Life Sciences Commons^™

Sleeping Through Anything: The Effects Of Unpredictable Disruptions On Mouse Sleep, Healing, And Affect, Amy Robinson-Junker, Bruce O'Hara, Abigail Durkes, Brianna Gaskill

Biology Faculty Publications

Many aspects of the laboratory environment are not tailored to the needs of rodents, which may cause stress. Unpredictable stressors can cause ulcers, prolonged pituitary-adrenal activation, and anhedonia. Similarly, pain has been demonstrated to slow wound healing, and mice experiencing pain exhibit altered behavior. However it is unknown how husbandry, which occurs when the mice are inactive, and lack of analgesia, specifically in a punch biopsy procedure, effects animal physiology, behavior, and welfare, particularly as it relates to sleep fragmentation. We hypothesized that sleep fragmentation, induced by unpredictable husbandry and lack of pain management will slow wound healing. Two main …

Morphogenetic Defects Underlie Superior Coloboma, A Newly Identified Closure Disorder Of The Dorsal Eye, Jennifer C. Hocking, Jakub K. Famulski, Kevin H. Yoon, Sonya A. Widen, Cassidy S. Bernstein, Sophie Koch, Omri Weiss, Forge Canada Consortium, Canada, Seema Agarwala, Adi Inbal, Ordan J. Lehmann, Andrew J. Waskiewicz

Biology Faculty Publications

The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma. The embryonic origin of superior coloboma could not be explained by conventional models of eye development, leading us to …

Fibroblast Reticular Cells Engineer A Blastema Extracellular Network During Digit Tip Regeneration In Mice, Luis Marrero, Jennifer Simkin, Mimi Sammarco, Ken Muneoka

Biology Faculty Publications

The regeneration blastema which forms following amputation of the mouse digit tip is composed of undifferentiated cells bound together by an organized network of fibers. A monoclonal antibody (ER‐TR7) that identifies extracellular matrix (ECM) fibers produced by fibroblast reticular cells during lymphoid organogenesis was used to characterize the ECM of the digit, the blastema, and the regenerate. Digit fibroblast reticular cells produce an ER‐TR7⁺ ECM network associated with different tissues and represent a subset of loose connective tissue fibroblasts. During blastema formation there is an upregulation of matrix production that returns to its pre‐existing level and anatomical pattern in …

High-Fat Feeding Does Not Disrupt Daily Rhythms In Female Mice Because Of Protection By Ovarian Hormones, Brian T. Palmisano, John M. Stafford, Julie S. Pendergast

Biology Faculty Publications

Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured …

Disruption Of Daily Rhythms By High-Fat Diet Is Reversible, Katrina L. Branecky, Kevin D. Niswender, Julie S. Pendergast

Biology Faculty Publications

In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low-fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered …

Toward The Beginning Of Time: Circadian Rhythms In Metabolism Precede Rhythms In Clock Gene Expression In Mouse Embryonic Stem Cells, Jiffin K. Paulose, Edmund B. Rucker Iii, Vincent M. Cassone

Biology Faculty Publications

The appearance, progression, and potential role for circadian rhythms during early development have previously focused mainly on the suprachiasmatic nucleus (SCN) and peri- and postnatal expression of canonical clock genes. More recently, gene expression studies in embryonic stem cells have shown that some clock genes are expressed in undifferentiated cells; however rhythmicity was only established when cells are directed toward a neural fate. These studies also concluded that a functional clock is not present in ESCs, based solely on their gene expression. The null hypothesis underlying the present study is that embryonic stem cells become rhythmic in both clock gene …

Assessment Of A Non-Invasive High-Throughput Classifier For Behaviours Associated With Sleep And Wake In Mice, Kevin D. Donohue, Dharshan C. Medonza, Eli R. Crane, Bruce F. O'Hara

Biology Faculty Publications

This work presents a non-invasive high-throughput system for automatically detecting characteristic behaviours in mice over extended periods of time, useful for phenotyping experiments. The system classifies time intervals on the order of 2 to 4 seconds as corresponding to motions consistent with either active wake or inactivity associated with sleep. A single Polyvinylidine Difluoride (PVDF) sensor on the cage floor generates signals from motion resulting in pressure. This paper develops a linear classifier based on robust features extracted from normalized power spectra and autocorrelation functions, as well as novel features from the collapsed average (autocorrelation of complex spectrum), which characterize …

A Non-Circadian Role For Clock-Genes In Sleep Homeostasis: A Strain Comparison, Paul Franken, Ryan Thomason, H. Craig Heller, Bruce F. O'Hara

Biology Faculty Publications

BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which …

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

Gene Expression And Discovery During Lens Regeneration In Mouse: Regulation Of Epithelial To Mesenchymal Transition And Lens Differentiation, Mario Medvedovic, Craig R. Tomlinson, Mindy Kay Call, Matthew Grogg, Panagiotis A. Tsonis

Biology Faculty Publications

Purpose: It has been shown that after extracapsular lens removal by anterior capsulotomy in the mouse, the lens can be regenerated. However, as the capsular bag is filled with fibers, epithelial to mesenchymal transition (EMT), an event which is common after cataract surgery as well, takes place during early stages. This study, using a unique mouse model, was undertaken to identify novel regulators and networks in order to more clearly understand secondary cataracts at the molecular level.