Search

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1-92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1-77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed - a usually weak - CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p = 0.0295) and shortened recurrence-free (p = 0.0094) and overall survival (p = 0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p = 0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors.

B7-H3 is a member of the B7 superfamily of immune checkpoint molecules. B7-H3 up regulation has been linked to cancer development and progression in many tumors including prostate cancer. To clarify the potential utility of B7-H3 as a prognostic biomarker, B7-H3 expression was analyzed by immunohistochemistry in more than 17 000 prostate cancers. Normal prostatic glands were largely B7-H3 negative, while membranous B7-H3 immunostaining was seen in 47.0% of analyzed cancers. B7-H3 immunostaining was weak in 12.3%, moderate in 21.1% and strong in 13.5% of cases. High B7-H3 expression was associated with pT, Gleason score, lymph node metastasis, high Ki67 labeling index and early prostate-specific antigen recurrence (P < 0.0001 each). High B7-H3 expression was also linked to high androgen receptor expression and TMPRSS2:V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusions (P < 0.0001 each). Multivariate analyses showed a strong independent prognostic impact of high B7-H3 expression in all cancers and in the ERG negative subgroup. Comparison with previously analyzed frequent chromosomal deletions revealed a close association with Phosphatase and Tensin Homolog deletions. Analysis of B7-H3, alone or in combination with other markers, might be of clinical utility, especially in the subgroup of ERG negative prostate cancers.

Altered expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity. Immunostaining was interpretable in 13,625 cancers and was considered high in 28%, low in 43% and absent in 29% of tumors. Low and lost CEACAM1 expression was strongly linked to adverse tumor features including high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, a high number of genomic deletions and early biochemical recurrence (p < 0.0001 each). Subset analysis of molecularly defined cancer subsets revealed that these associations were strongest in V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-positive cancers and that CEACAM1 loss was prognostic even in tumors harboring genomic deletions of the phosphatase and tensin homolog tumor suppressor (p < 0.0001). Multivariate analysis suggested that CEACAM1 analysis can provide independent prognostic information beyond established prognosis parameters at the stage of the initial biopsy when therapy decisions must be taken. In conclusion, loss of CEACAM1 expression predicts poor prognosis in prostate cancer and might provide clinically useful prognostic information particularly in cancers harboring the TMPRSS2:ERG fusion.

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P, Survivin encoded by the BIRC5 gene was analyzed by immunochemistry on a tissue microarray of 12 432 prostate cancers. We found loss of survivin expression linked to early PSA recurrence in patients treated with radical prostatectomy. Loss of survivin expression showed a moderate and independent impact on PSA recurrence‐free survival. This effect remained also in PTEN‐deleted cancers.

The chromatin‐organizing factor CCCTC‐binding factor (CTCF) is involved in transcriptional regulation, DNA‐loop formation, and telomere maintenance. To evaluate the clinical impact of CTCF in prostate cancer, we analyzed CTCF expression by immunohistochemistry on a tissue microarray containing 17 747 prostate cancers. Normal prostate tissue showed negative to low CTCF expression, while in prostate cancers, CTCF expression was seen in 7726 of our 12 555 (61.5%) tumors and was considered low in 44.6% and high in 17% of cancers. Particularly, high CTCF expression was significantly associated with the presence of the transmembrane protease, serine 2:ETS‐related gene fusion: Only 10% of ERG‐negative cancers, but 30% of ERG‐positive cancers had high‐level CTCF expression (P, The transcriptional repressor CCCTC‐binding factor, which is involved in modeling the chromatin face in the nucleus of a cell, was analyzed for its expression in prostate cancer. We report here that its upregulation was associated with a shorter prostate‐specific antigen recurrence‐free survival after prostatectomy in a large cohort of prostate cancer patients.

Recent expansion of oil palm agriculture has resulted in loss of forest habitat and forest-dependent species. However, large numbers of species—particularly insects—can persist within plantations. This study focuses on Odonata (dragonflies and damselflies): a charismatic indicator taxon and a potentially valuable pest control agent. We surveyed adult Odonata populations biannually over three years within an industrial oil palm plantation in Sumatra, Indonesia. We assessed the effects of rainfall (including an El Niño Southern Oscillation-associated drought), the role of roadside ditches, and the importance of understory vegetation on Odonata populations. To assess the impacts of vegetation, we took advantage of a long-term vegetation management experiment that is part of the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme. We found 41 Odonata species, and communities varied between plantation core and roadside edge microhabitats, and between seasons. Abundance was significantly related to rainfall levels four months before surveys, probably indicating the importance of high water levels in roadside ditches for successful larval development. We found no significant effect of the BEFTA understory vegetation treatments on Odonata abundance, and only limited effects on community composition, suggesting that local understory vegetation structure plays a relatively unimportant role in determining communities. Our findings highlight that there are large numbers of Odonata species present within oil palm plantations and suggest that their abundance could potentially be increased by maintaining or establishing waterbodies. As Odonata are predators, this could bring pest control benefits, in addition to enhancing biodiversity within intensive agricultural landscapes. Published version We thank RISTEK for permission to establish the BEFTA Understory Vegetation Project and to conduct research in Indonesia (permit numbers 426/SIP/FRP/SM/XI/2012, 72/EXT/ SIP/FRP/SM/IX/2013, 44/EXT/SIP/FRP/SM/IX/2014). We thank Pt Ivo Mas Tunggal and Golden Agri Resources, and Sinar Mas Agro Resources Technology Research Institute (SMARTRI) for allowing us to conduct research in their plantations, and we are grateful to the staff of SMARTRI for their help with fieldwork. This work was funded by The Isaac Newton Trust Cambridge, Golden Agri Resources, and the Natural Environment Research Council [grant number NE/P00458X/1]. We thank the reviewers of this manuscript for their helpful comments.

Interface engineering and passivating contacts are key enablers to reach the highest efficiencies in photovoltaic devices. While printed carbon-graphite back electrodes for hole-transporting material (HTM)-free perovskite solar cells (PSCs) are appealing for fast commercialization of PSCs due to low processing costs and extraordinary stability, this device architecture so far suffers from severe performance losses at the back electrode interface. Herein, a 2D perovskite passivation layer as an electron blocking layer (EBL) at this interface to substantially reduce interfacial recombination losses is introduced. The formation of the 2D perovskite EBL is confirmed through X-ray diffraction, photoemission spectroscopy, and an advanced spectrally resolved photoluminescence microscopy mapping technique. Reduced losses that lead to an enhanced fill factor and V-OC are quantified by electrochemical impedance spectroscopy and J(SC)-V-OC measurements. This enables reaching one of the highest reported efficiencies of 18.5% for HTM-free PSCs using 2D perovskite as an EBL with a significantly improved device stability.

Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow-up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P

Integration of detrital zircon geochronology and three-dimensional (3D) seismic-reflection data from the Molasse basin of Austria yields new insight into Oligocene-early Miocene paleogeography and patterns of sediment routing within the Alpine foreland of central Europe. Three-dimensional seismic-reflection data show a network of deep-water tributaries and a long-lived (>8 Ma) foredeep-axial channel belt that transported Alpine detritus greater than 100 km from west to east. We present 793 new detrital zircon ages from ten sandstone samples collected from subsurface cores located within the seismically mapped network of deep-water tributaries and the axial channel belt. Grain age populations correspond with major pre-Alpine orogenic cycles: the Cadomian (750-530 Ma), the Caledonian (490-380 Ma), and the Variscan (350-250 Ma). Additional age populations correspond with Eocene-Oligocene Periadriatic magmatism (40-30 Ma) and pre-Alpine, Precambrian sources (>750 Ma). Although many samples share the same age populations, the abundances of these populations vary significantly. Sediment that entered the deep-water axial channel belt from the west (Freshwater Molasse) and southwest (Inntal fault zone) is characterized by statistically indistinguishable age distributions that include populations of Variscan, Caledonian, and Cadomian zircon at modest abundances (15-32% each). Sandstone from a shallow marine unit proximal to the northern basin margin consists of >75% Variscan (350-300 Ma) zircon, which originated from the adjacent Bohemian Massif. Mixing calculations based on the Kolmogorov-Smirnoff statistic suggest that the Alpine fold-thrust belt south of the foreland was also an important source of detritus to the deep-water Molasse basin. We interpret evolving detrital zircon age distributions within the axial foredeep to reflect a progressive increase in longitudinal sediment input from the west (Freshwater Molasse) and/or southwest (Inntal fault zone) relative to transverse sediment input from the fold-thrust belt to the south. We infer that these changes reflect a major reorganization of catchment boundaries and denudation rates in the Alpine Orogen that resulted in the Alpine foreland evolving to dominantly longitudinal sediment dispersal. This change was most notably marked by the development of a submarine canyon during deposition of the Upper Puchkirchen Formation that promoted sediment bypass eastward from Freshwater Molasse depozones to the Molasse basin deep-water axial channel belt. The integration of 3D seismic-reflection data with detrital zircon geochronology illustrates sediment dispersal patterns within a continental-scale orogen, with implications for the relative role of longitudinal versus transverse sediment delivery in peripheral foreland basins. This article is protected by copyright. All rights reserved.

Background Glyoxalase 1 (GLO1) is an enzyme involved in removal of toxic byproducts accumulating during glycolysis from the cell. GLO1 is up regulated in many cancer types but its role in prostate cancer is largely unknown. Methods Here, we employed GLO1 immunohistochemistry on a tissue microarray including 11 152 tumors and an attached clinical and molecular database. Results Normal prostate epithelium was negative for GLO1, whereas 2059 (27.3%) of 7552 interpretable cancers showed cytoplasmic GLO1 staining, which was considered weak in 8.8%, moderate in 12.5%, and strong in 6.1% of tumors. Up regulation of GLO1 was significantly linked to high original Gleason grade, advanced pathological tumor stage and positive lymph node status (P

To investigate its susceptibility to ergot infection, we inoculated Brachypodium distachyon with Claviceps purpurea and compared the infection symptoms with those on rye (Secale cereale). We showed that, after inoculation of Brachypodium with Claviceps, the same disease symptoms occurred in comparable temporal and spatial patterns to those on rye. The infection rate of Claviceps on this host was reduced compared with rye, but the disease could be surveyed by fungal genomic DNA quantification. Mutants of Claviceps which were virulence attenuated on rye were also affected on Brachypodium. We were able to show that pathogenesis‐related gene expression changed in a typical manner for biotrophic pathogen attack. Our results indicated that the Claviceps–Brachypodium interaction was dependent on salicylic acid, cytokinin and auxin. We consider Brachypodium to be a suitable and useful alternative host; the increased sensitivity compared with rye will be valuable for the identification of infection mechanisms. Future progess in understanding the Claviceps–plant interaction will be facilitated by the use of a well‐characterized model host system.

Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20.2%, moderate in 36.7%, and strong in 33.4% of cancers. Strong APE1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (52.9%) than in ERG-negative cancers (19.1%, P

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) and other psychotropics are receiving increasing attention due to reports on inhibition of thrombocyte function and an increased bleeding risk in surgical settings. Studies in total hip and total knee arthroplasty (THA and TKA, respectively) have shown conflicting results, questioning whether the potential increased bleeding risk is of clinical importance. STUDY DESIGN AND METHODS Prospective consecutive collection of data on preoperative comorbidity in patients undergoing primary unilateral THA or TKA was cross-referenced with regional transfusion databases and The Danish National Database of Reimbursed Prescriptions for information regarding blood transfusions and psychopharmacologic treatment. All participating orthopedic centers followed similar perioperative guidelines. Multiple logistic regression analysis was applied to calculate odds ratios (ORs) for transfusion between preoperative users and nonusers of psychotropics. RESULTS Of 8402 patients, 569 (6.8%) were SSRI users versus 7833 (93.2%) nonusers. A total of 109 (19,2%) patients in the SSRI group and 700 (8.9%) in the “no-SSRI” group received blood intra- or postoperatively. Preoperative SSRI treatment was a risk factor for perioperative transfusion (OR, 1.98; 95% confidence interval [CI], 1.44-2.70). Other antidepressants (OAs) were associated with an increased risk of transfusion (OR, 1.69; 95% CI, 1.17-2.44) as well as the combination of SSRIs and OAs (OR, 3.31; 95% CI, 1.79-6.13). Singular use of antipsychotics (APs) increased the transfusion risk (OR, 2.37; 95% CI, 1.04-2.41), while AP medicine in combination with antidepressants did not. CONCLUSIONS Preoperative treatment with SSRIs, OAs, or APs are independent risk factors for blood transfusion in elective fast-track THA and TKA.

Summary Disease symptoms of some phytopathogenic fungi are associated with changes in cytokinin (CK) levels. Here, we show that the CK profile of ergot-infected rye plants is also altered, although no pronounced changes occur in the expression of the host plant's CK biosynthesis genes. Instead, we demonstrate a clearly different mechanism: we report on the first fungal de novo CK biosynthesis genes, prove their functions and constitute a biosynthetic pathway. The ergot fungus Claviceps purpurea produces substantial quantities of CKs in culture and, like plants, expresses enzymes containing the isopentenyltransferase and lonely guy domains necessary for de novo isopentenyladenine production. Uniquely, two of these domains are combined in one bifunctional enzyme, CpIPT-LOG, depicting a novel and potent mechanism for CK production. The fungus also forms trans-zeatin, a reaction catalysed by a CK-specific cytochrome P450 monooxygenase, which is encoded by cpp450 forming a small cluster with cpipt-log. Deletion of cpipt-log and cpp450 did not affect virulence of the fungus, but Δcpp450 mutants exhibit a hyper-sporulating phenotype, implying that CKs are environmental factors influencing fungal development.

Background and Objective Cyclin D1 is an important regulator protein for the G1-S cell cycle phase transition. The aim of this trial was to evaluate the impact of the CCND1 polymorphism G870A and corresponding protein expression and CCND1 amplification on the survival of the patients. Methods 425 patients with ductal pancreatic adenocarcinoma who underwent resection were included after histopathological confirmation. DNA was analyzed for Cyclin D1 polymorphisms, immunhistochemical examination and fluorescence in situ hybridization analysis of the tumor were performed. Results Overall, the mean survival was 22.9 months (20.5–25.3). The survival in patients with Cyclin D1 G870A polymorphism Adenine/Adenine was 15.1 months (95% CI 11.3–18.9), 21.5 months (17.4–25.6) for Adenine/Guanine, and 29.4 months (95% CI 23.8–35.0) for Guanine/Guanine (P = 0.003). A shorter survival was associated with strong/moderate protein expression in immunohistochemistry (IHC) compared to weak/no expression (P = 0.028). Additionally, a significant coherency between unfavourable polymorphism (AA/AG) and increased protein expression was detected (P = 0.005). Conclusions A strong impact on survival of Cyclin D1 G870A polymorphism and the detected corresponding protein expression was found. The biological mechanism of CCND1 in carcinogenesis has not been fully examined; but at present Cyclin D1 seems to be an interesting biomarker for the prognosis of ductal adenocarcinoma. J. Surg. Oncol. 2015 111:316–323. © 2014 Wiley Periodicals, Inc.

A growing interest in the use of naturally produced pigments for textile dyeing has led to increased efforts towards the identification of such pigments that are less toxic, more sustainable, and more stable over time than currently used synthetic compounds. This work utilised various concentrations of green, red, and yellow pigments extracted with dichloromethane from the wood-staining fungi Chlorociboria aeruginosa, Scytalidium cuboideum, and S. ganodermophthorum, respectively, for the effective dyeing of bleached cotton, spun polyamide (nylon 6.6), spun polyester (Dacron 54), spun polyacrylic, and worsted wool. All three pigments utilised in this study show significant potential for use as textile dyes. Colour changes suggested that drip application methods were superior to submersion using dichloromethane. Colour changes as compared with the untreated fabrics were most significant on polyester, which is likely due to increased levels of polymer swelling in polyester exposed to dichloromethane.

Users are the primary source of new techniques, i.e. systematic activities by which a complex task is accomplished. Even though user-generated techniques are a pervasive phenomenon which can be observed in many different contexts, existing research on user innovation has focused on product and service innovations. We focus on this important area of user innovation by studying four cases in the field of medical devices to analyse the processes by which users generate and diffuse new techniques as well as the interdependencies between user-generated techniques and subsequent changes to product use and product innovation. Our findings suggest that user innovation in techniques triggers product innovation by users and manufacturers. Therefore, users' contributions to total innovation output are much higher than previously considered. Additionally, the diffusion of techniques differs significantly from the diffusion of new products. It can only be achieved with the involvement of diffusion agents and their interpersonal interaction and joint performance of the technique with possible adopters. As the diffusion of a technique is often a prerequisite for the diffusion of any related product, companies are forced to re-think their marketing strategies.

Recently, the first commercial dye solar cell (DSC) products based on the mesoscopic principle were successfully launched. Introduction to the market has been accompanied by a strong increase in patent applications in the field during the last four years, which is a good indication of further commercialization activity. Materials and cell concepts have been developed to such extent that easy uptake by industrial manufacturers is possible. The critical phase for broad market acceptance has therefore been reached, which implies focusing on standardization-related research topics. In parallel the number of scientific publications on DSC is growing further (>3500 since 2012), and the range of new or renewed fundamental topics is broadening. A recent example is the introduction of the perovskite mesoscopic cell, for which an efficiency of 14.1 % has been certified. Thus, a growing divergence between market introduction and research could be the consequence. Herein, an attempt is made to show that such an unwanted divergence can be prevented, for example, by developing suitable reference-type cell and module concepts as well as manufacturing routes. An in situ cell manufacturing concept that can be applied to mesoscopic-based solar cells in a broader sense is proposed. As a guideline for future module concepts, recent results for large-area, glass-frit-sealed DSC modules from efficiency studies (6.6 % active-area efficiency) and outdoor analysis are discussed. Electroluminescence measurements are introduced as a quality tool. Another important point that is addressed is sustainability, which affects both market introduction and the direction of fundamental research.

Twelve solvents were tested for their ability to extract the pigments of Chlorociboria aeruginosa and Scytalidium cuboideum, two fungi used primarily for the spalting of decorative wood. Solvents were assessed on the basis of the saturation of pigment produced, their ability to diffuse through filter paper, and whether they reacted with the extracted pigments. Solvents that performed well in extraction testing were then tested to determine whether they could also dissolve the extracted pigment once dried. Of the solvents tested, only dichloromethane was capable of quick, non-reactive extraction with filter paper diffusion, as well as being able fully to redissolve dried pigment extracted from C. aeruginosa. The results of this study show dichloromethane to be an ideal solvent for extracting and applying fungal pigments that offers new possibilities for spalting in which fungi do not need to be grown directly on a substrate in order to produce pigmented wood.

Organizations are frequently turning to social Internet applications in an effort to form bonds with consumers. However, little research has addressed the impact of social Internet consumption on the individual. Two studies of regular social Internet consumers (i.e., users of Facebook and socially connected online games) examined the effects of prompted usage reduction or cessation upon participants. In both studies, participants benefitted on average during the reduction/cessation period, reporting increased life satisfaction and decreased procrastination. The Facebooker versus gamer factor had remarkably few effects (i.e., results generalized across these two groups). Implications are discussed for both consumers and organizations involved in social Internet activities. Copyright © 2013 John Wiley & Sons, Ltd.