Dallas, TX, United States

The University of Texas Southwestern Medical Center is one of the leading medical education and biomedical research institutions in the United States. UT Southwestern is located in Southwestern Medical District, a 231-acre campus in Dallas incorporating UT Southwestern Medical School, UT Southwestern Graduate School of Biomedical science, UT Southwestern School of Health Professions, and four affiliated hospitals: Parkland Memorial Hospital, Children's Medical Center, Zale Lipshy University Hospital, and St. Paul University Hospital. It also has programs with affiliated hospitals at several sites in Dallas, Richardson, Fort Worth, Waco, Austin, and Wichita Falls. Wikipedia.

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Philips and University of Texas Southwestern Medical Center | Date: 2015-03-31

A method of operating a magnetic resonance imaging system (10) with regard to acquiring multiple-phase dynamic contrast-enhanced magnetic resonance images, the method comprising steps of acquiring (48) a first set of magnetic resonance image data (x_(pre)) prior to administering a contrast agent to the subject of interest (20), by employing a water/fat magnetic resonance signal separation technique, determining (52) a first image of the spatial distribution of fat (I_(pre)) of at least the portion of the subject of interest (20), acquiring (50) at least a second set of magnetic resonance image data (x_(2)) of at least the portion of the subject of interest (20) after administering the contrast agent to the subject of interest (20), by employing a water/fat magnetic resonance signal separation technique, determining (54) at least a second image of the spatial distribution of fat (I_(2)^(ph)) of at least the portion of the subject of interest (20), applying (56) an image registration method to the second image of the spatial distribution of fat with reference to the first image of the spatial distribution of fat (I_(pre)) for correcting a potential motion of the subject of interest (20); and a magnetic resonance imaging system (10) having a control unit (26) that is configured to carry out steps (56-64) of such a method; and a software module (44) for carrying out such a method, wherein the method steps (56-64) to be conducted are converted into a program code that is implementable in a memory unit (30) and is executable by a processor unit (32) of the magnetic resonance imaging system (10).

Jiang X.,University of Texas Southwestern Medical Center
Immunity | Year: 2012

RIG-I and MDA5 detect viral RNA in the cytoplasm and activate signaling cascades leading to the production of type-I interferons. RIG-I is activated through sequential binding of viral RNA and unanchored lysine-63 (K63) polyubiquitin chains, but how polyubiquitin activates RIG-I and whether MDA5 is activated through a similar mechanism remain unresolved. Here, we showed that the CARD domains of MDA5 bound to K63 polyubiquitin and that this binding was essential for MDA5 to activate the transcription factor IRF3. Mutations of conserved residues in MDA5 and RIG-I that disrupt their ubiquitin binding also abrogated their ability to activate IRF3. Polyubiquitin binding induced the formation of a large complex consisting of four RIG-I and four ubiquitin chains. This hetero-tetrameric complex was highly potent in activating the antiviral signaling cascades. These results suggest a unified mechanism of RIG-I and MDA5 activation and reveal a unique mechanism by which ubiquitin regulates cell signaling and immune response. Copyright © 2012 Elsevier Inc. All rights reserved.

Lee H.C.,University of Texas Southwestern Medical Center
Molecular cell | Year: 2010

A variety of small RNAs, including the Dicer-dependent miRNAs and the Dicer-independent Piwi-interacting RNAs, associate with Argonaute family proteins to regulate gene expression in diverse cellular processes. These two species of small RNA have not been found in fungi. Here, by analyzing small RNAs associated with the Neurospora Argonaute protein QDE-2, we show that diverse pathways generate miRNA-like small RNAs (milRNAs) and Dicer-independent small interfering RNAs (disiRNAs) in this filamentous fungus. Surprisingly, milRNAs are produced by at least four different mechanisms that use a distinct combination of factors, including Dicers, QDE-2, the exonuclease QIP, and an RNase III domain-containing protein, MRPL3. In contrast, disiRNAs originate from loci producing overlapping sense and antisense transcripts, and do not require the known RNAi components for their production. Taken together, these results uncover several pathways for small RNA production in filamentous fungi, shedding light on the diversity and evolutionary origins of eukaryotic small RNAs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Terman J.R.,University of Texas Southwestern Medical Center
Current opinion in cell biology | Year: 2013

Many of the best-studied actin regulatory proteins use non-covalent means to modulate the properties of actin. Yet, actin is also susceptible to covalent modifications of its amino acids. Recent work is increasingly revealing that actin processing and its covalent modifications regulate important cellular events. In addition, numerous pathogens express enzymes that specifically use actin as a substrate to regulate their hosts' cells. Actin post-translational alterations have been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight specific co-translational and post-translational modifications of actin and discuss the current understanding of the role that these modifications play in regulating actin. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vongpatanasin W.,University of Texas Southwestern Medical Center
JAMA - Journal of the American Medical Association | Year: 2014

Resistant hypertension-uncontrolled hypertension with 3 or more antihypertensive agents - is increasingly common in clinical practice. Clinicians should exclude pseudoresistant hypertension, which results from nonadherence to medications or from elevated blood pressure related to the white coat syndrome. In patients with truly resistant hypertension, thiazide diuretics, particularly chlorthalidone, should be considered as one of the initial agents. The other 2 agents should include calcium channel blockers and angiotensin-converting enzyme inhibitors for cardiovascular protection. An increasing body of evidence has suggested benefits of mineralocorticoid receptor antagonists, such as eplerenone and spironolactone, in improving blood pressure control in patients with resistant hypertension, regardless of circulating aldosterone levels. Thus, this class of drugs should be considered for patients whose blood pressure remains elevated after treatment with a 3-drug regimen to maximal or near maximal doses. Resistant hypertension may be associated with secondary causes of hypertension including obstructive sleep apnea or primary aldosteronism. Treating these disorders can significantly improve blood pressure beyond medical therapy alone. The role of device therapy for treating the typical patient with resistant hypertension remains unclear. Copyright 2014 American Medical Association. All rights reserved.

Olson E.N.,University of Texas Southwestern Medical Center
Science Translational Medicine | Year: 2014

MicroRNAs play central roles in cardiovascular disease, and their therapeutic manipulation raises exciting opportunities as well as challenges in the path toward clinical development.

Kavalali E.T.,University of Texas Southwestern Medical Center
Nature Reviews Neuroscience | Year: 2015

Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca 2+ influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release. © 2014 Macmillan Publishers Limited. All rights reserved.

Chen Z.J.,University of Texas Southwestern Medical Center
Immunological Reviews | Year: 2012

A role for polyubiquitination in the activation of inhibitor of NF-κB (IκB) kinase (IKK) through a proteasome-independent mechanism was first reported in 1996, but the physiological significance of this finding was not clear until 2000 when TRAF6 was found to be a ubiquitin E3 ligase that catalyzes lysine-63 (K63) polyubiquitination. Since then, several proteins known to regulate IKK have been linked to the ubiquitin pathway. These include the deubiquitination enzymes CYLD and A20 that inhibit IKK, and the ubiquitin binding proteins NEMO and TAB2 which are the regulatory subunits of IKK and TAK1 kinase complexes, respectively. Now accumulating evidence strongly supports a central role of K63 polyubiquitination in IKK activation by multiple immune and inflammatory pathways. Interestingly, recent research suggests that some alternative ubiquitin chains such as linear or K11 ubiquitin chains may also play a role in certain pathways such as the TNF pathway. Here I present a historical narrative of the discovery of the role of ubiquitin in IKK activation, review recent advances in understanding the role and mechanism of ubiquitin-mediated IKK activation, and raise some questions to be resolved in future research. © 2012 John Wiley & Sons A/S.

Hsieh J.,University of Texas Southwestern Medical Center
Genes and Development | Year: 2012

Stem cells have captured our imagination and generated hope, representing a source of replacement cells to treat a host of medical conditions. Tucked away in specialized niches, stem cells maintain tissue function and rejuvenate organs. Balancing the equation between cellular supply and demand is especially important in the adult brain, as neural stem cells (NSCs) in two discrete regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) next to the lateral ventricles, continuously self-renew and differentiate into neurons in a process called adult neurogenesis. Through the interplay of intrinsic and extrinsic factors, adult neurogenic niches ensure neuronal turnover throughout life, contributing to plasticity and homeostatic processes in the brain. This review summarizes recent progress on the molecular control of adult neurogenesis in the SGZ and SVZ, focusing on the role of specific transcription factors that mediate the progression from NSCs to lineagecommitted progenitors and, ultimately, the generation of mature neurons and glia. © 2012 by Cold Spring Harbor Laboratory Press.

Durinck S.,University of Texas Southwestern Medical Center
Nature genetics | Year: 2015

To further understand the molecular distinctions between kidney cancer subtypes, we analyzed exome, transcriptome and copy number alteration data from 167 primary human tumors that included renal oncocytomas and non-clear cell renal cell carcinomas (nccRCCs), consisting of papillary (pRCC), chromophobe (chRCC) and translocation (tRCC) subtypes. We identified ten significantly mutated genes in pRCC, including MET, NF2, SLC5A3, PNKD and CPQ. MET mutations occurred in 15% (10/65) of pRCC samples and included previously unreported recurrent activating mutations. In chRCC, we found TP53, PTEN, FAAH2, PDHB, PDXDC1 and ZNF765 to be significantly mutated. Gene expression analysis identified a five-gene set that enabled the molecular classification of chRCC, renal oncocytoma and pRCC. Using RNA sequencing, we identified previously unreported gene fusions, including ACTG1-MITF fusion. Ectopic expression of the ACTG1-MITF fusion led to cellular transformation and induced the expression of downstream target genes. Finally, we observed upregulation of the anti-apoptotic factor BIRC7 in MiTF-high RCC tumors, suggesting a potential therapeutic role for BIRC7 inhibitors.

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