Genetic modulation of the gene reduces anxiety-related behavior in mice.

The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the receptor gene.

Implementation of a pooled surveillance testing program for asymptomatic SARS-CoV-2 infections in K-12 schools and universities.

Background: The negative impact of continued school closures during the height of the COVID-19 pandemic warrants the establishment of cost-effective strategies for surveillance and screening to safely reopen and monitor for potential in-school transmission. Here, we present a novel approach to increase the availability of repetitive and routine COVID-19 testing that may ultimately reduce the overall viral burden in the community.

Methods: We implemented a testing program using the SalivaClear࣪ pooled surveillance method that included students, faculty and staff from K-12 schools (student age range 5-18 years) and universities (student age range >18 years) across the country (Mirimus Clinical Labs, Brooklyn, NY).

Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.

Introduction: To improve the standard treatment paradigm for glioblastoma (GBM), efforts have been made to explore the efficacy of epigenetic agents as chemosensitizers. Recent data suggest possible synergy between decitabine (DAC), a DNA hypomethylating agent, and temozolomide (TMZ) in GBM, but the mechanism remains unclear. The objective of this study was to determine the effects of DAC on TMZ sensitization in a consecutively derived set of primary GBM cultures, with a focus on mismatch repair (MMR) proteins.

Treatment-associated DNA-binding domain missense mutations in the pathogenesis of secondary gliosarcoma.

Background: Gliosarcoma is a rare variant of glioblastoma (GBM) that exhibits frequent mutations in and can develop in a secondary fashion after chemoradiation of a primary GBM. Whether temozolomide (TMZ)-induced mutagenesis of the DNA-binding domain (DBD) can drive the pathogenesis of gliosarcoma is unclear.

Methods: We identified a case of a primary GBM that rapidly progressed into secondary gliosarcoma shortly after chemoradiation was initiated.

Sensitivity to Inhibition Defines an Alternative Classification of Glioblastoma.

Glioblastoma multiforme (GBM) remains a mainly incurable disease in desperate need of more effective treatments. In this study, we develop evidence that the mitotic spindle checkpoint molecule may offer a predictive marker for aggressiveness and effective drug response. A subset of GBM tumor isolates requires to suppress lethal kinetochore-microtubule attachment defects.

Plexin-B2 promotes invasive growth of malignant glioma.

Invasive growth is a major determinant of the high lethality of malignant gliomas. Plexin-B2, an axon guidance receptor important for mediating neural progenitor cell migration during development, is upregulated in gliomas, but its function therein remains poorly understood. Combining bioinformatic analyses, immunoblotting and immunohistochemistry of patient samples, we demonstrate that Plexin-B2 is consistently upregulated in all types of human gliomas and that its expression levels correlate with glioma grade and poor survival.

Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression.

Mice have been a long-standing model for human biology and disease. Here we characterize, by RNA sequencing, the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution.

Cell transcriptional state alters genomic patterns of DNA double-strand break repair in human astrocytes.

The misrepair of DNA double-strand breaks in close spatial proximity within the nucleus can result in chromosomal rearrangements that are important in the pathogenesis of haematopoietic and solid malignancies. It is unknown why certain epigenetic states, such as those found in stem or progenitor cells, appear to facilitate neoplastic transformation. Here we show that altering the transcriptional state of human astrocytes alters patterns of DNA damage repair from ionizing radiation at a gene locus-specific and genome-wide level.

Comparative analysis of the transcriptome across distant species.

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly.

Landscape of transcription in human cells.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function.

An encyclopedia of mouse DNA elements (Mouse ENCODE).

To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions.

Linking promoters to functional transcripts in small samples with nanoCAGE and CAGEscan.

Large-scale sequencing projects have revealed an unexpected complexity in the origins, structures and functions of mammalian transcripts. Many loci are known to produce overlapping coding and noncoding RNAs with capped 5' ends that vary in size. Methods to identify the 5' ends of transcripts will facilitate the discovery of new promoters and 5' ends derived from secondary capping events.

Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body.

In humans and many other animals, memory consolidation occurs through multiple temporal phases and usually involves more than one neuroanatomical brain system. Genetic dissection of Pavlovian olfactory learning in Drosophila melanogaster has revealed multiple memory phases, but the predominant view holds that all memory phases occur in mushroom body neurons. Here, we demonstrate an acute requirement for NMDA receptors (NMDARs) outside of the mushroom body during long-term memory (LTM) consolidation.

Mutation analysis of Drosophila dikar/CG32394, homologue of the chromatin-remodelling gene CECR2.

The mammalian CECR2 protein contains a highly conserved bromodomain and forms a chromatin-remodelling complex with the ISWI homologue SNF2L. Mutation of the mouse CECR2 homologue results in a neural tube defect. Here we describe the characterization of the Drosophila melanogaster homologue of CECR2.