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Sequencing the human genome was a huge milestone in genetic research that revealed almost the total DNA sequence required to create a human being. However, in order to function, the DNA genome needs to be expressed as an RNA transcriptome. This article reviews how knowledge of genome sequence information has led to fundamental discoveries in how the transcriptome is processed, with a focus on new system-wide insights into how pre-mRNAs that are encoded by split genes in the genome are rearranged by splicing into functional mRNAs. These advances have been made possible by the development of new post-genome technologies to probe splicing patterns. Transcriptome-wide approaches have characterised a "splicing code" that is embedded within and has a significant role in deciphering the genome, and is deciphered by RNA binding proteins. These analyses have also found that most human genes encode multiple mRNA isoforms, and in some cases proteins, leading in turn to a re-assessment of what exactly a gene is. Analysis of the transcriptome has given insights into how the genome is packaged and transcribed, and is helping to explain important aspects of genome evolution. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue which includes the patriotic and national sentiments and identities found in music and music education practices, influence of corporate interests on schooling and music education, and repositioning elements of music.

An introduction is presented in which the editor discusses various reports within the issue on topics including music appropriate for school music programs, aims of music education from different perspective, and intrapersonal aims of music education with emphasis on musical identity.

The splicing regulator proteins SRSF1 (also known as ASF/SF2) and SRSF3 (also known as SRP20) belong to the SR family of proteins and can be upregulated in cancer. The SRSF1 gene itself is amplified in some cancer cells, and cancer-associated changes in the expression of MYC also increase SRSF1 gene expression. Increased concentrations of SRSF1 protein promote prooncogenic splicing patterns of a number of key regulators of cell growth. Here, we review the evidence that upregulation of the SR-related Tra2β protein might have a similar role in cancer cells. The TRA2B gene encoding Tra2β is amplified in particular tumours including those of the lung, ovary, cervix, stomach, head, and neck. Both TRA2BRNAand Tra2β protein levels are upregulated in breast, cervical, ovarian, and colon cancer, and Tra2β expression is associated with cancer cell survival. The TRA2B gene is a transcriptional target of the protooncogene ETS-1 which might cause higher levels of expression in some cancer cells which express this transcription factor. Known Tra2β splicing targets have important roles in cancer cells, where they affect metastasis, proliferation, and cell survival. Tra2β protein is also known to interact directly with the RBMY protein which is implicated in liver cancer. [ABSTRACT FROM AUTHOR]

The author describes music education as an artistic citizenship which consists of all forms of music-making and listening musical interactions at school and communities level. He discusses several themes related to artistic citizenship which include music-making for intrinsic musical experiences, music-making as ethical action and ethic of care. He informs about the praxial music education which teaches the traditional musical- cultural values and transformation of students and communities.

An introduction to the journal is presented in which the editor discusses various issues surrounding the music education in the U.S.

Copyright of Journal of Pathology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder caused by expansion of 55–200 CGG repeats in the 5′-UTR of the FMR1 gene. FXTAS is characterized by action tremor, gait ataxia and impaired executive cognitive functioning. It has been proposed that FXTAS is caused by titration of RNA-binding proteins by the expanded CGG repeats. Sam68 is an RNA-binding protein involved in alternative splicing regulation and its ablation in mouse leads to motor coordination defects. Here, we report that mRNAs containing expanded CGG repeats form large and dynamic intranuclear RNA aggregates that recruit several RNA-binding proteins sequentially, first Sam68, then hnRNP-G and MBNL1. Importantly, Sam68 is sequestered by expanded CGG repeats and thereby loses its splicing-regulatory function. Consequently, Sam68-responsive splicing is altered in FXTAS patients. Finally, we found that regulation of Sam68 tyrosine phosphorylation modulates its localization within CGG aggregates and that tautomycin prevents both Sam68 and CGG RNA aggregate formation. Overall, these data support an RNA gain-of-function mechanism for FXTAS neuropathology, and suggest possible target routes for treatment options. [ABSTRACT FROM AUTHOR]

The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2b is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 59 splice site and surrounding splicingrepressive intronic regions. TLE4-T RNA pulls down Tra2b and hnRNP G proteins which activate its inclusion. The germ cellspecific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 39 splice site normally weakly selected in the testis. Co-expression of Tra2b with either hnRNP G-T or RBMY reestablished the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein. [ABSTRACT FROM AUTHOR]

Background: Medulloblastoma is the most common malignant brain tumour of childhood. The identification of critical genes involved in its pathogenesis will be central to advances in our understanding of its molecular basis, and the development of improved therapeutic approaches. Methodology/Principal Findings: We performed a SNP-array based genome-wide copy number analysis in medulloblastoma cell lines, to identify regions of genomic amplification and homozygous deletion, which may harbour critical disease genes. A series of novel and established medulloblastoma defects were detected (MYC amplification (n=4), 17q21.31 high-level gain (n=1); 9p21.1-p21.3 (n=1) and 6q23.1 (n=1) homozygous deletion). Most notably, a novel recurrent region of genomic amplification at 8q24.22-q24.23 was identified (n=2), and selected for further investigation. Additional analysis by interphase fluorescence in situ hybridisation (iFISH), PCR-based mapping and SNP-array revealed this novel amplification at 8q24.22-q24.23 is independent of MYC amplification at 8q24.21, and is unique to medulloblastoma in over 800 cancer cell lines assessed from different tumour types, suggesting it contains key genes specifically involved in medulloblastoma development. Detailed mapping identified a 3Mb common minimal region of amplification harbouring 3 coding genes (ZFAT1, LOC286094, KHDRBS3) and two genes encoding micro-RNAs (hsa-miR-30b, hsa-miR-30d). Of these, only expression of hsa-miR-30b, hsa-miR-30d and KHDRBS3 correlated with copy number status, and all three of these transcripts also displayed evidence of elevated expression in sub-sets of primary medulloblastomas, measured relative to the normal cerebellum. Conclusions/Significance: These data implicate hsa-miR-30b, hsa-miR-30d and KHDRBS3 as putative oncogenic target(s) of a novel recurrent medulloblastoma amplicon at 8q24.22-q24.23. Our findings suggest critical roles for these genes in medulloblastoma development, and further support the contribution of micro-RNA species to medulloblastoma pathogenesis. [ABSTRACT FROM AUTHOR]

The article presents a commentary on the book "Democracy and Music Education: Liberalism, Ethics, and the Politics of Practice," by Paul Woodford. It examines the basic themes presented in the work of Woodford, indicating his purpose for the music education. It indicates the emphasis of Woodford on the undeniable need for music teachers, philosophers, as well as students to model empathy, civility, and compassion. The author also explores the assertion of Woodford regarding the difficulty of the coupling of education with democracy.

An essay is presented on socialize and social justice in music education. It reflects on the concept of social justice in terms of several facets, strands or dimensions. It discusses this concept in relation to selected social movements. It examines the work of two music educators/community musicians whose efforts illustrate aspects of music education as-and-for social justice.

The article discusses the critical performative pedagogy of music education in Puerto Rico. The three concepts that ground critical performative pedagogy namely performance studies, performatives, and performativity and the nature of critical performative pedagogy are examined. The author describes the teaching-learning processes that illustrate how he and his students engaged in critical performative pedagogy. According to the author, a performative approach to education is fundamentally and powerfully liberating at the human, educational, and theoretical levels; critical performative pedagogy is transformative.

The RBMY (RNA-binding motif gene on Y chromosome) protein encoded by the human Y chromosome is important for normal sperm development. Although its precise molecular RNA targets are unknown at present, it is suggested that human RBMY (hRBMY) participates in splicing in the testis. Using systematic evolution of ligands by exponential enrichment, we found that RNA stem–loops capped by a CA/UCAA pentaloop are high-affinity binding targets for hRBMY. Subsequent nuclear magnetic resonance structural determination of the hRBMY RNA recognition motif (RRM) in complex with a high-affinity target showed two distinct modes of RNA recognition. First, the RRM β-sheet surface binds to the RNA loop in a sequence-specific fashion. Second, the β2–β3 loop of the hRBMY inserts into the major groove of the RNA stem. The first binding mode might be conserved in the paralogous protein heterogeneous nuclear RNP G, whereas the second mode of binding is found only in hRBMY. This structural difference could be at the origin of the function of RBMY in spermatogenesis. [ABSTRACT FROM AUTHOR]

Cdc20 and cdh1 are coactivators of the anaphase-promoting complex (APC). APCcdc20 is necessary for the metaphase–anaphase transition and, at the end of mitosis, vertebrate cdc20 itself becomes a target for degradation through KEN-box-dependent APCcdh1 activity. By studying the degradation of fluorescent protein chimaeras in mammalian oocytes and early embryos, we found that cdc20 was degraded through two independent degradation signals (degrons), the KEN box and a newly described CRY box. In both oocytes and G1-stage embryos, the rate of degradation through the CRY box was greater than through the KEN box, although both were mediated by APCcdh1. Thus, mammalian oocytes and embryos have the capacity to recognize two degrons in cdc20. [ABSTRACT FROM AUTHOR]