Anatomy Commons^™

Beclin-1 Expression Is Retained In High-Grade Serous Ovarian Cancer Yet Is Not Essential For Autophagy Induction In Vitro, Rohann J.M. Correa, Yudith R. Valdes, Trevor G. Shepherd, Gabriel E. Dimattia

Anatomy and Cell Biology Publications

Background: Autophagy is a conserved cellular self-digestion mechanism that can either suppress or promote cancer in a context-dependent manner. In ovarian cancer, prevalent mono-allelic deletion of BECN1 (a canonical autophagy-inducer) suggests that autophagy is impaired to promote carcinogenesis and that Beclin-1 is a haploinsufficient tumor suppressor. Nonetheless, autophagy is known to be readily inducible in ovarian cancer cells. We sought to clarify whether Beclin-1 expression is in fact disrupted in ovarian cancer and whether this impacts autophagy regulation.

Methods: BECN1 expression levels were assessed using The Cancer Genome Atlas (TCGA) datasets from 398 ovarian high-grade serous cystadenocarcinomas (HGSC) and protein …

Variation In Brain Morphology Of Intertidal Gobies: A Comparison Of Methodologies Used To Quantitatively Assess Brain Volumes In Fish, Gemma E. White, Culum Brown

Veterinary Science and Medicine Collection

When correlating brain size and structure with behavioural and environmental characteristics, a range of techniques can be utilised. This study used gobiid fishes to quantitatively compare brain volumes obtained via three different methods; these included the commonly used techniques of histology and approximating brain volume to an idealised ellipsoid, and the recently established technique of X-ray micro-computed tomography (micro-CT). It was found that all three methods differed significantly from one another in their volume estimates for most brain lobes. The ellipsoid method was prone to over- or under-estimation of lobe size, histology caused shrinkage in the telencephalon, and although micro-CT …

The Search For High-Impact Diagnostic And Management Tools For Low-And Middle-Income Countries: A Self-Powered Low-Cost Blood Pressure Measurement Device Powered By A Solid-State Vibration Energy Harvester, Onur Bilgen, John G. Kenerson, Muge Akpinar-Elci, Rebecca Hattery, Lisbet M. Hanson

Mechanical & Aerospace Engineering Faculty Publications

The World Health Organization has established recommendations for blood pressure measurement devices for use in low-resource venues, setting the triple A expectations of Accuracy, Affordability, and Availability. Because of issues related to training and assessment of proficiency, the pendulum has swung away from manual blood pressure devices and auscultatory techniques towards automatic oscillometric devices. As a result of power challenges in the developing world, there has also been a push towards semiautomatic devices that are not dependent on external power sources or batteries. Beyond solar solutions, disruptive technology related to solid-state vibrational energy harvesting may be the next iterative solution …

Effects Of Pelvis Impact Angle And Hip Muscle Forces On Hip Fracture Risk During A Fall Using An Advanced Hip Impact Simulator, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of hip fractures in older adults are caused by falls [1]. Whether a given fall will cause hip fracture depends on bone strength, and on the impact force and stress applied to the bone during impact [2]. Improved understanding is required on how peak bone stresses during a fall depend on the mechanics of a fall, and on the state of contraction at the moment of impact of the muscles spanning the hip. Recently, Choi et al showed that, for lateral impact to the hip, peak stresses decrease with increases in hip abductor muscle force [3]. In the …

Influence Of Pelvis Impact Angle During A Fall: On The Protective Benefit Of Hip Protectors, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of hip fractures are due to falls [1]. Laboratory measures have shown that wearable hip protectors reduce impact forces to the proximal femur during a simulated sideways fall on the hip [2, 3]. However, clinical evidence suggests that hip fractures still occur when hip protectors are worn [4]. Furthermore, while falls in real life result in a variety of impact configurations, biomechanical tests to date have focused only on lateral impact to the pelvis. In the current study, we examined how the force reduction provided by wearable hip protectors is affected by pelvis impact configuration during simulated sideways …

Negative Skeletal Effects Of Locally Produced Adiponectin, Marcia J. Abbott, Theresa M. Roth, Linh Ho, Liping Wang, Dylan O'Carroll, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

Epidemiological studies show that high circulating levels of adiponectin are associated with low bone mineral density. The effect of adiponectin on skeletal homeostasis, on osteoblasts in particular, remains controversial. We investigated this issue using mice with adipocyte-specific over-expression of adiponectin (AdTg). MicroCT and histomorphometric analysis revealed decreases (15%) in fractional bone volume in AdTg mice at the proximal tibia with no changes at the distal femur. Cortical bone thickness at mid-shafts of the tibia and at the tibiofibular junction was reduced (3–4%) in AdTg mice. Dynamic histomorphometry at the proximal tibia in AdTg mice revealed inhibition of bone formation. AdTg …

Whole-Retina Reduced Electrophysiological Activity In Mice Bearing Retina-Specific Deletion Of Vesicular Acetylcholine Transporter, Jake Bedore, Amanda C. Martyn, Anson K. C. Li, Eric A. Dolinar, Ian S. Mcdonald, Stuart G. Coupland, Vania F. Prado, Marco A. Prado, Kathleen A. Hill

Anatomy and Cell Biology Publications

Background: Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina. Methods & Results A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina-targeted (embryonic day …

Diffusion Tensor Imaging Of Dolphin Brains Reveals Direct Auditory Pathway To Temporal Lobe, Gregory S. Berns, Peter F. Cook, Sean Foxley, Saad Jbabdi, Karla L. Miller, Lori Marino

Veterinary Science and Medicine Collection

The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes’ auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of ‘associative0 regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, …

Increased Resting-State Functional Connectivity Of Visual- And Cognitive-Control Brain Networks After Training In Children With Reading Difficulties, Tzipi Horowitz-Kraus, Mark Difrancesco, Benjamin Kay, Yingying Wang, Scott K. Holland

Center for Brain, Biology, and Behavior: Faculty Publications

The Reading Acceleration Program, a computerized reading-training program, increases activation in neural circuits related to reading.We examined the effect of the training on the functional connectivity between independent components related to visual processing, executive functions, attention, memory, and language during rest after the training. Children 8–12 years old with reading difficulties and typical readers participated in the study. Behavioral testing and functional magnetic resonance imaging were performed before and after the training. Imaging data were analyzed using an independent component analysis approach. After training, both reading groups showed increased single-word contextual reading and reading comprehension scores. Greater positive correlations between …

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

Vascular Regulation Via Kir Channels And Na+ /K+-Atpase, Anne R. Crecelius, Frank A. Dinenno

Health and Sport Science Faculty Publications

Despite the longstanding knowledge that blood flow increases in proportion to metabolic activity of skeletal muscle, the underlying mechanisms that govern this response have only recently been identified.¹ Given the role of endothelial cells in mediating exercise hyperemia,² interest has been focused on endothelium-derived vasodilation occurring via the synthesis of nitric oxide (NO) and vasodilating prostaglandins (PGs; i.e. prostacyclin) or endothelium- derived hyperpolarization. A number of studies performed in humans have established a minimal-to-modest role for NO and PGs during mild- and moderate- intensity exercise. In animal preparations, prevention of hyperpolarization attenuates contraction-induced hyperemia; however, performing similar studies …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

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 …

Exercise Improves Host Response To Influenza Viral Infection In Obese And Non-Obese Mice Through Different Mechanisms., Kristi J. Warren, Molly M. Olson, Nicholas J. Thompson, Mackenzie L. Cahill, Todd A. Wyatt, Kyoungjin J. Yoon, Christina M. Loiacono, Marian L. Kohut

Journal Articles: Pulmonary & Critical Care Med

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary …

Increased Expression Of Simple Ganglioside Species Gm2 And Gm3 Detected By Maldi Imaging Mass Spectrometry In A Combined Rat Model Of A Beta Toxicity And Stroke, Sarah Caughlin, Jeffrey D. Hepburn, Dae Hee Park, Kristina Jurcic, Ken K. -C. Yeung, David F. Cechetto, Shawn N. Whitehead

Anatomy and Cell Biology Publications

The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer's disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain's response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in …

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 …

Visual Feedback Dominates The Sense Of Agency For Brain-Machine Actions, Nathan Evans, Steven Gale, Aaron Schurger, Olaf Blanke

Psychology Faculty Articles and Research

Recent advances in neuroscience and engineering have led to the development of technologies that permit the control of external devices through real-time decoding of brain activity (brain-machine interfaces; BMI). Though the feeling of controlling bodily movements (sense of agency; SOA) has been well studied and a number of well-defined sensorimotor and cognitive mechanisms have been put forth, very little is known about the SOA for BMI-actions. Using an on-line BMI, and verifying that our subjects achieved a reasonable level of control, we sought to describe the SOA for BMI-mediated actions. Our results demonstrate that discrepancies between decoded neural activity and …

Intact Lkb1 Activity Is Required For Survival Of Dormant Ovarian Cancer Spheroids, Teresa M. Peart, Yudith R. Valdes, Rohann J.M. Correa, Elena Fazio, Monique Bertrand, Jacob Mcgee, Michel Prefontaine, Akira Sugimoto, Gabriel E. Dimattia, Trevor G. Shepherd

Anatomy and Cell Biology Publications

Metastatic epithelial ovarian cancer (EOC) cells can form multicellular spheroids while in suspension and disperse directly throughout the peritoneum to seed secondary lesions. There is growing evidence that EOC spheroids are key mediators of metastasis, and they use specific intracellular signalling pathways to control cancer cell growth and metabolism for increased survival. Our laboratory discovered that AKT signalling is reduced during spheroid formation leading to cellular quiescence and autophagy, and these may be defining features of tumour cell dormancy. To further define the phenotype of EOC spheroids, we have initiated studies of the Liver kinase B1 (LKB1)-5′-AMP-activated protein kinase (AMPK) …

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Tslp-Induced Mechanisms And Potential Therapies For Crlf2 B-Cell Acute Lymphoblastic Leukemia, Olivia L. Francis

Loma Linda University Electronic Theses, Dissertations & Projects

Childhood CRLF2 B-cell Acute Lymphoblastic Leukemia (CRLF2 B-ALL) is a high-risk form of leukemia that is associated with poor patient survival outcomes. CRLF2 B-ALL is five times more prevalent in Hispanic children than others and is associated with a higher rate of relapse, thus contributing significantly to childhood cancer health disparities. This disease occurs due to alterations of the CRLF2 gene, leading to overexpression of the CRLF2 protein- a component of the receptor signaling complex for the cytokine Thymic Stromal LymphoPoietin (TSLP) on the surface of B-ALL cells. TSLP has been shown to induce proliferation of human and mouse B-cell …