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Placental Fkbp5 Genetic And Epigenetic Variation Is Associated With Infant Neurobehavioral Outcomes In The Richs Cohort, Alison G. Paquette, Barry M. Lester, Devin C. Koestler, Corina Lesseur, David A. Armstrong, Carmen J. Marsit Aug 2014

Placental Fkbp5 Genetic And Epigenetic Variation Is Associated With Infant Neurobehavioral Outcomes In The Richs Cohort, Alison G. Paquette, Barry M. Lester, Devin C. Koestler, Corina Lesseur, David A. Armstrong, Carmen J. Marsit

Dartmouth Scholarship

Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network …


Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky Aug 2014

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …


Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis Aug 2014

Hair Cortisol As A Biomarker Of Stress In Mindfulness Training For Smokers., Simon B Goldberg, Alison R Manley, Stevens S Smith, Jeffrey M Greeson, Evan Russell, Stan Van Uum, Gideon Koren, James M Davis

College of Science & Mathematics Departmental Research

OBJECTIVES: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group.

PARTICIPANTS: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation.

OUTCOME MEASURES: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods. Self-reported negative affect was also assessed before and after …


Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah Aug 2014

Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah

Obstetrics & Gynaecology Publications

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse …


Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon Aug 2014

Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy. Our objective was to determine any associations between risk factors for sleep-related deaths at different ages.

METHODS: A cross-sectional study of sleep-related infant deaths from 24 states during 2004-2012 contained in the National Center for the Review and Prevention of Child Deaths Case Reporting System, a database of death reports from state child death review teams. The main exposure was age, divided into younger (0-3 months) and older …


Neurotrophic Factor Gdnf Promotes Survival Of Salivary Stem Cells, Nan (Tori) Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le Aug 2014

Neurotrophic Factor Gdnf Promotes Survival Of Salivary Stem Cells, Nan (Tori) Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le

All Dugoni School of Dentistry Faculty Articles

Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland …


Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu Aug 2014

Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu

Markey Cancer Center Faculty Publications

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC …


Population And Demographic Structure Of Ixodes Scapularis Say In The Eastern United States., Joyce M. Sakamoto, Jerome Goddard, Jason L. Rasgon Jul 2014

Population And Demographic Structure Of Ixodes Scapularis Say In The Eastern United States., Joyce M. Sakamoto, Jerome Goddard, Jason L. Rasgon

CALS Publications

INTRODUCTION: The most significant vector of tick-borne pathogens in the United States is Ixodes scapularis Say (the blacklegged tick). Previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. Because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission. METHODS: We investigated population genetic variation of I. scapularis populations in the eastern United States using a multilocus approach. We sequenced and analyzed the mitochondrial COI and 16S genes and three nuclear genes (serpin2, …


Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng Jul 2014

Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng

CALS Publications

Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein …


The Anoikis Effector Bit1 Displays Tumor Suppressive Function In Lung Cancer Cells., Xin Yao, Scott Jennings, Shubha Kale Ireland, Tri Pham Jul 2014

The Anoikis Effector Bit1 Displays Tumor Suppressive Function In Lung Cancer Cells., Xin Yao, Scott Jennings, Shubha Kale Ireland, Tri Pham

Faculty and Staff Publications

The mitochondrial Bit1 (Bcl-2 inhibitor of transcription 1) protein is a part of an apoptotic pathway that is uniquely regulated by integrin-mediated attachment. As an anoikis effector, Bit1 is released into the cytoplasm following loss of cell attachment and induces a caspase-independent form of apoptosis. Considering that anoikis resistance is a critical determinant of transformation, we hypothesized that cancer cells may circumvent the Bit1 apoptotic pathway to attain anchorageindependence and tumorigenic potential. Here, we provide the first evidence of the tumor suppressive effect of Bit1 through a mechanism involving anoikis induction in human lung adenocarcinoma derived A549 cells. Restitution of …


Espacios Femeninos En Posesas De La Habana: Un Caso De Llaves Desaparecidas, Olympia Gonzalez Jul 2014

Espacios Femeninos En Posesas De La Habana: Un Caso De Llaves Desaparecidas, Olympia Gonzalez

Modern Languages and Literatures: Faculty Publications and Other Works

No abstract provided.


Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki Jul 2014

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …


Sex Hormones Regulate Tenofovir-Diphosphate In Female Reproductive Tract Cells In Culture, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Angela D.M Kashuba, Charles R. Wira Jun 2014

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

Dartmouth Scholarship

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


Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse., Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy Jun 2014

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse., Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

All Faculty Articles - School of Engineering and Computer Science

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …


Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio Jun 2014

Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio

Open Access Publications

The Wallenda (Wnd)/dual leucine zipper kinase (DLK)-Jnk pathway is an evolutionarily conserved MAPK signaling pathway that functions during neuronal development and following axonal injury. Improper pathway activation causes defects in axonal guidance and synaptic growth, whereas loss-of-function mutations in pathway components impairs axonal regeneration and degeneration after injury. Regulation of this pathway is in part through the E3 ubiquitin ligase Highwire (Hiw), which targets Wnd/DLK for degradation to limit MAPK signaling. To explore mechanisms controlling Wnd/DLK signaling, we performed a large-scale genetic screen in Drosophila to identify negative regulators of the pathway. Here we describe the identification and characterization of …


Resistant Starch Type 4-Enriched Diet Lowered Blood Cholesterols And Improved Body Composition In A Double Blind Controlled Cross-Over Intervention, Sailendra N Nichenametla, Lee A. Weidauer, Howard Wey, Tianna Beare, Bonny Specker, Moul Dey Jun 2014

Resistant Starch Type 4-Enriched Diet Lowered Blood Cholesterols And Improved Body Composition In A Double Blind Controlled Cross-Over Intervention, Sailendra N Nichenametla, Lee A. Weidauer, Howard Wey, Tianna Beare, Bonny Specker, Moul Dey

Health and Nutritional Sciences Faculty Publications

A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in the United States. Effects of resistant starch type 4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of RS4-enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double blind (participants-investigators), placebo-controlled, cluster cross-over intervention (n = 86, age≥18, 2-12 week interventions, 2-week washout) in the United States, individuals were classified as having MetS (With-MetS) or not (No-MetS) following International Diabetes Federation (IDF)-criteria. RS4 …


Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio Jun 2014

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …


Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger Jun 2014

Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger

Department of Medicine Faculty Papers

No abstract provided.


The Effect Of Maternal Separation And Postnatal Oxytocin Administration On Social Recognition In Adolescent Female Mice, Nathaniel Richard Thomas May 2014

The Effect Of Maternal Separation And Postnatal Oxytocin Administration On Social Recognition In Adolescent Female Mice, Nathaniel Richard Thomas

Dissertations - ALL

A vast body of literature indicates that exposing rodents to maternal separation during infancy results in long - term developmental changes in physiological, behavioral, and psychological domains. Because several previous studies have indicated that maternal separation may be detrimental to the processing and discrimination of social cues, the primary aim of this dissertation was to determine whether separating female infant mouse pups from their mother, but not siblings, for 3 hrs daily, during the first two weeks of life, influences social recognition during adolescence (Experiment 1). This dissertation also sought to evaluate whether postnatal administration of the oxytocin would influence …


Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore May 2014

Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, …


On Individual, Sex And Age Differentiation Of Indian House Crow (Corvus Splendens) Call: A Preliminary Study In Potohar, Pakistan, Waqas Hameed, Inayat Ullah, Safia Janjua, Fakhar -I- Abbas, Afsar Mian May 2014

On Individual, Sex And Age Differentiation Of Indian House Crow (Corvus Splendens) Call: A Preliminary Study In Potohar, Pakistan, Waqas Hameed, Inayat Ullah, Safia Janjua, Fakhar -I- Abbas, Afsar Mian

Journal of Bioresource Management

Considering importance of acoustics studies in population biology, 500 calls of the Indian House Crow (Corvus splendens) were recorded in morning - mid-afternoon hours (January-February, 2009) from 23 sites of urban areas of Potahar (Punjab, Pakistan). Calls were recorded using Sony CFS 1030 S sound records (sampling rate = 48 KHz) and edited using Sound Analysis Pro (Version 1.02). software using FFT method rate 50%, data window 9.27 ms, advanced window 1.36 ms. Through editing of calls, we selected 60 (37 ♂♂, 17 ♀♀, 6 Juvenile ♂♂) good quality spectrograms for detailed analysis. Spectrograms were characterized by rapid frequency modulations …


Regional-Specific Effects Of Ovarian Hormone Loss On Synaptic Plasticity In Adult Human Apoe Targeted Replacement Mice, Rebecca C. Klein, Shyla Saini, Mary-Louise Risher, Shawn K. Acheson, Rebekah L. Fleming, Hannah G. Sexton, H. Scott Swartzwelder, Scott D. Moore Apr 2014

Regional-Specific Effects Of Ovarian Hormone Loss On Synaptic Plasticity In Adult Human Apoe Targeted Replacement Mice, Rebecca C. Klein, Shyla Saini, Mary-Louise Risher, Shawn K. Acheson, Rebekah L. Fleming, Hannah G. Sexton, H. Scott Swartzwelder, Scott D. Moore

Biomedical Sciences

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE …


Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian Apr 2014

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …


Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari Apr 2014

Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari

Medical Biophysics Publications

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …


Comparative Analysis Of Gingival Tissue Antigen Presentation Pathways In Ageing And Periodontitis, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Luis Orraca, Kuey-Chu Chen, Arnold J. Stromberg, Janis Gonzalez-Martinez, Jeffrey L. Ebersole Apr 2014

Comparative Analysis Of Gingival Tissue Antigen Presentation Pathways In Ageing And Periodontitis, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Luis Orraca, Kuey-Chu Chen, Arnold J. Stromberg, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens.

MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy …


Long-Term High-Level Exercise Promotes Muscle Reinnervation With Age., Simone Mosole, Ugo Carraro, Helmut Kern, Stefan Loefler, Hannah Fruhmann, Michael Vogelauer, Samantha Burggraf, Winfried Mayr, Matthias Krenn, Tatjana Paternostro-Sluga, Dusan Hamar, Jan Cvecka, Milan Sedliak, Veronika Tirpakova, Nejc Sarabon, Antonio Musarò, Marco Sandri, Feliciano Protasi, Alessandra Nori, Amber Pond, Sandra Zampieri Apr 2014

Long-Term High-Level Exercise Promotes Muscle Reinnervation With Age., Simone Mosole, Ugo Carraro, Helmut Kern, Stefan Loefler, Hannah Fruhmann, Michael Vogelauer, Samantha Burggraf, Winfried Mayr, Matthias Krenn, Tatjana Paternostro-Sluga, Dusan Hamar, Jan Cvecka, Milan Sedliak, Veronika Tirpakova, Nejc Sarabon, Antonio Musarò, Marco Sandri, Feliciano Protasi, Alessandra Nori, Amber Pond, Sandra Zampieri

Publications

The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were …


Gene Co-Citation Networks Associated With Worker Sterility In Honey Bees., Emma Kate Mullen, Mark Daley, Alanna Gabrielle Backx, Graham James Thompson Mar 2014

Gene Co-Citation Networks Associated With Worker Sterility In Honey Bees., Emma Kate Mullen, Mark Daley, Alanna Gabrielle Backx, Graham James Thompson

Brain and Mind Institute Researchers' Publications

BACKGROUND: The evolution of reproductive self-sacrifice is well understood from kin theory, yet our understanding of how actual genes influence the expression of reproductive altruism is only beginning to take shape. As a model in the molecular study of social behaviour, the honey bee Apis mellifera has yielded hundreds of genes associated in their expression with differences in reproductive status of females, including genes directly associated with sterility, yet there has not been an attempt to link these candidates into functional networks that explain how workers regulate sterility in the presence of queen pheromone. In this study we use available …


Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu Mar 2014

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …


Palatal Mucosa Derived Fibroblasts Present An Adaptive Behavior Regarding Cytokine Secretion When Grafted Onto The Gingival Margin, Fabíola Pontes Azevedo, Ana Carolina Morandini, Carla Renata Sipert, Thiago José Dionísio, Carlos Ferreira Santos, Carla Andreotti Damante, Maria Lúcia Rubo De Rezende, Adriana Campos Passanezi Sant'ana, Sebastião Luiz Aguiar Greghi Mar 2014

Palatal Mucosa Derived Fibroblasts Present An Adaptive Behavior Regarding Cytokine Secretion When Grafted Onto The Gingival Margin, Fabíola Pontes Azevedo, Ana Carolina Morandini, Carla Renata Sipert, Thiago José Dionísio, Carlos Ferreira Santos, Carla Andreotti Damante, Maria Lúcia Rubo De Rezende, Adriana Campos Passanezi Sant'ana, Sebastião Luiz Aguiar Greghi

All Dugoni School of Dentistry Faculty Articles

BACKGROUND: Considering that grafted gingival tissue might have to be adapted to the receptor area and that fibroblasts have the ability to respond to bacterial stimuli through the release of various cytokines, this study investigated whether fibroblasts from the palatal mucosa behave differently when grafted onto the gingival margin regarding cytokine secretion.

METHODS: Biopsies from the palatal mucosa were collected at the time of free gingival graft surgery, and after four months re-collection was performed upon surgery for root coverage. Fibroblasts were isolated by the explant technique, cultured and stimulated with Porphyromonas gingivalis (Pg) and Escherichia coli (Ec) LPS for …


Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding Mar 2014

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …