Furuya T, Cao X X, Liu X L, Li Q Q, Wang W J, Xu J W, Xu Z D, Sasaki K & Liu X P (2010) Histopathology57, 814–824 Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma Aims:  BCL2L10 protein is an apoptosis‐related member of the Bcl‐2 protein family. The clinical significance of its expression in gastric carcinoma is poorly understood. The aim was to investigate BCL2L10 expression and its clinical and prognostic significance in gastric carcinoma patients.Methods and results:  Immunohistochemistry, real–time polymerase chain reaction (PCR) and immunoblotting all revealed extensive loss of BCL2L10 expression in gastric cancer cells. The scaled BCL2L10 expression data was categorized into three groups (groups 0–2) to facilitate statistical analysis. A significant correlation was observed between the lower BCL2L10 expression group and shorter disease‐free survival (P = 1.956 × 10−18). Multivariate regression analysis showed that loss of BCL2L10 protein expression [P = 4.883 × 10−8, hazard ratio (HR) = 0.252] is an independent prognostic predictor of gastric carcinoma. The receiver operator characteristic (ROC) curve showed that the area for BCL2L10 protein was 0.817 (P = 8.331 × 10−14), indicating that loss of BCL2L10 protein expression is an excellent prognostic predictor of gastric carcinoma.Conclusions:  Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.
Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma
Authors: Souza Ludmilla R , Fonseca‐Silva Thiago , Santos Carolina C O , Oliveira Marcos V M , Corrêa‐Oliveira Rodrigo , Guimarães André L S , De Paula Alfredo M B 
Published: December 2010

Souza L R, Fonseca‐Silva T, Santos C C O, Oliveira M V M, Corrêa‐Oliveira R, Guimarães A L S & De Paula A M B (2010) Histopathology57, 796–805 Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma Aims:  To determine the contributions of mast cells (MC), eosinophil leucocytes (EL) and microvessel density (MVD) in lip carcinogenesis, and to establish the relationships between these biomarkers and their possible prognostic value in lip squamous cell carcinoma (LSCC).Methods and results:  Archived specimens of lip mucosa (n = 13), actinic cheilitis (n = 29) and LSCC (n = 29) were formalin‐fixed, paraffin‐embedded, sectioned and stained with toluidine blue and haematoxylin and eosin (H&E) in order to identify MC and EL and to measure their densities. Tumour angiogenesis was estimated by determining, with the use of CD31 antibody MVD in areas with the highest number of stained microvessels (‘hot spots’). Progressive increases of MC, EL and MVD were observed during lip tumour development. Correlation analysis revealed positive associations between the biomarkers during tumour progression. In LSCC samples, significant associations were found between MVD values and metastatic disease. On multivariate analysis, MVD was a predictor of risk of cervical metastasis.Conclusions:  The densities of MC, EL and microvessels increase during lip carcinogenesis, and for MC and EL this may be related to the stimulation of tumour angiogenesis. MVD could be a useful predictor of cervical metastasis in LSCC.
Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations
Authors: Pristauz Gunda , Petru Edgar , Stacher Elvira , Geigl Jochen B , Schwarzbraun Thomas , Tsybrovskyy Oleksiy , Winter Raimund , Moinfar Farid 
Published: December 2010

Pristauz G, Petru E, Stacher E, Geigl J B, Schwarzbraun T, Tsybrovskyy O, Winter R & Moinfar F (2010) Histopathology57, 877–884 Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations Aim:  To assess the expression of receptors for androgen (AR), oestrogen (ER) and progesterone (PR) as well as human epidermal growth factor receptor type 2 (Her‐2/neu) status of breast carcinomas in breast cancer susceptibility gene (BRCA) BRCA1/2 mutation carriers and BRCA1/2 negative tested women.Methods:  One hundred and thirty‐five breast cancers in women tested for BRCA1/2 mutations. Screening for BRCA1 and BRCA2 mutations was performed by direct sequencing of all BRCA1 and BRCA2 exons as well as the surrounding intronic sequences. Additionally, BRCA genes were analysed with multiplex ligation‐dependent probe amplification. Consecutive paraffin sections were examined immunhistochemically for AR, ER, PR and Her‐2/neu.Results:  Of the 135 tumours, 43 (32%) were BRCA1‐related, 18 (13%) were BRCA2‐related and 74 (55%) were BRCA1/2‐negative. Seventy‐two per cent of the BRCA1‐related, 22% of the BRCA2‐related and 12% of the BRCA1/2‐negative tumours were triple (ER, PR, Her2neu)‐negative. Eighty‐four per cent of BRCA1 mutated cancers were high‐grade (G3) tumours. ARs were expressed in 30% (13 of 43) of BRCA1‐related, in 78% (14 of 18) in BRCA2‐related tumours and in 76% (56 of 74) in BRCA1/2 negative tumours. Twenty‐one per cent of ER‐negative BRCA1‐related tumours expressed androgen receptors.Conclusion:  Approximately one in five BRCA1 mutated breast cancers negative for ER and PR express androgen receptors. Modulation of AR might open a new avenue for treating these high‐risk cancers.
Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16INK4A overexpression and clinicopathological correlations
Authors: Fuste Victoria , del Pino Marta , Perez Assumpta , Garcia Angel , Torne Aureli , Pahisa Jaume , Ordi Jaume 
Published: December 2010

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J (2010) Histopathology57, 907–916 Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16

INK4A

overexpression and clinicopathological correlations Aim:  To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance.Methods and results:  All cases of SCCVa diagnosed over a 15‐year period from two hospitals in Barcelona, Spain (n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV‐positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P = 0.01). HPV‐positive tumours were more frequently of non‐keratinizing, basaloid or warty type than HPV‐negative neoplasms (84% versus 14.3%; P < 0.001), and showed diffuse positive immunoreactivity for p16INK4a (96%, versus 14.3%; P < 0.001). The sensitivity and specificity of p16 to identify HPV‐positive tumours were 96% and 85.7%, respectively.Conclusions:  A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV‐positive tumours tend to affect women with history of cervical neoplasia.
Conventional and surgical endodontic treatment of a maxillary first molar with unusual anatomy – a case report
Authors: Floratos S. , Kratchman S. I. 
Published: December 2010

Floratos S, Kratchman SI. Conventional and surgical endodontic treatment of a maxillary first molar with unusual anatomy – a case report. International Endodontic Journal.AbstractAim  To describe conventional and surgical endodontic treatment of a maxillary left first molar with two canals on the distobuccal root and to discuss the treatment outcome.Summary  According to the literature, the presence of a second canal on the distobuccal root of a maxillary first molar is rare. This anatomical anomaly might lead to an unfavourable outcome if clinicians fail to identify and treat it properly. The following case report describes conventional and surgical endodontic treatment of a maxillary left first molar with two canals on the distobuccal root.Key learning points

Anatomical variations of the root canal system are a challenge for clinicians during root canal retreatment.
The principles and techniques of endodontic microsurgery are of utmost importance in clinical practice, and clinicians should be aware of them.
Using presence‐only and presence–absence data to estimate the current and potential distributions of established invasive species
Authors: Gormley Andrew M. , Forsyth David M. , Griffioen Peter , Lindeman Michael , Ramsey David S.L. , Scroggie Michael P. , Woodford Luke 
Published: December 2010

Summary1. Predicting the current and potential distributions of established invasive species is critical for evaluating management options, but methods for differentiating these distributions have received little attention. In particular, there is uncertainty among invasive species managers about the value of information from incidental sightings compared to data from designed field surveys. This study compares the two approaches, and develops a unifying framework, using the case of invasive sambar deerCervus unicolorin Victoria, Australia.2. We first used 391 incidental sightings of sambar deer and 12 biophysical variables to construct a presence‐only habitat suitability model using Maxent. We then used that model to stratify field sampling, with proportionately greater sampling of cells with high predicted habitat suitability. Field sampling, consisting of faecal pellet surveys, sign surveys and camera trapping, was conducted in 80 4‐km2grid cells. A Bayesian state‐space occupancy model was used to predict probability of suitable habitat from the field data.3. The Maxent and occupancy models predicted similar spatial distributions of habitat suitability for sambar deer in Victoria and there was a strong positive correlation between the rankings of cells by the two approaches. The congruence of the two models suggests that any spatial and detection biases in the presence‐only data were relatively unimportant in our study.4. We predicted the extent of suitable habitat from the occupancy model using a threshold that gave a false negative error rate of 0·05. The current distribution was the suitable habitat within a kernel that had a 99·5% chance of including the presence locations pooled from incidental sightings and field surveys: the potential distribution was suitable habitat outside that kernel. Several discrete areas of potential distribution were identified as priorities for surveillance monitoring with the aim of detecting and managing incursions of sambar deer.5. Synthesis and applications. Our framework enables managers to robustly estimate the current and potential distributions of established invasive species using either presence‐only and/or presence–absence data. Managers can then focus control and/or containment actions within the current distribution and establish surveillance monitoring to detect incursions within the potential distribution.
Modelling community dynamics based on species‐level abundance models from detection/nondetection data
Authors: Yamaura Yuichi , Andrew Royle J. , Kuboi Kouji , Tada Tsuneo , Ikeno Susumu , Makino Shun’ichi 
Published: December 2010

Summary1. In large‐scale field surveys, a binary recording of each species’ detection or nondetection has been increasingly adopted for its simplicity and low cost. Because of the importance of abundance in many studies, it is desirable to obtain inferences about abundance at species‐, functional group‐, and community‐levels from such binary data.2. We developed a novel hierarchical multi‐species abundance model based on species‐level detection/nondetection data. The model accounts for the existence of undetected species, and variability in abundance and detectability among species. Species‐level detection/nondetection is linked to species‐level abundance via a detection model that accommodates the expectation that probability of detection (at least one individuals is detected) increases with local abundance of the species. We applied this model to a 9‐year dataset composed of the detection/nondetection of forest birds, at a single post‐fire site (from 7 to 15 years after fire) in a montane area of central Japan. The model allocated undetected species into one of the predefined functional groups by assuming a prior distribution on individual group membership.3. The results suggest that 15–20 species were missed in each year, and that species richness of communities and functional groups did not change with post‐fire forest succession. Overall abundance of birds and abundance of functional groups tended to increase over time, although only in the winter, while decreases in detectabilities were observed in several species.4. Synthesis and applications. Understanding and prediction of large‐scale biodiversity dynamics partly hinge on how we can use data effectively. Our hierarchical model for detection/nondetection data estimates abundance in space/time at species‐, functional group‐, and community‐levels while accounting for undetected individuals and species. It also permits comparison of multiple communities by many types of abundance‐based diversity and similarity measures under imperfect detection.
Divergent Protein Kinase A isoforms co‐ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus
Authors: Fuller Kevin K. , Richie Daryl L. , Feng Xizhi , Krishnan Karthik , Stephens Timothy J. , Wikenheiser‐Brokamp Kathryn A. , Askew David S. , Rhodes Judith C. 
Published: December 2010

SummaryThe genome of Aspergillus fumigatus encodes two isoforms of the catalytic subunit of the cAMP‐dependent Protein Kinase (PKA). Although deletion of the class I isoform, pkaC1, leads to an attenuation of virulence, the function of the class II subunit, PkaC2, was previously uninvestigated. In this report, we demonstrate that both isoforms act in concert to support various physiologic processes that promote the virulence of this pathogen. Whereas pkaC1 and pkaC2 single‐deletion mutants display wild‐type conidial germination, a double‐deletion mutant is delayed in germination in response to environmental nutrients. Furthermore, PkaC1 and PkaC2 interact to positively regulate flux through the carbohydrate catabolic pathway and, consequently, the ΔpkaC1ΔpkaC2 mutant is unable to grow on low glucose concentrations. Importantly, the reduced germinative capacity and inability to utilize glucose observed for the ΔpkaC1ΔpkaC2 strain correlated with an inability of the mutant to establish infection in a murine model. Conversely, overexpression of pkaC2 both promotes the in vitro growth on glucose, and restores the fungal burden and mortality associated with the ΔpkaC1 to that of the wild‐type organism. Taken together, these data demonstrate the functional capacity of pkaC2 and emphasize the importance of PKA‐mediated metabolic control in the pathogenic potential of A. fumigatus.
Cell surface display of minor pilin adhesins in the form of a simple heterodimeric assembly in Corynebacterium diphtheriae
Authors: Chang Chungyu , Mandlik Anjali , Das Asis , Ton‐That Hung 
Published: December 2010

SummaryPilus assembly in Gram‐positive bacteria occurs by a two‐step mechanism, whereby pilins are polymerized and then covalently anchored to the cell wall. In Corynebacterium diphtheriae, the pilin‐specific sortase SrtA catalyses polymerization of the SpaA‐type pilus, consisting of the shaft pilin SpaA, tip pilin SpaC and minor pilin SpaB. Cell wall anchoring of the SpaA polymers is triggered when SrtA incorporates SpaB into the pilus base via lysine‐mediated transpeptidation; anchoring to the cell wall peptidoglycan is subsequently catalysed by the housekeeping sortase SrtF. Here we show that SpaB and SpaC formed a heterodimer independent of SpaA polymerization. SrtA was absolutely required for the formation of the SpaBC heterodimer, while SrtF facilitated the optimal cell wall anchoring of this heterodimer. Alanine substitution of the SpaB lysine residue K139 or truncation of the SpaB cell wall‐sorting signal (CWSS) abolished assembly of the SpaBC heterodimer, hence underscoring SpaB function in transpeptidation and cell wall linkage. Importantly, sortase specificity for the cell wall‐anchoring step was found to be dependent on the LAFTG motif within the SpaB CWSS. Thus, C. diphtheriae employs a common sortase‐catalysed mechanism involving lysine‐mediated transpeptidation to generate both adhesive pilus and simple heterodimeric structures on the bacterial the cell wall.
The Pseudomonas aeruginosa flagellum confers resistance to pulmonary surfactant protein‐A by impacting the production of exoproteases through quorum‐sensing
Authors: Kuang Zhizhou , Hao Yonghua , Hwang Sunghei , Zhang Shiping , Kim Eunice , Akinbi Henry T. , Schurr Michael J. , Irvin Randall T. , Hassett Daniel J. , Lau Gee W. 
Published: December 2010

SummarySurfactant protein‐A (SP‐A) is an important antimicrobial protein that opsonizes and permeabilizes membranes of microbial pathogens in mammalian lungs. Previously, we have shown that Pseudomonas aeruginosa flagellum‐deficient mutants are preferentially cleared in the lungs of wild‐type mice by SP‐A‐mediated membrane permeabilization, and not by opsonization. In this study, we report a flagellum‐mediated mechanism of P. aeruginosa resistance to SP‐A. We discovered that flagellum‐deficient (ΔfliC) bacteria are unable to produce adequate amounts of exoproteases to degrade SP‐A in vitro and in vivo, leading to its preferential clearance in the lungs of SP‐A+/+ mice. In addition, ΔfliC bacteria failed to degrade another important lung antimicrobial protein lysozyme. Detailed analyses showed that ΔfliC bacteria are unable to upregulate the transcription of lasI and rhlI genes, impairing the production of homoserine lactones necessary for quorum‐sensing, an important virulence process that regulates the production of multiple exoproteases. Thus, reduced ability of ΔfliC bacteria to quorum‐sense attenuates production of exoproteases and limits degradation of SP‐A, thereby conferring susceptibility to this major pulmonary host defence protein.
Descensus and Development: A Response to Recent Rejoinders
Authors: OAKES EDWARD T. 
Published: December 2010

AbstractTwo articles were published in this journal in 2009 responding to and criticizing my 2007 article on Hans Urs von Balthasar's theology of Holy Saturday. The article below responds to those critiques by establishing the following points: (1) Balthasar's theology of Christ's expiatory descent into hell (that is, one in which Christ's human soul suffered the pains of hell) is thoroughly traditional and can be found asserted throughout theological literature; (2) on the question of (the possibility of) universal salvation, the development from Augustine's consigning of the majority of the human race to hell to Vatican II's assertion that all human beings are connected to the paschal mystery took place independently of Balthasar's theology (a development which of course he accepts), and thus to criticize him on this point is implicitly to deny the very rules for authentic development as outlined by John Henry Newman that both my interlocutors claim to accept.
Effects of visual processing and congenital nystagmus on visually guided ocular motor behaviour
Authors: PEL JOHAN , DOES LISETTE VAN DER , BOOT FLEUR , FABER TJEERD DE , STEEN‐KANT SANNY VAN DER , WILLEMSEN STEN , STEEN HANS VAN DER 
Published: December 2010

Aim  The aim of this study was to compare visually guided ocular motor behaviour in children with visual processing and/or motor deficits with an age‐matched comparison group and an adult group.Method  Visual stimuli were shown to 28 children with visual processing and/or motor deficits (11 females, 17 males; mean age 7y 5mo, SD 2y 9mo, range 2–14y;) and an age‐matched comparison group of 213 typically developing children (115 females, 98 males; mean age 5y 8mo, SD 3y 5mo, range 0–12y). The adult group consisted of nine females and two males with (mean age of 24y 4mo, SD 4y 8mo). Individuals who had a likely diagnosis of cerebral visual impairment (CVI), an opticopathy with unknown location, nystagmus, glaucoma, or a cataract were included in the study. Exclusion criteria were a visual acuity below 0.2, a developmental age under 1 year, and the presence of brain tumours, autism, and anxiety disorders. Orientating eye movements to large cartoons were quantified using the reaction time to fixation (RTF) and gaze fixation area (GFA). A Mann–Whitney U test was used to compare the differences between groups and Bonferroni post‐hoc testing was used to analyse age dependence of RTF and GFA values within the comparison group.Results  Individuals with CVI showed significantly prolonged RTF values; those with congenital nystagmus showed significantly increased GFA values. In the comparison group, RTF was significantly longer in children under the age of 2 years than in children aged 4 years and older (290 and 200ms respectively; p<0.001). No developmental change was found for GFA values.Interpretation  Increased RTF values in individuals with CVI relate to visual processing deficits. The data suggest that visually guided ocular motor responses mature during the first 3 years of life.