Relative judgement is relatively difficult: evidence against the role of relative judgement in absolute identification

A variety of processes have been put forward to explain absolute identification performance. One difference between current models of absolute identification is the extent to which the task involves accessing stored representations in long-term memory (e.g. exemplars in memory, Kent & Lamberts, Journal of Experimental Psychology: Learning Memory and Cognition, 31, 289–305, 2005) or relative judgement (comparison of the current stimulus to the stimulus on the previous trial, Stewart, Brown & Chater, Psychological Review, 112, 881–911, 2005). In two experiments we explored this by tapping into these processes. In Experiment 1 participants completed an absolute identification task using eight line lengths whereby a single stimulus was presented on each trial for identification. They also completed a matching task aimed at mirroring exemplar comparison in which eight line lengths were presented in a circular array and the task was to report which of these matched a target presented centrally. Experiment 2 was a relative judgement task and was similar to Experiment 1 except that the task was to report the difference (jump-size) between the current stimulus and that on the previous trial. The absolute identification and matching data showed clear similarities (faster and more accurate responding for stimuli near the edges of the range and similar stimulus-response confusions). In contrast, relative judgment performance was poor suggesting relative judgement is not straightforward. Moreover, performance as a function of jump-size differed considerably between the relative judgement and absolute identification tasks. Similarly, in the relative judgement task, predicting correct stimulus identification based on successful relative judgement yielded the reverse pattern of performance observed in the absolute identification task. Overall, the data suggest that relative judgement does not underlie absolute identification and that the task is more likely reliant on an exemplar comparison process

A new method for measuring torsional deformity in scoliosis

<p>Abstract</p> <p>Background</p> <p>The importance of spinal rotational and torsional deformity in the etiology and the management of scoliosis are well-recognized. For measuring the posterior spinal component rotation, Ho's method was reported to be reliable. However, there is no practical method to measure the anterior spinal component rotation. Moreover, there is also no method to quantify the spinal torsional deformity in scoliosis. The goal of this study is to characterize scoliosis and its deformity to hypothesize the etiology and the development of scoliosis, and to establish a new method for the measurement of the vertebral body rotation and spinal torsional deformity in scoliosis using CT scans.</p> <p>Methods</p> <p>Pre-operative CT scans of 25 non-congenital scoliosis patients were recruited and the apical vertebral rotation was measured by a newly developed method and Ho's method. Ho's method adopts the laminae as the rotational landmark. For a new method to measure the apical vertebral rotation, the posterior point just beneath each pedicle was used as a landmark. For quantifying the spinal torsional deformity angle, the rotational angle difference between the two methods was calculated.</p> <p>Results</p> <p>Intraobserver and interobserver reliability analyses showed both methods to be reliable. Apical vertebral rotation revealed 13.9 ± 6.8 (mean ± standard deviation) degrees by the new method and 7.9 ± 6.3 by Ho's method. Right spinal rotation was assigned a positive value. The discrepancy of rotation (6.1 ± 3.9 degrees), meaning that the anterior component rotated more than the posterior component, was considered to express the spinal torsional deformity to the convex side.</p> <p>Conclusions</p> <p>We have developed an easy, reliable and practical method to measure the rotation of the spinal anterior component using a CT scan. Furthermore, we quantified the spinal torsional deformity to the convex side in scoliosis by comparing the rotation between the anterior and posterior components.</p

NOX4-dependent ROS production by stromal mammary cells modulates epithelial MCF-7 cell migration

BACKGROUND: The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated. Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy. It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility. METHODS: We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked down the expression of NOX4 using siRNA strategy. The effect of TGF-b1 on NOX4 expression and activity was analysed by qPCR, and intracellular ROS production was measured by a fluorescent method. RESULTS: Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-b1 enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-b1 seems to be a major component of the epithelial soluble factors that stimulate NOX4 expression. CONCLUSIONS: Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4 expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among which TGF-b1 have a decisive role.This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile

Elevated Expression of Stromal Palladin Predicts Poor Clinical Outcome in Renal Cell Carcinoma

The role that stromal renal cell carcinoma (RCC) plays in support of tumor progression is unclear. Here we sought to determine the predictive value on patient survival of several markers of stromal activation and the feasibility of a fibroblast-derived extracellular matrix (ECM) based three-dimensional (3D) culture stemming from clinical specimens to recapitulate stromal behavior in vitro. The clinical relevance of selected stromal markers was assessed using a well annotated tumor microarray where stromal-marker levels of expression were evaluated and compared to patient outcomes. Also, an in vitro 3D system derived from fibroblasts harvested from patient matched normal kidney, primary RCC and metastatic tumors was employed to evaluate levels and localizations of known stromal markers such as the actin binding proteins palladin, alpha-smooth muscle actin (α-SMA), fibronectin and its spliced form EDA. Results suggested that RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis, as demonstrated by overall survival time. Conversely, cases of RCCs where stroma presents low levels of palladin expression indicate increased survival times and, hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the categorization of stromal RCCs into discrete progressive stromal stages, also show increased levels of expression and stress fiber localization of α-SMA and palladin, as well as topographical organization of fibronectin and its splice variant EDA. These observations are concordant with expression levels of these markers in vivo. The study proposes that palladin constitutes a useful marker of poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately represent the specific patient's tumor-associated stromal compartment. Our observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC-associated stroma and stroma-dependent mechanisms affecting tumorigenesis. The clinical value of assessing RCC stromal activation merits further study

50 years experience with Dupuytren's contracture in the Erlangen University Hospital – A retrospective analysis of 2919 operated hands from 1956 to 2006

<p>Abstract</p> <p>Background</p> <p>Dupuytren's disease (DD) is a hand disorder mainly among the northern population. In contrast it is rare in the mediterranean population. Therefore typical habits and dietetic influences have been discussed as well as genetic predisposition. Still, since the first description by Dupuytren in 1834 only little is known about the etiology and pathogenesis of this disease. Some hints were found for a higher prevalence among people with diabetes, alcohol abuse or smoking. Also, intensive manual work or hand injuries have been discussed to have an influence on DD. To our knowledge this is the largest retrospectively evaluated series of symptomatic patients published to date. The study includes patients from the last 50 years. It was performed to show possible correlations between DD and typical risk factors such as diabetes, alcohol consumption, and smoking.</p> <p>Methods</p> <p>We retrospectively analysed all patient records with DD documented between 1956 and 2006 in the Surgical University Hospital in Erlangen. Data acquisition was conducted by reviewing the medical records from 1956 to 2006 including data from all patients who were surgically treated because of DD.</p> <p>Results</p> <p>We reviewed 2579 male and 340 female surgically treated patients with DD. More than 80% of the patients were between 40 and 70 years old. In 28.9% only the right hand was effected by DD, in 25.3% only the left hand and in 45.8% both hands. In 10.3% of all Patients suffered from Diabetes mellitus. Statistical analysis revealed no significant correlation between diabetes, alcoholism or smoking on the degree of DD in our patients.</p> <p>Conclusion</p> <p>Most data are consistent with previously published results from smaller, comparable retrospective studies with regard to right- or left handedness. We could not confirm a statistically significant correlation of DD with diabetes mellitus, severe alcohol consumption, heavy smoking or epilepsy and the stage of the disease as described in other studies. However, in the whole cohort of our operated patients during the last 50 years the prevalence of the above mentioned risk factors is slightly higher than in the normal population.</p

Evidence for Epithelial-Mesenchymal Transition in Cancer Stem Cells of Head and Neck Squamous Cell Carcinoma

Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC) have been related to the behavior of cancer stem cells (CSC) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1+ cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC) and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF) Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1+ cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44+/CD24− was highly variable (0.5% to 96%) in monolayer and spheroid cultures and overlapped in 0%–33% with the CD44+/CD24−/ALDH1+ cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis

Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A

Background The pattern of gene transcripts in the yeast Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. In S. cerevisiae three genes, TPK1, TPK2, and TPK3, encode catalytic subunits of PKA. The lack of viability of tpk1 tpk2 tpk3 triple mutants may be suppressed by mutations such as yak1 or msn2/msn4. To investigate the requirement for PKA in glucose control of gene expression, we have compared the effects of glucose on global transcription in a wild-type strain and in two strains devoid of PKA activity, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4. Results We have identified different classes of genes that can be induced -or repressed- by glucose in the absence of PKA. Representative examples are genes required for glucose utilization and genes involved in the metabolism of other carbon sources, respectively. Among the genes responding to glucose in strains devoid of PKA some are also controlled by a redundant signalling pathway involving PKA activation, while others are not affected when PKA is activated through an increase in cAMP concentration. On the other hand, among genes that do not respond to glucose in the absence of PKA, some give a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways. We show also that, for a number of genes controlled by glucose through a PKA-dependent pathway, the changes in mRNA levels are transient. We found that, in cells grown in gluconeogenic conditions, expression of a small number of genes, mainly connected with the response to stress, is reduced in the strains lacking PKA. Conclusions In S. cerevisiae, the transcriptional responses to glucose are triggered by a variety of pathways, alone or in combination, in which PKA is often involved. Redundant signalling pathways confer a greater robustness to the response to glucose, while cooperative pathways provide a greater flexibility.BT/BiotechnologyApplied Science

Collagen density promotes mammary tumor initiation and progression

<p>Abstract</p> <p>Background</p> <p>Mammographically dense breast tissue is one of the greatest risk factors for developing breast carcinoma. Despite the strong clinical correlation, breast density has not been causally linked to tumorigenesis, largely because no animal model has existed for studying breast tissue density. Importantly, regions of high breast density are associated with increased stromal collagen. Thus, the influence of the extracellular matrix on breast carcinoma development and the underlying molecular mechanisms are not understood.</p> <p>Methods</p> <p>To study the effects of collagen density on mammary tumor formation and progression, we utilized a bi-transgenic tumor model with increased stromal collagen in mouse mammary tissue. Imaging of the tumors and tumor-stromal interface in live tumor tissue was performed with multiphoton laser-scanning microscopy to generate multiphoton excitation and spectrally resolved fluorescent lifetimes of endogenous fluorophores. Second harmonic generation was utilized to image stromal collagen.</p> <p>Results</p> <p>Herein we demonstrate that increased stromal collagen in mouse mammary tissue significantly increases tumor formation approximately three-fold (<it>p </it>< 0.00001) and results in a significantly more invasive phenotype with approximately three times more lung metastasis (<it>p </it>< 0.05). Furthermore, the increased invasive phenotype of tumor cells that arose within collagen-dense mammary tissues remains after tumor explants are cultured within reconstituted three-dimensional collagen gels. To better understand this behavior we imaged live tumors using nonlinear optical imaging approaches to demonstrate that local invasion is facilitated by stromal collagen re-organization and that this behavior is significantly increased in collagen-dense tissues. In addition, using multiphoton fluorescence and spectral lifetime imaging we identify a metabolic signature for flavin adenine dinucleotide, with increased fluorescent intensity and lifetime, in invading metastatic cells.</p> <p>Conclusion</p> <p>This study provides the first data causally linking increased stromal collagen to mammary tumor formation and metastasis, and demonstrates that fundamental differences arise and persist in epithelial tumor cells that progressed within collagen-dense microenvironments. Furthermore, the imaging techniques and signature identified in this work may provide useful diagnostic tools to rapidly assess fresh tissue biopsies.</p

Cancer-Stromal Cell Interaction and Tumor Angiogenesis in Gastric Cancer

Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interaction contributes functionally to tumor growth and metastasis. Angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, and platelet-derived endothelial cell growth factor. The microenvironment in the gastric mucosa may also influence the angiogenic phenotype of gastric cancer. Helicobacter pylori infection increases expression of several angiogenic factors by tumor cells. Activated fibroblasts and macrophages in tumor stroma also play an important role in angiogenesis and tumor progression. We review the current understanding of cancer-stromal cell interaction as it pertains to tumor angiogenesis in gastric cancer