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Nutrition Intervention To Decrease Symptoms In Patients With Advanced Heart Failure, Terry A. Lennie, Debra K. Moser, Martha J. Biddle, Darlene Welsh, Geza G. Bruckner, D. Travis Thomas, Mary Kay Rayens, Alison L. Bailey Apr 2013

Nutrition Intervention To Decrease Symptoms In Patients With Advanced Heart Failure, Terry A. Lennie, Debra K. Moser, Martha J. Biddle, Darlene Welsh, Geza G. Bruckner, D. Travis Thomas, Mary Kay Rayens, Alison L. Bailey

Nursing Faculty Publications

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, …


Fuzzy Complex Formation Between The Intrinsically Disordered Prothymosin Α And The Kelch Domain Of Keap1 Involved In The Oxidative Stress Response., Halema Khan, Elio A Cino, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy Mar 2013

Fuzzy Complex Formation Between The Intrinsically Disordered Prothymosin Α And The Kelch Domain Of Keap1 Involved In The Oxidative Stress Response., Halema Khan, Elio A Cino, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy

Biochemistry Publications

Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor for cytoprotective gene activation in the oxidative stress response. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses the transcriptional activity of Nrf2. During oxidative stress, Nrf2 is released from Keap1 and is translocated into the nucleus, where it interacts with the small Maf protein to initiate gene transcription. Prothymosin α (ProTα), an intrinsically disordered protein, also interacts with the Kelch domain of Keap1 and mediates the import of Keap1 into the nucleus …


Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra Mar 2013

Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients.

METHODS: The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance.

RESULTS: The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, …


Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou Mar 2013

Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou

Toxicology and Cancer Biology Faculty Publications

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing …


Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen Mar 2013

Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen

Dartmouth Scholarship

Marine food webs are the most important link between the global contaminant, methylmercury (MeHg), and human exposure through consumption of seafood. Warming temperatures may increase human exposure to MeHg, a potent neurotoxin, by increasing MeHg production as well as bioaccumulation and trophic transfer through marine food webs. Studies of the effects of temperature on MeHg bioaccumulation are rare and no study has specifically related temperature to MeHg fate by linking laboratory experiments with natural field manipulations in coastal ecosystems. We performed laboratory and field experiments on MeHg accumulation under varying temperature regimes using the killifish, Fundulus heteroclitus. Temperature treatments …


High-Throughput Phenotyping Of Uropathogenic E. Coli Isolates With Fourier Transform Infrared Spectroscopy., Haitham Alrabiah, Elon Correa, Mathew Upton, Royston Goodacre Mar 2013

High-Throughput Phenotyping Of Uropathogenic E. Coli Isolates With Fourier Transform Infrared Spectroscopy., Haitham Alrabiah, Elon Correa, Mathew Upton, Royston Goodacre

School of Biomedical Sciences

Fourier transform infrared (FT-IR) spectroscopy is an established rapid whole-organism fingerprinting method that generates metabolic fingerprints from bacteria that reflect the phenotype of the microorganism under investigation. However, whilst FT-IR spectroscopy is fast (typically 10 s to 1 min per sample), the approaches for microbial sample preparation can be time consuming as plate culture or shake flasks are used for growth of the organism. We report a new approach that allows micro-cultivation of bacteria from low volumes (typically 200 μL) to be coupled with FT-IR spectroscopy. This approach is fast and easy to perform and gives equivalent data to the …


Detection And Quantification Of Methylation In Dna Using Solid-State Nanopores., Jiwook Shim, Gwendolyn I Humphreys, Bala Murali Venkatesan, Jan Marie Munz, Xueqing Zou, Chaitanya Sathe, Klaus Schulten, Farhad Kosari, Ann M Nardulli, George Vasmatzis, Rashid Bashir Mar 2013

Detection And Quantification Of Methylation In Dna Using Solid-State Nanopores., Jiwook Shim, Gwendolyn I Humphreys, Bala Murali Venkatesan, Jan Marie Munz, Xueqing Zou, Chaitanya Sathe, Klaus Schulten, Farhad Kosari, Ann M Nardulli, George Vasmatzis, Rashid Bashir

College of Science & Mathematics Departmental Research

Epigenetic modifications in eukaryotic genomes occur primarily in the form of 5-methylcytosine (5 mC). These modifications are heavily involved in transcriptional repression, gene regulation, development and the progression of diseases including cancer. We report a new single-molecule assay for the detection of DNA methylation using solid-state nanopores. Methylation is detected by selectively labeling methylation sites with MBD1 (MBD-1x) proteins, the complex inducing a 3 fold increase in ionic blockage current relative to unmethylated DNA. Furthermore, the discrimination of methylated and unmethylated DNA is demonstrated in the presence of only a single bound protein, thereby giving a resolution of a single …


The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner Mar 2013

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …


Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh Mar 2013

Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry …


Excitatory Amino Acids Display Compartmental Disparity Between Plasma And Synovial Fluid In Clinical Arthropathies, Terry A. Mcnearney, Karin N. Westlund Mar 2013

Excitatory Amino Acids Display Compartmental Disparity Between Plasma And Synovial Fluid In Clinical Arthropathies, Terry A. Mcnearney, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Previous studies have demonstrated elevated levels of excitatory amino acids (EAA) glutamate (Glu) and aspartate (Asp) in the synovial fluid (SF) of patients with active arthritis. The source of SF EAA concentrations are thought in large part to be secondary to passive diffusion from the plasma across synovial membranes and less so, reflective of local synovial pathology.

OBJECTIVE: This descriptive report assesses the hypothesis that the SF EAA levels reflect inflammatory processes of the joint and are not dependent on plasma levels.

METHODS: Simultaneously drawn plasma and SF samples were obtained from 14 recently deceased cadavers and 10 patients …


Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos Mar 2013

Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos

All Dugoni School of Dentistry Faculty Articles

OBJECTIVE: The aim of this study was to compare the production of the chemokines CCL3 and CXCL12 by cultured dental pulp fibroblasts from permanent (PDPF) and deciduous (DDPF) teeth under stimulation by Porphyromonas gingivalis LPS (PgLPS).

MATERIAL AND METHODS: Primary culture of fibroblasts from permanent (n=3) and deciduous (n=2) teeth were established using an explant technique. After the fourth passage, fibroblasts were stimulated by increasing concentrations of PgLPS (0-10 µg/mL) at 1, 6 and 24 h. The cells were tested for viability through MTT assay, and production of the chemokines CCL3 and CXCL12 was determined through ELISA. Comparisons among samples …


Melanopsin, Photosensitive Ganglion Cells, And Seasonal Affective Disorder., Kathryn A Roecklein, Patricia M Wong, Megan A Miller, Shannon D Donofry, Marissa L Kamarck, George C Brainard Mar 2013

Melanopsin, Photosensitive Ganglion Cells, And Seasonal Affective Disorder., Kathryn A Roecklein, Patricia M Wong, Megan A Miller, Shannon D Donofry, Marissa L Kamarck, George C Brainard

Department of Neurology Faculty Papers

In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood …


Simultaneous Measurement Of Deep Tissue Blood Flow And Oxygenation Using Noncontact Diffuse Correlation Spectroscopy Flow-Oximeter, Ting Li, Yu Lin, Yu Shang, Lian He, Chong Huang, Margaret M. Szabunio, Guoqiang Yu Feb 2013

Simultaneous Measurement Of Deep Tissue Blood Flow And Oxygenation Using Noncontact Diffuse Correlation Spectroscopy Flow-Oximeter, Ting Li, Yu Lin, Yu Shang, Lian He, Chong Huang, Margaret M. Szabunio, Guoqiang Yu

Biomedical Engineering Faculty Publications

We report a novel noncontact diffuse correlation spectroscopy flow-oximeter for simultaneous quantification of relative changes in tissue blood flow (rBF) and oxygenation (Δ[oxygenation]). The noncontact probe was compared against a contact probe in tissue-like phantoms and forearm muscles (n = 10), and the dynamic trends in both rBF and Δ[oxygenation] were found to be highly correlated. However, the magnitudes of Δ[oxygenation] measured by the two probes were significantly different. Monte Carlo simulations and phantom experiments revealed that the arm curvature resulted in a significant underestimation (~-20%) for the noncontact measurements in Δ[ …


Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo Feb 2013

Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo

Dartmouth Scholarship

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here …


Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev Feb 2013

Molecular Basis Of Differential Sensitivity Of Myeloma Cells To Clinically Relevant Bolus Treatment With Bortezomib, Tamer B. Shabaneh, Sondra L. Downey, Ayrton L. Goddard, Michael Screen, Marcella M. Lucas, Alan Eastman, Alexei F. Kisselev

Dartmouth Scholarship

The proteasome inhibitor bortezomib (Velcade) is prescribed for the treatment of multiple myeloma. Clinically achievable concentrations of bortezomib cause less than 85% inhibition of the chymotrypsin-like activity of the proteasome, but little attention has been paid as to whether in vitro studies are representative of this level of inhibition. Patients receive bortezomib as an intravenous or subcutaneous bolus injection, resulting in maximum proteasome inhibition within one hour followed by a gradual recovery of activity. In contrast, most in vitro studies use continuous treatment so that activity never recovers. Replacing continuous treatment with 1 h-pulse treatment increases differences in sensitivity in …


Observational Intensity Bias Associated With Illness Adjustment: Cross Sectional Analysis Of Insurance Claims, J. E. Wennberg, D. O. Staiger, S. M. Sharp, D. J. Gottlieb Feb 2013

Observational Intensity Bias Associated With Illness Adjustment: Cross Sectional Analysis Of Insurance Claims, J. E. Wennberg, D. O. Staiger, S. M. Sharp, D. J. Gottlieb

Dartmouth Scholarship

Objective: To determine the bias associated with frequency of visits by physicians in adjusting for illness, using diagnoses recorded in administrative databases.

Setting: Claims data from the US Medicare program for services provided in 2007 among 306 US hospital referral regions.

Design: Cross sectional analysis. Participants 20% sample of fee for service Medicare beneficiaries residing in the United States in 2007 (n=5 153 877).


Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton Feb 2013

Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton

Dartmouth Scholarship

Humans have a fundamental need for social relationships. Rejection from social groups is especially detrimental, rendering the ability to detect threats to social relationships and respond in adaptive ways critical. Indeed, previous research has shown that experiencing social rejection alters the processing of subsequent social cues in a variety of socially affiliative and avoidant ways. Because social perception and cognition occurs spontaneously and automatically, detecting threats to social relationships may occur without conscious awareness or control. Here, we investigated the automaticity of social threat detection by examining how implicit primes affect neural responses to social stimuli. However, despite using a …


Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel Feb 2013

Evolutionarily Novel Functional Networks In The Human Brain?, Dante Mantini, Maurizio Corbetta, Gian Luca Romani, Guy A. Orban, Wim Vanduffel

Open Access Publications

Primate evolution has been accompanied by complex reorganizations in brain anatomy and function. Little is known, however, about the relationship between anatomical and functional changes induced through primate evolution. Using functional magnetic resonance imaging, we assessed spatial and temporal correspondences of cortical networks in humans and monkeys. We provided evidence for topologically and functionally correspondent networks in sensory-motor and attention regions. More specifically, we revealed a possible monkey equivalent of the human ventral attention network. For other human networks, such as the language and the default-mode networks, we detected topological correspondent networks in the monkey, but with different functional signatures. …


The Disruption Of Celf6, A Gene Identified By Translational Profiling Of Serotonergic Neurons, Results In Autism-Related Behaviors, Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz Feb 2013

The Disruption Of Celf6, A Gene Identified By Translational Profiling Of Serotonergic Neurons, Results In Autism-Related Behaviors, Joseph D. Dougherty, Susan E. Maloney, David F. Wozniak, Michael A. Rieger, Lisa Sonnenblick, Giovanni Coppola, Nathaniel G. Mahieu, Juliet Zhang, Jinlu Cai, Gary J. Patti, Brett S. Abrahams, Daniel H. Geschwind, Nathaniel Heintz

Open Access Publications

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, …


A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles Feb 2013

A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

UNLABELLED: To enhance the research capabilities of investigators interested in Staphylococcus aureus, the Nebraska Center for Staphylococcal Research (CSR) has generated a sequence-defined transposon mutant library consisting of 1,952 strains, each containing a single mutation within a nonessential gene of the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300. To demonstrate the utility of this library for large-scale screening of phenotypic alterations, we spotted the library on indicator plates to assess hemolytic potential, protease production, pigmentation, and mannitol utilization. As expected, we identified many genes known to function in these processes, thus validating the utility of this approach. Importantly, we …


Stallion Sperm Transcriptome Comprises Functionally Coherent Coding And Regulatory Rnas As Revealed By Microarray Analysis And Rna-Seq., Pranab J. Das, Fiona M. Mccarthy, Monika Vishnoi, Nandina Paria, Cathy Gresham, Gang Li, Priyanka Kachroo, A. Kendrick Sudderth, Sheila Teague, Charles C. Love, Dickson D. Varner, Bhanu P. Chowdhary, Terje Raudsepp Feb 2013

Stallion Sperm Transcriptome Comprises Functionally Coherent Coding And Regulatory Rnas As Revealed By Microarray Analysis And Rna-Seq., Pranab J. Das, Fiona M. Mccarthy, Monika Vishnoi, Nandina Paria, Cathy Gresham, Gang Li, Priyanka Kachroo, A. Kendrick Sudderth, Sheila Teague, Charles C. Love, Dickson D. Varner, Bhanu P. Chowdhary, Terje Raudsepp

CVM Publications

Mature mammalian sperm contain a complex population of RNAs some of which might regulate spermatogenesis while others probably play a role in fertilization and early development. Due to this limited knowledge, the biological functions of sperm RNAs remain enigmatic. Here we report the first characterization of the global transcriptome of the sperm of fertile stallions. The findings improved understanding of the biological significance of sperm RNAs which in turn will allow the discovery of sperm-based biomarkers for stallion fertility. The stallion sperm transcriptome was interrogated by analyzing sperm and testes RNA on a 21,000-element equine whole-genome oligoarray and by RNA-seq. …


Muc4 Overexpression Augments Cell Migration And Metastasis Through Egfr Family Proteins In Triple Negative Breast Cancer Cells., Partha Mukhopadhyay, Imayavaramban Lakshmanan, Moorthy P. Ponnusamy, Subhankar Chakraborty, Maneesh Jain, Priya Pai, Lynette M. Smith, Subodh M. Lele, Surinder K. Batra Feb 2013

Muc4 Overexpression Augments Cell Migration And Metastasis Through Egfr Family Proteins In Triple Negative Breast Cancer Cells., Partha Mukhopadhyay, Imayavaramban Lakshmanan, Moorthy P. Ponnusamy, Subhankar Chakraborty, Maneesh Jain, Priya Pai, Lynette M. Smith, Subodh M. Lele, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

INTRODUCTION: Current studies indicate that triple negative breast cancer (TNBC), an aggressive breast cancer subtype, is associated with poor prognosis and an early pattern of metastasis. Emerging evidence suggests that MUC4 mucin is associated with metastasis of various cancers, including breast cancer. However, the functional role of MUC4 remains unclear in breast cancers, especially in TNBCs.

METHOD: In the present study, we investigated the functional and mechanistic roles of MUC4 in potentiating pathogenic signals including EGFR family proteins to promote TNBC aggressiveness using in vitro and in vivo studies. Further, we studied the expression of MUC4 in invasive TNBC tissue …


Pyrvinium Pamoate Changes Alternative Splicing Of The Serotonin Receptor 2c By Influencing Its Rna Structure, Manli Shen, Stanislav Bellaousov, Michael Hiller, Pierre De La Grange, Trevor O. Creamer, Orit Malina, Ruth Sperling, David H. Mathews, Peter Stoilov, Stefan Stamm Feb 2013

Pyrvinium Pamoate Changes Alternative Splicing Of The Serotonin Receptor 2c By Influencing Its Rna Structure, Manli Shen, Stanislav Bellaousov, Michael Hiller, Pierre De La Grange, Trevor O. Creamer, Orit Malina, Ruth Sperling, David H. Mathews, Peter Stoilov, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2'-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5'-splice site forms intramolecular base pairs that …


Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao Feb 2013

Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao

Dartmouth Scholarship

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of …


Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright Feb 2013

Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright

Dartmouth Scholarship

Background: Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III).

Methods: NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), …


Honokiol Blocks Store Operated Calcium Entry In Cho Cells Expressing The M3 Muscarinic Receptor: Honokiol And Muscarinic Signaling, Hsiu-Jen Wang, Alexis Martin, Po-Kuan Chao, Rhett A. Reichard, Adam L. Martin, Yue-Wern Huang, Ming-Huan Chan, Robert Aronstam Feb 2013

Honokiol Blocks Store Operated Calcium Entry In Cho Cells Expressing The M3 Muscarinic Receptor: Honokiol And Muscarinic Signaling, Hsiu-Jen Wang, Alexis Martin, Po-Kuan Chao, Rhett A. Reichard, Adam L. Martin, Yue-Wern Huang, Ming-Huan Chan, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Background: Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.

Results: Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store …


Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band Feb 2013

Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer …


Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer Feb 2013

Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of


Mindfulness-Based Relapse Prevention For Substance Craving., Katie Witkiewitz, Sarah Bowen, Haley Douglas, Sharon H Hsu Feb 2013

Mindfulness-Based Relapse Prevention For Substance Craving., Katie Witkiewitz, Sarah Bowen, Haley Douglas, Sharon H Hsu

Articles, Abstracts, and Reports

Craving, defined as the subjective experience of an urge or desire to use substances, has been identified in clinical, laboratory, and preclinical studies as a significant predictor of substance use, substance use disorder, and relapse following treatment for a substance use disorder. Various models of craving have been proposed from biological, cognitive, and/or affective perspectives, and, collectively, these models of craving have informed the research and treatment of addictive behaviors. In this article we discuss craving from a mindfulness perspective, and specifically how mindfulness-based relapse prevention (MBRP) may be effective in reducing substance craving. We present secondary analyses of data …


Sector Expansion And Elliptical Modeling Of Blue-Gray Ovoids For Basal Cell Carcinoma Discrimination In Dermoscopy Images, Pelin Guvenc, Robert W. Leander, Serkan Kefel, William V. Stoecker, Ryan K. Rader, Kristen A. Hinton, Sherea Monica Stricklin, Harold S. Rabinovitz, Margaret C. Oliviero, Randy Hays Moss Feb 2013

Sector Expansion And Elliptical Modeling Of Blue-Gray Ovoids For Basal Cell Carcinoma Discrimination In Dermoscopy Images, Pelin Guvenc, Robert W. Leander, Serkan Kefel, William V. Stoecker, Ryan K. Rader, Kristen A. Hinton, Sherea Monica Stricklin, Harold S. Rabinovitz, Margaret C. Oliviero, Randy Hays Moss

Chemistry Faculty Research & Creative Works

Background: Blue-gray ovoids (B-GOs), a critical dermoscopic structure for basal cell carcinoma (BCC), offer an opportunity for automatic detection of BCC. Due to variation in size and color, B-GOs can be easily mistaken for similar structures in benign lesions. Analysis of these structures could afford accurate characterization and automatic recognition of B-GOs, furthering the goal of automatic BCC detection. This study utilizes a novel segmentation method to discriminate B-GOs from their benign mimics.

Methods: Contact dermoscopy images of 68 confirmed BCCs with B-GOs were obtained. Another set of 131 contact dermoscopic images of benign lesions possessing B-GO mimics provided a …