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Articles 2491 - 2520 of 3617

Full-Text Articles in Medicine and Health Sciences

Trefoil Factor(S) And Ca19.9: A Promising Panel For Early Detection Of Pancreatic Cancer, Rahat Jahan, Koelina Ganguly, Lynette M. Smith, Pranita Atri, Joseph Carmicheal, Yuri Sheinin, Satyanarayana Rachagani, Gopalakrishnan Natarajan, Randall E. Brand, Muzafar A. Macha, Paul M. Grandgenett, Sukhwinder Kaur, Surinder K. Batra Jan 2019

Trefoil Factor(S) And Ca19.9: A Promising Panel For Early Detection Of Pancreatic Cancer, Rahat Jahan, Koelina Ganguly, Lynette M. Smith, Pranita Atri, Joseph Carmicheal, Yuri Sheinin, Satyanarayana Rachagani, Gopalakrishnan Natarajan, Randall E. Brand, Muzafar A. Macha, Paul M. Grandgenett, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Trefoil factors (TFF1, TFF2, and TFF3) are small secretory molecules that recently have gained significant attention in multiple studies as an integral component of pancreatic cancer (PC) subtype-specific gene signature. Here, we comprehensively investigated the diagnostic potential of all the member of trefoil family, i.e., TFF1, TFF2, and TFF3 in combination with CA19.9 for detection of PC.

METHODS: Trefoil factors (TFFs) gene expression was analyzed in publicly available cancer genome datasets, followed by assessment of their expression in genetically engineered spontaneous mouse model (GEM) of PC (KrasG12D; Pdx1-Cre (KC)) and in human tissue microarray consisting of normal pancreas adjacent …


Pr55Α Regulatory Subunit Of Pp2a Inhibits The Mob1/Lats Cascade And Activates Yap In Pancreatic Cancer Cells, Ashley L. Hein, Nichole D. Brandquist, Caroline Y. Ouellette, Parthasarathy Seshacharyulu, Charles A. Enke, Michel M. Ouellette, Surinder K. Batra, Ying Yan Jan 2019

Pr55Α Regulatory Subunit Of Pp2a Inhibits The Mob1/Lats Cascade And Activates Yap In Pancreatic Cancer Cells, Ashley L. Hein, Nichole D. Brandquist, Caroline Y. Ouellette, Parthasarathy Seshacharyulu, Charles A. Enke, Michel M. Ouellette, Surinder K. Batra, Ying Yan

Journal Articles: Biochemistry & Molecular Biology

PP2A holoenzyme complexes are responsible for the majority of Ser/Thr phosphatase activities in human cells. Each PP2A consists of a catalytic subunit (C), a scaffold subunit (A), and a regulatory subunit (B). While the A and C subunits each exists only in two highly conserved isoforms, a large number of B subunits share no homology, which determines PP2A substrate specificity and cellular localization. It is anticipated that different PP2A holoenzymes play distinct roles in cellular signaling networks, whereas PP2A has only generally been defined as a putative tumor suppressor, which is mostly based on the loss-of-function studies using pharmacological or …


Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo Jan 2019

Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo

Journal Articles: Pulmonary & Critical Care Med

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY …


Barriers Of Colorectal Cancer Screening In Rural Usa: A Systematic Review, Hongmei Wang, Shreya Roy, Jungyoon Kim, Evi A. Farazi, Mohammad Siahpush, Dejun Su Jan 2019

Barriers Of Colorectal Cancer Screening In Rural Usa: A Systematic Review, Hongmei Wang, Shreya Roy, Jungyoon Kim, Evi A. Farazi, Mohammad Siahpush, Dejun Su

Journal Articles: Epidemiology

INTRODUCTION: Colorectal cancer (CRC) screening rates are lower in rural areas in the USA. To guide the design of interventions to improve CRC screening, a systematic review was conducted to identify CRC screening barriers for rural populations.

METHODS: A search was conducted in four literature databases - Medline, CINAHL, Embase, and Scopus - for articles from 1998 to 2017 that examine CRC screening barriers in rural areas. This review included a total of 27 articles reporting perceived CRC screening barriers by rural residents or providers or examining factors associated with CRC screening of rural populations in the USA.

RESULTS: The …


Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong Jan 2019

Conformational Studies Of Glucose Transporter 1 (Glut1) As An Anticancer Drug Target, Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong

Journal Articles: Pharmaceutical Sciences

Glucose transporter 1 (GLUT1) is a facilitative glucose transporter overexpressed in various types of tumors; thus, it has been considered as an important target for cancer therapy. GLUT1 works through conformational switching from an outward-open (OOP) to an inward-open (IOP) conformation passing through an occluded conformation. It is critical to determine which conformation is preferred by bound ligands because the success of structure-based drug design depends on the appropriate starting conformation of the target protein. To find out the most favorable GLUT 1 conformation for ligand binding, we ran systemic molecular docking studies for different conformations of GLUT1 using known …


Spontaneous Self-Assembly Of Amyloid Β (1–40) Into Dimers, Mohtadin Hashemi, Yuliang Zhang, Zhengjian Lv, Yuri L. Lyubchenko Jan 2019

Spontaneous Self-Assembly Of Amyloid Β (1–40) Into Dimers, Mohtadin Hashemi, Yuliang Zhang, Zhengjian Lv, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The self-assembly and fibrillation of amyloid β (Aβ) proteins is the neuropathological hallmark of Alzheimer's disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of Aβ (1–40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are stabilized by interactions in the N-terminal region (residues 5–12), in the central hydrophobic region (residues 16–23), and in the C-terminal region (residues 30–40); with inter-peptide interactions focused around …


Risk Mitigation For Travelers: Managing Endemic And Emerging Threats, Shannon M. Wood, David Brett-Major Jan 2019

Risk Mitigation For Travelers: Managing Endemic And Emerging Threats, Shannon M. Wood, David Brett-Major

Journal Articles: Epidemiology

International travel continues to increase in numbers and complexity. Despite the availability of pretravel health advice, travelers remain at risk for exposure to common organisms as well as emerging pathogens. With low rates of travel clinic utilization, it is important for the general practitioner to remain aware of the importance of travel health, risk factors unique to individual patients, and evolving threats. This review highlights important considerations when evaluating ill travelers, incorporating emerging infectious threats.


Cardiovascular Magnetic Resonance Imaging Feature Tracking: Impact Of Training On Observer Performance And Reproducibility, Sören J. Backhaus, Georg Metschies, Marcus Billing, Johannes T. Kowallick, Roman J. Gertz, Tomas Lapinskas, Burkert Pieske, Joachim Lotz, Boris Bigalke, Shelby Kutty, Gerd Hasenfuß, Philipp Beerbaum, Sebastian Kelle, Andreas Schuster Jan 2019

Cardiovascular Magnetic Resonance Imaging Feature Tracking: Impact Of Training On Observer Performance And Reproducibility, Sören J. Backhaus, Georg Metschies, Marcus Billing, Johannes T. Kowallick, Roman J. Gertz, Tomas Lapinskas, Burkert Pieske, Joachim Lotz, Boris Bigalke, Shelby Kutty, Gerd Hasenfuß, Philipp Beerbaum, Sebastian Kelle, Andreas Schuster

Journal Articles: Pediatrics

BACKGROUND: Cardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software.

METHODS: Intra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential …


Vitamin E Δ-Tocotrienol Sensitizes Human Pancreatic Cancer Cells To Trail-Induced Apoptosis Through Proteasome-Mediated Down-Regulation Of C-Flip, Rony A. Francois, Anying Zhang, Kazim Husain, Chen Wang, Sean Hutchinson, Michael Kongnyuy, Surinder K. Batra, Domenico Coppola, Said M. Sebti, Mokenge P. Malafa Jan 2019

Vitamin E Δ-Tocotrienol Sensitizes Human Pancreatic Cancer Cells To Trail-Induced Apoptosis Through Proteasome-Mediated Down-Regulation Of C-Flip, Rony A. Francois, Anying Zhang, Kazim Husain, Chen Wang, Sean Hutchinson, Michael Kongnyuy, Surinder K. Batra, Domenico Coppola, Said M. Sebti, Mokenge P. Malafa

Journal Articles: Biochemistry & Molecular Biology

Background: Vitamin E δ-tocotrienol (VEDT), a vitamin E compound isolated from sources such as palm fruit and annatto beans, has been reported to have cancer chemopreventive and therapeutic effects.

Methods: We report a novel function of VEDT in augmenting tumor necrosis factor-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis in pancreatic cancer cells. The effects of VEDT were shown by its ability to trigger caspase-8-dependent apoptosis in pancreatic cancer cells.

Results: When combined with TRAIL, VEDT significantly augmented TRAIL-induced apoptosis of pancreatic cancer cells. VEDT decreased cellular FLICE inhibitory protein (c-FLIP) levels without consistently modulating the expression of decoy death receptors 1, …


Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma Jan 2019

Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma

Journal Articles: Biochemistry & Molecular Biology

Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with overexpression of various inflammatory transcripts including CXCR4. Co-culture of neoplastic cells with CAFs led to increased invasiveness that was abrogated by inhibition of CXCR4. Metabolite tracing revealed that lactate produced by neoplastic cells leads to increased production of alpha-ketoglutarate (aKG) within mesenchymal stem cells (MSCs). In turn, aKG mediated activation of the …


Patient Care In High-Level Containment Care Units: In A Resourced Setting, Angela M. Vasa, Kate C. Boulter, Jolene M. Horihan, David S. Cates, Craig A. Piquette, James N. Sullivan, Daniel W. Johnson, Angela L. Hewlett Jan 2019

Patient Care In High-Level Containment Care Units: In A Resourced Setting, Angela M. Vasa, Kate C. Boulter, Jolene M. Horihan, David S. Cates, Craig A. Piquette, James N. Sullivan, Daniel W. Johnson, Angela L. Hewlett

Books and Book Chapters: Nebraska Medicine

Vasa, A., Boulter, K., Horihan, Cates, D., Piquette, C., Sullivan, J., Johnson, D, & Hewlett, A. (2019). Patient Care in High-Level Containment Care Units. In T. Cieslak, M. Kortepeter, C. Kratochvil, & J. Lawler (Eds.), Nebraska Isolation and Quarantine Manual (pp. 87-101). Lincoln, NE: University of Nebraska Press.


Valuation Of Scholarly Activities For Physical Therapy Faculty, Tony Rost, Mitchell Thompson, Harlan Sayles, Gilbert M. Willett, Betsy J. Becker Jan 2019

Valuation Of Scholarly Activities For Physical Therapy Faculty, Tony Rost, Mitchell Thompson, Harlan Sayles, Gilbert M. Willett, Betsy J. Becker

Posters and Presentations: Physical Therapy

Purpose/Hypothesis: Physical therapy (PT) faculty are required to participate in scholarly endeavors. Scholarly productivity is frequently evaluated based on quantity of production.1-3 This approach fails to account for quality (e.g. authorship order, presentation audience, or funding). Study aims: 1) compare PT program scholarly productivity valuations between programs of varying Carnegie Classification, 2) establish a scholarly activity measure which accounts for quality, and 3) provide an applied example of the new measure. Number of Subjects: PT Program Directors from CAPTE institutions (n=226) were surveyed using Dillman’s protocol.4

Materials/Methods: Respondents were asked to value (0 – 20) 30 …


Coordinated Induction Of Antimicrobial Response Factors In Systemic Lupus Erythematosus, Prathapan Ayyappan, Robert Z. Harms, Jane H. Buckner, Nora E. Sarvetnick Jan 2019

Coordinated Induction Of Antimicrobial Response Factors In Systemic Lupus Erythematosus, Prathapan Ayyappan, Robert Z. Harms, Jane H. Buckner, Nora E. Sarvetnick

Journal Articles: Surgery

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated autoantibody production and complement activation leading to multi-organ damage. The disease is associated with increased intestinal permeability. In this study, we tested the hypothesis that SLE subjects have increased systemic exposure to bacteria. Since bacteria induce the expression of antimicrobial response factors (ARFs), we measured the levels of a series of clinically relevant ARFs in the plasma of SLE subjects. We found that levels of sCD14, lysozyme, and CXCL16 were significantly elevated in SLE subjects. A strong positive correlation was also observed between sCD14 and SELENA-SLEDAI score. Interestingly, …


Uncovering And Characterizing Splice Variants Associated With Survival In Lung Cancer Patients, Sean West, Sushil Kumar, Surinder K. Batra, Hesham Ali, Dario Ghersi Jan 2019

Uncovering And Characterizing Splice Variants Associated With Survival In Lung Cancer Patients, Sean West, Sushil Kumar, Surinder K. Batra, Hesham Ali, Dario Ghersi

Journal Articles: Biochemistry & Molecular Biology

Splice variants have been shown to play an important role in tumor initiation and progression and can serve as novel cancer biomarkers. However, the clinical importance of individual splice variants and the mechanisms by which they can perturb cellular functions are still poorly understood. To address these issues, we developed an efficient and robust computational method to: (1) identify splice variants that are associated with patient survival in a statistically significant manner; and (2) predict rewired protein-protein interactions that may result from altered patterns of expression of such variants. We applied our method to the lung adenocarcinoma dataset from TCGA …


Characterization Of The Plasma Proteome Of Nonhuman Primates During Ebola Virus Disease Or Melioidosis: A Host Response Comparison, Michael D. Ward, Ernst E. Brueggemann, Tara Kenny, Raven E. Reitstetter, Christopher R. Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C. Donnelly, Cary Retterer, Robert B. Norgren, Rekha G. Panchal, Travis K. Warren, Sina Bavari, Lisa H. Cazares Jan 2019

Characterization Of The Plasma Proteome Of Nonhuman Primates During Ebola Virus Disease Or Melioidosis: A Host Response Comparison, Michael D. Ward, Ernst E. Brueggemann, Tara Kenny, Raven E. Reitstetter, Christopher R. Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C. Donnelly, Cary Retterer, Robert B. Norgren, Rekha G. Panchal, Travis K. Warren, Sina Bavari, Lisa H. Cazares

Journal Articles: Genetics, Cell Biology & Anatomy

Background: In-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host's immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus

Methods: Herein we report the quantitative proteomic analysis of plasma collected at various times of disease progression from 10 EBOV-infected and 5

Results: A total of 41 plasma proteins displayed significant alterations in abundance during EBOV …


Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case Jan 2019

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O2-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O2- with no evident changes in hydrogen peroxide (H2O2), peroxynitrite (ONOO-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …


Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black Jan 2019

Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.


Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang Jan 2019

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …


Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh Jan 2019

Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …


The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang Jan 2019

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …


Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein Jan 2019

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …


Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin Jan 2019

Imaging-Based Clusters In Former Smokers Of The Copd Cohort Associate With Clinical Characteristics: The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Babak Haghighi, Sanghun Choi, Jiwoong Choi, Eric A. Hoffman, Alejandro P. Comellas, John D. Newell, Chang Hyun Lee, R. Graham Barr, Eugene Bleecker, Christopher B. Cooper, David Couper, Mei Lan Han, Nadia N. Hansel, Richard E. Kanner, Ella A. Kazerooni, Eric A.C. Kleerup, Fernando J. Martinez, Wanda O'Neal, Robert Paine, Stephen I. Rennard, Benjamin M. Smith, Prescott G. Woodruff, Ching-Long Lin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

METHODS: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, …


Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey Jan 2019

Protease-Mediated Growth Of Staphylococcus Aureus On Host Proteins Is Opp3 Dependent, Mckenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a …


Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn Skar, David Synhorst, Matthew K. Beaver, Jessica N. Snowden Jan 2019

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn Skar, David Synhorst, Matthew K. Beaver, Jessica N. Snowden

Journal Articles: Pediatrics

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

METHODS: We conducted a retrospective chart review of children with …


User Engagement Associated With Web-Intervention Features To Attain Clinically Meaningful Weight Loss And Weight Maintenance In Rural Women, Patricia A. Hageman, Joseph E. Mroz, Michael A. Yoerger, Carol H. Pullen Jan 2019

User Engagement Associated With Web-Intervention Features To Attain Clinically Meaningful Weight Loss And Weight Maintenance In Rural Women, Patricia A. Hageman, Joseph E. Mroz, Michael A. Yoerger, Carol H. Pullen

Journal Articles: Physical Therapy

Objective: Purely web-based weight loss and weight-loss maintenance interventions show promise to influence behavior change. Yet, little is known about user engagement with features of web-based interventions that predict clinically meaningful weight loss (≥5% bodyweight loss). This study examines level of website feature engagement with the likelihood of attaining ≥5% bodyweight loss after 6 and 18 months participation in a web-based intervention, among rural women at high risk of obesity-related diseases and disability.

Methods: In this secondary analysis of clinical trial data of 201 rural women, we examined weight change and user engagement, measured as clicks on specific web-based intervention …


Search Strategy For "The Benefits, Burdens, And Risks Of Participation In Pediatric Palliative Care And End Of Life Research: A Systematic Review", Pamela S. Hinds, Vanessa N. Madrigal, Cynthia J. Bell, Cynthia M. Schmidt, Amy R. Newman, Kim Mooney-Doyle, Jessica L. Spruit, Tessie October, Christine A. Fortney, Melissa Kurtz Uveges, Kitty Montgomery, Katherine Patterson Kelly, Meaghann S. Weaver Jan 2019

Search Strategy For "The Benefits, Burdens, And Risks Of Participation In Pediatric Palliative Care And End Of Life Research: A Systematic Review", Pamela S. Hinds, Vanessa N. Madrigal, Cynthia J. Bell, Cynthia M. Schmidt, Amy R. Newman, Kim Mooney-Doyle, Jessica L. Spruit, Tessie October, Christine A. Fortney, Melissa Kurtz Uveges, Kitty Montgomery, Katherine Patterson Kelly, Meaghann S. Weaver

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.


Search Strategies For "The Interactions Between Anticonvulsants And Novel Oral Anticoagulants: A Systematic Review", Mohamed Taha, Wenyang Li, Cynthia M. Schmidt, Marco Gonzalez-Castellon, Olga Taraschenko Jan 2019

Search Strategies For "The Interactions Between Anticonvulsants And Novel Oral Anticoagulants: A Systematic Review", Mohamed Taha, Wenyang Li, Cynthia M. Schmidt, Marco Gonzalez-Castellon, Olga Taraschenko

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.


Search Strategies For "Targeted Therapy With Pde5i In Patients With Pulmonary Hypertension Due To Heart Failure And Elevated Pulmonary Vascular Resistance: A Systematic Review", Galo Sanchez Palacios, Cynthia M. Schmidt, Tammy Wichman Jan 2019

Search Strategies For "Targeted Therapy With Pde5i In Patients With Pulmonary Hypertension Due To Heart Failure And Elevated Pulmonary Vascular Resistance: A Systematic Review", Galo Sanchez Palacios, Cynthia M. Schmidt, Tammy Wichman

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.


Search Strategies For "Cutaneous Angiosarcoma: A Systematic Review Of The Literature", Zachary Kwapnoski, Dillon Clarey, Shauna Higgins, Marissa Lobl, Cynthia M. Schmidt, Kathryn Rentfro, Heidi Vieira, Ashley Wysong Jan 2019

Search Strategies For "Cutaneous Angiosarcoma: A Systematic Review Of The Literature", Zachary Kwapnoski, Dillon Clarey, Shauna Higgins, Marissa Lobl, Cynthia M. Schmidt, Kathryn Rentfro, Heidi Vieira, Ashley Wysong

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.


Human-Like Nsg Mouse Glycoproteins Sialylation Pattern Changes The Phenotype Of Human Lymphocytes And Sensitivity To Hiv-1 Infection, Raghubendra S. Dagur, Amanda Branch-Woods, Saumi Mathews, Poonam S. Joshi, Rolen M. Quadros, Donald W. Harms, Yan Cheng, Shana M. Miles, Samuel J. Pirruccello, Channabasavaiah B. Gurumurthy, Santhi Gorantla, Larisa Y. Poluektova Jan 2019

Human-Like Nsg Mouse Glycoproteins Sialylation Pattern Changes The Phenotype Of Human Lymphocytes And Sensitivity To Hiv-1 Infection, Raghubendra S. Dagur, Amanda Branch-Woods, Saumi Mathews, Poonam S. Joshi, Rolen M. Quadros, Donald W. Harms, Yan Cheng, Shana M. Miles, Samuel J. Pirruccello, Channabasavaiah B. Gurumurthy, Santhi Gorantla, Larisa Y. Poluektova

Journal Articles: Munroe-Meyer Institute

BACKGROUND: The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins' chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known.

RESULTS: We mutated mouse …