Dataset Information

When Genome Maintenance Goes Badly Awry.

ABSTRACT: Genetic abnormalities are present in all tumor types, although the frequency and type can vary. Chromosome abnormalities include highly aberrant structures, particularly chromothriptic chromosomes. The generation of massive sequencing data has illuminated the scope of the mutational burden in cancer genomes, identifying patterns of mutations (mutation signatures), which have the potential to shed light on the relatedness and etiologies of cancers and impact therapy response. Some mutation patterns are clearly attributable to disruptions in pathways that maintain genomic integrity. Here we review recent advances in our understanding of genetic changes occurring in cancers and the roles of genome maintenance pathways.

SUBMITTER: Kass EM

PROVIDER: S-EPMC4966655 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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When Genome Maintenance Goes Badly Awry.

Kass Elizabeth M EM Moynahan Mary Ellen ME Jasin Maria M

Molecular cell 20160601 5

Genetic abnormalities are present in all tumor types, although the frequency and type can vary. Chromosome abnormalities include highly aberrant structures, particularly chromothriptic chromosomes. The generation of massive sequencing data has illuminated the scope of the mutational burden in cancer genomes, identifying patterns of mutations (mutation signatures), which have the potential to shed light on the relatedness and etiologies of cancers and impact therapy response. Some mutation patter ...[more]

PMID: 27259208

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Project description:Age-related chronic inflammatory activation of microglia and their dysfunction are observed in many neurodegenerative diseases, and the potential contributions of these dysfunctional cells to neurodegeneration have been demonstrated recently. The housekeeping and defensive functions of microglia, such as surveying the brain parenchyma and phagocytosis of neuronal debris after injury, are important for brain homeostasis and immunity. During neurodegenerative diseases, loss of these functions can promote disease pathology by producing proinflammatory cytokines and increasing oxidative stress, which can exaggerate the ongoing neuroinflammation. A recent surge in microglial research has unraveled myriads of microglial phenotypes associated with aging and neurodegenerative diseases, in addition to the conventional M1/M2 paradigm. Each of these phenotypes can be characterized by distinct transcriptional profiles as well as altered metabolism, migration, and phagocytosis characteristics. Mutations in triggering receptor expressed on myeloid cells 2 (Trem2) and granulin (GRN) are associated with various neurodegenerative diseases, and these genes are dysregulated in the majority of recently identified microglial phenotypes. These genes act as checkpoint regulators and maintain microglial inflammatory fitness, principally through metabolic modulation. Dysfunctional microglia typically show mitochondrial deficits, glycolysis elevation, and lipid droplet accumulation, which results in reduced migration and phagocytosis and increased proinflammatory cytokine secretion and reactive oxygen species release. In this mini-review article, we discuss the existing data regarding metabolic perturbations in dysfunctional microglia and their documented associations with neurodegeneration, highlighting how aging-induced chronic microglial activation alters microglial bioenergetics, leading to impaired homeostatic and housekeeping functions. Dysfunctional microglia initiate or exacerbate neurodegeneration, and key pathways involved in the dysfunctional processes, including metabolism, may represent potential intervention targets for correcting imbalances.

Project description:ObjectiveTo identify the core components of digital behaviour change interventions for weight loss maintenance targeting physical activity, in terms of: (i) behaviour change techniques, (ii) mechanisms of action, (iii) modes of delivery, (iv) dose and (v) tailoring/personalization. In addition, the links between these components were investigated.MethodsA literature search was performed in five electronic databases: PubMed, Embase, CINHAL, PsycINFO and Web of Science. Two reviewers independently screened the identified articles and extracted data related with the study characteristics and behaviour change techniques, mechanism of action, mode of delivery, dose, and tailoring, using standardized classifications whenever available (e.g. behaviour change techniques taxonomy).ResultsSeventeen articles reporting 11 original studies were selected. Two studies were protocols, 9 studies presented results for weight change and all but one showed no significant differences between the intervention and control groups. Eight studies (73%) provided adequate information on behaviour change techniques. Five studies (45%) provided partial information about how the behaviour change techniques were linked to mechanisms of action, and only one study (0.9%) described these links for all the techniques. Around half of the studies reported the modes through which behaviour change techniques were delivered. Descriptions of dose were present in most studies, but with minimal information. The use of tailoring or personalization approaches was mentioned in eight studies (73%), but descriptions of what was tailored and how were minimal.ConclusionsThe compilation of information regarding intervention components was difficult due to the lack of information and systematization in reporting across papers. This is particularly true for the reporting of the links between behaviour change techniques and the other core intervention components. This information is crucial to help us understand in the context of behaviour change interventions what works or does not work, how it works and why.

Dataset Information

When Genome Maintenance Goes Badly Awry.

Publications

When Genome Maintenance Goes Badly Awry.

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