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C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm Jun 2017

C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …


An Extended Vascular Model For Less Biased Estimation Of Permeability Parameters In Dce-T1 Images, Siamak P. Nejad-Davarani, Hassan Bagher-Ebadian, James R. Ewing, Douglas C. Noll, Tom Mikkelsen, Michael Chopp, Quan Jiang Jun 2017

An Extended Vascular Model For Less Biased Estimation Of Permeability Parameters In Dce-T1 Images, Siamak P. Nejad-Davarani, Hassan Bagher-Ebadian, James R. Ewing, Douglas C. Noll, Tom Mikkelsen, Michael Chopp, Quan Jiang

Neurology Articles

One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent …


Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody Jun 2017

Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has …


Investigator And Independent Review Committee Exploratory Assessment And Verification Of Tumor Response In A Non-Hodgkin Lymphoma Study, Robert R Ford, Robert W Ford, Michael O'Neal, Brad S Kahl, Ling Chen, Mihaela Munteanu, Bruce D Cheson Jun 2017

Investigator And Independent Review Committee Exploratory Assessment And Verification Of Tumor Response In A Non-Hodgkin Lymphoma Study, Robert R Ford, Robert W Ford, Michael O'Neal, Brad S Kahl, Ling Chen, Mihaela Munteanu, Bruce D Cheson

Open Access Publications

Interpretation of endpoints (e.g. overall response rate) in clinical trials depends on the accurate and reliable measurement and identification of tumors. Regulatory agencies recommend blinded reviews of imaging data by independent review committees (IRCs). Differences in response outcomes that arise between IRCs and site investigators raise regulatory/sponsor concerns. Here, we evaluate discrepant tumor response assessments by the IRC and unblinded investigators (complete versus partial response, respectively) occurring in 52 (13% of 393 IRC-assessed responders) of 447 enrolled patients with treatment-naïve non-Hodgkin lymphoma from a randomized study. The IRC and investigators were 'likely correct' in 73% and 25% of cases, respectively …


Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng Jun 2017

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …


Discovering And Linking Public Omics Data Sets Using The Omics Discovery Index., Yasset Perez-Riverol, Mingze Bai, Felipe Da Veiga Leprevost, Silvano Squizzato, Young Mi Park, Kenneth Haug, Adam J Carroll, Dylan Spalding, Justin Paschall, Mingxun Wang, Noemi Del-Toro, Tobias Ternent, Peng Zhang, Nicola Buso, Nuno Bandeira, Eric W Deutsch, David S Campbell, Ronald C Beavis, Reza M Salek, Ugis Sarkans, Robert Petryszak, Maria Keays, Eoin Fahy, Manish Sud, Shankar Subramaniam, Ariana Barbera, Rafael C Jiménez, Alexey I Nesvizhskii, Susanna-Assunta Sansone, Christoph Steinbeck, Rodrigo Lopez, Juan A Vizcaíno, Peipei Ping, Henning Hermjakob May 2017

Discovering And Linking Public Omics Data Sets Using The Omics Discovery Index., Yasset Perez-Riverol, Mingze Bai, Felipe Da Veiga Leprevost, Silvano Squizzato, Young Mi Park, Kenneth Haug, Adam J Carroll, Dylan Spalding, Justin Paschall, Mingxun Wang, Noemi Del-Toro, Tobias Ternent, Peng Zhang, Nicola Buso, Nuno Bandeira, Eric W Deutsch, David S Campbell, Ronald C Beavis, Reza M Salek, Ugis Sarkans, Robert Petryszak, Maria Keays, Eoin Fahy, Manish Sud, Shankar Subramaniam, Ariana Barbera, Rafael C Jiménez, Alexey I Nesvizhskii, Susanna-Assunta Sansone, Christoph Steinbeck, Rodrigo Lopez, Juan A Vizcaíno, Peipei Ping, Henning Hermjakob

Articles, Abstracts, and Reports

No abstract provided.


A Novel Agonist Of The Trif Pathway Induces A Cellular State Refractory To Replication Of Zika, Chikungunya, And Dengue Viruses., Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason R Baird, Michael J. Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R Defilippis May 2017

A Novel Agonist Of The Trif Pathway Induces A Cellular State Refractory To Replication Of Zika, Chikungunya, And Dengue Viruses., Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason R Baird, Michael J. Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R Defilippis

Articles, Abstracts, and Reports

The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe …


Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley May 2017

Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Recent papers highlight the presence of large numbers of compressed angles in metal ion coordination geometries for metalloprotein entries in the worldwide Protein Data Bank, due mainly to multidentate coordination. The prevalence of these compressed angles has raised the controversial idea that significantly populated aberrant or even novel coordination geometries may exist. Some of these papers have undergone severe criticism, apparently due to views held that only canonical coordination geometries exist in significant numbers. While criticism of controversial ideas is warranted and to be expected, we believe that a line was crossed where unfair criticism was put forth to discredit …


Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma May 2017

Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile …


A Discussion Regarding Various Animals' Abilities To Make Music And Move Rhythmically To Songs, Emilie R. Bufford May 2017

A Discussion Regarding Various Animals' Abilities To Make Music And Move Rhythmically To Songs, Emilie R. Bufford

Capstone Projects and Master's Theses

This project involves exploring the presence of music and rhythmic abilities in specific animal species. The main subjects are whales, sea lions, gorillas, elephants, birds, and mice. The goal of this project was to compare their abilities to those of humans, and overall, determine whether such abilities are considered musical. Cases where animals demonstrate the ability, both learned and innate, to move to a beat are analyzed, along with animals who demonstrate musical vocal abilities naturally in the wild. The previously unknown frequencies of whales, mice, and elephants, are brought to light. These findings bring up the possibility of even …


Cholinergic, But Not Dopaminergic Or Noradrenergic, Enhancement Sharpens Visual Spatial Perception In Humans, Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L. Wallace, Mark D'Esposito, Michael A. Silver Apr 2017

Cholinergic, But Not Dopaminergic Or Noradrenergic, Enhancement Sharpens Visual Spatial Perception In Humans, Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L. Wallace, Mark D'Esposito, Michael A. Silver

Open Access Publications

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker …


Fate Of Neural Progenitor Cells Transplanted Into Jaundiced And Nonjaundiced Rat Brains., Fu-Chen Yang, Sean M. Riordan, Michelle Winter, Li Gan, Peter G. Smith, Jay L. Vivian, Steven Shapiro, John A. Stanford Apr 2017

Fate Of Neural Progenitor Cells Transplanted Into Jaundiced And Nonjaundiced Rat Brains., Fu-Chen Yang, Sean M. Riordan, Michelle Winter, Li Gan, Peter G. Smith, Jay L. Vivian, Steven Shapiro, John A. Stanford

Manuscripts, Articles, Book Chapters and Other Papers

High levels of bilirubin in infants can cause kernicterus, which includes basal ganglia damage and dystonia. Stem cell transplantation may be an effective treatment for this disease. In this study, we transplanted human neural progenitor cells differentiated toward propriospinal interneurons into the striatum of 20-day-old spontaneously jaundiced (jj) Gunn rats and nonjaundiced (Nj) littermates. Using immunohistochemical methods, we found that grafted cells survived and grew fibers in jj and Nj brains 3 weeks after transplantation. Grafted cells had a higher survival rate in jj than in Nj brains, suggesting that slightly elevated bilirubin may protect graft survival due to its …


Seasonality Of Auricular Amputations In Rabbits, Kathleen Yaremchuk, Vigen Darian, Amy M. Williams Apr 2017

Seasonality Of Auricular Amputations In Rabbits, Kathleen Yaremchuk, Vigen Darian, Amy M. Williams

Otolaryngology Articles

This retrospective observational analysis hypothesizes that an increase occurs in online reports and images of auricular amputations of confectionary rabbits during the spring. Using the online search engine Google, online content and visual portrayals of confectionary rabbit auricular amputations from 2012 to 2017 were identified and trended against seasonal variations. To determine incidence, commercial availability of chocolate rabbits in retail facilities were assayed. A statistically significant increase in mention of rabbit auricular amputations occurred during the spring. Mapping techniques showed the annual peak incidence for 2012 to 2017 to be near Easter for each year studied. Human adults and children …


Crispr: Redefining Gmos—One Edit At A Time, Eric E. Williams Apr 2017

Crispr: Redefining Gmos—One Edit At A Time, Eric E. Williams

University of Arkansas at Little Rock Law Review

No abstract provided.


White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith Apr 2017

White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith

Biomedical Engineering Faculty Publications

Objective: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Methods: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluidattenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slicebased techniques. Results: dWMHs but not …


Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho Apr 2017

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels.

Results

In CA3 pyramidal neurons, kainic …


State Emergency Department Opioid Guidelines: Current Status., Robert I Broida, Tanner Gronowski, Andrew F Kalnow, Andrew G Little, Christopher M Lloyd Apr 2017

State Emergency Department Opioid Guidelines: Current Status., Robert I Broida, Tanner Gronowski, Andrew F Kalnow, Andrew G Little, Christopher M Lloyd

Trauma and Acute Care Articles

INTRODUCTION: The purpose of this study was to evaluate and categorize current state-sponsored opioid guidelines for the practice of emergency medicine (EM).

METHODS: We conducted a comprehensive search of EM-specific opioid prescribing guidelines and/or policies in each state to determine current state involvement in EM opioid prescribing, as well as to evaluate some of the specifics of each guideline or policy. The search was conducted using an online query and a follow-up email request to each state chapter of ACEP.

RESULTS: We found that 17 states had emergency department-specific guidelines. We further organized the guidelines into four categories: limiting prescriptions …


Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews Mar 2017

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …


Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues, Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews Mar 2017

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues, Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews

Hematology/Oncology Articles

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS² runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In …


Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye Mar 2017

Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt-/-) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25.24±2.22% body weight loss, after the tamoxifen induction of NamptF/F × Cre mice. These results substantiate that Nampt …


Lactate Dehydrogenase In Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, And Chronic Infection, Abdelbaset E. Abdelbaset, Barbara A. Fox, Mohamed H. Karram, Mahmoud R. Abd Ellah, David J. Bzik, Makoto Igarashi Mar 2017

Lactate Dehydrogenase In Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, And Chronic Infection, Abdelbaset E. Abdelbaset, Barbara A. Fox, Mohamed H. Karram, Mahmoud R. Abd Ellah, David J. Bzik, Makoto Igarashi

Dartmouth Scholarship

In the asexual stages, Toxoplasma gondii stage converts between acute phase rapidly replicating tachyzoites and chronic phase slowly dividing bradyzoites. Correspondingly, T. gondii differentially expresses two distinct genes and isoforms of the lactate dehydrogenase enzyme, expressing LDH1 exclusively in the tachyzoite stage and LDH2 preferentially in the bradyzoite stage. LDH catalyzes the interconversion of pyruvate and lactate in anaerobic growth conditions and is utilized for energy supply, however, the precise role of LDH1 and LDH2 in parasite biology in the asexual stages is still unclear. Here, we investigated the biological role of LDH1 and LDH2 in the asexual stages, …


Pseudomonas Aeruginosa Alginate Overproduction Promotes Coexistence With Staphylococcus Aureus In A Model Of Cystic Fibrosis Respiratory Infection, Dominique H. Limoli, Gregory B. Whitfield, Tomoe Kitao, Melissa L. Ivey, Michael R. Davis, Nora Grahl, Deborah A. Hogan, Laurence G. Rahme, P. Lynne Howell, George A. O'Toole, Joanna B. Goldberg Mar 2017

Pseudomonas Aeruginosa Alginate Overproduction Promotes Coexistence With Staphylococcus Aureus In A Model Of Cystic Fibrosis Respiratory Infection, Dominique H. Limoli, Gregory B. Whitfield, Tomoe Kitao, Melissa L. Ivey, Michael R. Davis, Nora Grahl, Deborah A. Hogan, Laurence G. Rahme, P. Lynne Howell, George A. O'Toole, Joanna B. Goldberg

Dartmouth Scholarship

While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa …


A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal Mar 2017

A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …


Clinical Performance Measures And Quality Improvement System Considerations For Dental Education, Joseph W. Parkinson, Gregory G. Zeller Mar 2017

Clinical Performance Measures And Quality Improvement System Considerations For Dental Education, Joseph W. Parkinson, Gregory G. Zeller

Oral Health Practice Faculty Publications

Quality improvement and quality assurance programs are an integral part of providing excellence in health care delivery. The Dental Quality Alliance and the Commission on Dental Accreditation recognize this and have created standards and recommendations to advise health care providers and health care delivery systems, including dental schools, on measuring the quality of the care delivered to patients. Overall health care expenditures have increased, and the Affordable Care Act has made health care, including dentistry, available to more people in the United States. These increases in cost and in the number of patients accessing care contribute to a heightened interest …


Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt Mar 2017

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …


Blue-Light Induced Accumulation Of Reactive Oxygen Species Is A Consequence Of The Drosophila Cryptochrome Photocycle, Louis David Arthaut, Margaret Ahmad, Nathalie Jourdan, Ali Mteyrek, Maria Procopio, Mohamed A. El-Esawi, Alain D'Harlingue, Pierre Etienne Bouchet, Jacques Witczak, Carlos F. Martino Mar 2017

Blue-Light Induced Accumulation Of Reactive Oxygen Species Is A Consequence Of The Drosophila Cryptochrome Photocycle, Louis David Arthaut, Margaret Ahmad, Nathalie Jourdan, Ali Mteyrek, Maria Procopio, Mohamed A. El-Esawi, Alain D'Harlingue, Pierre Etienne Bouchet, Jacques Witczak, Carlos F. Martino

Biomedical Engineering and Sciences Faculty Publications

Cryptochromes are evolutionarily conserved blue-light absorbing flavoproteins which participate in many important cellular processes including in entrainment of the circadian clock in plants, Drosophila and humans. Drosophila melanogaster cryptochrome (DmCry) absorbs light through a flavin (FAD) cofactor that undergoes photoreduction to the anionic radical (FAD) redox state both in vitro and in vivo. However, recent efforts to link this photoconversion to the initiation of a biological response have remained controversial. Here, we show by kinetic modeling of the DmCry photocycle that the fluence dependence, quantum yield, and half-life of flavin redox state interconversion are consistent with the anionic radical (FAD∗-) …


Building Proteometools Based On A Complete Synthetic Human Proteome., Daniel P Zolg, Mathias Wilhelm, Karsten Schnatbaum, Johannes Zerweck, Tobias Knaute, Bernard Delanghe, Derek J Bailey, Siegfried Gessulat, Hans-Christian Ehrlich, Maximilian Weininger, Peng Yu, Judith Schlegl, Karl Kramer, Tobias Schmidt, Ulrike Kusebauch, Eric W Deutsch, Ruedi Aebersold, Robert L Moritz, Holger Wenschuh, Thomas Moehring, Stephan Aiche, Andreas Huhmer, Ulf Reimer, Bernhard Kuster Mar 2017

Building Proteometools Based On A Complete Synthetic Human Proteome., Daniel P Zolg, Mathias Wilhelm, Karsten Schnatbaum, Johannes Zerweck, Tobias Knaute, Bernard Delanghe, Derek J Bailey, Siegfried Gessulat, Hans-Christian Ehrlich, Maximilian Weininger, Peng Yu, Judith Schlegl, Karl Kramer, Tobias Schmidt, Ulrike Kusebauch, Eric W Deutsch, Ruedi Aebersold, Robert L Moritz, Holger Wenschuh, Thomas Moehring, Stephan Aiche, Andreas Huhmer, Ulf Reimer, Bernhard Kuster

Articles, Abstracts, and Reports

We describe ProteomeTools, a project building molecular and digital tools from the human proteome to facilitate biomedical research. Here we report the generation and multimodal liquid chromatography-tandem mass spectrometry analysis of >330,000 synthetic tryptic peptides representing essentially all canonical human gene products, and we exemplify the utility of these data in several applications. The resource (available at http://www.proteometools.org) will be extended to >1 million peptides, and all data will be shared with the community via ProteomicsDB and ProteomeXchange.


Timing And Magnitude Of Lumbar Spine Contribution To Trunk Forward Bending And Backward Return In Patients With Acute Low Back Pain, Iman Shojaei, Milad Vazirian, Elizabeth G. Salt, Linda R. Van Dillen, Babak Bazrgari Feb 2017

Timing And Magnitude Of Lumbar Spine Contribution To Trunk Forward Bending And Backward Return In Patients With Acute Low Back Pain, Iman Shojaei, Milad Vazirian, Elizabeth G. Salt, Linda R. Van Dillen, Babak Bazrgari

Biomedical Engineering Faculty Publications

Alterations in the lumbo-pelvic coordination denote changes in neuromuscular control of trunk motion as well as load sharing between passive and active tissues in the lower back. Differences in timing and magnitude aspects of lumbo-pelvic coordination between patients with chronic low back pain (LBP) and asymptomatic individuals have been reported; yet, the literature on lumbo-pelvic coordination in patients with acute LBP is scant. A case-control study was conducted to explore the differences in timing and magnitude aspects of lumbo-pelvic coordination between females with (n=19) and without (n=19) acute LBP. Participants in each group completed one experimental session wherein they performed …


Genetic Drivers Of Kidney Defects In The Digeorge Syndrome., Esther Lopez-Rivera, Yangfan P. Liu, Miguel Verbitsky, Blair R. Anderson, Valentina P. Capone, Edgar A. Otto, Zhonghai Yan, Adele Mitrotti, Jeremiah Martino, Nicholas J. Steers, David A. Fasel, Katarina Vukojevic, Rong Deng, Silvia E. Racedo, Qingxue Liu, Max Werth, Rik Westland, Asaf Vivante, Gabriel S. Makar, Monica Bodria, Matthew G. Sampson, Christopher E. Gillies, Virginia Vega-Warner, Mariarosa Maiorana, Donald S. Petrey, Barry Honig, Vladimir J. Lozanovski, Rémi Salomon, Laurence Heidet, Wassila Carpentier, Dominique Gaillard, Alba Carrea, Loreto Gesualdo, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Adela Arapovic, Mirna Saraga-Babic, Marijan Saraga, Nenad Kunac, Ali Samii, Donna M. Mcdonald-Mcginn, Terrence B. Crowley, Elaine H. Zackai, Dorota Drozdz, Monika Miklaszewska, Marcin Tkaczyk, Przemyslaw Sikora, Maria Szczepanska, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, John M. Darlow, Prem Puri, David Barton, Emilio Casolari, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Hakon Hakonarson, Hana Flogelova, Velibor Tasic, Anna Latos-Bielenska, Anna Materna-Kiryluk, Landino Allegri, Craig S. Wong, Iain A Drummond, Vivette D'Agati, Akira Imamoto, Jonathan M. Barasch, Friedhelm Hildebrandt, Krzysztof Kiryluk, Richard P. Lifton, Bernice E. Morrow, Cecile Jeanpierre, Virginia E. Papaioannou, Gian Marco Ghiggeri, Ali G. Gharavi, Nicholas Katsanis, Simone Sanna-Cherchi Feb 2017

Genetic Drivers Of Kidney Defects In The Digeorge Syndrome., Esther Lopez-Rivera, Yangfan P. Liu, Miguel Verbitsky, Blair R. Anderson, Valentina P. Capone, Edgar A. Otto, Zhonghai Yan, Adele Mitrotti, Jeremiah Martino, Nicholas J. Steers, David A. Fasel, Katarina Vukojevic, Rong Deng, Silvia E. Racedo, Qingxue Liu, Max Werth, Rik Westland, Asaf Vivante, Gabriel S. Makar, Monica Bodria, Matthew G. Sampson, Christopher E. Gillies, Virginia Vega-Warner, Mariarosa Maiorana, Donald S. Petrey, Barry Honig, Vladimir J. Lozanovski, Rémi Salomon, Laurence Heidet, Wassila Carpentier, Dominique Gaillard, Alba Carrea, Loreto Gesualdo, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Adela Arapovic, Mirna Saraga-Babic, Marijan Saraga, Nenad Kunac, Ali Samii, Donna M. Mcdonald-Mcginn, Terrence B. Crowley, Elaine H. Zackai, Dorota Drozdz, Monika Miklaszewska, Marcin Tkaczyk, Przemyslaw Sikora, Maria Szczepanska, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, John M. Darlow, Prem Puri, David Barton, Emilio Casolari, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Hakon Hakonarson, Hana Flogelova, Velibor Tasic, Anna Latos-Bielenska, Anna Materna-Kiryluk, Landino Allegri, Craig S. Wong, Iain A Drummond, Vivette D'Agati, Akira Imamoto, Jonathan M. Barasch, Friedhelm Hildebrandt, Krzysztof Kiryluk, Richard P. Lifton, Bernice E. Morrow, Cecile Jeanpierre, Virginia E. Papaioannou, Gian Marco Ghiggeri, Ali G. Gharavi, Nicholas Katsanis, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice.

RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% …


Topical Anaesthetics For Pain Control During Repair Of Dermal Laceration., Baraa O. Tayeb, Anthony Eidelman, Cristy L. Eidelman, Ewan D. Mcnicol, Daniel B. Carr Feb 2017

Topical Anaesthetics For Pain Control During Repair Of Dermal Laceration., Baraa O. Tayeb, Anthony Eidelman, Cristy L. Eidelman, Ewan D. Mcnicol, Daniel B. Carr

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017.

OBJECTIVES: To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application …