Medicine and Health Sciences Commons^™

Improving Follow-Up Of Abnormal Cancer Screens Using Electronic Health Records: Trust But Verify Test Result Communication, Hardeep Singh, Lindsey Wilson, Laura A Petersen, Mona K Sawhney, Brian Reis, Donna Espadas, Dean F Sittig

Faculty, Staff and Student Publications

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response.

METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. …

Ontology Driven Integration Platform For Clinical And Translational Research, Parsa Mirhaji, Min Zhu, Mattew Vagnoni, Elmer V. Bernstam, Jiajie Zhang, Jack W. Smith

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Semantic Web technologies offer a promising framework for integration of disparate biomedical data. In this paper we present the semantic information integration platform under development at the Center for Clinical and Translational Sciences (CCTS) at the University of Texas Health Science Center at Houston (UTHSC-H) as part of our Clinical and Translational Science Award (CTSA) program. We utilize the Semantic Web technologies not only for integrating, repurposing and classification of multi-source clinical data, but also to construct a distributed environment for information sharing, and collaboration online. Service Oriented Architecture (SOA) is used to modularize and distribute reusable services in a …

Ca125/Muc16 Is Dispensable For Mouse Development And Reproduction, Dong-Joo Cheon, Ying Wang, Jian Min Deng, Zhen Lu, Lianchun Xiao, Chun-Ming Chen, Robert C Bast, Richard R Behringer

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Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 …

Reduced Neutrophil Count In People Of African Descent Is Due To A Regulatory Variant In The Duffy Antigen Receptor For Chemokines Gene, David Reich, Michael A. Nalls, W H Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

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Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. to identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. …

Comparative Efficacy Of 2 Topical Anesthetics For The Placement Of Orthodontic Temporary Anchorage Devices, Derek S Reznik, Arthur H Jeske, Jung-Wei Chen, Jeryl English

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This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P …

Incidental Detection Of An Occult Oral Malignancy With Autofluorescence Imaging: A Case Report, Nadarajah Vigneswaran, Sheila Koh, Ann Gillenwater

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BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma.

CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during …

Morphoproteomic Evidence Of Constitutively Activated And Overexpressed Mtor Pathway In Cervical Squamous Carcinoma And High Grade Squamous Intraepithelial Lesions, Wei Feng, Xiuzhen Duan, Jinsong Liu, Jianguo Xiao, Robert E Brown

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Human papilloma virus (HPV) infection of the uterine cervix is linked to the pathogenesis of cervical cancer. Preclinical in vitro and in vivo studies using HPV-containing human cervical carcinoma cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, erlotinib, can induce growth delay of xenografts. Activation of Akt and mTOR are also observed in cervical squamous cell carcinoma and, the expression of phosphorylated mTOR was reported to serve as a marker to predict response to chemotherapy and survival of cervical cancer patients. Therefore, we investigated: a) the expression …

Computerized Provider Order Entry Adoption: Implications For Clinical Workflow, Emily M. Campbell, Kenneth P. Guappone, Dean F. Sittig, Richard H. Dykstra, Joan S. Ash

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OBJECTIVE: To identify and describe unintended adverse consequences related to clinical workflow when implementing or using computerized provider order entry (CPOE) systems. METHODS: We analyzed qualitative data from field observations and formal interviews gathered over a three-year period at five hospitals in three organizations. Five multidisciplinary researchers worked together to identify themes related to the impacts of CPOE systems on clinical workflow. RESULTS: CPOE systems can affect clinical work by 1) introducing or exposing human/computer interaction problems, 2) altering the pace, sequencing, and dynamics of clinical activities, 3) providing only partial support for the work activities of all types of …

Taxonomy Development And Knowledge Representation Of Nurses' Personal Cognitive Artifacts, Sharon Mclane, James P Turley

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Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive …

Upregulation Of Defensins In Burn Sheep Small Intestine, Brian J Poindexter, Gordon L Klein, Stephen M Milner, Roger J Bick

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OBJECTIVE: The aim of this study was to visualize and localize the sheep antimicrobials, beta-defensins 1, 2, and 3, (SBD-1, SBD-2, SBD-3), sheep neutrophil defensin alpha (SNP-1), and the cathelicidin LL-37 in sheep small intestine after burn injury, our hypothesis being that these compounds would be upregulated in an effort to overcome a compromised endothelial lining. Response to burn injury includes the release of proinflammatory cytokines and systemic immune suppression that, if untreated, can progress to multiple organ failure and death, so protective mechanisms have to be initiated and implemented.

METHODS: Tissue sections were probed with antibodies to the antimicrobials …

Structure Altering Effects Of A Multicomponent Reading Intervention: An Application Of The Direct And Inferential Mediation (Dime) Model Of Reading Comprehension In Upper Elementary Grades, Georgios Kalantzis, Harel Z Shouval

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BACKGROUND: Synaptic plasticity underlies many aspect of learning memory and development. The properties of synaptic plasticity can change as a function of previous plasticity and previous activation of synapses, a phenomenon called metaplasticity. Synaptic plasticity not only changes the functional connectivity between neurons but in some cases produces a structural change in synaptic spines; a change thought to form a basis for this observed plasticity. Here we examine to what extent structural plasticity of spines can be a cause for metaplasticity. This study is motivated by the observation that structural changes in spines are likely to affect the calcium dynamics …

Molluscan Memory Of Injury: Evolutionary Insights Into Chronic Pain And Neurological Disorders, Edgar T Walters, Leonid L Moroz

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Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan …

Is Paromomycin An Effective And Safe Treatment Against Cutaneous Leishmaniasis? A Meta-Analysis Of 14 Randomized Controlled Trials, Dae Hyun Kim, Hye Jin Chung, Joachim Bleys, Reza F Ghohestani

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BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting.

METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled …

Denaturation And Unfolding Of Human Anaphylatoxin C3a: An Unusually Low Covalent Stability Of Its Native Disulfide Bonds, Jui-Yoa Chang, Curtis C-J Lin, Silvia Salamanca, Michael K Pangburn, Rick A Wetsel

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The complement C3a anaphylatoxin is a major molecular mediator of innate immunity. It is a potent activator of mast cells, basophils and eosinophils and causes smooth muscle contraction. Structurally, C3a is a relatively small protein (77 amino acids) comprising a N-terminal domain connected by 3 native disulfide bonds and a helical C-terminal segment. The structural stability of C3a has been investigated here using three different methods: Disulfide scrambling; Differential CD spectroscopy; and Reductive unfolding. Two uncommon features regarding the stability of C3a and the structure of denatured C3a have been observed in this study. (a) There is an unusual disconnection …

Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat–Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne

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Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol …

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

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Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

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It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …

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

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No abstract provided.

Foxm1b Transcriptionally Regulates Vascular Endothelial Growth Factor Expression And Promotes The Angiogenesis And Growth Of Glioma Cells, Yujian Zhang, Nu Zhang, Bingbing Dai, Mingguang Liu, Raymond Sawaya, Keping Xie, Suyun Huang

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We previously found that FoxM1B is overexpressed in human glioblastomas and that forced FoxM1B expression in anaplastic astrocytoma cells leads to the formation of highly angiogenic glioblastoma in nude mice. However, the molecular mechanisms by which FoxM1B enhances glioma angiogenesis are currently unknown. In this study, we found that vascular endothelial growth factor (VEGF) is a direct transcriptional target of FoxM1B. FoxM1B overexpression increased VEGF expression, whereas blockade of FoxM1 expression suppressed VEGF expression in glioma cells. Transfection of FoxM1 into glioma cells directly activated the VEGF promoter, and inhibition of FoxM1 expression by FoxM1 siRNA suppressed VEGF promoter activation. …

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

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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

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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 …

Sustained Attention In Children With Two Etiologies Of Early Hydrocephalus, Maegan D. Swartwout, Paul T. Cirino, Amy W. Hampson, Jack M. Fletcher, Michael E. Brandt, Maureen Dennis

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Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive …

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

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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. …

Concept, Design And Implementation Of A Cardiovascular Gene-Centric 50 K Snp Array For Large-Scale Genomic Association Studies, Brendan J. Keating, Sam Tischfield, Sarah S. Murray, Tushar Bhangale, Thomas S. Price, Joseph T. Glessner, Luana Galver, Jeffrey C. Barrett, Struan F A Grant, Deborah N. Farlow, Hareesh R. Chandrupatla, Mark Hansen, Saad Ajmal, George J. Papanicolaou, Yiran Guo, Mingyao Li, Stephanie Derohannessian, Paul I W. De Bakker, Swneke D. Bailey, Alexandre Montpetit, Andrew C. Edmondson, Kent Taylor, Xiaowu Gai, Susanna S. Wang, Myriam Fornage, Tamim Shaikh, Leif Groop, Michael Boehnke, Alistair S. Hall, Andrew T. Hattersley, Edward Frackelton, Nick Patterson, Charleston K W Chiang, Cecelia E. Kim, Richard R. Fabsitz, Willem Ouwehand, Alkes L. Price, Patricia Munroe, Mark Caulfield, Thomas Drake, Eric Boerwinkle, David Reich, A Stephen Whitehead, Thomas P. Cappola, Nilesh J. Samani, A Jake Lusis, Eric Schadt, James G. Wilson, Wolfgang Koenig, Mark I. Mccarthy, Sekar Kathiresan, Stacey B. Gabriel, Hakon Hakonarson, Sonia S. Anand, Muredach Reilly, James C. Engert, Deborah A. Nickerson, Daniel J. Rader, Joel N. Hirschhorn, Garret A. Fitzgerald

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A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 …

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

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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 …

A Schiff Base Connectivity Switch In Sensory Rhodopsin Signaling, Oleg A Sineshchekov, Jun Sasaki, Brian J Phillips, John L Spudich

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Sensory rhodopsin I (SRI) in Halobacterium salinarum acts as a receptor for single-quantum attractant and two-quantum repellent phototaxis, transmitting light stimuli via its bound transducer HtrI. Signal-inverting mutations in the SRI-HtrI complex reverse the single-quantum response from attractant to repellent. Fast intramolecular charge movements reported here reveal that the unphotolyzed SRI-HtrI complex exists in two conformational states, which differ by their connection of the retinylidene Schiff base in the SRI photoactive site to inner or outer half-channels. In single-quantum photochemical reactions, the conformer with the Schiff base connected to the cytoplasmic (CP) half-channel generates an attractant signal, whereas the conformer …

Syntaxin 3b Is Essential For The Exocytosis Of Synaptic Vesicles In Ribbon Synapses Of The Retina, Leigh B Curtis, Blair Doneske, Xiaoqin Liu, Christina Thaller, James A Mcnew, Roger Janz

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Previous studies have demonstrated that ribbon synapses in the retina do not contain the t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the retina contain the related isoform syntaxin 3. In addition to its localization in ribbon synapses, syntaxin 3 is also found in nonneuronal cells, where it has been implicated in the trafficking of transport vesicles to the apical plasma membrane of polarized cells. The syntaxin 3 gene codes for four different splice forms, syntaxins 3A, 3B, 3C, and 3D. We demonstrate here …

The Untapped Power Of "We Don't Know": Epistemological Humility In The Era Of Covid-19, Diasinou Fioravante, Rong-Yu Liu, John H. Byrne

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The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated …

Role Of The N- And C-Lobes Of Calmodulin In The Activation Of Ca2+/Calmodulin-Dependent Protein Kinase Ii, Amelie Forest, Matthew T Swulius, Joyce K Y Tse, J Michael Bradshaw, Tara Gaertner, M Neal Waxham

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Understanding the principles of calmodulin (CaM) activation of target enzymes will help delineate how this seemingly simple molecule can play such a complex role in transducing Ca (2+)-signals to a variety of downstream pathways. In the work reported here, we use biochemical and biophysical tools and a panel of CaM constructs to examine the lobe specific interactions between CaM and CaMKII necessary for the activation and autophosphorylation of the enzyme. Interestingly, the N-terminal lobe of CaM by itself was able to partially activate and allow autophosphorylation of CaMKII while the C-terminal lobe was inactive. When used together, CaMN and CaMC …

Identification And Phenotypic Characterization Of A Second Collagen Adhesin, Scm, And Genome-Based Identification And Analysis Of 13 Other Predicted Mscramms, Including Four Distinct Pilus Loci, In Enterococcus Faecium, Jouko Sillanpää, Sreedhar R Nallapareddy, Vittal P Prakash, Xiang Qin, Magnus Höök, George M Weinstock, Barbara E Murray

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Attention has recently been drawn to Enterococcus faecium because of an increasing number of nosocomial infections caused by this species and its resistance to multiple antibacterial agents. However, relatively little is known about the pathogenic determinants of this organism. We have previously identified a cell-wall-anchored collagen adhesin, Acm, produced by some isolates of E. faecium, and a secreted antigen, SagA, exhibiting broad-spectrum binding to extracellular matrix proteins. Here, we analysed the draft genome of strain TX0016 for potential microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Genome-based bioinformatics identified 22 predicted cell-wall-anchored E. faecium surface proteins (Fms), of which 15 …