Showing papers in "Cell Reports in 2015"

TL;DR: It injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory.

TL;DR: The data support a model of animal circRNA biogenesis in which competing RNA-RNA interactions of introns form larger structures that promote circularization of embedded exons, whereas ADAR1 antagonizes circRNA expression by melting stems within these interactions.

TL;DR: It is shown that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF, and that large-scale domains are reorganized during genome evolution as intact modules.

TL;DR: It is found that no specific circRNA exon sequence is necessary and that potential flanking intron structures can modulate circularization efficiency, arguing that the canonical spliceosomal machinery functions in circRNA biogenesis, constituting an alternative splicing mode.

TL;DR: This work has identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression, providing a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

TL;DR: Human-ESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.

TL;DR: The authors used RNA sequencing (RNA-seq) data to annotate the transcriptomes of 16 vertebrates and the echinoid sea urchin, uncovering thousands of previously unannotated genes, most of which produce long intervening noncoding RNAs.

TL;DR: The findings suggest that the microbiome alterations detected in industrialized societies might arise from modern lifestyle factors limiting bacterial dispersal, which has implications for human health and the development of strategies aimed to redress the impact of westernization.

TL;DR: It is shown that spliceosome gene mutations drive clonal expansion under selection pressures particular to the aging hemopoietic system and explains the high incidence of clonal disorders associated with these mutations in advanced old age.

TL;DR: It is shown that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligod endodermal cell death in two animal models of MS and in culture.

TL;DR: It is shown here that these antibiotics induce a mitonuclear protein imbalance through their effects on mitochondrial translation, an effect that likely reflects the evolutionary relationship between mitochondria and proteobacteria.

TL;DR: The described WGBS assay enables single-cell analysis of DNA methylation in a broad range of biological systems, including embryonic development, stem cell differentiation, and cancer, and can be used to establish composite methylomes that account for cell-to-cell heterogeneity in complex tissue samples.

TL;DR: It is shown that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila, and that a distinct shift in microbiota composition follows intestine barrier dysfunction, leading to systemic immune activation and organismal death.

TL;DR: This paper performed whole-exome sequencing on 143 multiplex consanguineous families in which known disease genes had been excluded by autozygosity mapping and candidate gene analysis and identified 69 recessive genes not previously associated with disease.

TL;DR: It is found that expression of IDO by tumor cells results in aggressive tumor growth and resistance to T-cell-targeting immunotherapies, and treatment with a selective IDO inhibitor in vivo reversed tumor-associated immunosuppression by decreasing numbers of tumor-infiltrating MDSCs and Tregs and abolishing their suppressive function.

TL;DR: It is reported that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect.

TL;DR: In this paper, the metabolome of Escherichia coli was profiled after treatment with three different classes of bactericidal antibiotics (?-lactams, aminoglycosides, quinolones).

TL;DR: The use of the CRISPR-Cas9 system is described to generate site-specific mutations in Ae.

TL;DR: A drug-inducible small guide RNA (sgRNA) vector system allowing for ubiquitous and efficient gene deletion in murine and human cells mediates the efficient, temporally controlled deletion of MCL-1 in human Burkitt lymphoma cell lines that require this anti-apoptotic BCL-2 protein for sustained survival and growth.

TL;DR: In this paper, the first murine definitive erythro-myeloid progenitors (EMPs) have an immunophenotype distinct from primitive hematopoietic progenitor, maturing megakaryocytes and macrophages, and rare B cell potential.

TL;DR: It is demonstrated that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation and that hexokinase 1 (HK1)-dependent glyCOlysis, under the regulation of m TORC1, represents a critical metabolic pathway forNLRP3Inflammasomes activation.

TL;DR: In this article, the authors performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 as a powerful modifier of cholesterol metabolism and RCT.

TL;DR: This work engineered the enteric bacterium, Escherichia coli, to manipulate the levels of the interspecies quorum sensing signal, autoinducer-2 (AI-2), in the mouse intestine and investigated the effect upon antibiotic-induced gut microbiota dysbiosis.

TL;DR: A realistic model is described that simulates light and heat propagation during optogenetic experiments and is demonstrated that high-intensity light, delivered through an optical fiber, is capable of elevating firing rate locally, even in the absence of opsin expression.

TL;DR: The hypothesis that MCU may be dispensable for homeostatic cardiac function but required to modulate Ca(2+)-dependent metabolism during acute stress is supported.

TL;DR: To make the tumor response to single kinase inhibitors durable, the adaptive kinome response itself must be inhibited, and combining inhibitors of kinases and chromatin readers prevents kinome adaptation by blocking transcription, generating a durable response to lapatinib, and overcoming the dilemma of heterogeneity in the adaptive response.

TL;DR: MCU is a dedicated regulator of short-term mitochondrial Ca(2+) loading underlying a "fight-or-flight" response that acutely matches cardiac workload with ATP production in mice generated with adult and cardiomyocyte-specific deletion of Mcu.

TL;DR: This work introduces a simple, versatile method for achieving cell-type-specific expression of transgenes that leverages the untapped potential of "coding introns" (i.e., introns between coding exons).

TL;DR: It is shown that the periodic subcortical actin structure is in fact present in both axons and dendrites, and also found in the peripheral nervous system, specifically at the nodes of Ranvier.

TL;DR: Comparison of embryonic stem cells, somatic cells, and senescent cells shows a unidirectional loss in local chromatin connectivity, suggesting that senescence is an endpoint of the continuous nuclear remodelling process during differentiation.