Medicine and Health Sciences Commons^™

Study Protocol: Identifying Transcriptional Regulatory Alterations Of Chronic Effects Of Blast And Disturbed Sleep In United States Veterans, Molly J. Sullan, Kelly A. Stearns-Yoder, Zhaoyu Wang, Andrew J. Hoisington, Adam D. Brenoweth, Walter Carr, Yongchao Ge, Hanga Galfalvy, Fatemah Haghighi, Lisa A. Brenner

Faculty Publications

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of …

A Quantum Logic Gate In The Dna Deoxyribose Moiety, F. Matthew Mihelic

Faculty Publications

The deoxyribose moiety of a nucleotide in the DNA molecule can act as a quantumlogic gate, in which the enantiomeric shift between the C2-endo and C3-endo conformations of each nucleotide, occurs within a logically and thermodynamically reversible situation of electron spin qubits, that are coherently held within the topologically insulating DNA crystalline nanostructure, and that are coherently conducted along the delocalized electrons of the pi-stacked nucleotide base pairs. The enantiomeric symmetry between the C2-endo and C3-endo conformations is logically and thermodynamically reversible because it functions as a symmetry-breaking Szilard engine that is effectively built out of the physicality of the …

A Bayesian Phase I/Ii Biomarker-Based Design For Identifying Subgroup-Specific Optimal Dose For Immunotherapy, Beibei Guo, Yong Zang

Faculty Publications

Immunotherapy is an innovative treatment that enlists the patient's immune system to battle tumors. The optimal dose for treating patients with an immunotherapeutic agent may differ according to their biomarker status. In this article, we propose a biomarker-based phase I/II dose-finding design for identifying subgroup-specific optimal dose for immunotherapy (BSOI) that jointly models the immune response, toxicity, and efficacy outcomes. We propose parsimonious yet flexible models to borrow information across different types of outcomes and subgroups. We quantify the desirability of the dose using a utility function and adopt a two-stage dose-finding algorithm to find the optimal dose for each …

Implications Of The Quantum Dna Model For Information Sciences, F. Matthew Mihelic

Faculty Publications

The DNA molecule can be modeled as a quantum logic processor, and this model has been supported by pilot research that experimentally demonstrated non-local communication between cells in separated cell cultures. This modeling and pilot research have important implications for information sciences, providing a potential architecture for quantum computing that operates at room temperature and is scalable to millions of qubits, and including the potential for an entanglement communication system based upon the quantum DNA architecture. Such a system could be used to provide non-local quantum key distribution that could not be blocked by any shielding or water depth, would …

Magnetic Vector Potential Manipulation Of Majorana Fermions In Dna Quantum Logic, F. Matthew Mihelic

Faculty Publications

In the quantum logic of the DNA molecule, electrons are held and conducted coherently as spinless Cooper pairs and are shielded from electromagnetic energy by a Faraday cage effect of the double lipid bilayer of the nuclear membrane. The magnetic vector potential generated by cellular depolarization can synchronize logical activity in portions of the DNA molecule by affecting spin directions of appropriately oriented spinless electrons via the Aharonov-Bohm effect, but is not blocked by that Faraday cage effect. Within the logically and thermodynamically reversible chiral enantiomeric symmetry of the deoxyribose moieties the decoherent transition of Cooper pair to Dirac pair …

The Acute Effects Of 5 Fluorouracil On Skeletal Muscle Resident And Infiltrating Immune Cells In Mice, Brandon N. Vanderveen, Alexander T. Sougiannis, Kandy T. Velazquez, James A. Carson, Daping Fan, E. Angela Murphy

Faculty Publications

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis …

Female Family Members Lack Understanding Of Indeterminate Negative Brca1/2 Test Results Shared By Probands, Deborah Himes, Deborah K. Gibbons, Wendy C. Birmingham, Renea L. Beckstrand, Amanda Gammon, Anita Y. Kinney, Margaret F. Clayton

Faculty Publications

Genetic test results have important implications for close family members. Indeterminate negative results are the most common outcome of BRCA1/2 mutation testing. Little is known about family members’ understanding of indeterminate negative BRCA1/2 test results. The purpose of this mixed-methods study was to investigate how daughters and sisters received and understood genetic test results as shared by their mothers or sisters. Participants included 81 women aged 40-74 with mothers or sisters previously diagnosed with breast cancer and who received indeterminate negative BRCA1/2 test results. Participants had never been diagnosed with breast cancer nor received their own genetic testing or counseling. …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Deborah Himes, Sarah H. Davis, Jane Lassetter Phd, Rn, Neil E. Peterson, Margaret F. Clayton, Wendy C. Birmingham, Anita Y. Kinney

Faculty Publications

Purpose: Knowledge of breast cancer genetics is critical for those at increased hereditary risk who must make decisions about breast cancer screening options. This descriptive study explored theory-based relationships among cognitive and emotional variables related to knowledge of breast cancer genetics in cancer families. Methods: Participants included first-degree relatives of women with breast cancer who had received genetic counseling and testing. Study participants themselves did not have breast cancer and had not received genetic counseling or testing. Data were collected by telephone interviews and surveys. Variables analyzed included numeracy, health literacy, cancer-related distress, age, education, and the reported amount of …

The Underdeveloped Innate Immunity In Embryonic Stem Cells: The Molecular Basis And Biological Perspectives From Early Embryogenesis, Yan-Lin Guo

Faculty Publications

Embryonic stem cells (ESCs) have been intensively studied as a promising cell source for regenerative medicine. The rapid advancements in the field have not only proven the feasibility of ESC‐based cell therapy, but also led to a better understanding of pluripotent stem cells (PSCs) as a unique cell population at an early stage of embryogenesis. Recent studies have revealed that both human and mouse ESCs have attenuated innate immune responses to infectious agents and inflammatory cytokines. These findings raise interesting questions about the rationale for ESCs, the PSCs experimentally derived from preimplantation stage embryos, to not have an innate defense …

Effectiveness Of Plant Species For Removing Atmospheric Ammonia, Marife B. Anunciado, Sheryll B. Jerez, Hans Williams, Joey Bray, Dean W. Coble, Rena Saito

Faculty Publications

Six plant species of Yaupon, Eastern red cedar, American holly, Arizona cypress, Arborvitae and Roughleaf dogwood were utilized to determine their effectiveness in the removal of atmospheric ammonia. All species were exposed to three ammonia levels (1, 5 and 10 ppm) in an environmental chamber. Foliar ammonia content was quantified using an enzymatic technique. The effects of exposure to ammonia on the physiological responses (e.g. photosynthetic activity, stomatal conductance, and transpiration rate) of plants in ambient condition were also determined using an open design photosynthetic gas exchange system. Foliar ammonia content was significantly different among the six plant species (p<0.0001) with Eastern red cedar exhibiting the highest content. The physiological responses differed significantly depending on the plant species and the ammonia treatment level. The photosynthetic response of plants to the presence of ammonia was mixed. At low exposure level, all species except Arborvitae had decreased photosynthetic activity, reducing by as much as 44.5% for Yaupon. At the highest concentration, however, Yaupon’s photosynthetic activity improved by about 10%. Exposure to ammonia caused increased stomatal conductance and transpiration rate on American holly and Arizona cypress, making them more susceptible to water loss.

Breaking The Paradigm: Dr Insight Empowers Signature-Free, Enhanced Drug Repurposing, Jinyan Chan, Xuan Wang, Jacob A. Turner, Nicole E. Baldwin, Jinghua Gu

Faculty Publications

Motivation: Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures. Results: The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the …

Structural And Functional Determinants Of Rodent And Human Surfactant Protein A: A Synthesis Of Binding And Computational Data, Armen Nalian, Todd M. Umstead, Ching-Hui Yang, Patricia Silveyra, Neal J. Thomas, Joanna Floros, Francis X. Mccormack, Zissis C. Chroneos

Faculty Publications

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), …

Domain Rearrangement And Denaturation In Ebola Virus Protein Vp40, Rudramani Pokhrel, Pornthep Sompornpisut, Prem Chapagain, Brian Olson, Bernard Gertsman, Ras B. Pandey

Faculty Publications

The VP40 protein plays a critical role in coordinating the virion assembly, budding, and replication of the Ebola virus. Efforts have been made in recent years to understand various aspects of VP40 structure, dynamics, and function such as assembly of the protein and its roles in virus replication and penetration of the protein into the plasma membrane. A major conformational transformation is necessary for VP40 to form some of its oligomeric structures and to perform various functions. This conformational change from a compact structure with the N-terminal domain (NTD) and C-terminal domain (CTD) closely associated involves a dissociation or springing-out …

Hair Cortisol And Lifetime Discrimination: Moderation By Subjective Social Status, Kymberlee O'Brien, Jerrold Meyer, Edward Tronick, Celia L. Moore

Faculty Publications

Discrimination has been associated with elevated cortisol as measured in saliva, blood, and urine. This study investigated the association between lifetime discrimination and hair cortisol concentrations, considered a measure of chronic stress. We recruited 180 young adults from diverse backgrounds. Participant responses to lifetime discrimination, home stress, and subjective status measures were recorded. Lifetime discrimination significantly predicted hair cortisol concentrations, supporting past research that discrimination experiences impact neuroendocrine systems. To our knowledge, these are the first findings associating hair cortisol concentrations with discrimination and supports prior evidence positing discrimination as a chronic stressor that serves as a risk factor for …

Back Of The Envelope Calculations Regarding Alexandrov, Et Al. 2009, F. Matthew Mihelic

Faculty Publications

The paper entitled “DNA Breathing Dynamics in the Presence of a Terahertz Field” written by Alexandrov, Gelev, Bishop, Usheva, and Rasmussen that was posted on the Physics ArXiv on October 28, 2009, dealt with the effects of terahertz electromagnetic radiation on the DNA molecule. Figure 4 of the paper indicates that a segment of DNA that is between 60 and 70 base pairs in length will develop a “bubble” (i.e. separation of the hydrogen bonds between base pairs) at a location of about 45 base pairs, when exposed to 2 THz electromagnetic radiation for a time period of at least …

Manual Unloading Of The Lumbar Spine: Can It Identify Immediate Responders To Mechanical Traction In A Low Back Pain Population? A Study Of Reliability And Criterion Referenced Predictive Validity, John Carlos Jr., Brian T. Swanson, Sean P. Riley, Mark P. Cote, Robin L. Leger, Isaac L. Moss

Faculty Publications

Background:: To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction.

Purpose:: To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test.

Methods:: Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50·86±11·51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49·53±25·52 …

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb., Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …

The Adaptive Change Of Hla-Drb1 Allele Frequencies Caused By Natural Selection In A Mongolian Population That Migrated To The South Of China, Hao Sun, Zhaoqing Yang, Keqin Lin, Shuyuan Liu, Kai Huang, Xiuyun Wang, Jiayou Chu, Xinyu Huang

Faculty Publications

Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA) alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT) was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another …

Consistency Between Research And Clinical Diagnoses Of Autism Among Boys And Girls With Fragile X Syndrome, Jessica Klusek, G E. Martin, M Losh

Faculty Publications

No abstract provided.

Lineage Ii Of Southeast Asian/American Denv-2 Is Associated With A Severe Dengue Outbreak In The Peruvian Amazon, Maya Williams, Sandra V. Mayer, William L. Johnson, Rubing Chen, Evgeniya Volkova, Stalin Vilcarromeor, Steven G. Widen, Thomas G. Wood, Luis Suarez-Ognio, Kanya C. Long, Katherine A. Hanley, Amy C. Morrison, Nikos Vasilakis, Eric S. Halsey

Faculty Publications

During 2010 and 2011, the Loreto region of Peru experienced a dengue outbreak of unprecedented magnitude and severity for the region. This outbreak coincided with the reappearance of dengue virus-2 (DENV-2) in Loreto after almost 8 years. Whole-genome sequence indicated that DENV-2 from the outbreak belonged to lineage II of the southeast Asian/American genotype and was most closely related to viruses circulating in Brazil during 2007 and 2008, whereas DENV-2 previously circulating in Loreto grouped with lineage I (DENV-2 strains circulating in South America since 1990). One amino acid substitution (NS5 A811V) in the 2010 and 2011 isolates resulted from …

Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh

Faculty Publications

Background

Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration.

Methods

To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHY_TG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to …

Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner

Faculty Publications

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 …

Information Fusion And Quantum Logic In Family Medicine, F. Matthew Mihelic

Faculty Publications

A time-tested model for information fusion and analysis is provided by Family Medicine. Family Medicine is a discipline that operates in the realms of botJ1 technical and social sciences to analyze massive amounts of information from mulriple sources in order to make decisions that bring about tJie integration and coordination of interdisciplinary interventions involving scientific, psychological, and social aspects of medical care. This generalist function serves to lower the organizational entropy of complex systems and thereby improve efficiency while reducing ilie risk of catastrophic failure. Simply bringing a group of specialists together in one place does not bring about the …

Novel Role Of Antioxidant-1 (Atox1) As A Copper-Dependent Transcription Factor Involved In Cell Proliferation, S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, Susan M. Lessner, H. Aoki, K. Akram, R. D. Mckinney, M. Ushio-Fukai, T. Fukai

Faculty Publications

Copper plays a fundamental role in regulating cell growth. Many types of human cancer tissues have higher copper levels than normal tissues. Copper can also induce gene expression. However, transcription factors that mediate copper-induced cell proliferation have not been identified in mammals. Here we show that antioxidant-1 (Atox1), previously appreciated as a copper chaperone, represents a novel copper-dependent transcription factor that mediates copper-induced cell proliferation. Stimulation of mouse embryonic fibroblasts (MEFs) with copper markedly increased cell proliferation, cyclin D1 expression, and entry into S phase, which were completely abolished in Atox1^-/- MEFs. Promoter analysis and EMSA revealed that copper …

Politics Of Embryonic Discourse, Kevin Quinn

Faculty Publications

In our brave new world of stem cells, clones, and parthenotes, how should we talk about early human embryos? In fashioning a response to this very thorny question, Ann Kiessling has a core message. It is: (1)that new science produces "new" conceptuses;(2) that science and scientists have failed to differentiate (with appropriate clarity) these new ex vivo conceptuses from those createdin vivo; (3) that new, more appropriate and scientifically-informed, terms are necessary; and (4) that this new language should transform the public discourse about human embryos. No one would deny that the subtleties of human embryology are neglected in public …

Genetic Health And Eugenics Precedents: A Voice Of Caution, Larry I. Palmer

Faculty Publications

No abstract provided.

Disease Management And Liability In The Human Genome Era, Larry I. Palmer

Faculty Publications

No abstract provided.