Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations

Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma

Consensus Paper: Cerebellum and Social Cognition.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions

Perceptions of the Muslim religious leaders and their attitudes on herbal medicine in Bangladesh: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Herbal Medicines (HMs) are playing major roles in the health of the millions of people worldwide. Muslim Religious Leader (MRLs), being an important component of the society with huge influence on it, could contribute a lot to promote HM. This study was aimed at evaluating perceptions of the MRLs, their satisfaction and attitudes towards HM in Bangladesh.</p> <p>Methods</p> <p>This cross-sectional study collected data from a purposive sample of 503 MRLs using an interviewer-administered structured questionnaire during December 2010 and January 2011. Main outcome measures included sociodemographic variables, MRLs' preferences in using HMs, their satisfaction and intent to use HMs in the future, and finally MRLs' attitudes toward HM use.</p> <p>Results</p> <p>Although two-fifth (40.4%) of the MRLs preferred HM among different form of complementary and alternative medicines, they used orthodox medicine (OM) more frequently than HM in last one year. Majority believed that HM was effective for all age groups (52.6%) and both sexes (74.5%). One-third felt that HM was more effective for chronic diseases, 68.5% felt that it only promotes health, and 40.8% said it keeps them relaxed. About 98.0% of the respondents experienced 'no harm' but 'benefit' from HM; naturally, they were satisfied with HM and were willing to recommend it to others. Urban, older (>40 years), and 'single' respondents were more likely to use HM (gender and education adjusted odds ratios = 1.7 [95% confidence interval, CI = 1.1-2.6], 1.9 [95% CI = 1.3-3.0], and 1.6 [95% CI = 1.2-2.1], respectively). Overall, respondents exhibited very positive attitude towards HM with mean score of 4.2 (range, 3.7-4.6) of a 5-point Likert scale (Score 5 for strongly agree to 1 for strongly disagree).</p> <p>Conclusions</p> <p>We report adequate perceptions, satisfaction, and very positive attitudes towards HM among MRLs. Mass media had a significant contribution towards its promotion. If HM are to assume a respected place in the contemporary healthcare, its acceptance among general population needs to be established through incorporating MRLs in the process of HM promotion in Bangladesh.</p