Medicine and Health Sciences Commons^™

Isolation Of Mycobacterium Avium From Potable Water In Homes And Institutions Of Patients With Hiv Infection In Finland And The United States, Matti Ristola, Robert D. Arbeit, C. Fordham Von Reyn, C. Robert Horsburgh

Dartmouth Scholarship

Symptomatic disease by nontuberculous mycobacteria has been linked to potable water from institutional and domestic potable water systems. Potable water samples were collected from homes and institutions of patients with AIDS. Colonization of potable water with nontuberculous mycobacteria was demonstrated in 230 (15%) of 1489 samples collected from domestic and institutional water systems of patients with HIV infection in the United States and Finland. Mycobacterium avium was the most common species and colonization was favored at temperatures of 40–50°C in recirculating hot water systems. Such systems are a plausible source of human infection and disease.

Pseudomonas Aeruginosa Reduces Vx-809 Stimulated F508del-Cftr Chloride Secretion By Airway Epithelial Cells, Bruce A. Stanton, Bonita Coutermarsh, Roxanna Barnaby, Deborah Hogan

Dartmouth Scholarship

Background:

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and …

Electrocardiographic Patch Devices And Contemporary Wireless Cardiac Monitoring, Erik Fung, Marjo-Riitta Järvelin, Rahul N. Doshi, Jerold S. Shinbane, Steven K. Carlson, Luanda P. Grazette, Philip M. Chang, Rajbir S. Sangha, Heikki V. Huikuri, Nicholas S. Peters

Dartmouth Scholarship

Cardiac electrophysiologic derangements often coexist with disorders of the circulatory system. Capturing and diagnosing arrhythmias and conduction system disease may lead to a change in diagnosis, clinical management and patient outcomes. Standard 12-lead electrocardiogram (ECG), Holter monitors and event recorders have served as useful diagnostic tools over the last few decades. However, their shortcomings are only recently being addressed by emerging technologies. With advances in device miniaturization and wireless technologies, and changing consumer expectations, wearable “on-body” ECG patch devices have evolved to meet contemporary needs. These devices are unobtrusive and easy to use, leading to increased device wear time and …

Intestinal Colonization Dynamics Of Vibrio Cholerae, Salvador Almagro-Moreno, Kali Pruss, Ronald K. Taylor

Dartmouth Scholarship

To cause the diarrheal disease cholera, Vibrio cholerae must effectively colonize the small intestine. In order to do so, the bacterium needs to successfully travel through the stomach and withstand the presence of agents such as bile and antimicrobial peptides in the intestinal lumen and mucus. The bacterial cells penetrate the viscous mucus layer covering the epithelium and attach and proliferate on its surface. In this review, we discuss recent developments and known aspects of the early stages of V. cholerae intestinal colonization and highlight areas that remain to be fully understood. We propose mechanisms and postulate a model …

Regulators Associated With Clinical Outcomes Revealed By Dna Methylation Data In Breast Cancer, Matthew H. Ung, Frederick S. Varn, Shaoke Lou, Chao Cheng

Dartmouth Scholarship

The regulatory architecture of breast cancer is extraordinarily complex and gene misregulation can occur at many levels, with transcriptional malfunction being a major cause. This dysfunctional process typically involves additional regulatory modulators including DNA methylation. Thus, the interplay between transcription factor (TF) binding and DNA methylation are two components of a cancer regulatory interactome presumed to display correlated signals. As proof of concept, we performed a systematic motif-based in silico analysis to infer all potential TFs that are involved in breast cancer prognosis through an association with DNA methylation changes. Using breast cancer DNA methylation and clinical data derived from …

Haemophilus Influenzae Responds To Glucocorticoids Used In Asthma Therapy By Modulation Of Biofilm Formation And Antibiotic Resistance, Chris S. Earl, Tee Wooi Keong, Shi-Qi An, Sarah Murdoch, Yvonne Mccarthy, Junkal Garmendia, Joseph Ward, J Maxwell Dow, Liang Yang, George A. O'Toole, Robert P. Ryan

Dartmouth Scholarship

Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associ- ated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that cortico- steroid treatment promotes H. influenzae persistence. Transcrip- tomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of …

Assessment Of Patient Empowerment - A Systematic Review Of Measures, Paul Barr, Isabelle Scholl, Paulina Bravo, Marjan J. Faber, Glyn Elwyn, Marion Mcallister

Dartmouth Scholarship

Patient empowerment has gained considerable importance but uncertainty remains about the best way to define and measure it. The validity of empirical findings depends on the quality of measures used. This systematic review aims to provide an overview of studies as- sessing psychometric properties of questionnaires purporting to capture patient empower- ment, evaluate the methodological quality of these studies and assess the psychometric properties of measures identified.

Clustered Regularly Interspaced Short Palindromic Repeat-Dependent, Biofilm-Specific Death Of Pseudomonas Aeruginosa Mediated By Increased Expression Of Phage-Related Genes, Gary E. E. Heussler, Kyle C. Cady, Katja Koeppen, Sabin Bhuju, Bruce A. Stanton, George A. O’Toole

Dartmouth Scholarship

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (CRISPR/Cas) system is an adaptive immune system present in many archaea and bacteria. CRISPR/Cas systems are incredibly diverse, and there is increasing evidence of CRISPR/Cas systems playing a role in cellular functions distinct from phage immunity. Previously, our laboratory reported one such alternate function in which the type 1-F CRISPR/Cas system of the opportunistic pathogen Pseudomonas aeruginosa strain UCBPP-PA14 (abbreviated as P. aeruginosa PA14) inhibits both biofilm formation and swarming motility when the bacterium is lysogenized by the bacteriophage DMS3. In this study, we demonstrated that the presence of just the DMS3 …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Sex-Specific Parental Effects On Offspring Lipid Levels, Irene M. Predazzi, Rafal S. Sobota, Serena Sanna, William S. Bush, Jacquelaine Bartlett, Jessica S. Lilley, Macrae F. Linton, David Schlessinger, Francesco Cucca, Sergio Fazio, Scott M. Williams

Dartmouth Scholarship

Background:

Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.

Methods and Results:

In this study, we analyzed the role of parental levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL‐C, HDL‐C, and TG levels. …

Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik

Dartmouth Scholarship

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of …

Patients Covertly Recording Clinical Encounters: Threat Or Opportunity? A Qualitative Analysis Of Online Texts, Maka Tsulukidze, Stuart W. W. Grande, Rachel Thompson, Kenneth Rudd, Glyn Elwyn

Dartmouth Scholarship

Background: The phenomenon of patients covertly recording clinical encounters has generated controversial media reports. This study aims to examine the phenomenon and analyze the underlying issues. Methods and Findings: We conducted a qualitative analysis of online posts, articles, blogs, and forums (texts) discussing patients covertly recording clinical encounters. Using Google and Google Blog search engines, we identified and analyzed 62 eligible texts published in multiple countries between 2006 and 2013. Thematic analysis revealed four key themes: 1) a new behavior that elicits strong reactions, both positive and negative, 2) an erosion of trust, 3) shifting patient-clinician roles and relationships, and …

Estimated Exposure To Arsenic In Breastfed And Formula-Fed Infants In A United States Cohort, Courtney C. Carignan, Kathryn L. Cottingham, Brian P. Jackson, Shohreh F. Farzan, A Jay Gandolfi, Tracy Punshon, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Background: Previous studies indicate that concentrations of arsenic in breast milk are relatively low even in areas with high drinking-water arsenic. However, it is uncertain whether breastfeeding leads to reduced infant exposure to arsenic in regions with lower arsenic concentrations.

Objective: We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. population.

Methods: We measured arsenic in home tap water (n = 874), urine from 6-week-old infants (n = 72), and breast milk from mothers (n = 9) enrolled in the New Hampshire Birth Cohort Study (NHBCS) using …

Shugoshin-1 Balances Aurora B Kinase Activity Via Pp2a To Promote Chromosome Bi-Orientation, Amanda Meppelink, Lilian Kabeche, Martijn J.M. Vromans, Duane A. Compton, Susanne M.A. Lens

Dartmouth Scholarship

Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule …

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Coculture Of Staphylococcus Aureus With Pseudomonas Aeruginosa Drives S. Aureus Towards Fermentative Metabolism And Reduced Viability In A Cystic Fibrosis Model, Laura M. Filkins, Jyoti A. Graber, Daniel G. Olson, Emily L. Dolben, Lee Lynd, Sabin Bhuju, George A. O'Toole

Dartmouth Scholarship

The airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood. Staphylococcus aureus is the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading to Pseudomonas aeruginosa community predominance in ∼50% of adults. We developed a robust dual-bacterial in vitro coculture system of P. aeruginosa and S. aureus on monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show that P. …

Molecular Dyes Used For Surgical Specimen Margin Orientation Allow For Intraoperative Optical Assessment During Breast Conserving Surgery, David M. Mcclatchy, Venkataramanan Krishnaswamy, Stephen C. Kanick, Jonathan T. Elliott, Wendy A. Wells, Richard J. Barth Jr., Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

A variety of optical techniques utilizing near-infrared (NIR) light are being proposed for intraoperative breast tumor margin assessment. However, immediately following a lumpectomy excision, the margins are inked, which preserves the orientation of the specimen but prevents optical interrogation of the tissue margins. Here, a workflow is proposed that allows for both NIR optical assessment following full specimen marking using molecular dyes which have negligible absorption and scattering in the NIR. The effect of standard surgical inks in contrast to molecular dyes for an NIR signal is shown. Further, the proposed workflow is demonstrated with full specimen intraoperative imaging on …

Sec17 Can Trigger Fusion Of Trans-Snare Paired Membranes Without Sec18, Michael Zick, Amy Orr, Matthew L. Schwartz, Alexey J. Merz, William Wickner

Dartmouth Scholarship

Sec17 [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. …

Can Shared Decision-Making Reduce Medical Malpractice Litigation? A Systematic Review, Marie-Anne Durand, Benjamin Moulton, Elizabeth Cockle, Mala Mann, Glyn Elwyn

Dartmouth Scholarship

Background: To explore the likely influence and impact of shared decision-making on medical malpractice litigation and patients’ intentions to initiate litigation.

Methods: We included all observational, interventional and qualitative studies published in all languages, which assessed the effect or likely influence of shared decision-making or shared decision-making interventions on medical malpractice litigation or on patients ’ intentions to litigate. The following databases were searched from inception until January 2014: CINAHL, Cochrane Register of Controlled Trials, Cochrane Da tabase of Systematic Reviews, EMBASE, HMIC, Lexis library, MEDLINE, NHS Economic Evaluation Database, Open SIGLE, PsycINFO and Web of Knowledge. We also hand …

Early Inflammatory Mediator Gene Expression In Two Models Of Traumatic Brain Injury: Ex Vivo Cortical Slice In Mice And In Vivo Cortical Impact In Piglets, David J. Graber, Beth A. Costine, William F. Hickey

Dartmouth Scholarship

Background: The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression.

Methods: To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury.

Measuring Intensity Of End Of Life Care: A Systematic Review, Xhyljeta Luta, Maud Maessen, Matthias Egger, Andreas E. Stuck, David Goodman, Kerri M. Clough-Gorr

Dartmouth Scholarship

Background: Many studies have measured the intensity of end of life care. However, no summary of the measures used in the field is currently available. Objectives: To summarise features, characteristics of use and reported validity of measures used for evaluating intensity of end of life care. Methods: This was a systematic review according to PRISMA guidelines. We performed a comprehensive literature search in Ovid Medline, Embase, The Cochrane Library of Systematic Reviews and reference lists published between 1990-2014. Two reviewers independently screened titles, abstracts, full texts and extracted data. Studies were eligible if they used a measure of end of …

Proteolysis Of Virulence Regulator Toxr Is Associated With Entry Of Vibrio Cholerae Into A Dormant State, Salvador Almagro-Moreno, Tae K. Kim, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP) in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human …

Trends In Initial Management Of Prostate Cancer In New Hampshire, Johann Ingimarsson, Maria Celaya, Michael Laviolette, Judy R. Rees, Elias Hyams

Dartmouth Scholarship

Purpose Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that ‘‘low-risk’’ cancer is best treated with observation, while localized ‘‘high-risk’’ cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence- based practice. Methods From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004–2011 were identified and classified according to D’Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square …

Antibody-Mediated Targeting Of Iron Oxide Nanoparticles To The Folate Receptor Alpha Increases Tumor Cell Association In Vitro And In Vivo, Christian Ndong, Seiko Toraya-Brown, Katsiaryna Kekalo, Ian Baker, Tillman U. Gerngross, Steven N. Fiering, Karl E. Griswold

Dartmouth Scholarship

Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm …

The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau

Dartmouth Scholarship

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize …

Preliminary Analysis Of In Utero Low-Level Arsenic Exposure And Fetal Growth Using Biometric Measurements Extracted From Fetal Ultrasound Reports, Matthew A. Davis, John Higgins, Zhigang Li, Diane Gilbert-Diamond, Emily R. Baker, Amar Das, Margaret R. Karagas

Dartmouth Scholarship

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero.

Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth …

Developing Integrate: A Fast And Frugal Patient-Reported Measure Of Integration In Health Care Delivery, Glyn Elwyn, Rachel Thompson, Roshen John, Stuart W. Grande

Dartmouth Scholarship

Efforts have been made to measure integration in health care delivery, but few existing instruments have adopted a patient perspective, and none is sufficiently generic and brief for administration at scale. We sought to develop a brief and generic patient-reported measure of integration in health care delivery. Drawing on both existing conceptualisations of integrated care and research on patients’ perspectives, we chose to focus on four distinct domains of integration: information sharing, consistent advice, mutual respect and role clarity. We formulated candidate items and conducted cognitive interviews with end users to further develop and refine the items. …

Development And Pilot Feasibility Study Of A Health Information Technology Tool To Calculate Mortality Risk For Patients With Asymptomatic Carotid Stenosis: The Carotid Risk Assessment Tool (Carat), Adrienne E. Faerber, Rebecca Horvath, Carey Stillman, Melissa L. O'Connell, Amy L. Hamilton, Karina A. Newhall, Donald S. Likosky, Philip P. Goodney

Dartmouth Scholarship

Patients with no history of stroke but with stenosis of the carotid arteries can reduce the risk of future stroke with surgery or stenting. At present, a physicians’ ability to recommend optimal treatments based on an individual’s risk profile requires estimating the likelihood that a patient will have a poor peri-operative outcomes and the likelihood that the patient will survive long enough to gain benefit from the procedure. We describe the development of the CArotid Risk Assessment Tool (CARAT) into a 2-year mortality risk calculator within the electronic medical record, integrating the tool into the clinical workflow, training the clinical …

Sparcoc: A New Framework For Molecular Pattern Discovery And Cancer Gene Identification, Shiqian Ma, Daniel Johnson, Cody Ashby, Donghai Xiong, Carole L. Cramer, Jason H. Moore, Shuzhong Zhang, Xiuzhen Huang

Dartmouth Scholarship

It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization (NMF). We apply SPARCoC to the study of lung …

Lipid And Protein Co-Regulation Of Pi3k Effectors Akt And Itk In Lymphocytes, Xinxin Wang, Leonard B. Hills, Yina H. Huang

Dartmouth Scholarship

The phosphoinositide 3-kinase (PI 3-kinase, PI3K) pathway transduces signals critical for lymphocyte function. PI3K generates the phospholipid PIP3 at the plasma membrane to recruit proteins that contain pleckstrin homology (PH) domains - a conserved domain found in hundreds of mammalian proteins. PH domain-PIP3 interactions allow for rapid signal propagation and confer a spatial component to these signals. The kinases Akt and Itk are key PI3K effectors that bind PIP3 via their PH domains and mediate vital processes - such as survival, activation, and differentiation - in lymphocytes. Here, we review the roles and regulation of PI3K signaling in lymphocytes with …