Orienting Attention Based on Long-Term Memory Improves Perceptual Discriminations

The role of attentional orienting in daily life is to selectively deploy both behavioural and neural resources towards events, based on continually changing task goals and expectations, in order to optimize performance. In the following experiment, we show that attentional orienting is influenced by long-term memories in a perceptual discrimination task. In the learning phase, participants were trained on 120 ecologically valid natural scenes, of which 80 contained a target. Their task was to locate the target (a small key) on the screen by clicking on it with the mouse. One or two days later, participants completed a cued perceptual discrimination task. The same scenes that were studied before, but without any targets, were presented as cues (50 ms duration), followed, after a delay (450ms), by the scene again with or without the target (200ms). Participants discriminated covertly whether the key was present or absent from the second scene. There were three conditions: valid (key in learning and discrimination task was in same location), invalid (key in learning and discrimination task were in different location) and neutral (there was no key in learning phase). Behavioural results indicated that memory-guided attention benefits both the sensitivity (d’) and speed of target identification within natural scenes. A replication of the study is being carried out with event-related potentials to chart the neural modulations that accompany the perceptual enhancements observed behaviourally

Potential L-Type Voltage-Operated Calcium Channel Blocking Effect of Drotaverine on Functional Models

Drotaverine is considered as an inhibitor of cyclic-3′,5′-nucleotide-phophodiesterase (PDE) enzymes. However, published receptor binding data supports the potential Ltype Voltage Operated Calcium Channel (L-VOCC) blocking effect of drotaverine too. Hence, in this work we are focusing on the potential L-VOCC blocking effect of drotaverine using L-VOCC associated functional in vitro models. Accordingly, drotaverine and reference agents were tested on KCl-induced guinea pig tracheal contraction. It was found that drotaverine, like the L-VOCC blockers nifedipine or diltiazem, inhibited the KCl-induced inward Ca2+- induced contraction in a concentration dependent fashion. The PDE-inhibitor theophylline had no effect on the KCl-evoked contractions indicating its lack of inhibition on inward Ca2+ flow. Drotaverine was also tested on the L-VOCC mediated resting Ca2+ refill model. In this model the extracellular Ca2+ enters the cells to replenish the emptied intracellular Ca2+ stores. Drotaverine and L-VOCC blocker reference molecules inhibited the Ca2+ replenishment of Ca2+ depleted preparations detected by agonist-induced contractions in post Ca2+ replenishment Ca2+ free medium. Theophylline didn’t modify the Ca2+ store replenishment following contraction. It seems that drotaverine but not theophylline inhibit the inward Ca2+ flux. Addition of CaCl2 to Ca2+ free medium containing the agonist, induced inward Ca2+ flow and subsequent contraction of Ca2+ depleted tracheal preparations. Drotaverine similar to the L-VOCC blockers, inhibited inward Ca2+ flow and blunted the slope of CaCl2-induced contraction in agonist containing Ca2+ free medium withCa2+ depleted tracheal preparations. These results show that drotaverine behaves like L-VOCC blockers but unlike PDE inhibitors using L-VOCC associated in vitro experimental models

Leiomyosarcoma of the skin with osteoclast-like giant cells: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteoclast-like giant cells have been noted in various malignant tumors, such as, carcinomas of pancreas and liver and leiomyosarcomas of non-cutaneous locations, such as, uterus and rectum. We were unable to find any reported case of a leiomyosarcoma of the skin where osteoclast-like giant cells were present in the tumor.</p> <p>Case presentation</p> <p>We report a case of a 59-year-old woman with a cutaneous leiomyosarcoma associated with osteoclast-like giant cells arising from the subcutaneous artery of the leg. The nature of the giant cells is discussed in light of the findings from the immunostaining as well as survey of the literature.</p> <p>Conclusion</p> <p>A rare case of cutaneous leiomyosarcoma with osteoclast-like giant cells is reported. The giant cells in the tumor appear to be reactive histiocytic cells.</p

Bridging the GUI gap with reactive values and relations

There are at present two ways to write GUIs for functional code. One is to use standard GUI toolkits, with all the benefits they bring in terms of feature completeness, choice of platform, conformance to platform-specific look-and-feel, long-term viability, etc. However, such GUI APIs mandate an imperative programming style for the GUI and related parts of the application. Alternatively, we can use a functional GUI toolkit. The GUI can then be written in a functional style, but at the cost of foregoing many advantages of standard toolkits that often will be of critical importance. This paper introduces a light-weight framework structured around the notions of reactive values and reactive relations . It allows standard toolkits to be used from functional code written in a functional style. We thus bridge the gap between the two worlds, bringing the advantages of both to the developer. Our framework is available on Hackage and has been been validated through the development of non-trivial applications in a commercial context, and with different standard GUI toolkits

Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory

Sport and British Jewish identity

This article examines the relationship between sport and Jewish identity. The experiences of Jewish people have rarely been considered in previous sport-related research which has typically focused on ‘Black’ and South Asian individuals, sports clubs, and organisations. Drawing on data generated from interviews ( n = 20) and focus groups ( n = 2) with individuals based in one British city, this article explores how their Jewish identity was informed, and shaped by, different sports activities and spaces. This study’s participants were quick to correct the idea that sport was alien to Jewish culture and did not accept the stereotype that ‘Jews don’t play sport’. The limited historical research on sport and Jewish people and the ongoing debates around Jewish identity are noted before exploring the role of religion and the suggestion that Jewish participation in sport is affected by the Shabbat (sabbath). Participants discussed how sports clubs acted as spaces for the expression and re/affirmation of their Jewish identity, before they reflected on the threats posed to the wider Jewish community by secularism, assimilation, and antisemitism. The article concludes by discussing how the sporting experiences of the study’s British Jewish participants compare with the experiences of individuals from other ethnic minority communities

Hippocampal and retrosplenial goal distance coding after long-term consolidation of a real-world environment

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and imperial College London students navigated virtual simulations of their own familiar campus (> 2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation

Myofibroblast-Derived SFRP1 as Potential Inhibitor of Colorectal Carcinoma Field Effect

Epigenetic changes of stromal-epithelial interactions are of key importance in the regulation of colorectal carcinoma (CRC) cells and morphologically normal, but genetically and epigenetically altered epithelium in normal adjacent tumor (NAT) areas. Here we demonstrated retained protein expression of well-known Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) in stromal myofibroblasts and decreasing epithelial expression from NAT tissues towards the tumor. SFRP1 was unmethylated in laser microdissected myofibroblasts and partially hypermethylated in epithelial cells in these areas. In contrast, we found epigenetically silenced myofibroblast-derived SFRP1 in CRC stroma. Our results suggest that the myofibroblast-derived SFRP1 protein might be a paracrine inhibitor of epithelial proliferation in NAT areas and loss of this signal may support tumor proliferation in CRC

Response of the neurovascular unit to brain metastatic breast cancer cells

Therapeutic resistance of cerebral secondary tumours largely depends on unique aspects linked to the neurovascular unit, especially cerebral endothelial cells and astrocytes. By using advanced microscopy techniques, here we explored novel mechanisms related to the neurovascular unit during extravasation and proliferation of triple negative breast cancer cells in the brain. Metastatic mammary carcinoma cells arrested and elongated within one hour in cerebral microvessels, but their number decreased by almost 80% in the first two days. Interestingly, malignant cells induced vasoconstriction and development of intraluminal endothelial plugs, which isolated invading cells from the circulation. During diapedesis - which usually took place on day four and five after inoculation of the tumour cells - continuity of cerebral endothelial tight junctions remained intact, indicating migration of cancer cells through the transcellular pathway. In addition, metastatic cells induced formation of multiluminal vessels and claudin-5-positive endothelial blebs. However, even severe endothelial blebbing could be reversed and the vessel morphology was restored shortly after the tumour cells completed transendothelial migration. Similar to neuro-inflammatory leukocytes, tumour cells migrated not only through the endothelial layer, but through the glia limitans perivascularis as well. Nevertheless, along with the growth of metastatic lesions by co-option of pre-existing capillaries, astrocytes and astrocyte end-feet were gradually expelled from the vessels to the border of the tumour. Taken together, we identified previously unknown mechanisms involved in the reaction of brain resident cells to invading breast cancer cells. Our results contribute to a better understanding of the complex cross-talk between tumour cells and host cells in the brain, which is essential for the identification of new therapeutic targets in this devastating disease