University of Utah

About: University of Utah is a education organization based out in Salt Lake City, Utah, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 52894 authors who have published 124076 publications receiving 5265834 citations. The organization is also known as: The U & The University of Utah.

Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era.

Abstract: Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs) in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β) signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curacao) diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed.

Transformation by the R Enantiomer of 2-Hydroxyglutarate Linked to EglN Activation

Abstract: The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.

Expansion of C4 ecosystems as an indicator of global ecological change in the late Miocene

Abstract: THE most common and the most primitive pathway of the three different photosynthetic pathways used by plants is the C3 pathway, or Calvin cycle, which is characterized by an initial CO2 carboxylation to form phosphoglyceric acid, a 3-carbon acid. The carbon isotope composition (δ13C) of C3 plants varies from about −23 to −35%l–3 and averages about −26%. Virtually all trees, most shrubs, herbs and forbs, and cool-season grasses and sedges use the C3 pathway. In the C4 pathway (Hatch–Slack cycle), CO2 initially combines with phosphoenol pyruvate to form the 4-carbon acids malate or aspartic acid, which are translocated to bundle sheath cells where CO2 is released and used in Calvin cycle reactions1–4. The carbon isotope composition of C4 plants ranges from about −10 to −14%, averaging about −13% for modern plants1–3. Warm-season grasses and sedges are the most abundant C4 plants, although C4 photosynthesis is found in about twenty families5. The third photosynthetic pathway, CAM, combines features of both C3 and C4 pathways. CAM plants, which include many succulents, have intermediate carbon isotope compositions and are also adapted to conditions of water and CO2 stress. The modern global ecosystem has a significant component of C4 plants, primarily in tropical savannas, temperate grasslands and semi-desert scrublands. Studies of palaeovegetation from palaeosols and palaeodiet from fossil tooth enamel indicate a rapid expansion of C4 biomass in both the Old World and the New World starting 7 to 5 million years ago. We propose that the global expansion of C4 biomass may be related to lower atmospheric carbon dioxide levels because C4 photosynthesis is favoured over C3 photosynthesis when there are low concentrations of carbon dioxide in the atmosphere.

Modelling accessibility using space-time prism concepts within geographical information systems

Abstract: The space-time Of time geographical framework is a powerful perspective from which to analyse human behaviour. One of the central concepts in this framework is the space-time prism, which models individual accessibility to an environment. In this paper, the derivation and manipulation of space-time prism concepts within a geographical information system (GIS) are discussed. The required system inputs and desired outputs are identified and a generic GIS based procedure is presented Given these basic requirements, issues are discussed which can determine the feasibility of current GIS technology to handle the derivation of space-time prism concepts.

NCCN Guidelines® Insights Colon Cancer, Version 2.2018 Featured Updates to the NCCN Guidelines

Abstract: The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.