Medicine and Health Sciences Commons^™

Partition Decoupling For Multi-Gene Analysis Of Gene Expression Profiling Data, Rosemary Braun, Gregory Leibon, Scott Pauls, Daniel Rockmore

Dartmouth Scholarship

Background:

Multi-gene interactions likely play an important role in the development of complex phenotypes, and relationships between interacting genes pose a challenging statistical problem in microarray analysis, since the genes involved in these interactions may not exhibit marginal differential expression. As a result, it is necessary to develop tools that can identify sets of interacting genes that discriminate phenotypes without requiring that the classification boundary between phenotypes be convex.

Results:

We describe an extension and application of a new unsupervised statistical learning technique, known as the Partition Decoupling Method (PDM), to gene expression microarray data. This method may be used …

Prevalence And Risk Factors Of Major Depressive Disorder In Hiv/Aids As Seen In Semi-Urban Entebbe District, Uganda, Eugene Kinyanda, Susan Hoskins, Juliet Nakku, Saira Nawaz, Vikram Patel

Dartmouth Scholarship

Background:

Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda.

Methods:

A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda.

Results:

Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

Rice Consumption Contributes To Arsenic Exposure In Us Women, Diane Gilbert-Diamond, Kathryn L. Cottingham, Joann F. Gruber, Tracy Punshon, Vicki Sayarath, A. Jay Gandolfi, Emily R. Baker, Brian P. Jackson, Carol L. Folt, Margaret R. Karagas

Dartmouth Scholarship

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n …

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio

Dartmouth Scholarship

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of …

Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib

Dartmouth Scholarship

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), …

Lymphotoxin-Beta Receptor Blockade Reduces Cxcl13 In Lacrimal Glands And Improves Corneal Integrity In The Nod Model Of Sjögren's Syndrome, Roy A. Fava, Susan M. Kennedy, Sheryl G. Wood, Anne I. Bolstad, Jadwiga Bienkowska, Adrian Papandile, John A. Kelly

Dartmouth Scholarship

In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome.

Combined Fluorescence And Reflectance Spectroscopy For In Vivo Quantification Of Cancer Biomarkers In Low- And High-Grade Glioma Surgery, Pablo A. ValdéS, Anthony Kim, Keith D. Paulsen, Frederic Leblond, Olga M. Conde, Brent T. Harris, David W. Roberts

Dartmouth Scholarship

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin …

Chromosome Missegregation In Human Cells Arises Through Specific Types Of Kinetochore–Microtubule Attachment Errors, Sarah L. Thompson, Duane A. Compton

Dartmouth Scholarship

Most solid tumors are aneuploid, and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). CIN reflects the erosion of mitotic fidelity, and it correlates with poor patient prognosis and drug resistance. The most common mechanism causing CIN is the persistence of improper kinetochore–microtubule attachments called merotely. Chromosomes with merotelic kinetochores often manifest as lagging chromosomes in anaphase, suggesting that lagging chromosomes fail to segregate properly. However, it remains unknown whether the lagging chromosomes observed in anaphase segregate to the correct or incorrect daughter cell. To address this question, we tracked the segregation of a single …

Characterization Of Street Food Consumption In Palermo: Possible Effects On Health, Silvio Buscemi, Annamaria Barile, Vincenza Maniaci, John A. Batsis

Dartmouth Scholarship

Background: Street Food (SF) consists of out-of-home food consumption and has old, historical roots with complex social-economic and cultural implications. Despite the emergence of modern fast food, traditional SF persists worldwide, but the relationship of SF consumption with overall health, well-being, and obesity is unknown.

Methods: This is an observational, cross-sectional study. The study was performed in Palermo, the largest town of Sicily, Italy. Two groups were identified: consumers of SF (n = 687) and conventional restaurant food (RES) consumers (n = 315). Study subjects answered a questionnaire concerning their health conditions, nutritional preferences, frequency of consumption of SF and …

Adapt-Lite: Privacy-Aware, Secure, And Efficient Mhealth Sensing, Shrirang Mare, Jacob Sorber, Minho Shin, Cory Cornelius, David Kotz

Dartmouth Scholarship

As healthcare in many countries faces an aging population and rising costs, mobile sensing technologies promise a new opportunity. Using mobile health (mHealth) sensing, which uses medical sensors to collect data about the patients, and mobile phones to act as a gateway between sensors and electronic health record systems, caregivers can continuously monitor the patients and deliver better care. Although some work on mHealth sensing has addressed security, achieving strong security and privacy for low-power sensors remains a challenge. \par We make three contributions. First, we propose Adapt-lite, a set of two techniques that can be applied to existing wireless …

Protective Cd8 Memory T Cell Responses To Mouse Melanoma Are Generated In The Absence Of Cd4 T Cell Help, Anik L. Côté, Katelyn T. Byrne, Shannon M. Steinberg, Peisheng Zhang, Mary Jo Turk

Dartmouth Scholarship

Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma.

2-Heptyl-4-Quinolone, A Precursor Of The Pseudomonas Quinolone Signal Molecule, Modulates Swarming Motility In Pseudomonas Aeruginosa, Dae-Gon Ha, Judith H. Merritt, Thomas H. Hampton, James T. Hodgkinson, Matej Janecek, David R. Spring, Martin Welch, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen capable of group behaviors, including biofilm formation and swarming motility. These group behaviors are regulated by both the intracellular signaling molecule c-di-GMP and acylhomoserine lactone quorum-sensing systems. Here, we show that the Pseudomonas quinolone signal (PQS) system also contributes to the regulation of swarming motility. Specifically, our data indicate that 2-heptyl-4-quinolone (HHQ), a precursor of PQS, likely induces the production of the phenazine-1-carboxylic acid (PCA), which in turn acts via an as-yet-unknown downstream mechanism to repress swarming motility. We show that this HHQ- and PCA-dependent swarming repression is apparently independent of changes in global …

Use Of Dried-Blood-Spot Samples And In-House Assays To Identify Antiretroviral Drug Resistance In Hiv-Infected Children In Resource-Constrained Settings, Carrie Ziemniak, Yohannes Mengistu, Andrea Ruff, Ya-Hui Chen, Leila Khaki, Abubaker Bedri, Birgitte B. Simen, Paul Palumbo

Dartmouth Scholarship

Monitoring HIV drug resistance is an important component of the World Health Organization's global HIV program. HIV drug resistance testing is optimal with commercially available clinically validated test kits using plasma; however, that type of testing may not be feasible or affordable in resource-constrained settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in-house) assays may facilitate the capture of HIV drug resistance outcomes in resource-constrained settings but has had varying rates of success. With in-house assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS samples collected from HIV-infected children who were enrolled in two clinical …

Strain-Dependent Variation In The Early Transcriptional Response To Cns Injury Using A Cortical Explant System, David J. Graber, Brent T. Harris, William F. Hickey

Dartmouth Scholarship

While it is clear that inbred strains of mice have variations in immunological responsiveness, the influence of genetic background following tissue damage in the central nervous system is not fully understood. A cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains. Immunological mRNAs were measured in cerebral cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. Levels of mRNA, normalized to β-actin, were compared using one way analysis …

Supplier-Induced Demand For Psychiatric Admissions In Northern New England, Bradley V. Watts, Brian Shiner, Gunnar Klauss, William B. Weeks

Dartmouth Scholarship

The development of hospital service areas (HSAs) using small area analysis has been useful in examining variation in medical and surgical care; however, the techniques of small area analysis are underdeveloped in understanding psychiatric admission rates. We sought to develop these techniques in order to understand the relationship between psychiatric bed supply and admission rates in Northern New England. Our primary hypotheses were that there would be substantial variation in psychiatric admission across geographic settings and that bed availability would be positively correlated with admission rates, reflecting a supplier-induced demand phenomenon. Our secondary hypothesis was that the construction of psychiatric …

Coordinated Regulation By Agra, Sara, And Sarr To Control Agr Expression In Staphylococcus Aureus, Dindo Reyes, Diego O. Andrey, Antoinette Monod, William L. Kelley, Gongyi Zhang, Ambrose L. Cheung

Dartmouth Scholarship

The agr locus of Staphylococcus aureus is composed of two divergent transcripts (RNAII and RNAIII) driven by the P2 and P3 promoters. The P2-P3 intergenic region comprises the SarA/SarR binding sites and the four AgrA boxes to which AgrA binds. We reported here the role of AgrA, SarA, and SarR on agr P2 and P3 transcription. Using real-time reverse transcription (RT)-PCR and promoter fusion studies with selected single, double, triple, and complemented mutants, we showed that AgrA is indispensable to agr P2 and P3 transcription, whereas SarA activates and SarR represses P2 transcription. In vitro runoff transcription assays revealed that …

Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib

Dartmouth Scholarship

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factorsignal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat12/2 and IFNaßcR2/2 mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat12/2 mice and in IFNaßcR2/2 mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat12/2(N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day …

Deletion Of Rb Accelerates Pancreatic Carcinogenesis By Oncogenic Kras And Impairs Senescence In Pre-Malignant Lesions, Catherine Carrière, A. Jesse Gore, Alixanna M. Norris, Jason R. Gunn, Alison Young, Daniel Longnecker, Murray Korc

Dartmouth Scholarship

Rb1 encodes a cell-cycle regulator that is functionally disrupted in most human cancers. Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB). To determine the role of loss of RB function in PDAC progression, we investigated the effects of Rb disruption during pancreatic malignant transformation initiated by oncogenic Kras.We generated mice with pancreas-specific disruption of Rb, in the absence or presence of oncogenic Kras, to examine the role of RB in pancreatic carcinogenesis.

Protoporphyrin Ix Fluorescence Contrast In Invasive Glioblastomas Is Linearly Correlated With Gd Enhanced Magnetic Resonance Image Contrast But Has Higher Diagnostic Accuracy, Kimberley S. Samkoe, Summer L. Gibbs-Strauss, Harold H. Yang, S. Khan Hekmatyar, P. Jack Hoopes, Julia A. O'Hara, Risto A. Kauppinen, Brian W. Pogue

Dartmouth Scholarship

The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 …

Estimating Water Supply Arsenic Levels In The New England Bladder Cancer Study, John R. Nuckols, Laura E. Beane-Freeman, Jay H. Lubin, Matthew S. Airola, Dalsu Baris, Joseph D. Ayotte, Anne Taylor, Chris Paulu, Margaret R. Karagas, Joanne Colt

Dartmouth Scholarship

Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer.

Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case–control study in northern New England.

Methods: Estimates covered the lifetimes of most study participants and were …

Step-Wise Loss Of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion, Rustin R. Lovewell, Ryan M. Collins, Julie L. Acker, George A. O'Toole, Matthew J. Wargo, Brent Berwin, Craig R. Roy

Dartmouth Scholarship

Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate …

Characterization Of Vibrio Cholerae O1 El Tor Biotype Variant Clinical Isolates From Bangladesh And Haiti, Including A Molecular Genetic Analysis Of Virulence Genes, Mike S. Son, Christina J. Megli, Gabriela Kovacikova, Firdausi Qadri, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and …

Alpha-Defensins 1-3 Release By Dendritic Cells Is Reduced By Estrogen, Maria M. Escribese, Marta Rodríguez-García, Rhoda Sperling, Stephanie M. Engel

Dartmouth Scholarship

During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown …

Adaptive Security And Privacy For Mhealth Sensing, Shrirang Mare, Jacob Sorber, Minho Shin, Cory Cornelius, David Kotz

Dartmouth Scholarship

As healthcare in many countries faces an aging population and rising costs, mobile Health (mHealth) sensing technologies promise a new opportunity. However, the privacy concerns associated with mHealth sensing are a limiting factor for their widespread adoption. The use of wireless body area networks pose a particular challenge. Although there exist protocols that provide a secure and private communication channel between two devices, the large transmission overhead associated with these protocols limit their application to low-power mHealth sensing devices. We propose an adaptive security model that enables use of privacy-preserving protocols in low-power mHealth sensing by reducing the network overhead …

Exposing Privacy Concerns In Mhealth, Aarathi Prasad, Jacob Sorber, Timothy Stablein, Denise Anthony, David Kotz

Dartmouth Scholarship

We conducted several exploratory focus groups to understand what privacy concerns Patients might have with the collection, storage and sharing of their personal health information, when using mHealth devices. We found that Patients want control over their health information, and we noticed privacy trends that were particular to Patients in the same age group and with similar health experiences.

Synergistic Combination Of Hyperoxygenation And Radiotherapy By Repeated Assessments Of Tumor Po2 With Epr Oximetry, Huagang Hou, Ruhong Dong, Jean P. Lariviere, Sriram P. Mupparaju, Harold M. Swartz, Nadeem Khan

Dartmouth Scholarship

The effect of hyperoxygenation with carbogen (95% O₂ + 5% CO₂) inhalation on RIF-1 tumor pO₂and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO₂ were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O₂ or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO₂ of 5–9 mmHg. Carbogen (CB) breathing significantly increased tumor pO₂, …

Protection And Attachment Of Vibrio Cholerae Mediated By The Toxin-Coregulated Pilus In The Infant Mouse Model, Shelly J. Krebs, Ronald K. Taylor

Dartmouth Scholarship

Colonization of the human small intestine by Vibrio cholerae is an essential step in pathogenesis that requires the type IV toxin-coregulated pilus (TCP). To date, three functions of TCP have been characterized: it serves as the CTXΦ receptor, secretes the colonization factor TcpF, and functions in microcolony formation by mediating bacterium-bacterium interactions. Although type IV pili in other pathogenic bacteria have been characterized as playing a major role in attachment to epithelial cells, there are very few studies to suggest that TCP acts as an attachment factor. Taking this into consideration, we investigated the function of TCP in attachment to …

Assessing Medicare Beneficiaries’ Strength‐Of‐Preference Scores For Health Care Options: How Engaging Does The Elicitation Technique Need To Be?, Trafford Crump, Hilary A. Llewellyn-Thomas

Dartmouth Scholarship

The objective was to determine if participants’ strength‐of‐preference scores for elective health care interventions at the end‐of‐life (EOL) elicited using a non‐engaging technique are affected by their prior use of an engaging elicitation technique.

Systematic Analysis Of Diguanylate Cyclases That Promote Biofilm Formation By Pseudomonas Fluorescens Pf0-1, Peter D. Newell, Shiro Yoshioka, Kelli L. Hvorecny, Russell D. Monds, George A. O'Toole

Dartmouth Scholarship

Cyclic di-GMP (c-di-GMP) is a broadly conserved, intracellular second-messenger molecule that regulates biofilm formation by many bacteria. The synthesis of c-di-GMP is catalyzed by diguanylate cyclases (DGCs) containing the GGDEF domain, while its degradation is achieved through the phosphodiesterase activities of EAL and HD-GYP domains. c-di-GMP controls biofilm formation by Pseudomonas fluorescens Pf0-1 by promoting the cell surface localization of a large adhesive protein, LapA. LapA localization is regulated posttranslationally by a c-di-GMP effector system consisting of LapD and LapG, which senses cytoplasmic c-di-GMP and modifies the LapA protein in the outer membrane. Despite the apparent requirement for c-di-GMP for …