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Type Ii Protein Arginine Methyltransferase 5 (Prmt5) Is Required For Circadian Pperiod Determination In Arabidopsis Thaliana, Sunghyun Hong, Hae-Ryoung Song, Kerry Lutz, Randall A. Kerstetter, Todd P. Michael, C. Robertson Mcclung

Dartmouth Scholarship

Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that protein arginine methyltransferase 5 (PRMT5; At4g31120) is a critical determinant of circadian period in Arabidopsis. PRMT5 is coregulated with a set of 1,253 genes that shows alterations in phase of expression in response to entrainment to thermocycles versus photocycles in constant temperature. PRMT5 encodes a type II protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine residues (Rsme2). …

The Effects Of Resveratrol On Oxidative Stress And Muscle Atrophy, Janna Renee Jackson

Graduate Theses, Dissertations, and Problem Reports

Resveratrol (3,5,4,trihydroxystilbene) is a naturally occurring polyphenol found in over seventy plant species that has been shown to have anti-oxidant, anti-apoptotic and anti-aging properties. Resveratrols' capacity to enhance the endogenous anti-oxidant system, upregulate anti-apoptotic proteins and improve mitochondrial function, presumably through the activation of the N AD+ dependent deacetylase Sirtuin1, suggests that supplementation with resveratrol may potentially protect skeletal muscle from the detrimental effects of increases in oxidative stress and the subsequent increase in apoptotic signaling that are present in many atrophic conditions. Therefore, the major goals of this dissertation are to further understand the interplay between oxidative stress and …

Toxicity Of Transition Metal Oxide Nanoparticles: Recent Insights From In Vitro Studies, Yue-Wern Huang, Chi-Heng Wu, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Nanotechnology has evolved to play a prominent role in our economy. Increased use of nanomaterials poses potential human health risk. It is therefore critical to understand the nature and origin of the toxicity imposed by nanomaterials (nanotoxicity). In this article we review the toxicity of the transition metal oxides in the 4th period that are widely used in industry and biotechnology. Nanoparticle toxicity is compellingly related to oxidative stress and alteration of calcium homeostasis, gene expression, pro-inflammatory responses, and cellular signaling events. The precise physicochemical properties that dictate the toxicity of nanoparticles have yet to be defined, but may include …

The Armadillo Repeat Protein Pf16 Is Essential For Flagellar Structure And Function In Plasmodium Male Gametes, Ursula Straschil, Arthur M. Talman, David J. P. Ferguson, Karen A. Bunting, Zhengyao Xu, Elizabeth Bailes, Robert E. Sinden, Anthony A. Holder, Elizabeth F. Smith

Dartmouth Scholarship

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world's population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite's flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that …

Physical Interaction Between Vivid And White Collar Complex Regulates Photoadaptation In Neurospora, Chen-Hui H. Chen, Bradley S. Demay, Amy S. Gladfelter, Jay Dunlap, Jennifer J. Loros

Dartmouth Scholarship

Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular mechanisms are poorly understood. In Neurospora crassa, VIVID (VVD), a small LOV domain containing blue-light photoreceptor protein, affects photoadaptation for most if not all light-responsive genes. We report that there is a physical interaction between VVD and the white collar complex (WCC), the primary blue-light photoreceptor and the transcription factor complex that initiates light-regulated transcriptional responses in Neurospora. Using two previously characterized VVD mutants, we show …

Theme-Based Instruction: Making Conceptual Ties With The Sickle Cell Story, Sherry S. Herron, John Parr, Bridgette Davis, Parker Nelson

Faculty Publications

We describe the concepts and resources presented during a workshop offered to high school biology teachers using sickle cell disease as a theme in a biology course. We provide their pretest and posttest results and reactions.

Relationships Of Developmental Traits In Young Alpaca Crias And Lambs, Sara Elizabeth Lewis

Graduate Theses, Dissertations, and Problem Reports

Successful reproduction in alpacas is highly dependent upon postnatal survival, which in turn is dependent upon a pattern of continuous gain in weight as an indicator of health. Weighing alpacas is the primary method used to assess their general health. Unfortunately, the measurement of cria weight is not always a simple, routine, or easy determination. The purpose of this study was to determine if, as in other species such as cattle and horses, morphometric body measurements can be used to estimate weight. In this study, continuous weight and girth measurements were taken on 34 alpaca cria. Age and girth were …

Dietary Cholesterol Effects On Learning, Memory And Amyloid Beta: Learning And Memory Effects On Brain Cholesterol And Sulfatide Levels, Deya S. Darwish

Graduate Theses, Dissertations, and Problem Reports

Recent studies have revealed ambiguous findings on the effects of dietary cholesterol on learning. In one study by Schreurs and coworkers it was reported that a 2% cholesterol diet had a positive effect on learning. However, it was realized that metals, specifically copper, could potentially exacerbate the aggregation of amyloid beta (Abeta), a protein associated with Alzheimer's disease (AD) leading to the formation of Abeta plaques. In a subsequent publication by Sparks and Schreurs it was reported that a 2% cholesterol diet with the addition of 0.12 ppm copper had a detrimental effect on learning and resulted in the formation …

Systemic Lipopolysaccharide Stimulates Airway Transepithelial Na+ Transport By Increasing Enac And Na+,K+ -Pump Activity, Michael W. Dodrill

Graduate Theses, Dissertations, and Problem Reports

Our laboratory found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V t) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. We hypothesized that LPS stimulates the transepithelial movement of Na+ via the epithelial sodium channel (ENaC)/Na+,K+-pump axis, leading to hyperpolarization of Vt. LPS increased the Vt response to amiloride, i.e., offset the effect of LPS, indicating that Na+ transport was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na+,K+-pump with basolateral amphotericin B. LPS had no effect on the …

Hypercholesterolemia And Microvascular Dysfunction: Altered Mechanisms And Interventional Strategies, Phoebe Stapleton

Graduate Theses, Dissertations, and Problem Reports

Cardiovascular disease has a number of risk factors and confounding variables associated with the development and progression of the condition. Hypercholesterolemia is one of the few independent risk factors of peripheral vascular disease (PVD) and coronary artery disease (CAD) with causes stemming from a genetic predisposition and lifestyle management. The primary symptom of these diseases can be described as an endothelial cell dysfunction, which hypercholesterolemia can exacerbate, leading to a pro-inflammatory state of elevated oxidant stress and significant reduction in nitric oxide (NO) bioavailability, a key mediator of endothelium-dependent dilation. This environment can culminate into an impairment of the vascular …

Mitochondrial Dysfunction In The Diabetic Heart: Cardioprotection From A Novel Mitochondrially-Targeted Therapeutic, Erinne Rose Dabkowski

Graduate Theses, Dissertations, and Problem Reports

Cardiovascular complications leading to heart failure are the leading cause of death amongst both type 1 and type 2 diabetic patients. Increased reactive oxygen species (ROS) generation due to hyperglycemia and an enhanced fatty acid environment has been suggested to lead to mitochondrial dysfunction. Mitochondria are particularly susceptible to oxidative damage because the inner mitochondrial membrane (IMM) is the main site of ROS generation. Mitochondrial dysfunction is complicated by the fact that two spatially-distinct subpopulations of mitochondria reside in the heart. The subsarcolemmal mitochondria (SSM) are located at the cell periphery, while the interfibrillar mitochondria (IFM) situate along the myofibrils. …

Avirulent Uracil Auxotrophs Based On Disruption Of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity To Toxoplasma Gondii, Barbara A. Fox, David J. Bzik

Dartmouth Scholarship

The orotidine-5'-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the de novo pyrimidine biosynthesis pathway, was deleted using Toxoplasma gondii KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting DeltaOMPDC, DeltaUP, and DeltaOMPDC DeltaUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The DeltaUP knockout strain was replication competent and virulent. In …

Lung Impedance Measurements Using Tracked Breathing, Daphtary Nirav

Graduate College Dissertations and Theses

The forced Oscillation Technique (FOT) can be used to measure lung impedance continuously during breathing. However, spectral overlap between the breathing waveform and the applied flow oscillation can be problematic if the frequency content of spontaneous breathing is unknown. This problem motivated us to develop a modification to the FOT system called the Tracked Breathing Trainer. The modification uses biofeedback to constrain subjects to breathe at a single predetermined frequency. This thesis investigates the engineering and physiological aspects of the modification we made. We studied 8 adult non-asthmatic and 8 adult asthmatic subjects. Three 16 s perturbatory flow oscillation signals …

Behavioural Display Systems Across Nine Anolis Lizard Species: Sexual Dimorphisms In Structure And Function, Michele A. Johnson, J. Wade

Biology Faculty Research

Relationships between structure and function are a primary focus in biology, yet they are most often considered within individual species. Sexually dimorphic communication behaviours and the morphology of associated structures can vary widely, even among closely related species, and these traits provide an ideal opportunity to investigate the evolution of structure-function patterns. Using nine Anolis lizard species, we addressed a series of questions regarding sex differences in and the evolution of relationships between extension of the throat fan (dewlap) and morphology of the muscles and cartilage controlling it. The main results indicated that within species, males displayed the dewlap more …

Aging-Dependent Effects Of Repetitive Loading Exercise And Antioxidant Supplementation On Oxidative Stress In Skeletal Muscle, Michael J. Ryan

Graduate Theses, Dissertations, and Problem Reports

Aging is associated with a reduced ability to buffer oxidants along with an increase in oxidant production, resulting in chronic oxidative stress. Oxidative stress is a putative factor responsible for reducing function ability of skeletal muscle and increasing oxidative damage. The objective of this set of investigations was to evaluate the efficacy of reducing oxidative stress on improving muscle function the adaptive response of skeletal muscle to repetitive loading exercise in aging rodents. To achieve this objective, three methods of reducing oxidative stress were utilized; the antioxidant vitamins E&C were used to buffer oxidants, the nutraceutical resveratrol was used to …

Sex Differences In The Myocardial Response To Prenatal And Behavioral Stress, Heather Rose Mullenax

Graduate Theses, Dissertations, and Problem Reports

Prenatal stress (PS) has been shown to exert profound effects on many organs in a variety of species. There is considerable evidence for sex-specific effects of prenatal stress. Our laboratory is the first to report effects of prenatal stress on myocardial function in male rats. The purpose of this study was to confirm our previous evidence of differences in myocardial function among prenatally stressed male and female rats and to explore possible mechanisms responsible for this difference. In this study, male and female Sprague-Dawley rats were subjected to prenatal stress (mother was stressed on day 14--21 of gestation) followed by …

Long Term Ampk Activation Limits Obesity Induced Muscle Atrophy, Joshua C. Drake

Graduate Theses, Dissertations, and Problem Reports

The aim of this study was to identify obesity-induced alterations in regulatory mechanisms of skeletal muscle mass and how they would be altered with long term (8 weeks) AMPK-agonist treatment. 8 week old male, lean (L) wild type [body weight (BW) = 26.9 g] and ob/ob (O) [BW = 46.2 g] mice were fed an AMP kinase (AMPK) activator, beta-GPA (F), mixed at a 1% concentration within their food or normal chow as control (C) for 8 weeks. Following an overnight (12 hr) fast, all mice were sacrificed and the gastrocnemius complex was excised for analysis. Muscle mass was lower …

A Brief Description Of The Biomechanics And Physiology Of A Strongman Event: The Tire Flip, Justin W.L. Keogh, Amenda L. Payne, Brad B. Anderson, Paul J. Atkins

Justin Keogh

The purpose of this study was to (a) characterize the temporal aspects of a popular strongman event, the tire flip; (b) gain some insight into the temporal factors that could distinguish the slowest and fastest flips; and (c) obtain preliminary data on the physiological stress of this exercise. Five resistance-trained subjects with experience in performing the tire flip gave informed consent to participate in this study. Each subject performed 2 sets of 6 tire flips with a 232-kg tire with 3 minutes of rest between sets. Temporal variables were obtained from video cameras positioned 10 m from the tire, perpendicular …

Optimal Bone Strength And Mineralization Requires The Type 2 Iodothyronine Deiodinase In Osteoblasts, J. H. D. Bassett, Alan Boyde, Peter G. T. Howell, Richard H. Bassett, Thomas M. Galliford, Marta Archanco, Holly Evans, Michelle A. Lawson, Peter Croucher, Donald L. St. Germain, Valerie A. Galton, Graham R. Williams

Dartmouth Scholarship

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3'-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone …

Estrogen Regulates Estrogen Receptors And Antioxidant Gene Expression In Mouse Skeletal Muscle, Kristen A. Baltgalvis, Sarah M. Greising, Gordon L. Warren, Dawn A. Lowe

Physical Therapy Faculty Publications

Background: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17β-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER) to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue.

Methodology/Principal Findings: Adult …

Role Of Flgt In Anchoring The Flagellum Of Vibrio Cholerae, Raquel M. Martinez, Brooke A. Jude, Thomas J. Kirn, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Flagellar motility has long been regarded as an important virulence factor. In Vibrio cholerae, the single polar flagellum is essential for motility as well as for proper attachment and colonization. In this study, we demonstrate that the novel flagellar protein FlgT is involved in anchoring the flagellum to the V. cholerae cell. A screen for novel colonization factors by use of TnphoA mutagenesis identified flgT. An in-frame deletion of flgT established that FlgT is required for attachment, colonization, and motility. Transmission electron microscopy revealed that while the flgT mutant is capable of assembling a phenotypically normal flagellum, …

Differential Activation Of Frontoparietal Attention Networks By Social And Symbolic Spatial Cues, Andrew D. Engell, Lauri Nummenmaa, Nikolaas N. Oosterhof, Richard N. Henson, James V. Haxby, Andrew J. Calder

Dartmouth Scholarship

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally …

Microrna-31 Functions As An Oncogenic Microrna In Mouse And Human Lung Cancer Cells By Repressing Specific Tumor Suppressors, Xi Liu, Lorenzo F. Sempere, Haoxu Ouyang, Vincent A. Memoli, Angeline S. Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir Preis, Konstantin H. Dragnev, Hua Li, James Direnzo, Mads Bak, Sarah J. Freemantle, Sakari Kauppinen, Ethan Dmitrovsky

Dartmouth Scholarship

MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially …

Erk1/2-Akt1 Crosstalk Regulates Arteriogenesis In Mice And Zebrafish, Bin Ren, Yong Deng, Arpita Mukhopadhyay, Anthony A. Lanahan, Zhen W. Zhuang, Karen L. Moodie, Mary Jo Mulligan-Kehoe, Tatiana V. Byzova, Randall T. Peterson, Michael Simons

Dartmouth Scholarship

Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient …

Renin-Angiotensin System Activation Correlates With Microvascular Dysfunction In A Prospective Cohort Study Of Clinical Sepsis, Kevin C. Doerschug, Angela S. Delsing, Gregory A. Schmidt, Alix Ashare

Dartmouth Scholarship

Microvascular dysregulation characterized by hyporesponsive vessels and heterogeneous bloodflow is implicated in the pathogenesis of organ failure in sepsis. The renin-angiotensin system (RAS) affects the microvasculature, yet the relationships between RAS and organ injury in clinical sepsis remain unclear. We tested our hypothesis that systemic RAS mediators are associated with dysregulation of the microvasculature and with organ failure in clinical severe sepsis.

Behind The Mask: The Influence Of Mask-Type On Amygdala Response To Fearful Faces, M Justin Kim, Rebecca A. Loucks, Maital Neta, F. Caroline Davis, Jonathan A. Oler, Emily C. Mazzulla, Paul J. Whalen

Dartmouth Scholarship

In this study, we compared the effects of using neutral face masks vs non-face pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects viewed 18 s blocks of either fearful or happy faces masked with either neutral faces or patterns, while their brain activity was measured using functional magnetic resonance imaging. Results replicated increased amygdala activation to face-masked fearful vs happy faces. In the pattern mask condition, the amygdala discriminated between masked fearful and happy faces, but this effect manifested as a decrease in activation to fearful faces compared to happy faces. This interactive effect between facial expression …

Cd4+ T Cell Regulation Of Cd25 Expression Controls Development Of Short-Lived Effector Cd8+ T Cells In Primary And Secondary Responses, Joshua J. Obar, Michael J. Molloy, Evan R. Jellison, Thomas A. Stoklasek, Weijun Zhang, Edward J. Usherwood, Leo Lefrançois

Dartmouth Scholarship

Both CD4(+) T cell help and IL-2 have been postulated to "program" activated CD8(+) T cells for memory cell development. However, the linkage between these two signals has not been well elucidated. Here we have studied effector and memory CD8(+) T cell differentiation following infection with three pathogens (Listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both CD4(+) T cells and IL-2 signaling. We found that expression of CD25 on antigen-specific CD8(+) T cells peaked 3-4 days after initial priming and was dependent on CD4(+) T cell help, likely through a CD28:CD80/86 mediated pathway. CD4(+) T …

The Female Athlete, Dilip R. Patel, Donald E. Greydanus, Hatim A. Omar

Pediatrics Faculty Publications

The female athlete has today became an accepted part of sports in elementary school, junior high, senior high, and college. This chapter covers various aspects of the prepubertal and pubertal female athlete. An historical perspective will be presented and selected comments provided on psychological and physiologic aspects of the female athlete. Concepts of adolescent gynecology are reviewed, including breast concerns and menstrual dilemmas in relation to sports activity. Exercise during pregnancy is also considered. Iron deficiency anemia and stress urinary incontinence

Menstrual Disorders In Adolescent Females, Donald E. Greydanus, Hatim A. Omar, Artemis Tsitsika, Dilip R. Patel

Pediatrics Faculty Publications

Onset of menstruation (i.e., menarche) is a determining event of the adolescent female signifying the progress of puberty, which in the majotity of cases is visibly initiated with thelarche (onset of breast development or breast buds). Menarche usually occurs during the earlier time of the second decade of life and ends with menopause, typically in the 5th decade of life. The adolescent can present with a wide variety of menstrual dilemmas and disorders which will be discussed in this chapter.

The Effectiveness Of Active And Traditional Teaching Techniques In The Orthopedic Assessment Laboratory, Sara Nottingham

Athletic Training Faculty Articles and Research

Active learning is a teaching methodology with a focus on student-centered learning that engages students in the educational process. This study implemented active learning techniques in an orthopedic assessment laboratory, and the effects of these teaching techniques. Mean scores from written exams, practical exams, and final course evaluations were compared for 79 human physiology students. One- and two-way analyses of variance were used to evaluate the effect of teaching methodology on test scores and evaluation responses. No significant differences were found for course evaluation responses and written and practical exam scores between the two learning groups. This study suggests that …