Regional gray matter correlates of vocational interests.

BackgroundPrevious studies have identified brain areas related to cognitive abilities and personality, respectively. In this exploratory study, we extend the application of modern neuroimaging techniques to another area of individual differences, vocational interests, and relate the results to an earlier study of cognitive abilities salient for vocations.FindingsFirst, we examined the psychometric relationships between vocational interests and abilities in a large sample. The primary relationships between those domains were between Investigative (scientific) interests and general intelligence and between Realistic ("blue-collar") interests and spatial ability. Then, using MRI and voxel-based morphometry, we investigated the relationships between regional gray matter volume and vocational interests. Specific clusters of gray matter were found to be correlated with Investigative and Realistic interests. Overlap analyses indicated some common brain areas between the correlates of Investigative interests and general intelligence and between the correlates of Realistic interests and spatial ability.ConclusionsTwo of six vocational-interest scales show substantial relationships with regional gray matter volume. The overlap between the brain correlates of these scales and cognitive-ability factors suggest there are relationships between individual differences in brain structure and vocations

Proficient brain for optimal performance: the MAP model perspective

Background. The main goal of the present study was to explore theta and alpha event-related desynchronization/synchronization (ERD/ERS) activity during shooting performance. We adopted the idiosyncratic framework of the multi-action plan (MAP) model to investigate different processing modes underpinning four types of performance. In particular, we were interested in examining the neural activity associated with optimal-automated (Type 1) and optimal-controlled (Type 2) performances. Methods. Ten elite shooters (6 male and 4 female) with extensive international experience participated in the study. ERD/ERS analysis was used to investigate cortical dynamics during performance. A 4 × 3 (performance types × time) repeated measures analysis of variance was performed to test the differences among the four types of performance during the three seconds preceding the shots for theta, low alpha, and high alpha frequency bands. The dependent variables were the ERD/ERS percentages in each frequency band (i.e., theta, low alpha, high alpha) for each electrode site across the scalp. This analysis was conducted on 120 shots for each participant in three different frequency bands and the individual data were then averaged. Results. We found ERS to be mainly associated with optimal-automatic performance, in agreement with the “neural efficiency hypothesis.” We also observed more ERD as related to optimal-controlled performance in conditions of “neural adaptability” and proficient use of cortical resources. Discussion. These findings are congruent with the MAP conceptualization of four performance states, in which unique psychophysiological states underlie distinct performance-related experiences. From an applied point of view, our findings suggest that the MAP model can be used as a framework to develop performance enhancement strategies based on cognitive and neurofeedback technique

Epigenetic regulation and role of metastasis suppressor genes in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is distinguished by rapid dissemination. Thus, genetic and/or epigenetic deregulation of metastasis suppressor genes (MSG) is a likely event during early pancreatic carcinogenesis and a potential diagnostic marker for the disease. We investigated 9 known MSGs for their role in the dissemination of PDAC and examined their promoters for methylation and its use in PDAC detection. Methods: MRNA expression of 9 MSGs was determined in 18 PDAC cell lines by quantitative RT-PCR and promoter methylation was analyzed by Methylation Specific PCR and validated by Bisulfite Sequencing PCR. These data were compared to the cell lines’ in vivo metastatic and invasive potential that had been previously established. Statistical analysis was performed with SPSS 20 using 2-tailed Spearman’s correlation with P  0.14). Conclusions: Genes with metastasis suppressing functions in other tumor entities did not show evidence of assuming the same role in PDAC. Inactivation of MSGs by promoter methylation was an infrequent event and unsuitable as a diagnostic marker of PDAC. A distinct methylation pattern was identified, that resulted in reduced mRNA expression in all cases. Thus, constant methylation patterns could predict regulatory significance of a promoter’s methylation prior to expression analysis and hence present an additional tool during target gene selection.<br

MicroRNAs and Their Impact on Radiotherapy for Cancer

Published version made available in accordance with publisher copyright policy.Resistance to radiation is considered to be an important reason for local failure after radiotherapy and tumor recurrence. However, the exact mechanisms of tumor resistance remain poorly understood. Current investigations of microRNAs as potential diagnostic and therapeutic tools for cancer treatment have shown promising results. With respect to radiotherapy resistance and response, there is now emerging evidence that microRNAs modulate key cellular pathways that mediate response to radiation. These data suggest that microRNAs might have significant potential as targets for the development of new therapeutic strategies to overcome radioresistance in cancer. This review summarizes the current literature pertinent to the influence of microRNAs in the response to radiotherapy for cancer treatment, with an emphasis on microRNAs as novel diagnostic and prognostic markers, as well as their potential to alter radiosensitivity

Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Neoadjuvant treatment plays a crucial role in the therapy of advanced esophageal cancer. However, response to radiochemotherapy varies widely. Proton pump inhibitors (PPIs) have been demonstrated to impact on chemotherapy in a variety of other cancers. We analyzed the impact of PPI treatment on esophageal cancer cell lines, and investigated mechanisms that mediate the effect of PPI treatment in this tumour. Methods We investigated the effect of esomeprazole treatment on cancer cell survival, adhesion, migration and chemotherapy in human adeno-(OE19) and squamous-cell-carcinoma (KYSE410) cell lines. Furthermore, we investigated the effect of PPI treatment on intra-/extracellular pH and on expression of resistance-relevant miRNAs. Results Esomeprazole significantly inhibited tumour cell survival (in a dose-dependent manner), adhesion and migration in both tumour subtypes. Furthermore, esomeprazole augmented the cytotoxic effect of cisplatin and 5-FU in both tumour subtypes. Surprisingly, PPI treatment led to a significant increase of intracellular pH and a decrease of the extracellular pH. Finally, we found esomeprazole affected expression of resistance-relevant miRNAs. Specifically, miR-141 and miR-200b were upregulated, whereas miR-376a was downregulated after PPI treatment in both tumour types. Conclusion Our study demonstrates for the first time that PPIs impact on tumour cell survival, metastatic potential and sensitivity towards chemotherapy in esophageal cancer cell lines. Furthermore, we observed that in this tumour entity, PPIs do not lead to intracellular acidification, but affect the expression of resistance-relevant miRNAs. Keywords: Proton pump inhibitor; PPI; Esophageal cancer; Metastasis; Chemotherapy; Resistance; microRN

Circulating microRNAs: emerging biomarkers for diagnosis and prognosis in patients with gastrointestinal cancers

Author version made available in accordance with the publisher's policy. Under embargo for 6 months from time of publication. The final version of record is available at http://www.clinsci.org/cs/128/0001/cs1280001.htmTo identify novel non-invasive biomarkers for improved detection, risk assessment and prognostic evaluation of cancer, expression profiles of circulating microRNAs are currently under evaluation. Circulating microRNAs are highly promising candidates in this context, as they present some key characteristics for cancer biomarkers: they are tissue-specific with reproducible expression and consistency among individuals from the same species, they are potentially derived directly from the tumor and therefore might correlate with tumor progression and recurrence, and they are bound to proteins or contained in sub-cellular particles such as microvesicles or exosomes, making them highly stable and resistant to degradation. This review highlights the origin of circulating microRNAs, their stability in blood samples, and techniques to isolate exosomal microRNAs, and then addresses the current evidence supporting potential clinical applications for circulating miRNAs for diagnostic and prognostic purposes

Concrete Vessel – Pavilion no.1 in China House Vision

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Multivariate risk measures in the non-convex setting

The family of admissible positions in a transaction costs model is a random closed set, which is convex in case of proportional transaction costs. However, the convexity fails, e.g. in case of fixed transaction costs or when only a finite number of transfers are possible. The paper presents an approach to measure risks of such positions based on the idea of considering all selections of the portfolio and checking if one of them is acceptable. Properties and basic examples of risk measures of non-convex portfolios are presented.Comment: 14 pages. Minor revisio

MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma

Background: No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern. Methods: Gemcitabine-resistant variants of two mutant p53 human PDAC cell lines were established. Survival rates were analyzed by cytotoxicity and apoptosis assays. Expression of 1733 human miRs was investigated by microarray and validated by qRT-PCR. After in-silico analysis of specific target genes and proteins of dysregulated miRs, expression of MRP-1, Bcl-2, mutant p53, and CDK1 was quantified by Western blot. Results: Both established PDAC clones showed a significant resistance to gemcitabine (p<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone. Conclusion: Consistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC