Metanephric adenoma of the kidney: an unusual diagnostic challenge

Although metanephric adenoma (MA) is a rare, benign neoplasm of epithelial cells, it is often difficult to distinguish this entity from other malignant neoplasms preoperatively. We report a case of a large renal mass for which preoperative diagnosis was indeterminate, with the differential diagnosis including Wilm’s tumor, MA, and papillary renal cell carcinoma (PRCC). Accurate postoperative differentiation of MA from PRCC is critical because adjuvant therapy is considered after surgical resection of PRCC tumors

Face or building superiority in peripheral vision reversed by task requirements

Peripheral vision has been the topic of few studies compared with central vision. Nevertheless, given that visual information covers all the visual field and that relevant information can originate from highly eccentric positions, the understanding of peripheral vision abilities for object perception seems essential. The poorer resolution of peripheral vision would first suggest that objects requiring large-scale feature integration such as buildings would be better processed than objects requiring finer analysis such as faces. Nevertheless, task requirements also determine the information (coarse or fine) necessary for a given object to be processed. We therefore investigated how task and eccentricity modulate object processing in peripheral vision. Three experiments were carried out requiring finer or coarser information processing of faces and buildings presented in central and peripheral vision. Our results showed that buildings were better judged as identical or familiar in periphery whilst faces were better categorised. We conclude that this superiority for a given stimulus in peripheral vision results (a) from the available information, which depends on the decrease of resolution with eccentricity, and (b) from the useful information, which depends on both the task and the semantic category

Innovating together for just and green urban transitions: Stories from Urban ReLeaf Cities

Nature-based solutions in urban environments can provide cooling effects, decrease air pollution, and improve mental health, amongst others important ecosystem services and health-related benefits. Ambitious plans, such as the pledge to plant 3 billion trees in the EU, the European Green Deal, or the Green City Accord support this direction. Their implementation, however, requires transformative changes on the ground to overcome business as usual approaches. The Urban ReLeaf project delivers change by bringing public authorities and citizen groups together to shape green infrastructure actions in their cities. Six pilot cities co-create citizen-centric innovations for the democratisation of urban greenspace monitoring and the wider policy making process in pursuit of urban climate resilience. This poster showcases the stories of the six cities and their approaches to participatory, and data-driven decision making. Athens is undergoing a greening transformation with a new, citizen-powered tree registry providing critical data for better management of greenspaces. Cascais engages citizens in sharing perceptions and thermal comfort levels while using greenspaces to validate the effectiveness of its parks. Meanwhile in Dundee, a city facing increasing grey infrastructure in deprived areas, actions to enhance the accessibility of greenspaces are co-developed with citizens and stakeholders. Mannheim has a heat action plan to safeguard its most vulnerable residents but has identified critical data gaps. Citizen observations of trees and thermal comfort, when integrated with official data streams, will aid the delivery of climate adaptation measures. Riga engages diverse audiences to address concerns about air pollution and greenspace usage, to ensure better informed policies. Finally, in Utrecht, data on temperature, humidity and heat stress, collected by and for citizens, will help them reduce the urban heat island effect and shape effective mitigation strategies

Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

<p>Abstract</p> <p>Background</p> <p>Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis.</p> <p>Methods</p> <p>To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the <it>in vitro </it>effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression.</p> <p>Results</p> <p>In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs.</p> <p>Conclusions</p> <p>These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.</p

A Novel Gene Signature for Molecular Diagnosis of Human Prostate Cancer by RT-qPCR

Prostate cancer (CaP) is one of the most relevant causes of cancer death in Western Countries. Although detection of CaP at early curable stage is highly desirable, actual screening methods present limitations and new molecular approaches are needed. Gene expression analysis increases our knowledge about the biology of CaP and may render novel molecular tools, but the identification of accurate biomarkers for reliable molecular diagnosis is a real challenge. We describe here the diagnostic power of a novel 8-genes signature: ornithine decarboxylase (ODC), ornithine decarboxylase antizyme (OAZ), adenosylmethionine decarboxylase (AdoMetDC), spermidine/spermine N(1)-acetyltransferase (SSAT), histone H3 (H3), growth arrest specific gene (GAS1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and Clusterin (CLU) in tumour detection/classification of human CaP. METHODOLOGY/PRINCIPAL FINDINGS: The 8-gene signature was detected by retrotranscription real-time quantitative PCR (RT-qPCR) in frozen prostate surgical specimens obtained from 41 patients diagnosed with CaP and recommended to undergo radical prostatectomy (RP). No therapy was given to patients at any time before RP. The bio-bank used for the study consisted of 66 specimens: 44 were benign-CaP paired from the same patient. Thirty-five were classified as benign and 31 as CaP after final pathological examination. Only molecular data were used for classification of specimens. The Nearest Neighbour (NN) classifier was used in order to discriminate CaP from benign tissue. Validation of final results was obtained with 10-fold cross-validation procedure. CaP versus benign specimens were discriminated with (80+/-5)% accuracy, (81+/-6)% sensitivity and (78+/-7)% specificity. The method also correctly classified 71% of patients with Gleason score&lt;7 versus &gt; or =7, an important predictor of final outcome. CONCLUSIONS/SIGNIFICANCE: The method showed high sensitivity in a collection of specimens in which a significant portion of the total (13/31, equal to 42%) was considered CaP on the basis of having less than 15% of cancer cells. This result supports the notion of the "cancer field effect", in which transformed cells extend beyond morphologically evident tumour. The molecular diagnosis method here described is objective and less subjected to human error. Although further confirmations are needed, this method poses the potential to enhance conventional diagnosis

Neuro-cognitive mechanisms of conscious and unconscious visual perception: From a plethora of phenomena to general principles

Psychological and neuroscience approaches have promoted much progress in elucidating the cognitive and neural mechanisms that underlie phenomenal visual awareness during the last decades. In this article, we provide an overview of the latest research investigating important phenomena in conscious and unconscious vision. We identify general principles to characterize conscious and unconscious visual perception, which may serve as important building blocks for a unified model to explain the plethora of findings. We argue that in particular the integration of principles from both conscious and unconscious vision is advantageous and provides critical constraints for developing adequate theoretical models. Based on the principles identified in our review, we outline essential components of a unified model of conscious and unconscious visual perception. We propose that awareness refers to consolidated visual representations, which are accessible to the entire brain and therefore globally available. However, visual awareness not only depends on consolidation within the visual system, but is additionally the result of a post-sensory gating process, which is mediated by higher-level cognitive control mechanisms. We further propose that amplification of visual representations by attentional sensitization is not exclusive to the domain of conscious perception, but also applies to visual stimuli, which remain unconscious. Conscious and unconscious processing modes are highly interdependent with influences in both directions. We therefore argue that exactly this interdependence renders a unified model of conscious and unconscious visual perception valuable. Computational modeling jointly with focused experimental research could lead to a better understanding of the plethora of empirical phenomena in consciousness research

Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm

Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechanism involving ECM cleavage. The murine serine protease inhibitor, Serpina3n (SA3N), is an extracellular inhibitor of GZMB. In the present study, administration of SA3N was assessed using a mouse Angiotensin II-induced AAA model. Mice were injected with SA3N (0–120 μg/kg) before pump implantation. A significant dose-dependent reduction in the frequency of aortic rupture and death was observed in mice that received SA3N treatment compared with controls. Reduced degradation of the proteoglycan decorin was observed while collagen density was increased in the aortas of mice receiving SA3N treatment compared with controls. In vitro studies confirmed that decorin, which regulates collagen spacing and fibrillogenesis, is cleaved by GZMB and that its cleavage can be prevented by SA3N. In conclusion, SA3N inhibits GZMB-mediated decorin degradation leading to enhanced collagen remodelling and reinforcement of the adventitia, thereby reducing the overall rate of rupture and death in a mouse model of AAA

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations

CMS physics technical design report : Addendum on high density QCD with heavy ions

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