Medicine and Health Sciences Commons^™

Structured Light Scatteroscopy, Venkataramanan Krishnaswamy, Jonathan T. Elliott, David M. Mcclatchy, Richard J. Barth Jr., Wendy A. Wells, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

A new imaging approach, structured light scatteroscopy (SLS), is demonstrated, which offers rapid wide-field imaging of microscopic morphological variations in bulk tissue surfaces. Elastic scattering of light offers exquisite sensitivity to ultrastructural changes at multiple size scales ranging from nanometers to millimeters, but in bulk tissues the confounding effects of molecular absorption and strong multiple scattering of light often lead to a dramatic reduction in scatter contrast and specificity. It is demonstrated that the SLS using structured high spatial frequency illumination and detection to probe the tissue achieves direct, absorption-independent, high-resolution maps of the scattering response. The scattering response is …

Wide-Field In Vivo Neocortical Calcium Dye Imaging Using A Convection-Enhanced Loading Technique Combined With Simultaneous Multiwavelength Imaging Of Voltage-Sensitive Dyes And Hemodynamic Signals, Hongtao Ma, Samuel Harris, Redi Rahmani, Clay O. Lacefield, Mingrui Zhao, Randy M. Bruno, Jason Berwick, Theodore H. Schwartz

Dartmouth Scholarship

In Vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique …

A Comparison Of Five Malaria Transmission Models: Benchmark Tests And Implications For Disease Control, Dorothy I. Wallace, Ben S. Southworth, Xun Shi, Jonathan W. Chipman, Andrew K. Githeko

Dartmouth Scholarship

Background: Models for malaria transmission are usually compared based on the quantities tracked, the form taken by each term in the equations, and the qualitative properties of the systems at equilibrium. Here five models are compared in detail in order to develop a set of performance measures that further illuminate the differences among models.

Methods: Five models of malaria transmission are compared. Parameters are adjusted to correspond to similar biological quantities across models. Nine choices of parameter sets/initial conditions are tested for all five models. The relationship between malaria incidence in humans and (1) malaria incidence in vectors, (2) man-biting …

Stag2 Promotes Error Correction In Mitosis By Regulating Kinetochore–Microtubule Attachments, Marianna Kleyman, Lilian Kabeche, Duane A. Compton

Dartmouth Scholarship

Mutations in the STAG2 gene are present in ∼20% of tumors from different tissues of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss-of-function mutations are usually aneuploid and display elevated frequencies of lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of chromosomal instability (CIN) arising from persistent errors in kinetochore-microtubule (kMT) attachment. To determine whether the loss of STAG2 increases the rate of formation of kMT attachment errors or decreases the rate of their correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does not impair bipolar spindle formation or delay mitotic progression. Instead, …

Comparison Of Magnetic Resonance Imaging-Compatible Optical Detectors For In-Magnet Tissue Spectroscopy: Photodiodes Versus Silicon Photomultipliers, Fadi El-Ghussein, Shudong Jiang, Brian W. Pogue, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

Tissue spectroscopy inside the magnetic resonance imaging (MRI) system adds a significant value by measuring fast vascular hemoglobin responses or completing spectroscopic identification of diagnostically relevant molecules. Advances in this type of spectroscopy instrumentation have largely focused on fiber coupling into and out of the MRI; however, nonmagnetic detectors can now be placed inside the scanner with signal amplification performed remotely to the high field environment for optimized light detection. In this study, the two possible detector options, such as silicon photodiodes (PD) and silicon photomultipliers (SiPM), were systematically examined for dynamic range and wavelength performance. Results show that PDs …

Evaluation Of An Emergency Department Lean Process Improvement Program To Reduce Length Of Stay, Marian J. Vermeulen, Therese A. Stukel, Astrid Guttmann, Brian H. Rowe

Dartmouth Scholarship

In recent years, lean principles have been applied to improve wait times in the emergency department (ED). In 2009, an ED process improvement program based on lean methods was introduced in Ontario as part of a broad strategy to reduce ED length of stay and improve patient flow. This study seeks to determine the effect of this program on ED wait times and quality of care. We conducted a retrospective cohort study of all ED visits at program and control sites during 3 program waves from April 1, 2007, to June 30, 2011, in Ontario, Canada. Time series analyses of …

Dual-Channel Red/Blue Fluorescence Dosimetry With Broadband Reflectance Spectroscopic Correction Measures Protoporphyrin Ix Production During Photodynamic Therapy Of Actinic Keratosis, Stephen Chad Kanick, Scott C. Davis, Yan Zhao, Tayyaba Hasan, Edward V. Maytin, Brian W. Pogue, M Shane Chapman

Dartmouth Scholarship

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for …

Sex Hormones Regulate Tenofovir-Diphosphate In Female Reproductive Tract Cells In Culture, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Angela D.M Kashuba, Charles R. Wira

Dartmouth Scholarship

The conflicting results of recent pre-exposure prophylaxis (PrEP) trials utilizing tenofovir (TFV) to prevent HIV infection in women led us to evaluate the accumulation of intracellular TFV-diphosphate (TFV-DP) in cells from the female reproductive tract (FRT) and whether sex hormones influence the presence of TFV-DP in these cells. Following incubation with TFV, isolated epithelial cells, fibroblasts, CD4⁺ T cells and CD14⁺ cells from the FRT as well as blood CD4⁺ T cells and monocyte-derived macrophages convert TFV to TFV-DP. Unexpectedly, we found that TFV-DP concentrations (fmol/million cells) vary significantly with the cell type analyzed and the site …

Diverse Convergent Evidence In The Genetic Analysis Of Complex Disease: Coordinating Omic, Informatic, And Experimental Evidence To Better Identify And Validate Risk Factors, Timothy H. Ciesielski, Sarah A. Pendergrass, Marquitta J. White, Nuri Kodaman, Rafal S. Sobota, Minjun Huang, Jacquelaine Bartlett, Jing Li, Qinxin Pan, Jiang Gui, Scott B. Selleck, Christopher I. Amos, Marylyn D. Ritchie, Jason H. Moore, Scott M. Williams

Dartmouth Scholarship

In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false …

Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder

Dartmouth Scholarship

Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these …

Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …

Neural Synchrony Examined With Magnetoencephalography (Meg) During Eye Gaze Processing In Autism Spectrum Disorders: Preliminary Findings, Renée Lajiness-O'Neill, Annette E. Richard, Joh E. Moran, Amy Olszewski, Lesley Pawluk, Daniel Jacobson, Alfred Mansour, Kelly Vogt, Laszlo A. Erdodi

Dartmouth Scholarship

Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M Age  = 16.6) compared to neurotypicals (NT) (MAge  = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), …

Non Melanoma Skin Cancer And Subsequent Cancer Risk, Judy R. Rees, M. Scot Zens, Jiang Gui, Maria O. Celaya, Bruce L. Riddle, Margaret R. Karagas

Dartmouth Scholarship

Introduction:

Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.

Purpose:

Methods:

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Integrating Addiction Treatment Into Primary Care Using Mobile Health Technology: Protocol For An Implementation Research Study, Andrew R. Quanbeck, David H. Gustafson, Lisa A. Marsch, Fiona Mctavish

Dartmouth Scholarship

Healthcare reform in the United States is encouraging Federally Qualified Health Centers and other primary-care practices to integrate treatment for addiction and other behavioral health conditions into their practices. The potential of mobile health technologies to manage addiction and comorbidities such as HIV in these settings is substantial but largely untested. This paper describes a protocol to evaluate the implementation of an E-Health integrated communication technology delivered via mobile phones, called Seva, into primary-care settings. Seva is an evidence-based system of addiction treatment and recovery support for patients and real-time caseload monitoring for clinicians.

Manage At Work: A Randomized, Controlled Trial Of A Self-Management Group Intervention To Overcome Workplace Challenges Associated With Chronic Physical Health Conditions, William S. Shaw, Elyssa Besen, Glenn Pransky, Cécile R. L. Boot, Michael K. Nicholas, Robert K. Mclellan, Torill H. Tveito

Dartmouth Scholarship

Background: The percentage of older and chronically ill workers is increasing rapidly in the US and in many other countries, but few interventions are available to help employees overcome the workplace challenges of chronic pain and other physical health conditions. While most workers are eligible for job accommodation and disability compensation benefits, other workplace strategies might improve individual-level coping and problem solving to prevent work disability. In this study, we hypothesize that an employer-sponsored group intervention program employing self-management principles may improve worker engagement and reduce functional limitation associated with chronic disorders.

Methods: In a randomized controlled trial (RCT), workers …

A Global Compendium Of Human Dengue Virus Occurrence, Jane P. Messina, Oliver J Brady, David M. Pigott, John S. Brownstein, Anne Hoen, Simon Hay

Dartmouth Scholarship

A global geographic database of human dengue virus occurrence was produced to generate a global risk map and associated burden estimates1. Herein we present the database, which comprises occurrence data linked to point or polygon locations, derived from peer-reviewed literature and case reports as well as informal online sources. Entries date from 1960 to 2012. We describe all data collection processes in full, as well as geo-positioning, database management and quality-control procedures. This is the most comprehensive database of confirmed human dengue infection to-date, consisting of 8,309 geo-positioned occurrences in total.

Safety Of Infusing Rituximab At A More Rapid Rate In Patients With Rheumatoid Arthritis: Results From The Rate-Ra Study, Charles H. Pritchard, Maria W. Greenwald, Joel M. Kremer, Norman B. Gaylis, William Rigby

Dartmouth Scholarship

As recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25hours for the first infusion and 3.25hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2hours in patients with RA.

Extraction Of Intrinsic Fluorescence From Single Fiber Fluorescence Measurements On A Turbid Medium: Experimental Validation, U. A. Gamm, C. L. Hoy, F. Van Leeuwen - Van Zaane, H. J. C. M. Sterenborg, S. C. Kanick, D J. Robinson, A. Amelink

Dartmouth Scholarship

Abstract

The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence. The validity of the Monte Carlo data and semi-empirical model is …

The Histone Methyltransferase Activity Of Mll1 Is Dispensable For Hematopoiesis And Leukemogenesis, Bibhu Mishra, Kristin M. Zaffuto, Erika L. Artinger, Tonis Org, Hannah K. A. Mikkola, Chao Cheng, Malek Djabali

Dartmouth Scholarship

Despite correlations between histone methyltransferase (HMT) activity and gene regulation, direct evidence that HMT activity is responsible for gene activation is sparse. We address the role of the HMT activity for MLL1, a histone H3 lysine 4 (H3K4) methyltransferase critical for maintaining hematopoietic stem cells (HSCs). Here, we show that the SET domain, and thus HMT activity of MLL1, is dispensable for maintaining HSCs and supporting leukemogenesis driven by the MLL-AF9 fusion oncoprotein. Upon Mll1 deletion, histone H4 lysine 16 (H4K16) acetylation is selectively depleted at MLL1 target genes in conjunction with reduced transcription. Surprisingly, inhibition of SIRT1 is sufficient …

Interventions To Improve Delivery Of Isoniazid Preventive Therapy: An Overview Of Systematic Reviews, Lisa V. Adams, Elizabeth A. Talbot, Karen Odato, Heather Blunt, Karen R. Steingart

Dartmouth Scholarship

Background:

Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals.

Methods:

We searched the Cochrane Database of Systematic Reviews, the …

Health System Characteristics And Rates Of Readmission After Acute Myocardial Infarction In The United States, Jeremiah R. Brown, Chiang-Hua Chang, Weiping Zhou, Todd A. Mackenzie, David J. Malenka, David C. Goodman

Dartmouth Scholarship

Background:

Interventions to reduce early readmissions have focused on patient characteristics and the importance of early follow‐up; however, less is known about the characteristics of health systems, including quality, capacity, and intensity, and their influence on readmission rates in the United States. Therefore, we examined the association of hospital patterns of medical care with rates of 30‐day readmission.

Methods and Results:

Medicare beneficiaries hospitalized for an AMI (n=188 611) between 2008 and 2009 in 1088 hospitals in the United States were included in our cohort. We tested the association between hospital patterns of medical care quality (discharge planning care quality), …

Structural Features Of The Pseudomonas Fluorescens Biofilm Adhesin Lapa Required For Lapg-Dependent Cleavage, Biofilm Formation, And Cell Surface Localization, Chelsea D. Boyd, T. Jarrod Smith, Sofiane El-Kirat-Chatel, Peter D. Newell, Yves F. Dufrêne, George A. O'Toole

Dartmouth Scholarship

The localization of the LapA protein to the cell surface is a key step required by Pseudomonas fluorescens Pf0-1 to irreversibly attach to a surface and form a biofilm. LapA is a member of a diverse family of predicted bacterial adhesins, and although lacking a high degree of sequence similarity, family members do share common predicted domains. Here, using mutational analysis, we determine the significance of each domain feature of LapA in relation to its export and localization to the cell surface and function in biofilm formation. Our previous work showed that the N terminus of LapA is required for …

Synthetic Triterpenoid Induces 15-Pgdh Expression And Suppresses Inflammation-Driven Colon Carcinogenesis, Sung Hee Choi, Byung-Gyu Kim, Janet Robinson, Steve Fink, Min Yan, Michael B. Sporn, Sanford D. Markowitz, John J. Letterio

Dartmouth Scholarship

Colitis-associated colon cancer (CAC) develops as a result of inflammation-induced epithelial transformation, which occurs in response to inflammatory cytokine-dependent downregulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and subsequent suppression of prostaglandin metabolism. Agents that both enhance 15-PGDH expression and suppress cyclooxygenase-2 (COX-2) production may more effectively prevent CAC. Synthetic triterpenoids are a class of small molecules that suppress COX-2 as well as inflammatory cytokine signaling. Here, we found that administration of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-C28-methyl ester (CDDO-Me) suppresses CAC in mice. In a spontaneous, inflammation-driven intestinal neoplasia model, deletion of Smad4 specifically in T cells led to progressive production of inflammatory cytokines, …

Lack Of Protection Following Passive Transfer Of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies, Anne-Sophie Dugast, Ying Chan, Michelle Hoffner, Anna Licht, Joseph Nkolola, Hualin Li, Hendrik Streeck, Todd J. Suscovich, Musie Ghebremichael, Margaret E. Ackerman, Dan H. Barouch, Galit Alter

Dartmouth Scholarship

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred …

Exome-Wide Association Study Of Endometrial Cancer In A Multiethnic Population, Maxine M. Chen, Marta Crous-Bou, Veronica W. Setiawan, Jennifer Prescott, Sarah H. Olson, Nicolas Wentzensen, Amanda Black, Louise Brinton, Chu Chen, Constance Chen, Linda S. Cook, Jennifer Doherty

Dartmouth Scholarship

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome- wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. …

Rnasel And Mir146a Snp-Snp Interaction As A Susceptibility Factor For Non-Melanoma Skin Cancer, Shohreh F. Farzan, Margaret R. Karagas, Brock C. Christensen, Zhongze Li, Jacquelyn K. Kuriger, Heather H. Nelson

Dartmouth Scholarship

Immunity and inflammatory pathways are important in the genesis of non-melanoma skin cancers (NMSC). Functional genetic variation in immune modulators has the potential to affect disease etiology. We investigated associations between common variants in two key regulators, MIR146A and RNASEL, and their relation to NMSCs. Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907). To examine associations between genotype and BCC and SCC, occurrence odds ratios (OR) …

Performance Of The Oraquick Hcv Rapid Antibody Test For Screening Exposed Patients In A Hepatitis C Outbreak Investigation, Fengxiang Gao, Elizabeth A. Talbot, Carol H. Loring, Jill J. Power, Jodie Dionne-Odom

Dartmouth Scholarship

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore

Dartmouth Scholarship

Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …