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Full-Text Articles in Medicine and Health Sciences

Summer-Long Grazing Of High Vs. Low Endophyte (Neotyphodium Coenophialum)-Infected Tall Fescue By Growing Beef Steers Results In Distinct Temporal Blood Analyte Response Patterns, With Poor Correlation To Serum Prolactin Levels, Joshua J. Jackson, Merlin D. Lindemann, James A. Boling, James C. Matthews Dec 2015

Summer-Long Grazing Of High Vs. Low Endophyte (Neotyphodium Coenophialum)-Infected Tall Fescue By Growing Beef Steers Results In Distinct Temporal Blood Analyte Response Patterns, With Poor Correlation To Serum Prolactin Levels, Joshua J. Jackson, Merlin D. Lindemann, James A. Boling, James C. Matthews

Animal and Food Sciences Faculty Publications

Previously, we reported the effects of fescue toxicosis on developing Angus-cross steer growth, carcass, hepatic mRNA, and protein expression profiles of selected serum proteins, and blood clinical and chemical profiles, after summer-long grazing (85 days) of high endophyte (HE)- vs. low endophyte (LE)-infected fescue pastures. We now report the temporal development of acute, intermediate, and chronic responses of biochemical and clinical blood analytes determined at specified time intervals (period 1, day 0–36; period 2, day 37–58; and period 3, day 59–85). Throughout the trial, the alkaloid concentrations of the HE forage was consistently 19–25 times greater (P ≤ 0.002) …


Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo Dec 2015

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …


Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton Dec 2015

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …


Individual Responses For Muscle Activation, Repetitions, And Volume During Three Sets To Failure Of High- (80% 1rm) Versus Low-Load (30% 1rm) Forearm Flexion Resistance Exercise, Nathaniel D. M. Jenkins, Terry J. Housh, Samuel L. Buckner, Haley C. Bergstrom, Kristen C. Cochrane, Cory M. Smith, Ethan C. Hill, Richard J. Schmidt, Joel T. Cramer Dec 2015

Individual Responses For Muscle Activation, Repetitions, And Volume During Three Sets To Failure Of High- (80% 1rm) Versus Low-Load (30% 1rm) Forearm Flexion Resistance Exercise, Nathaniel D. M. Jenkins, Terry J. Housh, Samuel L. Buckner, Haley C. Bergstrom, Kristen C. Cochrane, Cory M. Smith, Ethan C. Hill, Richard J. Schmidt, Joel T. Cramer

Kinesiology and Health Promotion Faculty Publications

This study compared electromyographic (EMG) amplitude, the number of repetitions completed, and exercise volume during three sets to failure of high- (80% 1RM) versus low-load (30% 1RM) forearm flexion resistance exercise on a subject-by-subject basis. Fifteen men were familiarized, completed forearm flexion 1RM testing. Forty-eight to 72 h later, the subjects completed three sets to failure of dumbbell forearm flexion resistance exercise with 80% (n = 8) or 30% (n = 7) 1RM. EMG amplitude was calculated for every repetition, and the number of repetitions performed and exercise volume were recorded. During sets 1, 2, and 3, one …


Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes Dec 2015

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.


Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo Dec 2015

Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of …


Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder Nov 2015

Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder

Neuroscience Faculty Publications

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after …


A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett Nov 2015

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium …


Short-Term, High-Fat Diet Accelerates Disuse Atrophy And Protein Degradation In A Muscle-Specific Manner In Mice, Steven L. Roseno, Patrick R. Davis, Lance M. Bollinger, Jonathan J. S. Powell, Carol A. Witczak, Jeffrey J. Brault Nov 2015

Short-Term, High-Fat Diet Accelerates Disuse Atrophy And Protein Degradation In A Muscle-Specific Manner In Mice, Steven L. Roseno, Patrick R. Davis, Lance M. Bollinger, Jonathan J. S. Powell, Carol A. Witczak, Jeffrey J. Brault

Kinesiology and Health Promotion Faculty Publications

BACKGROUND: A short-term high-fat diet impairs mitochondrial function and the ability of skeletal muscle to respond to growth stimuli, but it is unknown whether such a diet alters the ability to respond to atrophy signals. The purpose of this study was to determine whether rapid weigh gain induced by a high-fat (HF) diet accelerates denervation-induced muscle atrophy.

METHODS: Adult, male mice (C57BL/6) were fed a control or HF (60 % calories as fat) diet for 3 weeks (3wHF). Sciatic nerve was sectioned unilaterally for the final 5 or 14 days of the diet. Soleus and extensor digitorum longus …


Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy Oct 2015

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …


White Matter Microstructure Contributes To Age-Related Declines In Task-Induced Deactivation Of The Default Mode Network, Christopher A. Brown, Jonathan G. Hakun, Zude Zhu, Nathan F. Johnson, Brian T. Gold Oct 2015

White Matter Microstructure Contributes To Age-Related Declines In Task-Induced Deactivation Of The Default Mode Network, Christopher A. Brown, Jonathan G. Hakun, Zude Zhu, Nathan F. Johnson, Brian T. Gold

Neuroscience Faculty Publications

Task-induced deactivations within the brain’s default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) …


Cd151-Α3Β1 Integrin Complexes Are Prognostic Markers Of Glioblastoma And Cooperate With Egfr To Drive Tumor Cell Motility And Invasion, Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana L. Napier, Michael Lu, Jian-An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang Oct 2015

Cd151-Α3Β1 Integrin Complexes Are Prognostic Markers Of Glioblastoma And Cooperate With Egfr To Drive Tumor Cell Motility And Invasion, Pengcheng Zhou, Sonia Erfani, Zeyi Liu, Changhe Jia, Yecang Chen, Bingwei Xu, Xinyu Deng, Jose E. Alfáro, Li Chen, Dana L. Napier, Michael Lu, Jian-An Huang, Chunming Liu, Olivier Thibault, Rosalind Segal, Binhua P. Zhou, Natasha Kyprianou, Craig Horbinski, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based …


The Foot Of Homo Naledi, W. E. H. Harcourt-Smith, Z. Throckmorton, K. A. Congdon, B. Zipfel, Andrew S. Deane, M. S. M. Drapeau, S. E. Churchill, L. R. Berger, J. M. Desilva Oct 2015

The Foot Of Homo Naledi, W. E. H. Harcourt-Smith, Z. Throckmorton, K. A. Congdon, B. Zipfel, Andrew S. Deane, M. S. M. Drapeau, S. E. Churchill, L. R. Berger, J. M. Desilva

Neuroscience Faculty Publications

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having …


The Hand Of Homo Naledi, Tracy L. Kivell, Andrew S. Deane, Matthew W. Tocheri, Caley M. Orr, Peter Schmid, John Hawks, Lee R. Berger, Steven E. Churchill Oct 2015

The Hand Of Homo Naledi, Tracy L. Kivell, Andrew S. Deane, Matthew W. Tocheri, Caley M. Orr, Peter Schmid, John Hawks, Lee R. Berger, Steven E. Churchill

Neuroscience Faculty Publications

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like …


Distributed Encoding Of Spatial And Object Categories In Primate Hippocampal Microcircuits, Ioan Opris, Lucas M. Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler Oct 2015

Distributed Encoding Of Spatial And Object Categories In Primate Hippocampal Microcircuits, Ioan Opris, Lucas M. Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in …


Homo Naledi, A New Species Of The Genus Homo From The Dinaledi Chamber, South Africa, Lee R. Berger, John Hawks, Darryl J. De Ruiter, Steven E. Churchill, Peter Schmid, Lucas K. Delezene, Tracy L. Kivell, Heather M. Garvin, Scott A. Williams, Jeremy M. Desilva, Matthew M. Skinner, Charles M. Musiba, Noel Cameron, Trenton W. Holliday, William Harcourt-Smith, Rebecca R. Ackermann, Markus Bastir, Barry Bogin, Debra Bolter, Juliet Brophy, Zachary D. Cofran, Kimberly A. Congdon, Andrew S. Deane, Mana Dembo, Michelle Drapeau, Marina C. Elliott, Elen M. Feuerriegel, Daniel Garcia-Martinez, David J. Green, Alia Gurtov, Joel D. Irish, Ashley Kruger, Myra F. Laird, Damiano Marchi, Marc R. Meyer, Shahed Nalla, Enquye W. Negash, Caley M. Orr, Davorka Radovcic, Lauren Schroeder, Jill E. Scott, Zachary Throckmorton, Matthew W. Tocheri, Caroline Vansickle, Christopher S. Walker, Pianpian Wei, Bernhard Zipfel Sep 2015

Homo Naledi, A New Species Of The Genus Homo From The Dinaledi Chamber, South Africa, Lee R. Berger, John Hawks, Darryl J. De Ruiter, Steven E. Churchill, Peter Schmid, Lucas K. Delezene, Tracy L. Kivell, Heather M. Garvin, Scott A. Williams, Jeremy M. Desilva, Matthew M. Skinner, Charles M. Musiba, Noel Cameron, Trenton W. Holliday, William Harcourt-Smith, Rebecca R. Ackermann, Markus Bastir, Barry Bogin, Debra Bolter, Juliet Brophy, Zachary D. Cofran, Kimberly A. Congdon, Andrew S. Deane, Mana Dembo, Michelle Drapeau, Marina C. Elliott, Elen M. Feuerriegel, Daniel Garcia-Martinez, David J. Green, Alia Gurtov, Joel D. Irish, Ashley Kruger, Myra F. Laird, Damiano Marchi, Marc R. Meyer, Shahed Nalla, Enquye W. Negash, Caley M. Orr, Davorka Radovcic, Lauren Schroeder, Jill E. Scott, Zachary Throckmorton, Matthew W. Tocheri, Caroline Vansickle, Christopher S. Walker, Pianpian Wei, Bernhard Zipfel

Neuroscience Faculty Publications

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot …


Differential Expression Of Mrna Encoding Cytokines And Chemokines In The Reproductive Tract After Infection Of Mice With Chlamydia Trachomatis, Katheryn L. Cerny, Maranda Van Fleet, Anatoly Slepenkin, Ellena M. Peterson, Phillip J. Bridges Sep 2015

Differential Expression Of Mrna Encoding Cytokines And Chemokines In The Reproductive Tract After Infection Of Mice With Chlamydia Trachomatis, Katheryn L. Cerny, Maranda Van Fleet, Anatoly Slepenkin, Ellena M. Peterson, Phillip J. Bridges

Animal and Food Sciences Faculty Publications

Infection with Chlamydia trachomatis targets epithelial cells within the genital tract which respond by secreting chemokines and cytokines. Persistent inflammation can lead to fibrosis, tubal infertility and/or ectopic pregnancy; many infections are asymptomatic. Most studies have investigated the inflammatory response in the initial stages of infection, less is known about the later stages of infection, especially with a low, potentially asymptomatic, bacterial load. Our objective was to determine the inflammatory mediators involved in clearance of low-grade infection and the potential involvement in chronic inflammation. Six to eight week old C3H/HeJ mice were pretreated with 2.5 mg medroxyprogesterone acetate on day …


Borrelia Burgdorferi Reva Significantly Affects Pathogenicity And Host Response In The Mouse Model Of Lyme Disease, Rebecca Byram, Robert A. Gaultney, Angela M. Floden, Christopher Hellekson, Brandee L. Stone, Amy Bowman, Brian Stevenson, Barbara J. B. Johnson, Catherine A. Brissette Sep 2015

Borrelia Burgdorferi Reva Significantly Affects Pathogenicity And Host Response In The Mouse Model Of Lyme Disease, Rebecca Byram, Robert A. Gaultney, Angela M. Floden, Christopher Hellekson, Brandee L. Stone, Amy Bowman, Brian Stevenson, Barbara J. B. Johnson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, …


Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose Sep 2015

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …


Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor Sep 2015

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome …


Intracellular Na+ Concentration ([Na+]I) Is Elevated In Diabetic Hearts Due To Enhanced Na+–Glucose Cotransport, Rebekah Lambert, Sarah Srodulski, Xiaoli Peng, Kenneth B. Margulies, Florin Despa, Sanda Despa Sep 2015

Intracellular Na+ Concentration ([Na+]I) Is Elevated In Diabetic Hearts Due To Enhanced Na+–Glucose Cotransport, Rebekah Lambert, Sarah Srodulski, Xiaoli Peng, Kenneth B. Margulies, Florin Despa, Sanda Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Intracellular Na+ concentration ([Na+]i) regulates Ca2+ cycling, contractility, metabolism, and electrical stability of the heart. [Na+]i is elevated in heart failure, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na+]i is also increased in type 2 diabetes (T2D) due to enhanced activity of the Na+-glucose cotransporter.

METHODS AND RESULTS: To test this hypothesis, we used myocardial tissue from humans with T2D and a rat model of late-onset T2D (HIP rat). Western blot analysis showed increased Na+-glucose cotransporter expression in failing hearts from T2D patients compared …


Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields Aug 2015

Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …


Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio Aug 2015

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlAm-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …


Zbtb20 Is A Sequence-Specific Transcriptional Repressor Of Alpha-Fetoprotein Gene, Hai Zhang, Dongmei Cao, Luting Zhou, Ye Zhang, Xiaoqin Guo, Hui Li, Yuxia Chen, Brett T. Spear, Jia-Wei Wu, Zhifang Xie, Weiping J Zhang Jul 2015

Zbtb20 Is A Sequence-Specific Transcriptional Repressor Of Alpha-Fetoprotein Gene, Hai Zhang, Dongmei Cao, Luting Zhou, Ye Zhang, Xiaoqin Guo, Hui Li, Yuxia Chen, Brett T. Spear, Jia-Wei Wu, Zhifang Xie, Weiping J Zhang

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alpha-fetoprotein (AFP) represents a classical model system to study developmental gene regulation in mammalian cells. We previously reported that liver ZBTB20 is developmentally regulated and plays a central role in AFP postnatal repression. Here we show that ZBTB20 is a sequence-specific transcriptional repressor of AFP. By ELISA-based DNA-protein binding assay and conventional gel shift assay, we successfully identified a ZBTB20-binding site at -104/-86 of mouse AFP gene, flanked by two HNF1 sites and two C/EBP sites in the proximal promoter. Importantly, mutation of the core sequence in this site fully abolished its binding to ZBTB20 in vitro, as well …


Onset Time And Durability Of Huntingtin Suppression In Rhesus Putamen After Direct Infusion Of Antihuntingtin Sirna, Richard Grondin, Pei Ge, Qingmin Chen, Jessica E. Sutherland, Zhiming Zhang, Don M. Gash, David K. Stiles, Gregory R. Stewart, Dinah W. Y. Sah, William F. Kaemmerer Jun 2015

Onset Time And Durability Of Huntingtin Suppression In Rhesus Putamen After Direct Infusion Of Antihuntingtin Sirna, Richard Grondin, Pei Ge, Qingmin Chen, Jessica E. Sutherland, Zhiming Zhang, Don M. Gash, David K. Stiles, Gregory R. Stewart, Dinah W. Y. Sah, William F. Kaemmerer

Neuroscience Faculty Publications

One possible treatment for Huntington's disease involves direct infusion of a small, interfering RNA (siRNA) designed to reduce huntingtin expression into brain tissue from a chronically implanted programmable pump. Here, we studied the suppression of huntingtin mRNA achievable with short infusion times, and investigated how long suppression may persist after infusion ceases. Rhesus monkeys received 3 days of infusion of Magnevist into the putamen to confirm catheter patency and fluid distribution. After a 1-week washout period, monkeys received radiolabeled siRNA targeting huntingtin. After 1 or 3 days of siRNA delivery, monkeys were either terminated, or their pumps were shut off …


Public Health Metrics: Key Considerations And Criteria For Food Safety Modernization, Glen P. Mays Jun 2015

Public Health Metrics: Key Considerations And Criteria For Food Safety Modernization, Glen P. Mays

Health Management and Policy Presentations

Robust measures of public health impact are needed to guide implementation of the U.S. Food Safety Modernization Act. This session describes strategies used in the field of public health services research to specify and select measures based on considerations of relevance, tractability, attribution, precision, and feasibility.


Neuron-Based Heredity And Human Evolution, Don M. Gash, Andrew S. Deane Jun 2015

Neuron-Based Heredity And Human Evolution, Don M. Gash, Andrew S. Deane

Neuroscience Faculty Publications

It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission …


Disruption Of Columnar And Laminar Cognitive Processing In Primate Prefrontal Cortex Following Cocaine Exposure, Ioan Opris, Greg A. Gerhardt, Robert E. Hampson, Sam A. Deadwyler May 2015

Disruption Of Columnar And Laminar Cognitive Processing In Primate Prefrontal Cortex Following Cocaine Exposure, Ioan Opris, Greg A. Gerhardt, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell …


Angiotensin Ii Is Required To Induce Exaggerated Salt Sensitivity In Dahl Rats Exposed To Maternal Separation, Analia S. Loria, David M. Pollock, Jennifer S. Pollock May 2015

Angiotensin Ii Is Required To Induce Exaggerated Salt Sensitivity In Dahl Rats Exposed To Maternal Separation, Analia S. Loria, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

We previously reported that maternal separation, rat model of early life stress, enhances pressor responses to acute and chronic stressors. The aims of this study were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show exaggerated blood pressure responses to acute behavioral stressors, such as restraint stress or air jet stress (AJS), or, hypertensive stimuli including chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200 ng/Kg/min) during 1 week. MatSep was performed in male DS rats for 3 h/day from postnatal days 2-14. At 8 weeks …


Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson Apr 2015

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …