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Selection Of An Efficient Aav Vector For Robust Cns Transgene Expression, Killian S. Hanlon, Miguel Sena-Esteves, Eloise Hudry, Casey A. Maguire 2019 Harvard Medical School

Selection Of An Efficient Aav Vector For Robust Cns Transgene Expression, Killian S. Hanlon, Miguel Sena-Esteves, Eloise Hudry, Casey A. Maguire

Open Access Articles

Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent ...


Systemic Rage Ligands Are Upregulated In Tuberculosis Individuals With Diabetes Co-Morbidity And Modulated By Anti-Tuberculosis Treatment And Metformin Therapy, Nathella Pavan Kumar, Kadar Moideen, Arul Nancy, Vijay Viswanathan, Basavaradhya S. Shruthi, Shanmugam Sivakumar, Syed Hissar, Hardy Kornfeld, Subash Babu 2019 National Institutes of Health-NIRT- International Center for Excellence in Research

Systemic Rage Ligands Are Upregulated In Tuberculosis Individuals With Diabetes Co-Morbidity And Modulated By Anti-Tuberculosis Treatment And Metformin Therapy, Nathella Pavan Kumar, Kadar Moideen, Arul Nancy, Vijay Viswanathan, Basavaradhya S. Shruthi, Shanmugam Sivakumar, Syed Hissar, Hardy Kornfeld, Subash Babu

Open Access Articles

BACKGROUND: Ligands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated.

METHODS: We examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC).

RESULTS: Systemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to ...


Bone Strength And Distal Femur Trabecular Thickness In Sleep Deprived Ovariectomized Rats Treated With Zoledronate, Erin Nolte, Frank Frisch 2019 Chapman University

Bone Strength And Distal Femur Trabecular Thickness In Sleep Deprived Ovariectomized Rats Treated With Zoledronate, Erin Nolte, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Osteoporosis is a disease that causes the density and quality of bone to be decreased, which can increase the risk of fracture by 40%. 1 in 3 women over the age of 50 will be affected by osteoporosis. This study aimed to show how bone strength and distal femur trabecular thickness might be affected by Zoledronate and sleep-deprivation in estrogen-deficient rats. Wistar female rats were ovariectomized to contrive postmenopausal estrogen-deficiency. The rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in ...


Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry III, CJ DeLeon, Frank Frisch 2019 Chapman University

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five ...


Lattice Arrangement Of Myosin Filaments Correlates With Fiber Type In Rat Skeletal Muscle, Weikang Ma, Kyounghwan Lee, Shixin Yang, Thomas C. Irving, Roger Craig 2019 Illinois Institute of Technology

Lattice Arrangement Of Myosin Filaments Correlates With Fiber Type In Rat Skeletal Muscle, Weikang Ma, Kyounghwan Lee, Shixin Yang, Thomas C. Irving, Roger Craig

Radiology Publications

The thick (myosin-containing) filaments of vertebrate skeletal muscle are arranged in a hexagonal lattice, interleaved with an array of thin (actin-containing) filaments with which they interact to produce contraction. X-ray diffraction and EM have shown that there are two types of thick filament lattice. In the simple lattice, all filaments have the same orientation about their long axis, while in the superlattice, nearest neighbors have rotations differing by 0 degrees or 60 degrees . Tetrapods (amphibians, reptiles, birds, and mammals) typically have only a superlattice, while the simple lattice is confined to fish. We have performed x-ray diffraction and electron microscopy ...


Human Diseases Related To Different Body Systems [Biology], Richa Gupta 2019 CUNY La Guardia Community College

Human Diseases Related To Different Body Systems [Biology], Richa Gupta

Open Educational Resources

This assignment, aligned to LaGuardia Community College’s Global Learning Core Competency and Digital Communication Ability, was designed for the laboratory part of Human Anatomy and Physiology I (SCB203) course. The assignment, “Human Diseases Related to Different Body Systems,” aims to promote students’ learning and preparation towards their future major in STEM and in the Allied Health Programs. SCB203, taught by faculty in the Natural Sciences department, is a program-core course for Liberal Arts-Mathematics and Science majors and a key Pre-Clinical course (prerequisite) for future enrollment of students into several Allied Health majors such as Nursing, Occupational Therapy, Physical Therapy ...


Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes 2019 University of Tennessee, Knoxville

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.


Ulnar Collateral Ligament Reconstruction With Traditional Docking Compared To Novel Surgical Techniques, Kayley D. Guy, Brendon P. McDermott, Kaitlin Gallagher, Tyrone Washington 2019 University of Arkansas, Fayetteville

Ulnar Collateral Ligament Reconstruction With Traditional Docking Compared To Novel Surgical Techniques, Kayley D. Guy, Brendon P. Mcdermott, Kaitlin Gallagher, Tyrone Washington

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Ulnar Collateral Ligament Reconstruction (UCLR) is a surgical procedure on one of the main ligaments that provides normal stability for the elbow joint against excessive valgus stress. Damage to this ligament is common in athletes performing overhead throwing activities, primarily baseball players, due to excessive valgus stress during the throwing motion. The most common form of treatment for this type of injury is reconstructive surgery of the ligament, especially if athletes wish to return to sport participation. This type of surgery is extremely invasive and requires extensive post-operative rehabilitation in order to facilitate return to play. To date, many ...


The Anatomy Act Of 1832: The Story Of Bodysnatching, Dissections, And The Rise Of Anatomy, Rebecca Burrows 2019 Harding University

The Anatomy Act Of 1832: The Story Of Bodysnatching, Dissections, And The Rise Of Anatomy, Rebecca Burrows

Tenor of Our Times

The Anatomy Act of 1832, a story of bodysnatching and dissections, changed the face of anatomy in 19th century Britain with its somewhat violent beginnings, controversial creation, and important ramifications towards medicine and society.


Laryngeal Mucous Membrane Plasmacytosis With 15 Year Follow-Up: Case Report And Literature Review, Vladislav V. Makarenko, Alec E. Vaezi, Doreen B. Brettler, Lloyd Hutchinson, Bruce A. Woda, Benjamin J. Chen 2019 University of Massachusetts Medical School

Laryngeal Mucous Membrane Plasmacytosis With 15 Year Follow-Up: Case Report And Literature Review, Vladislav V. Makarenko, Alec E. Vaezi, Doreen B. Brettler, Lloyd Hutchinson, Bruce A. Woda, Benjamin J. Chen

Open Access Articles

Mucous membrane plasmacytosis (MMP) is an uncommon variant of mucositis represented by a polyclonal plasma cell infiltration of mucosal tissue. Various clinical presentations in the upper airway have been reported ranging from erythematous mucosa to fungating masses. Histologic features include mucosal epithelial hyperplasia or psoriasiform changes with a dense submucosal infiltrate of polytypic plasma cells. Molecular studies for immunoglobulin gene rearrangement should be performed in all cases of MMP to rule out clonal neoplastic expansion of plasma cells. We present a case of MMP with over 15 years of clinical follow-up, emphasizing the relatively benign clinical course of this disorder.


Solenodon Genome Reveals Convergent Evolution Of Venom In Eulipotyphlan Mammals, Nicholas R. Casewell, Elinor K. Karlsson 2019 Liverpool School of Tropical Medicine

Solenodon Genome Reveals Convergent Evolution Of Venom In Eulipotyphlan Mammals, Nicholas R. Casewell, Elinor K. Karlsson

Open Access Articles

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan ...


Functionally Overlapping Variants Control Tuberculosis Susceptibility In Collaborative Cross Mice, Clare M. Smith, Megan K. Proulx, Rocky Lai, Michael C. Kiritsy, Timothy A. Bell, Pablo Hock, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Richard E. Baker, Samuel M. Behar, Christopher M. Sassetti 2019 University of Massachusetts Medical School

Functionally Overlapping Variants Control Tuberculosis Susceptibility In Collaborative Cross Mice, Clare M. Smith, Megan K. Proulx, Rocky Lai, Michael C. Kiritsy, Timothy A. Bell, Pablo Hock, Fernando Pardo-Manuel De Villena, Martin T. Ferris, Richard E. Baker, Samuel M. Behar, Christopher M. Sassetti

Open Access Articles

Host genetics plays an important role in determining the outcome of Mycobacterium tuberculosis infection. We previously found that Collaborative Cross (CC) mouse strains differ in their susceptibility to M. tuberculosis and that the CC042/GeniUnc (CC042) strain suffered from a rapidly progressive disease and failed to produce the protective cytokine gamma interferon (IFN-gamma) in the lung. Here, we used parallel genetic and immunological approaches to investigate the basis of CC042 mouse susceptibility. Using a population derived from a CC001/Unc (CC001) x CC042 intercross, we mapped four quantitative trait loci (QTL) underlying tuberculosis immunophenotypes (Tip1 to Tip4). These included QTL ...


Differential Skewing Of Donor-Unrestricted And Gammadelta T Cell Repertoires In Tuberculosis-Infected Human Lungs, Paul Ogongo, Adrie Jc. Steyn, Farina Karim, Kaylesh J. Dullabh, Ismael Awala, Rajhmun Madansein, Alasdair Leslie, Samuel M. Behar 2019 University of KwaZulu-Natal

Differential Skewing Of Donor-Unrestricted And Gammadelta T Cell Repertoires In Tuberculosis-Infected Human Lungs, Paul Ogongo, Adrie Jc. Steyn, Farina Karim, Kaylesh J. Dullabh, Ismael Awala, Rajhmun Madansein, Alasdair Leslie, Samuel M. Behar

Open Access Articles

Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and gammadelta T cells. We exploited the distinctive nature of DURTs and gammadelta T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing. Making use of surgical lung resections, we investigated the distribution, frequency, and characteristics of TCRs in lung tissue and matched blood from individuals infected with TB. Despite depletion of MAITs and ...


In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins 2019 Stanford University

In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins

Open Access Articles

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two ...


Non-Equilibrium Critical Dynamics Of Bursts In Theta And Delta Rhythms As Fundamental Characteristic Of Sleep And Wake Micro-Architecture, Jilin W. J. L. Wang, Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, Plamen Ch. Ivanov 2019 Boston University

Non-Equilibrium Critical Dynamics Of Bursts In Theta And Delta Rhythms As Fundamental Characteristic Of Sleep And Wake Micro-Architecture, Jilin W. J. L. Wang, Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, Plamen Ch. Ivanov

Open Access Articles

Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate theta and delta wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in theta and delta rhythms exhibit a complex temporal organization, with long-range power-law correlations and ...


#2 - Atad3a As A Novel Mitochondrial Oncogene In Head And Neck Squamous Cell Carcinoma, Caleb Jensen 2019 Augusta University

#2 - Atad3a As A Novel Mitochondrial Oncogene In Head And Neck Squamous Cell Carcinoma, Caleb Jensen

Georgia Undergraduate Research Conference (GURC)

For patients with head and neck cancer whose tumors are HPV negative HPV(-), current therapy does not lead to significant longevity and most succumb to loco-regional recurrence of the primary tumor. We discovered that HPV(-) head and neck squamous cell carcinoma (HNSCC) highly expressed ATPase family AAA-domain containing protein 3A (ATAD3A). ATAD3A is the mitochondrial protein, which has been demonstrated as an oncogene in breast and lung cancer. However, nothing has been reported regarding its role in HNSCC. Using the HPV(-) HNSCC cell line HN12 as a cell model, we show here that knockout of ATAD3A expression by CRISPR-CAS9 in ...


#28 - Testing The Effectiveness Of Mnemonic Strategies In Learning And Retaining New Information, Kevin O'Donnell 2019 University of North Georgia, Dahlonega, GA 30597

#28 - Testing The Effectiveness Of Mnemonic Strategies In Learning And Retaining New Information, Kevin O'Donnell

Georgia Undergraduate Research Conference (GURC)

Learning new information can sometimes be a very demanding process, especially in very intense courses such as hard sciences, which can require a lot of reading, studying, and memorization. Simply reading the large walls of text within textbooks can be overwhelming to some students. Thus, applying mnemonic strategies may help in the simplification of otherwise overwhelming information and improving knowledge retention. This study was designed to test the effectiveness of such mnemonics in the memorization and retention of information both long-term and short-term. Twenty-five students separated two different lab sections of a Human Anatomy and Physiology II course were given ...


Safe And Effective Use Of A Hands-Free Intracorporeal Retractor For Suture-Based Liver Retraction During Minimally Invasive Bariatric Procedures: Results Of A Large Case Series, Roger De la Torre, Matthew Sappington, Tom Smith, Jeremy Bryner, David Mantilla, J Stephen Scott 2019 HCA Healthcare

Safe And Effective Use Of A Hands-Free Intracorporeal Retractor For Suture-Based Liver Retraction During Minimally Invasive Bariatric Procedures: Results Of A Large Case Series, Roger De La Torre, Matthew Sappington, Tom Smith, Jeremy Bryner, David Mantilla, J Stephen Scott

General Surgery

Background

Laparoscopic bariatric surgery requires retraction of the left lobe of the liver to provide adequate operative view and working space. Conventional approaches utilize a mechanical retractor that requires a dedicated incision, may cause liver damage, and often requires an assistant. This study evaluated the safety and efficacy of hands-free intracorporeal retractors in a large series of subjects undergoing laparoscopic bariatric surgery. This method eliminates the need for a subxiphoid incision, enables full surgeon autonomy, and allows for adjustments throughout the procedure.

Methods

Retrospective chart review identified all subjects at a single hospital undergoing bariatric surgery between September 2017-March 2019 ...


Single Cell Transcriptomic Profiling Of Large Intestinal Enteroendocrine Cells In Mice - Identification Of Selective Stimuli For Insulin-Like Peptide-5 And Glucagon-Like Peptide-1 Co-Expressing Cells, Lawrence J. Billing, Pierre Larraufie, Jo Lewis, Andrew B. Leiter, Joyce H. Li, Brian Lam, Giles Sh. Yeo, Deborah A. Goldspink, Richard G. Kay, Fiona M. Gribble, Frank Reimann 2019 University of Cambridge

Single Cell Transcriptomic Profiling Of Large Intestinal Enteroendocrine Cells In Mice - Identification Of Selective Stimuli For Insulin-Like Peptide-5 And Glucagon-Like Peptide-1 Co-Expressing Cells, Lawrence J. Billing, Pierre Larraufie, Jo Lewis, Andrew B. Leiter, Joyce H. Li, Brian Lam, Giles Sh. Yeo, Deborah A. Goldspink, Richard G. Kay, Fiona M. Gribble, Frank Reimann

Open Access Articles

OBJECTIVE: Enteroendocrine cells (EECs) of the large intestine, found scattered in the epithelial layer, are known to express different hormones, with at least partial co-expression of different hormones in the same cell. Here we aimed to categorize colonic EECs and to identify possible targets for selective recruitment of hormones.

METHODS: Single cell RNA-sequencing of sorted enteroendocrine cells, using NeuroD1-Cre x Rosa26-EYFP mice, was used to cluster EECs from the colon and rectum according to their transcriptome. G-protein coupled receptors differentially expressed across clusters were identified, and, as a proof of principle, agonists of Agtr1a and Avpr1b were tested as candidate ...


Redirection Of Skn-1 Abates The Negative Metabolic Outcomes Of A Perceived Pathogen Infection, James D. Nhan, Christian D. Turner, Sarah M. Anderson, Chia-An Yen, Hans M. Dalton, Hilary K. Cheesman, Dana L. Ruter, Nandhitha Uma Naresh, Cole M. Haynes, Alexander A. Soukas, Read Pukkila-Worley, Sean P. Curran 2019 University of Southern California

Redirection Of Skn-1 Abates The Negative Metabolic Outcomes Of A Perceived Pathogen Infection, James D. Nhan, Christian D. Turner, Sarah M. Anderson, Chia-An Yen, Hans M. Dalton, Hilary K. Cheesman, Dana L. Ruter, Nandhitha Uma Naresh, Cole M. Haynes, Alexander A. Soukas, Read Pukkila-Worley, Sean P. Curran

Open Access Articles

Early host responses toward pathogens are essential for defense against infection. In Caenorhabditis elegans, the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan. Here, we show that exposing C. elegans to Pseudomonas aeruginosa similarly drives the rapid depletion of somatic, but not germline, lipid stores. Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets, which alleviates negative metabolic outcomes. Similarly, exposure to oxidative stress redirects SKN-1 activity away from ...


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