ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification

Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor α/δ (Tcra/d) locus. Such translocations have been thought to result from aberrant repair of DNA double-strand breaks (DSBs) during Tcra locus V(D)J recombination, and to require the Tcra enhancer (Eα) for Tcra rearrangement or expression of the translocated oncogene. We now show that, in addition to the known chromosome 14 translocation, ATM-deficient mouse thymic lymphomas routinely contain a centromeric fragment of chromosome 14 that spans up to the 5′ boundary of the Tcra/d locus, at which position a 500-kb or larger region centromeric to Tcra/d is routinely amplified. In addition, they routinely contain a large deletion of the telomeric end of one copy of chromosome 12. In contrast to prior expectations, the recurrent translocations and amplifications involve V(D)J recombination–initiated breaks in the Tcrd locus, as opposed to the Tcra locus, and arise independently of the Eα. Overall, our studies reveal previously unexpected mechanisms that contribute to the oncogenic transformation of ATM-deficient T lineage cells

The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species.

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven\u27t been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Withdrawal-associated injury site pain (WISP): a descriptive case series of an opioid cessation phenomenon.

Withdrawal pain can be a barrier to opioid cessation. Yet, little is known about old injury site pain in this context. We conducted an exploratory mixed-methods descriptive case series using a web-based survey and in-person interviews with adults recruited from pain and addiction treatment and research settings. We included individuals who self-reported a past significant injury that was healed and pain-free before the initiation of opioids, which then became temporarily painful upon opioid cessation-a phenomenon we have named withdrawal-associated injury site pain (WISP). Screening identified WISP in 47 people, of whom 34 (72%) completed the descriptive survey, including 21 who completed qualitative interviews. Recalled pain severity scores for WISP were typically high (median: 8/10; interquartile range [IQR]: 2), emotionally and physically aversive, and took approximately 2 weeks to resolve (median: 14; IQR: 24 days). Withdrawal-associated injury site pain intensity was typically slightly less than participants' original injury pain (median: 10/10; IQR: 3), and more painful than other generalized withdrawal symptoms which also lasted approximately 2 weeks (median: 13; IQR: 25 days). Fifteen surveyed participants (44%) reported returning to opioid use because of WISP in the past. Participants developed theories about the etiology of WISP, including that the pain is the brain's way of communicating a desire for opioids. This research represents the first known documentation that previously healed, and pain-free injury sites can temporarily become painful again during opioid withdrawal, an experience which may be a barrier to opioid cessation, and a contributor to opioid reinitiation

Montaigne and bayle : variations on the theme of skepticism /

Oorpronkelijk verschenen als proefschrift Columbia University.Lit.opg.: p. [344]-351. - Index

Open Mesocosm Oyster 15N2 and N2O

Dataset: Open Mesocosm Oyster N2 and N2OOpen Mesocosm Oyster 15N2 and N2O For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/722433NSF Division of Ocean Sciences (NSF OCE) OCE-123337

Oyster density and size distribution from the coast of North Carolina in 2010

Dataset: Oyster density and size distributionOyster density and size distribution from the coast of North Carolina in 2010 For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/704333NSF Division of Ocean Sciences (NSF OCE) OCE-123337