Astronomy and Feng Shui in the project of the Tang, Ming and Qing royal mausoleums: a satellite imagery approach

The royal Chinese mausoleums of the Tang, Ming and Qing Chinese dynasties are astounding ensables of monuments, conceived and built to assure to the Emperors immortality in the afterlife and perennial fame on earth. To this aim, a series of cognitive elements were embodied in the funerary landscapes selected for such monuments, including astronomy, general topography, and traditional Chinese geomancy. Taking advantage of satellite imagery, we investigate here on this issue in a general manner. In particular, we develop and apply a rigorous approach to investigate if magnetic compass was used in the planning of such monuments

Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer

Gastric cancer cells often show altered Ras signaling, though the underlying molecular mechanism is not fully understood. We examined the expression profile of eight ras-association domain family (RASSF) genes plus MST1/2 and found that RASSF2A is the most frequently downregulated in gastric cancer. RASSF2A was completely silenced in 6 of 10 gastric cancer cell lines as a result of promoter methylation, and expression was restored by treating the cells with 5-aza-2′-deoxycytidine. Introduction of RASSF2A into non-expressing cell lines suppressed colony formation and induced apoptosis. These effects were associated with the cytoplasmic localization of RASSF2A and morphological changes to the cells. Complementary DNA microarray analysis revealed that RASSF2A suppresses the expression of inflammatory cytokines, which may in turn suppress angiogenesis and invasion. In primary gastric cancers, aberrant methylation of RASSF2A was detected in 23 of 78 (29.5%) cases, and methylation correlated significantly with an absence of the lymphatic invasion, absence of venous invasion, absence of lymph node metastasis, less advanced stages, Epstein–Barr virus, absence of p53 mutations and the presence of the CpG island methylator phenotype-high. These results suggest that epigenetic inactivation of RASSF2A is required for tumorigenesis in a subset of gastric cancers

Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features

Activation of RAS signalling induced by K-ras/BRAF mutations is a hallmark of colorectal tumours. In addition, Ras association domain families 1 and 2 (RASSF1 and RASSF2), the negative regulators of K-ras, are often inactivated by methylation of the promoter region in those tumours. However, reports showing differences in the occurrence of these alterations on the basis of tumour characteristics have been scarce. We analysed K-ras/BRAF mutations and the methylation status of RASSF1 and RASSF2 promoter regions in 120 colorectal adenomas with respect to their clinicopathological features. K-ras/BRAF mutations and RASSF2 methylation were observed in 49 (41%) and 30 (25%) of the samples, respectively, while RASSF1 methylation was observed in only 3 (2.5%). Adenomas with RASSF2 methylation often carried K-ras/BRAF mutations simultaneously (22 out of 30, P<0.01). Multivariate analysis revealed that the concomitance of these alterations was frequently observed in serrated adenomas (odds ratio (OR) 11.11; 95% confidence interval (CI) 1.96–63.00), but rarely in adenomas located in the sigmoid or descending colon (OR 0.13; 95% CI 0.03–0.58). A comparison between adenomas and cancers showed a significantly higher prevalence of these alterations in cancers than in adenomas in the proximal colon (58 vs 27%, P=0.02). Frequency and the time point of the occurrence of Ras signalling disorders differ according to colorectal neoplasia's characteristics, particularly the location

Identification of Vascular and Hematopoietic Genes Downstream of etsrp by Deep Sequencing in Zebrafish

The transcription factor etsrp/Er71/Etv2 is a master control gene for vasculogenesis in all species studied to date. It is also required for hematopoiesis in zebrafish and mice. Several novel genes expressed in vasculature have been identified through transcriptional profiling of zebrafish embryos overexpressing etsrp by microarrays. Here we re-examined this transcriptional profile by Illumina RNA-sequencing technology, revealing a substantially increased number of candidate genes regulated by etsrp. Expression studies of 50 selected candidate genes from this dataset resulted in the identification of 39 new genes that are expressed in vascular cells. Regulation of these genes by etsrp was confirmed by their ectopic induction in etsrp overexpressing and decreased expression in etsrp deficient embryos. Our studies demonstrate the effectiveness of the RNA-sequencing technology to identify biologically relevant genes in zebrfish and produced a comprehensive profile of genes previously unexplored in vascular endothelial cell biology

Genomic loss of the putative tumor suppressor gene E2A in human lymphoma

The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity

Neurocognitive and Social Cognitive Impairments in Early-Onset Psychosis and At-Risk Youth: Implications for Intervention Strategies

Early-onset psychosis (EOP), or onset of overt psychosis prior to age 18, is associated with particularly severe neurocognitive and social impairment, and poor prognosis (Frangou, 2010; Vyas &amp; Gogtay, 2012). While significant impairments have been documented in specific cognitive domains (Fioravanti, Carlone, Vitale, Cinti, &amp; Clare, 2005; Heinrichs &amp; Zakzanis, 1998), working memory (WM) in particular is an area that has been theorized to represent a reliable cognitive endophenotype of schizophrenia. However, the majority of literature to date has focused on adult-onset schizophrenia, in which relevant developmental processes have already unfolded. Adolescence provides a privileged opportunity to understand how psychosis-related abnormalities in the structure and function of neural networks affect the relationships between social cognition, neurocognition and functioning, as well as an opportunity to define biomarkers for development of treatments to improve functional outcomes. As such, the first study examined the relationship between individual WM capacity and task-based neural activation and functional connectivity. Results indicated that, relative to typically developing controls, patients with EOP have poorer WM performance, lower overall WM capacity, reduced neural activity in WM-associated brain regions, and reduced coupling of WM-associated regions. Additionally, EOP patients evidenced greater neural activation and connectivity with increasing age, suggesting an atypical developmental trajectory along with general inefficiency of WM circuitry. Additional insight into the neurodevelopmental processes relevant to psychosis can come from examining genetically defined high-risk cohorts, such as 22q11.2 deletion syndrome (22q11DS). The second study evaluated the phenotypic overlap between EOP and 22q11DS by investigating the profile of neurocognitive and social cognitive impairment in individuals with EOP relative to 22q11DS patients and healthy controls. Despite greater overall cognitive impairment in the 22q11DS group (with the exception of verbal fluency, for which EOP patients evidenced greater impairment), patients with EOP and 22q11DS had comparable deficits in processing speed. 22q11DS and EOP patients also evidenced similar patterns of relationships between cognitive measures and psychotic symptoms. However, neurocognition and social cognition largely did not predict future functioning among the groups. The third and final study examined plasticity-based cognitive training (CT) as a potential intervention for such cognitive impairments in EOP. Results from the feasibility study indicated that slightly over half of participants were able to complete at least 10 hours of CT; dropout was primarily due to finding training boring. However, patients completing training showed higher post- versus pre-CT social functioning, and pre- to post-CT reductions in general and anxiety symptoms. This investigation into neurocognitive and social cognitive dysfunction in EOP, which incorporates perspectives from an fMRI paradigm and a comparison to a genetic high-risk cohort, has the potential to generate knowledge on a clinically significant and understudied area, and potentially produce new treatment targets for EOP

Neurocognitive and Social Cognitive Impairments in Early-Onset Psychosis and At-Risk Youth: Implications for Intervention Strategies

Early-onset psychosis (EOP), or onset of overt psychosis prior to age 18, is associated with particularly severe neurocognitive and social impairment, and poor prognosis (Frangou, 2010; Vyas &amp; Gogtay, 2012). While significant impairments have been documented in specific cognitive domains (Fioravanti, Carlone, Vitale, Cinti, &amp; Clare, 2005; Heinrichs &amp; Zakzanis, 1998), working memory (WM) in particular is an area that has been theorized to represent a reliable cognitive endophenotype of schizophrenia. However, the majority of literature to date has focused on adult-onset schizophrenia, in which relevant developmental processes have already unfolded. Adolescence provides a privileged opportunity to understand how psychosis-related abnormalities in the structure and function of neural networks affect the relationships between social cognition, neurocognition and functioning, as well as an opportunity to define biomarkers for development of treatments to improve functional outcomes. As such, the first study examined the relationship between individual WM capacity and task-based neural activation and functional connectivity. Results indicated that, relative to typically developing controls, patients with EOP have poorer WM performance, lower overall WM capacity, reduced neural activity in WM-associated brain regions, and reduced coupling of WM-associated regions. Additionally, EOP patients evidenced greater neural activation and connectivity with increasing age, suggesting an atypical developmental trajectory along with general inefficiency of WM circuitry. Additional insight into the neurodevelopmental processes relevant to psychosis can come from examining genetically defined high-risk cohorts, such as 22q11.2 deletion syndrome (22q11DS). The second study evaluated the phenotypic overlap between EOP and 22q11DS by investigating the profile of neurocognitive and social cognitive impairment in individuals with EOP relative to 22q11DS patients and healthy controls. Despite greater overall cognitive impairment in the 22q11DS group (with the exception of verbal fluency, for which EOP patients evidenced greater impairment), patients with EOP and 22q11DS had comparable deficits in processing speed. 22q11DS and EOP patients also evidenced similar patterns of relationships between cognitive measures and psychotic symptoms. However, neurocognition and social cognition largely did not predict future functioning among the groups. The third and final study examined plasticity-based cognitive training (CT) as a potential intervention for such cognitive impairments in EOP. Results from the feasibility study indicated that slightly over half of participants were able to complete at least 10 hours of CT; dropout was primarily due to finding training boring. However, patients completing training showed higher post- versus pre-CT social functioning, and pre- to post-CT reductions in general and anxiety symptoms. This investigation into neurocognitive and social cognitive dysfunction in EOP, which incorporates perspectives from an fMRI paradigm and a comparison to a genetic high-risk cohort, has the potential to generate knowledge on a clinically significant and understudied area, and potentially produce new treatment targets for EOP