Internal Medicine Commons^™

Mrsa Usa300 Clone And Vref--A Us-Colombian Connection?, Cesar A Arias, Sandra Rincon, Shahreen Chowdhury, Ernesto Martínez, Wilfrido Coronell, Jinnethe Reyes, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

No abstract provided.

3d Mprage Improves Classification Of Cortical Lesions In Multiple Sclerosis, F Nelson, A Poonawalla, P Hou, J S Wolinsky, P A Narayana

Faculty, Staff and Student Publications

BACKGROUND: Gray matter lesions are known to be common in multiple sclerosis (MS) and are suspected to play an important role in disease progression and clinical disability. A combination of magnetic resonance imaging (MRI) techniques, double-inversion recovery (DIR), and phase-sensitive inversion recovery (PSIR), has been used for detection and classification of cortical lesions. This study shows that high-resolution three-dimensional (3D) magnetization-prepared rapid acquisition with gradient echo (MPRAGE) improves the classification of cortical lesions by allowing more accurate anatomic localization of lesion morphology.

METHODS: 11 patients with MS with previously identified cortical lesions were scanned using DIR, PSIR, and 3D MPRAGE. …

Rationale For Reading Fluconazole Mics At 24 Hours Rather Than 48 Hours When Testing Candida Spp By The Clsi M27-A2 Standard Method, Luis Ostrosky-Zeichner, John H Rex, Michael A Pfaller, Daniel J Diekema, Barbara D Alexander, David Andes, Steven D Brown, Vishnu Chaturvedi, Mahmoud A Ghannoum, Cindy C Knapp, Daniel J Sheehan, Thomas J Walsh

Faculty, Staff and Student Publications

We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.

Poly(A)-Binding Protein-Interacting Protein 1 Binds To Eukaryotic Translation Initiation Factor 3 To Stimulate Translation, Yvan Martineau, Mélanie C Derry, Xiaoshan Wang, Akiko Yanagiya, Juan José Berlanga, Ann-Bin Shyu, Hiroaki Imataka, Kalle Gehring, Nahum Sonenberg

Faculty, Staff and Student Publications

Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation by Paip1 in vivo was decreased upon deletion of the N-terminal sequence containing the eIF3-binding domain and upon silencing of PABP or several eIF3 subunits. We also show the formation of ternary complexes composed of Paip1-PABP-eIF4G and …

Aggressive Vs Conservative Phototherapy For Infants With Extremely Low Birth Weight, Brenda H Morris, William Oh, Jon E Tyson, David K Stevenson, Dale L Phelps, T Michael O'Shea, Georgia E Mcdavid, Rebecca L Perritt, Krisa P Van Meurs, Betty R Vohr, Cathy Grisby, Qing Yao, Claudia Pedroza, Abhik Das, W Kenneth Poole, Waldemar A Carlo, Shahnaz Duara, Abbot R Laptook, Walid A Salhab, Seetha Shankaran, Brenda B Poindexter, Avroy A Fanaroff, Michele C Walsh, Maynard R Rasmussen, Barbara J Stoll, C Michael Cotten, Edward F Donovan, Richard A Ehrenkranz, Ronnie Guillet, Rosemary D Higgins

Faculty, Staff and Student Publications

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).

METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.

RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 …

Characteristics Of A Spina Bifida Population Including North American Caucasian And Hispanic Individuals, Kit Sing Au, Phong X Tran, Chester C Tsai, Michelle R O'Byrne, Jone-Ing Lin, Alanna C Morrison, Amy W Hampson, Paul Cirino, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Sabine Doebel, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes.

METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and …

Characterization Of The Inflammatory Cells In Ascending Thoracic Aortic Aneurysms In Patients With Marfan Syndrome, Familial Thoracic Aortic Aneurysms, And Sporadic Aneurysms, Rumin He, Dong-Chuan Guo, Wei Sun, Christina L Papke, Senthil Duraisamy, Anthony L Estrera, Hazim J Safi, Chul Ahn, L Maximilian Buja, Frank C Arnett, Jingwu Zhang, Yong-Jian Geng, Dianna M Milewicz

Faculty, Staff and Student Publications

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm.

METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n …

Outcomes Of Safety And Effectiveness In A Multicenter Randomized, Controlled Trial Of Whole-Body Hypothermia For Neonatal Hypoxic-Ischemic Encephalopathy, Seetha Shankaran, Athina Pappas, Abbott R Laptook, Scott A Mcdonald, Richard A Ehrenkranz, Jon E Tyson, Michelle Walsh, Ronald N Goldberg, Rosemary D Higgins, Abhik Das

Faculty, Staff and Student Publications

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial.

OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age.

DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups.

RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions …

Contribution Of The Collagen Adhesin Acm To Pathogenesis Of Enterococcus Faecium In Experimental Endocarditis, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Deltaacm::cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations (P < 0.0001) and for valve colonization 1 and 3 hours after infection (P or=50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.

A Functional Collagen Adhesin Gene, Acm, In Clinical Isolates Of Enterococcus Faecium Correlates With The Recent Success Of This Emerging Nosocomial Pathogen, Sreedhar R Nallapareddy, Kavindra V Singh, Pablo C Okhuysen, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm(+)) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P

Effects Of Hypoxic-Ischemic Encephalopathy And Whole-Body Hypothermia On Neonatal Auditory Function: A Pilot Study, Ulrike Mietzsch, Nehal A Parikh, Amber L Williams, Seetha Shankaran, Robert E Lasky

Faculty, Staff and Student Publications

We assessed the effects of hypoxic-ischemic encephalopathy (HIE) and whole-body hypothermia therapy on auditory brain stem evoked responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We performed serial assessments of ABRs and DPOAEs in newborns with moderate or severe HIE, randomized to hypothermia ( N = 4) or usual care ( N = 5). Participants were five boys and four girls with mean gestational age (standard deviation) of 38.9 (1.8) weeks. During the first week of life, peripheral auditory function, as measured by the DPOAEs, was disrupted in all nine subjects. ABRs were delayed but central transmission was intact, suggesting …

Role Of Nono-Histone Interaction In Tnfα-Suppressed Prolyl-4-Hydroxylase Α1, Cheng Zhang, Ming-Xiang Zhang, Ying H Shen, Jared K Burks, Xiao-Nan Li, Scott A Lemaire, Koichi Yoshimura, Hiroki Aoki, Masunori Matsuzaki, Feng-Shuang An, David A Engler, Risë K Matsunami, Joseph S Coselli, Yun Zhang, Xing Li Wang

Faculty, Staff and Student Publications

Inflammation is a key process in cardiovascular diseases. The extracellular matrix (ECM) of the vasculature is a major target of inflammatory cytokines, and TNFalpha regulates ECM metabolism by affecting collagen production. In this study, we have examined the pathways mediating TNFalpha-induced suppression of prolyl-4 hydroxylase alpha1 (P4Halpha1), the rate-limiting isoform of P4H responsible for procollagen hydroxylation, maturation, and organization. Using human aortic smooth muscle cells, we found that TNFalpha activated the MKK4-JNK1 pathway, which induced histone (H) 4 lysine 12 acetylation within the TNFalpha response element in the P4Halpha1 promoter. The acetylated-H4 then recruited a transcription factor, NonO, which, in …

Influence Of Host Interleukin-10 Polymorphisms On Development Of Traveler's Diarrhea Due To Heat-Labile Enterotoxin-Producing Escherichia Coli In Travelers From The United States Who Are Visiting Mexico, Jose Flores, Herbert L Dupont, Stephanie A Lee, Jaime Belkind-Gerson, Mercedes Paredes, Jamal A Mohamed, Lisa Y Armitige, Dong-Chuan Guo, Pablo C Okhuysen

Faculty, Staff and Student Publications

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to …

Structures And Functions Of The Normal And Injured Human Olfactory Epithelium, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Faculty, Staff and Student Publications

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Generalized Fuzzy Clustering For Segmentation Of Multi-Spectral Magnetic Resonance Images, Renjie He, Sushmita Datta, Balasrinivasa Rao Sajja, Ponnada A Narayana

Faculty, Staff and Student Publications

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of intensity are added into the FCM cost functions. To reduce the computational complexity, the contextual regularizations are separated from the clustering iterations. Since the feature space is not isotropic, …

The Temporal Relationship Between The Coronavirus Disease 2019 (Covid-19) Pandemic And Preterm Birth, Harold E Bedell, Mahalakshmi Ramamurthy, Saumil S Patel, Shobana Subramaniam, Lan-Phuong Vu-Yu, Jianliang Tong

Faculty, Staff and Student Publications

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment …

Obesity And Cardiac Metabolism In Women, Heinrich Taegtmeyer, Mohamed F Algahim

Faculty, Staff and Student Publications

No abstract provided.

Pcr-Based Assay Using Occult Blood Detection Cards For Detection Of Diarrheagenic Escherichia Coli In Specimens From Us Travelers To Mexico With Acute Diarrhea, Kevin A Grimes, Jamal A Mohamed, Herbert L Dupont, Ranjit S Padda, Zhi-Dong Jiang, Jose Flores, Jaime Belkind-Gerson, Francisco G Martinez-Sandoval, Pablo C Okhuysen

Faculty, Staff and Student Publications

Large field studies of travelers' diarrhea for multiple destinations are limited by the need to perform stool cultures on site in a timely manner. A method for the collection, transport, and storage of fecal specimens that does not require immediate processing and refrigeration and that is stable for months would be advantageous. This study was designed to determine if enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E. coli (EAEC) DNA could be identified from cards that were processed for the evaluation of fecal occult blood. U.S. students traveling to Mexico during 2005 to 2007 were monitored for the occurrence of diarrheal …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Rtr1 Is The Saccharomyces Cerevisiae Homolog Of A Novel Family Of Rna Polymerase Ii-Binding Proteins, Patrick A Gibney, Thomas Fries, Susanne M Bailer, Kevin A Morano

Faculty, Staff and Student Publications

Cells must rapidly sense and respond to a wide variety of potentially cytotoxic external stressors to survive in a constantly changing environment. In a search for novel genes required for stress tolerance in Saccharomyces cerevisiae, we identified the uncharacterized open reading frame YER139C as a gene required for growth at 37 degrees C in the presence of the heat shock mimetic formamide. YER139C encodes the closest yeast homolog of the human RPAP2 protein, recently identified as a novel RNA polymerase II (RNAPII)-associated factor. Multiple lines of evidence support a role for this gene family in transcription, prompting us to rename …

Intensive Care For Extreme Prematurity--Moving Beyond Gestational Age, Jon E Tyson, Nehal A Parikh, John Langer, Charles Green, Rosemary D Higgins

Faculty, Staff and Student Publications

BACKGROUND: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients.

METHODS: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to …

Clinical And Microbiological Aspects Of Linezolid Resistance Mediated By The Cfr Gene Encoding A 23s Rrna Methyltransferase, Cesar A Arias, Martha Vallejo, Jinnethe Reyes, Diana Panesso, Jaime Moreno, Elizabeth Castañeda, Maria V Villegas, Barbara E Murray, John P Quinn

Faculty, Staff and Student Publications

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), …

Activation Of Heat Shock And Antioxidant Responses By The Natural Product Celastrol: Transcriptional Signatures Of A Thiol-Targeted Molecule, Amy Trott, James D West, Lada Klaić, Sandy D Westerheide, Richard B Silverman, Richard I Morimoto, Kevin A Morano

Faculty, Staff and Student Publications

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional …

Devices In Heart Failure: Potential Methods For Device-Based Monitoring Of Congestive Heart Failure, Shahzeb M Munir, Roberta C Bogaev, Ed Sobash, K J Shankar, Sreedevi Gondi, Igor V Stupin, Jillian Robertson, M Alan Brewer, S Ward Casscells, Reynolds M Delgado, Amany Ahmed

Faculty, Staff and Student Publications

Congestive heart failure has long been one of the most serious medical conditions in the United States; in fact, in the United States alone, heart failure accounts for 6.5 million days of hospitalization each year. One important goal of heart-failure therapy is to inhibit the progression of congestive heart failure through pharmacologic and device-based therapies. Therefore, there have been efforts to develop device-based therapies aimed at improving cardiac reserve and optimizing pump function to meet metabolic requirements. The course of congestive heart failure is often worsened by other conditions, including new-onset arrhythmias, ischemia and infarction, valvulopathy, decompensation, end-organ damage, and …

Juvenile Onset Central Nervous System Folate Deficiency And Rheumatoid Arthritis, Mary Kay Koenig, Maria Perez, Sheldon Rothenberg, Ian J Butler

Faculty, Staff and Student Publications

Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.

Messenger Rna Half-Life Measurements In Mammalian Cells, Chyi-Ying A Chen, Nader Ezzeddine, Ann-Bin Shyu

Faculty, Staff and Student Publications

The recognition of the importance of mRNA turnover in regulating eukaryotic gene expression has mandated the development of reliable, rigorous, and "user-friendly" methods to accurately measure changes in mRNA stability in mammalian cells. Frequently, mRNA stability is studied indirectly by analyzing the steady-state level of mRNA in the cytoplasm; in this case, changes in mRNA abundance are assumed to reflect only mRNA degradation, an assumption that is not always correct. Although direct measurements of mRNA decay rate can be performed with kinetic labeling techniques and transcriptional inhibitors, these techniques often introduce significant changes in cell physiology. Furthermore, many critical mechanistic …

Genes In Glucose Metabolism And Association With Spina Bifida, Christina M Davidson, Hope Northrup, Terri M King, Jack M Fletcher, Irene Townsend, Gayle H Tyerman, Kit Sing Au

Faculty, Staff and Student Publications

The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

Illusory Predictors: Generalizability Of Findings In Cocaine Treatment Retention Research, Angela L Stotts, Marc E Mooney, Shelly L Sayre, Meredith Novy, Joy M Schmitz, John Grabowski

Faculty, Staff and Student Publications

Treatment retention is of paramount importance in cocaine treatment research as treatment completion rates are often 50% or less. Failure to retain cocaine patients in treatment has both significant research and clinical implications. In this paper we qualitatively and quantitatively demonstrate the inconsistency found across analyses of retention predictors in order to highlight the problem. First, a qualitative review of the published literature was undertaken to identify the frequency of predictors studied and their relations to treatment retention. Second, an empirical demonstration of predictor stability was conducted by testing a common set of variables across three similar 12-week cocaine clinical …

Neurogranin Controls The Spatiotemporal Pattern Of Postsynaptic Ca2+/Cam Signaling, Yoshihisa Kubota, John A Putkey, M Neal Waxham

Faculty, Staff and Student Publications

Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle …

Human Tob, An Antiproliferative Transcription Factor, Is A Poly(A)-Binding Protein-Dependent Positive Regulator Of Cytoplasmic Mrna Deadenylation, Nader Ezzeddine, Tsung-Cheng Chang, Wenmiao Zhu, Akio Yamashita, Chyi-Ying A Chen, Zhenping Zhong, Yukiko Yamashita, Dinghai Zheng, Ann-Bin Shyu

Faculty, Staff and Student Publications

In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and …