Digital Commons Network^™

Predictive Oncology: A Review Of Multidisciplinary, Multiscale In Silico Modeling Linking Phenotype, Morphology And Growth, Sandeep Sanga, Hermann B. Frieboes, Xiaoming Zheng, Robert Gatenby, Elaine L. Bearer, Vittorio Cristini

Faculty, Staff and Student Publications

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable …

Computer Simulation Of Glioma Growth And Morphology, Hermann B. Frieboes, John S Lowengrub, S Wise, X Zheng, Paul Macklin, Elaine L. Bearer, Vittorio Cristini

Faculty, Staff and Student Publications

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques …

All In The Family: Atypical Hsp70 Chaperones Are Conserved Modulators Of Hsp70 Activity, Lance Shaner, Kevin A Morano

Faculty, Staff and Student Publications

Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170 families have been recognized for some time, yet their biochemical roles remained elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable complexes with classic Hsp70s where they exert a powerful nucleotide-exchange activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary transition from an independent protein-folding chaperone to what appears to be a dedicated cochaperone. Contributions of the atypical Hsp70s to established cellular roles for Hsp70 now must be deciphered.

Recent Advances In Basic Neurosciences And Brain Disease: From Synapses To Behavior, Guo-Qiang Bi, Vadim Bolshakov, Guojun Bu, Catherine M. Cahill, Zhou-Feng Chen, Graham L. Collingridge, Robin L. Cooper, Jens R. Coorssen, Alaa El-Husseini, Vasco Galhardo, Wen-Biao Gan, Jianguo Gu, Kazuhide Inoue, John Isaac, Koichi Iwata, Zhengping Jia, Bong-Kiun Kaang, Mikito Kawamata, Satoshi Kida, Eric Klann, Tatsuro Kohno, Min Li, Xiao-Jiang Li, John F. Macdonald, Karim Nader, Peter V. Nguyen, Uhtaek Oh, Ke Ren, John C. Roder, Michael W. Salter, Weihong Song, Shuzo Sugita, Shao-Jun Tang, Yuanxiang Tao, Yu Tian Wang, Newton Woo, Melanie A. Woodin, Zhen Yan, Megumu Yoshimura, Ming Xu, Zao C. Xu, Xia Zhang, Mei Zhen, Min Zhuo

Biology Faculty Publications

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting …

Characterization Of Hsp70 Binding And Nucleotide Exchange By The Yeast Hsp110 Chaperone Sse1, Lance Shaner, Rui Sousa, Kevin A Morano

Faculty, Staff and Student Publications

SSE1 and SSE2 encode the essential yeast members of the Hsp70-related Hsp110 molecular chaperone family. Both mammalian Hsp110 and the Sse proteins functionally interact with cognate cytosolic Hsp70s as nucleotide exchange factors. We demonstrate here that Sse1 forms high-affinity (Kd approximately 10-8 M) heterodimeric complexes with both yeast Ssa and mammalian Hsp70 chaperones and that binding of ATP to Sse1 is required for binding to Hsp70s. Sse1.Hsp70 heterodimerization confers resistance to exogenously added protease, indicative of conformational changes in Sse1 resulting in a more compact structure. The nucleotide binding domains of both Sse1/2 and the Hsp70s dictate interaction specificity and …

Glycosylation Regulates Turnover Of Cyclooxygenase-2., Mary B. Sevigny, Chai-Fei Li, Monika Alas, Millie Hughes-Fulford

Natural Sciences and Mathematics | Faculty Scholarship

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation. COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform.

Evidence That Talin Alternative Splice Variants From Ciona Intestinalis Have Different Roles In Cell Adhesion, Richard H. Singiser, Richard O. Mccann

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is …

Prior Experience As A Stimulus Category Confound: An Example Using Facial Expressions Of Emotion, Leah H. Somerville, Paul J. Whalen

Dartmouth Scholarship

Facial expressions of emotion represent a stimulus set widely used to assess a broad range of psychological processes. However, a consideration of systematic differences between expression categories, other than differences relating to characteristics of the expressions themselves, has remained largely unaddressed. By collecting experience rankings in a large sample of undergraduates, we observed that the amount of reported experience individuals have had with different facial expressions of emotion systematically differed between all expression categories. These findings shed light on the potential for identifying confounds inherent to comparing some stimulus categories and, in this case, may aid in the interpretation of …

Androgen-Regulated Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen E. Johnson, Xiao-Hong Song, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate …

Nucleolin Is Required For Rna Polymerase I Transcription In Vivo, Brendan Rickards, S. Flint, Michael D. Cole, Gary Leroy

Dartmouth Scholarship

Eukaryotic genomes are packaged with histones and accessory proteins in the form of chromatin. RNA polymerases and their accessory proteins are sufficient for transcription of naked DNA, but not of chromatin, templates in vitro. In this study, we purified and identified nucleolin as a protein that allows RNA polymerase II to transcribe nucleosomal templates in vitro. As immunofluorescence confirmed that nucleolin localizes primarily to nucleoli with RNA polymerase I, we demonstrated that nucleolin allows RNA polymerase I transcription of chromatin templates in vitro. The results of chromatin immunoprecipitation experiments established that nucleolin is associated with chromatin containing rRNA genes transcribed …

Insights Into Transcription Enhancer Factor 1 (Tef-1) Activity From The Solution Structure Of The Tea Domain, Asokan Anbanandam, Diana C Albarado, Catherine T Nguyen, Georg Halder, Xiaolian Gao, Sudha Veeraraghavan

Faculty, Staff and Student Publications

Transcription enhancer factor 1 is essential for cardiac, skeletal, and smooth muscle development and uses its N-terminal TEA domain (TEAD) to bind M-CAT elements. Here, we present the first structure of TEAD and show that it is a three-helix bundle with a homeodomain fold. Structural data reveal how TEAD binds DNA. Using structure-function correlations, we find that the L1 loop is essential for cooperative loading of TEAD molecules on to tandemly duplicated M-CAT sites. Furthermore, using a microarray chip-based assay, we establish that known binding sites of the full-length protein are only a subset of DNA elements recognized by TEAD. …

Gene Expression Patterns That Predict Sensitivity To Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors In Lung Cancer Cell Lines And Human Lung Tumors, Justin M. Balko, Anil Potti, Christopher Saunders, Arnold J. Stromberg, Eric B. Haura, Esther P. Black

Statistics Faculty Publications

BACKGROUND: Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a …

Vulnerability Of Pathogenic Biofilms To Micavibrio Aeruginosavorus, Daniel Kadouri, Nel C. Venzon, George A. O'Toole

Dartmouth Scholarship

The host specificity of the gram-negative exoparasitic predatory bacterium Micavibrio aeruginosavorus was examined. M. aeruginosavorus preyed on Pseudomonas aeruginosa, as previously reported, as well as Burkholderia cepacia, Klebsiella pneumoniae, and numerous clinical isolates of these species. In a static assay, a reduction in biofilm biomass was observed as early as 3 hours after exposure to M. aeruginosavorus, and an ∼100-fold reduction in biofilm cell viability was detected following a a 24-h exposure to the predator. We observed that an initial titer of Micavibrio as low as 10 PFU/well or a time of exposure to the predator as short as 30 …

Dermatology Is A Specialty; Dermatology Is Not A Subspecialty., Lawrence Parish, Larry E Millikan

Department of Dermatology and Cutaneous Biology Faculty Papers

Specialization began in American medicine about the time of the War Between the States. Several factors spurred the direction of practitioners away from being the so-called “complete physicians. Most important were the advances in instrumentation made by the 1860’s, which allowed ophthalmology and otolaryngology to develop into distinct divisions of allopathic medicine; sometimes, they even joined together, viz eye, ear, nose, and throat specialist. Dermatology, too, became one of the early specialties for a myriad of reasons ranging from the obvious – visual inspection - to the mundane, viz. default – syphilis was too ugly and complicated for every physician …

Time To Renal Disease And End-Stage Renal Disease In Profile: A Multiethnic Lupus Cohort, Graciela S. Alarcón, Gerald Mcgwin, Michelle Petri, Rosalind Ramsey-Goldman, Barri J. Fessler, Luis M. Vilá, Jeffrey C. Edberg, John D. Reveille, Robert P. Kimberly

Faculty, Staff and Student Publications

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).

METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of …

Minimizing Radiation Injury And Neoplastic Effects During Pediatric Fluoroscopy: What Should We Know?, Louis Kenneth Wagner

Faculty, Staff and Student Publications

Radiation-induced injuries from fluoroscopic procedures in pediatric patients have occurred, and young patients are at greatest risk of many radiation-induced neoplasms. Some fluoroscopists have been injured from their use of fluoroscopy, and they are known to be at risk of radiation-induced neoplasm when radiation is not well-controlled. This article reviews the circumstances that lead to radiation injury and delineates some procedural methods to avoid injury and limit radiation exposure to both the patient and the fluoroscopist.

Platelet-Activating Factor Is Crucial In Psoralen And Ultraviolet A-Induced Immune Suppression, Inflammation, And Apoptosis, Peter Wolf, Dat X Nghiem, Jeffrey P Walterscheid, Scott Byrne, Yumi Matsumura, Yasuhiro Matsumura, Cora Bucana, Honnavara N Ananthaswamy, Stephen E Ullrich

Faculty, Staff and Student Publications

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF …

From Healing The Whole Person: An Argument For Therapeutic Touch As A Complement To Traditional Medical Practice, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The growing popularity and use of therapeutic touch (TT) is an issue that has generated controversy and concern within the medical community. While anecdotal and traditional scientific evidence suggest that TT would be an advantageous addition for clinics and hospitals to include in their armamentarium of complementary interventions within the realm of traditional medicine, TT has not become widely available in the U.S. One reason for the lack of availability may be the dearth of conclusive scientific support for TT's efficacy and, therefore, its inclusion in clinic and hospital treatment planning would give it the appearance of legitimate practice, which …

Pregnant Teenager Involvement In Sexual Activity And The Social Context, Maria José Carvalho Sant'anna, Júlia Kerr Catunda, Kepler Alencar Mendes Carvalho, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

Pregnancy during adolescence represents a challenge to society as a whole. Its incidence is increasing and brings about social and medical consequences to both the teen mothers and their children. The purpose of this study was to evaluate pregnant teenager involvement in sexual activity and the social context. The group studied comprised 152 pregnant teenagers attending the Department of Pediatrics, Santa Casa de Sao Paulo (SCSP) General Hospital. All information was analyzed. The age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.4 years. Most pregnancies (75%) were neither planned nor wanted, …

Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.

Arsenic Exposure Is Associated With Decreased Dna Repair In Vitro And In Individuals Exposed To Drinking Water Arsenic, Angeline S. Andrew, Jefferey L. Burgess, Maria M. Meza, Eugene Demidenko, Mary G. Waugh, Joshua W. Hamilton, Margaret R. Karagas

Dartmouth Scholarship

The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora …

Natriuretic Peptides And Nitric Oxide Stimulate Cgmp Synthesis In Different Cellular Compartments, Leslie A Piggott, Kathryn A Hassell, Zuzana Berkova, Andrew P Morris, Michael Silberbach, Thomas C Rich

Faculty, Staff and Student Publications

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the …

Correlation Between Number Of Retrieved Oocytes And Pregnancy Rate After In Vitro Fertilization/Intracytoplasmic Sperm Infection, Tanya Timeva, Tanya Milachich, Irena Antonova, Tanya Arabaji, Atanas Shterev, Hatim A. Omar

Pediatrics Faculty Publications

The implementation of safe and maximally effective ovarian stimulation is a major aim for in vitro fertilization (IVF) teams. The goal of controlled ovarian hyperstimulation (COH) is to supply enough oocytes with normal maturation to insure the consequent biological procedures. A variety of different stimulation protocols have been suggested and an individual selection of the correct stimulation protocol is mandatory. The aim of the present study is to evaluate the correlation between number of retrieved oocytes and clinical pregnancy rate (CPR) after IVF or intracytoplasmic sperm injection (ICSI) procedures. We reviewed 1017 cycles in a total of 975 patients. The …

Depression, Sensation Seeking, And Maternal Smoking As Predictors Of Adolescent Cigarette Smoking, Judy Van De Venne, Kay Bradford, Catherine A. Martin, Megan Cox, Hatim A. Omar

Family Sciences Faculty Publications

The purpose of this study was to examine maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicated that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (β = 0.29, p < 0.001 and β = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (β = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (β = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use.

Biomolecular Study Of The Correlation Between Papillomatosis Of The Vulvar Vestibule In Adolescents And Human Papillomavirus, Geni Beznos, Verônica Coates, Jose Focchi, Hatim A. Omar

Pediatrics Faculty Publications

The main goal of this study was to investigate, through a biomolecular study, the correlation between papillomatosis of the vulvar vestibule and human papillomavirus (HPV) infection, as well as to establish the necessity of treatment. A total of 44 female adolescents between 12 and 18 years of age were selected through a prospective study with a confirmed diagnosis of papillomatosis of the vulvar vestibule. Vulvar biopsies were obtained for the histological and biomolecular detection of HPV DNA through polymerase chain reaction (PCR). Twenty (45%) adolescents were virgins (group A), the other 24 (55%) were sexually active. The virgin adolescents (group …

Imaging Breast Adipose And Fibroglandular Tissue Molecular Signatures By Using Hybrid Mri-Guided Near-Infrared Spectral Tomography, Ben Brooksby, Brian W. Pogue, Shudong Jiang, Hamid Dehghani, Subhadra Srinivasan, Christine Kogel, Tor D. Tosteson, John Weaver, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images.

Why Dentists Should Become Oral Physicians: A Response To Dr. Donald Giddon's "Why Dentists Should Be Called Oral Physicians Now", David A. Nash

Oral Health Science Faculty Publications

No abstract provided.

Medial Prefrontal Dissociations During Processing Of Trait Diagnostic And Nondiagnostic Person Information, Jason P. Mitchell, Jasmin Cloutier, Mahzarin R. Banaji, C Neil Macrae

Dartmouth Scholarship

Previous research has suggested that perceivers spontaneously extract trait-specific information from the behaviour of others. However, little is known about whether perceivers spontaneously engage in the same depth of social-cognitive processing for all person information or reserve such processing specifically for information that conveys diagnostic clues about another person's dispositions. Moreover, a question remains as to whether the processing of such nondiagnostic information can be affected by perceivers’ explicit goal to consider another's dispositions or not. To examine processing of diagnostic and nondiagnostic social information as a function of perceivers’ explicit social-cognitive goals, participants underwent functional magnetic resonance imaging (fMRI) …

Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati

Kimmel Cancer Center Faculty Papers

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH(2)-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH(2)-terminal residues and enhances the interaction with …

Lack Of Il-15 Results In The Suboptimal Priming Of Cd4+ T Cell Response Against An Intracellular Parasite, Crescent L. Combe, Magali M. Moretto, Joseph D. Schwartzman, Jason P. Gigley, David J. Bzik, Imtiaz A. Khan

Dartmouth Scholarship

IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced …