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Physiologic Effect Of Relaxation Therapies On Autonomic Tone Early After Acute Coronary Syndromes, Rachel Summer Claire Friedman Feb 2009

Physiologic Effect Of Relaxation Therapies On Autonomic Tone Early After Acute Coronary Syndromes, Rachel Summer Claire Friedman

Yale Medicine Thesis Digital Library

Post-MI patients are at increased risk of arrhythmic sudden death. Stress and sympathetic activation are known to influence arrhythmogenesis. While relaxation therapies improve psychological well-being in multiple medical illnesses, whether these therapies can positively influence sympathovagal balance in the post-MI population is unknown. We explored the physiologic effects of Reiki, a light-touch relaxation therapy, and music on post-acute coronary syndrome (ACS) inpatients, using heart rate variability (HRV) to assess changes in cardiac autonomic function during treatment. Forty-eight patients with ACS within the last 72 hours were randomized to received a single 20-minute session of either Reiki, classical music, or a …


Clinical And Demographic Predictors Of Short-Term Recovery From Arthroscopic Partial Meniscectomy, Peter Fabricant Feb 2009

Clinical And Demographic Predictors Of Short-Term Recovery From Arthroscopic Partial Meniscectomy, Peter Fabricant

Yale Medicine Thesis Digital Library

Patients undergoing orthopaedic surgery are concerned with returning to activities of daily living (recovery) in addition to the long-term result of their surgery (end result). As evidence of predictors of rate of short-term recovery is limited to date, this study seeks to determine which patient clinical and demographic factors can serve as prognostic indicators for rate of short-term recovery from arthroscopic partial meniscectomy in the year following surgery and how they may differ from previously published associations with long-term outcome. Clinical (depth of meniscal excision, involvement of one or both menisci, extent of meniscal tear, extent of osteoarthritis) and demographic …


Genotypic Confirmation Of Transimmunization-Induced Dendritic Cell Maturation, Kristin Elizabeth Hoffmann Feb 2009

Genotypic Confirmation Of Transimmunization-Induced Dendritic Cell Maturation, Kristin Elizabeth Hoffmann

Yale Medicine Thesis Digital Library

Transimmunization (TI), a novel modification of the widely used immunotherapy extracorporeal photopheresis (ECP), induces conversion of processed monocytes into cells expressing phenotypic and functional features of dendritic antigen presenting cells (DC). To further characterize TI-induced DC, we analyzed differential gene expression in the monocyte/DC population after TI treatment. Because ECP, the therapy upon which TI is based, has the unique capacity to induce both anti-cancer immune responses in cutaneous T cell lymphoma (CTCL) patients and tolerogenic responses in graft-versus-host disease (GVHD), we studied TI-induced gene expression changes in both of these patient populations as well as in healthy normal control …


Lymphocyte Proliferation To Mycobacterial Antigens Is Detectable Across A Spectrum Of Hiv-Associated Tuberculosis, Timothy Lahey, Mecky Matee, Lillian Mtei, Muhammad Bakari, Kisali Pallangyo, C Fordham Von Reyn Feb 2009

Lymphocyte Proliferation To Mycobacterial Antigens Is Detectable Across A Spectrum Of Hiv-Associated Tuberculosis, Timothy Lahey, Mecky Matee, Lillian Mtei, Muhammad Bakari, Kisali Pallangyo, C Fordham Von Reyn

Dartmouth Scholarship

Background:

Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIV-infected subjects with latent or active TB.

Methods:

HIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts ≥ 200 cells/mm3 entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-γ) release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened …


Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg Feb 2009

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …


Creb Mediates Prostaglandin F2alpha-Induced Muc5ac Overexpression, Wen-Cheng Chung, Seung-Hee Ryu, Hongxia Sun, Darryl C Zeldin, Ja Seok Koo Feb 2009

Creb Mediates Prostaglandin F2alpha-Induced Muc5ac Overexpression, Wen-Cheng Chung, Seung-Hee Ryu, Hongxia Sun, Darryl C Zeldin, Ja Seok Koo

Faculty, Staff and Student Publications

Mucus secretion is an important protective mechanism for the luminal lining of open tubular organs, but mucin overproduction in the respiratory tract can exacerbate the inflammatory process and cause airway obstruction. Production of MUC5AC, a predominant gel-forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators such as prostaglandins. The two major prostaglandins involved in inflammation are PGE(2) and PGF(2alpha). PGE(2)-induced mucin production has been well studied, but the effect of PGF(2alpha) on mucin production remains poorly understood. To elucidate the effect and underlying mechanism of PGF(2alpha) on MUC5AC production, we investigated the signal transduction of PGF(2alpha) …


Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon Feb 2009

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …


Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri Feb 2009

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …


Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman Feb 2009

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …


Interconnections Between Sigma B, Agr, And Proteolytic Activity In Staphylococcus Aureus Biofilm Maturation, Katherine J. Lauderdale, Blaise R. Boles, Ambrose L. Cheung, Alexander R. Horswill Feb 2009

Interconnections Between Sigma B, Agr, And Proteolytic Activity In Staphylococcus Aureus Biofilm Maturation, Katherine J. Lauderdale, Blaise R. Boles, Ambrose L. Cheung, Alexander R. Horswill

Dartmouth Scholarship

Staphylococcus aureus is a proficient biofilm former on host tissues and medical implants. We mutagenized S. aureus strain SH1000 to identify loci essential for ica-independent mechanisms of biofilm maturation and identified multiple insertions in the rsbUVW-sigB operon. Following construction and characterization of a sigB deletion, we determined that the biofilm phenotype was due to a lack of sigma factor B (SigB) activity. The phenotype was conserved in a sigB mutant of USA300 strain LAC, a well-studied community-associated methicillin-resistant S. aureus isolate. We determined that agr RNAIII levels were elevated in the sigB mutants, and high levels of RNAIII expression are …


Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March Feb 2009

Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March

Journal Articles: Psychiatry

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).

METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined …


Nonrigid Registration Of Three-Dimensional Ultrasound And Magnetic Resonance Images Of The Carotid Arteries, Nuwan D Nanayakkara, Bernard Chiu, Abbas Samani, J David Spence, Jagath Samarabandu, Grace Parraga, Aaron Fenster Feb 2009

Nonrigid Registration Of Three-Dimensional Ultrasound And Magnetic Resonance Images Of The Carotid Arteries, Nuwan D Nanayakkara, Bernard Chiu, Abbas Samani, J David Spence, Jagath Samarabandu, Grace Parraga, Aaron Fenster

Medical Biophysics Publications

Atherosclerosis at the carotid bifurcation can result in cerebral emboli, which in turn can block the blood supply to the brain causing ischemic strokes. Noninvasive imaging tools that better characterize arterial wall, and atherosclerotic plaque structure and composition may help to determine the factors which lead to the development of unstable lesions, and identify patients at risk of plaque disruption and stroke. Carotid magnetic resonance (MR) imaging allows for the characterization of carotid vessel wall and plaque composition, the characterization of normal and pathological arterial wall, the quantification of plaque size, and the detection of plaque integrity. On the other …


Proton Magnetic Resonance Spectroscopy In Multiple Sclerosis, Balasrinivasa R Sajja, Jerry S Wolinsky, Ponnada A Narayana Feb 2009

Proton Magnetic Resonance Spectroscopy In Multiple Sclerosis, Balasrinivasa R Sajja, Jerry S Wolinsky, Ponnada A Narayana

Faculty, Staff and Student Publications

Proton magnetic resonance spectroscopy ((1)H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathologic changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed. This potential metabolic information makes MRS a unique tool to follow MS disease evolution, understand its pathogenesis, evaluate the disease severity, establish a prognosis, and objectively evaluate the efficacy of therapeutic interventions.


Endothelial Progenitor Cell Number And Colony-Forming Capacity In Overweight And Obese Adults, O J Maceneaney, E J Kushner, Gary P. Van Guilder, J J Greiner, B L Stauffer, C A Desouza Feb 2009

Endothelial Progenitor Cell Number And Colony-Forming Capacity In Overweight And Obese Adults, O J Maceneaney, E J Kushner, Gary P. Van Guilder, J J Greiner, B L Stauffer, C A Desouza

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: To investigate whether adiposity influences endothelial progenitor cell (EPC) number and colony-forming capacity.
DESIGN: Cross-sectional study of normal weight, overweight and obese adult humans.
PARTICIPANTS: Sixty-seven sedentary adults (aged 45-65 years): 25 normal weight (body mass index (BMI) or=30 kg/m(2); 18 males/6 females). All participants were non-smokers and free of overt cardiometabolic disease.
MEASUREMENTS: Peripheral blood samples were collected and circulating EPC number was assessed by flow cytometry. Putative EPCs were defined as CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells. EPC colony-forming capacity was measured in vitro using a colony-forming unit (CFU) assay.
RESULTS: Number of circulating putative EPCs (either CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or …


Multimodality Education For Airway Endoscopy Skill Development., Ellen S. Deutsch, Thomas Christenson, Joseph Curry, Jobayer Hossain, Karen Zur, Ian Jacobs Feb 2009

Multimodality Education For Airway Endoscopy Skill Development., Ellen S. Deutsch, Thomas Christenson, Joseph Curry, Jobayer Hossain, Karen Zur, Ian Jacobs

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Airway endoscopy is a difficult skill to master. A unique practicum was designed to help otolaryngology residents develop endoscopy skills. The learning modalities included lectures, an animal laboratory, high-fidelity manikins, virtual bronchoscopy simulation, and standardized patients. This study compares the relative subjective value of these learning modalities for skill development and realism. METHODS: Participants used a Likert scale (1=disagree to 5=agree) and open responses to anonymously rate the efficacy of 5 learning modalities for teaching airway management, endoscopy skills, and clinical leadership and for providing a realistic experience. RESULTS: The results in 2007 were uniformly positive, with mean scores …


The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon Feb 2009

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …


Atorvastatin May Have No Effect On Acute Phase Reaction In Children After Intravenous Bisphosphonate Infusion., Tarak Srivastava, Connie J. Haney, Uri S. Alon Feb 2009

Atorvastatin May Have No Effect On Acute Phase Reaction In Children After Intravenous Bisphosphonate Infusion., Tarak Srivastava, Connie J. Haney, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Intravenous bisphosphonate therapy is associated with acute phase reaction characterized by fever and musculoskeletal pain. Bisphosphonates have been shown in vitro to activate gammadeltaT-cells to proliferate and produce cytokines, suggesting a role in acute phase reaction, which can be effectively blocked by statins. We conducted a double-blind randomized crossover placebo controlled study in 12 children (12.1 +/- 4.2 yr; 10 girls and 2 boys) receiving intravenous bisphosphonates to evaluate whether statins can be used to prevent acute phase reaction associated with therapy. Children received two cycles given 3-4 mo apart of intravenous bisphosphonate given on 2 consecutive days in each …


Cryptococcosis Of The Upper Genital Tract., Manish Gopal, Stacy Mccrosson, Pamela Edmonds, Thomas Klein Feb 2009

Cryptococcosis Of The Upper Genital Tract., Manish Gopal, Stacy Mccrosson, Pamela Edmonds, Thomas Klein

Department of Obstetrics and Gynecology Faculty Papers

Upper genital tract infection by Cryptococcus neoformans has not previously been reported. We describe such a case, in order to alert clinicians to the existence of this rare infection. A 34-year-old woman with AIDS presented with chronic menorrhagia, fever, anemia, and thrombocytopenia. Despite blood transfusions and hormonal therapy, her vaginal bleeding could not be controlled and she became hemodynamically unstable. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed, at which time granulomatous peritonitis and prominent myometrial blood vessels were found. Histologic examination revealed cryptococcal infection of all upper genital organs. This case demonstrates that disseminated cryptococcosis may involve the upper …


Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran Jan 2009

Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

METHODS: To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting …


Antenatal Peer Support Workers And Initiation Of Breast Feeding: Cluster Randomised Controlled Trial, Christine Macarthur, Kate Jolly, Lucy Annang Ingram Phd, Nick Freemantle, Cindy-Lee Dennis, Ros Hamburger, Julia Brown, Jackie Chambers, Khalid Khan Jan 2009

Antenatal Peer Support Workers And Initiation Of Breast Feeding: Cluster Randomised Controlled Trial, Christine Macarthur, Kate Jolly, Lucy Annang Ingram Phd, Nick Freemantle, Cindy-Lee Dennis, Ros Hamburger, Julia Brown, Jackie Chambers, Khalid Khan

Faculty Publications

OBJECTIVE: To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. DESIGN: Cluster randomised controlled trial. SETTING: Community antenatal clinics in one primary care trust in a multiethnic, deprived population. PARTICIPANTS: 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. INTERVENTION: An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 …


Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti Jan 2009

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Faculty, Staff and Student Publications

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …


Incompatibility With Formin Cdc12p Prevents Human Profilin From Substituting For Fission Yeast Profilin: Insights From Crystal Structures Of Fission Yeast Profilin., Obidimma Ezezika, Noah S Younger, Jia Lu, Donald A Kaiser, Zachary A Corbin, Bradley J Nolen, David R Kovar, Thomas D Pollard Jan 2009

Incompatibility With Formin Cdc12p Prevents Human Profilin From Substituting For Fission Yeast Profilin: Insights From Crystal Structures Of Fission Yeast Profilin., Obidimma Ezezika, Noah S Younger, Jia Lu, Donald A Kaiser, Zachary A Corbin, Bradley J Nolen, David R Kovar, Thomas D Pollard

Health Studies Publications

Expression of human profilin-I does not complement the temperature-sensitive cdc3-124 mutation of the single profilin gene in fission yeast Schizosaccharomyces pombe, resulting in death from cytokinesis defects. Human profilin-I and S. pombe profilin have similar affinities for actin monomers, the FH1 domain of fission yeast formin Cdc12p and poly-L-proline (Lu, J., and Pollard, T. D. (2001) Mol. Biol. Cell 12, 1161-1175), but human profilin-I does not stimulate actin filament elongation by formin Cdc12p like S. pombe profilin. Two crystal structures of S. pombe profilin and homology models of S. pombe profilin bound to actin show how the two profilins bind …


The Specificity Of The Search Template, Mary J. Bravo, Hany Farid Jan 2009

The Specificity Of The Search Template, Mary J. Bravo, Hany Farid

Dartmouth Scholarship

When searching for a target object, observers use an internal representation of the target's appearance as a search template. This study used naturalistic stimuli to examine the specificity of this template. Observers first learned several name-image pairs; they then participated in a search experiment in which the names served as cues and the images served as targets. To test whether the observers searched for the targets using an exact image template, we included targets that were transformations of the studied image and targets that belonged to the same subordinate-level category as the studied image. The same stimuli were also used …


Systems-Level Interactions Between Insulin-Egf Networks Amplify Mitogenic Signaling., Nikolay Borisov, Edita Aksamitiene, Anatoly Kiyatkin, Stefan Legewie, Jan Berkhout, Thomas Maiwald, Nikolai P Kaimachnikov, Jens Timmer, Jan B Hoek, Boris N Kholodenko Jan 2009

Systems-Level Interactions Between Insulin-Egf Networks Amplify Mitogenic Signaling., Nikolay Borisov, Edita Aksamitiene, Anatoly Kiyatkin, Stefan Legewie, Jan Berkhout, Thomas Maiwald, Nikolai P Kaimachnikov, Jens Timmer, Jan B Hoek, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Crosstalk mechanisms have not been studied as thoroughly as individual signaling pathways. We exploit experimental and computational approaches to reveal how a concordant interplay between the insulin and epidermal growth factor (EGF) signaling networks can potentiate mitogenic signaling. In HEK293 cells, insulin is a poor activator of the Ras/ERK (extracellular signal-regulated kinase) cascade, yet it enhances ERK activation by low EGF doses. We find that major crosstalk mechanisms that amplify ERK signaling are localized upstream of Ras and at the Ras/Raf level. Computational modeling unveils how critical network nodes, the adaptor proteins GAB1 and insulin receptor substrate (IRS), Src kinase, …


Corr4a And Vrt325 Do Not Reduce The Inflammatory Response To P. Aeruginosa In Human Cystic Fibrosis Airway Epithelial Cells, Laleh Talebian, Bonita Coutermarsh, Jacqueline Y. Channon, Bruce A. Stanton Jan 2009

Corr4a And Vrt325 Do Not Reduce The Inflammatory Response To P. Aeruginosa In Human Cystic Fibrosis Airway Epithelial Cells, Laleh Talebian, Bonita Coutermarsh, Jacqueline Y. Channon, Bruce A. Stanton

Dartmouth Scholarship

P. aeruginosa chronically colonizes the lung in CF patients and elicits a proinflammatory response. Excessive secretion of IL-6 and IL-8 by CF airway cells in response to P. aeruginosa infection in the CF airway is though to contribute to lung injury. Accordingly, the goal of this study was to test the hypothesis that Corr4a and VRT325, investigational compounds that increase ΔF508-CFTR mediated Cl− secretion in human CF airway cells, reduce the pro-inflammatory response to P. aeruginosa.


Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa Jan 2009

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …


Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss Jan 2009

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …


The Sleeping Brain's Influence On Verbal Memory: Boosting Resistance To Interference, Jeffrey M. Ellenbogen, Justin C. Hulbert, Ying Jiang, Robert Stickgold Jan 2009

The Sleeping Brain's Influence On Verbal Memory: Boosting Resistance To Interference, Jeffrey M. Ellenbogen, Justin C. Hulbert, Ying Jiang, Robert Stickgold

Dartmouth Scholarship

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater …


Iatrogenic Bile Duct Injury Associated With Anomalies Of The Right Hepatic Sectoral Ducts: A Misunderstood And Underappreciated Problem, Nitin Babel, Sujit Vijay Sakpal, Prakash Paragi, Jason Wellen, Stephen Feldman, Ronald Scott Chamberlain Jan 2009

Iatrogenic Bile Duct Injury Associated With Anomalies Of The Right Hepatic Sectoral Ducts: A Misunderstood And Underappreciated Problem, Nitin Babel, Sujit Vijay Sakpal, Prakash Paragi, Jason Wellen, Stephen Feldman, Ronald Scott Chamberlain

Department of Surgery

Although laparoscopic cholecystectomy (LC) has been widely accepted as the standard of care, it continues to have a higher complication rate than open cholecystectomy. Bile duct injury with LC has often been attributed to surgical inexperience, but it is also clear that aberrant bile ducts are present in a significant number of patients who sustain biliary injuries during these procedures. We present three cases of right sectoral hepatic duct injuries which occurred during LC and provide a discussion of the conditions which are likely to lead to these injuries, as part of a strategy to prevent them.


Sand Fly Fever: What Have We Learned In One Hundred Years?, David Brett-Major, David M. Claborn Jan 2009

Sand Fly Fever: What Have We Learned In One Hundred Years?, David Brett-Major, David M. Claborn

Journal Articles: Epidemiology

Sand fly fever has severely impacted military missions in southern Europe and the Middle East for hundreds of years. After a brief respite following the malaria eradication programs of World War II, it has returned as a significant disease among residents in and travelers to the Mediterranean rim. It is a more severe disease now, with potential vectors in the United States. Sand fly fever is discussed in terms of its viruses, vectors, disease, control, and potential domestic impact.