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Full-Text Articles in Biotechnology

Role Of Simulation In Open Varicose Veins Surgery: A Systematic Review, Muhammad Ammar Pirzada, Fareed Ahmed Shaikh, Shoaib Badini, Nadeem Ahmed Siddiqui Feb 2022

Role Of Simulation In Open Varicose Veins Surgery: A Systematic Review, Muhammad Ammar Pirzada, Fareed Ahmed Shaikh, Shoaib Badini, Nadeem Ahmed Siddiqui

Department of Surgery Docs

Objective: To assess the types and effectiveness of simulators present for open varicose vein surgery.
Methods: The systematic review was conducted at The Aga Khan University Hospital Karachi and comprised studies published from 1st January 2000 to 30th June 2020 related to open varicose vein surgical procedures done on simulators. Databases searched were PubMed, Medline, Google Scholar, Cochrane and Scopus using appropriate key words. The primary outcome of the review was to assess the effectiveness of different types of simulators used for varicose vein surgery.
Results: Of the 286 articles found, 6(2%) were included. A variety of simulators ranging from …


Innovations In Surgery Between The Past And Future: A Narrative Review Of Targeted Literature, Obada Hasan, Ahmed Ayaz, Laiba Masood, Abdul Mannan Baig, Naveed Baloch Feb 2022

Innovations In Surgery Between The Past And Future: A Narrative Review Of Targeted Literature, Obada Hasan, Ahmed Ayaz, Laiba Masood, Abdul Mannan Baig, Naveed Baloch

Medical College Documents

Innovation is the introduction of a new method or technology designed to change the way things are done. History is full of remarkable innovations in surgery over the years as surgeons have always been innovating and pioneering latest techniques and equipment that can benefit the mankind. Though persistent, progress has been far from uniform. Despite all the bells and whistles that these innovations bring to the table, the little acknowledged fact is that they are only accessible to a very small proportion of the global population. Five billion people on this planet do not even have access to an operating …


Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede May 2021

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …


Importance Of Understanding Genetic Predisposition, Andrew Carter Apr 2021

Importance Of Understanding Genetic Predisposition, Andrew Carter

Thinking Matters Symposium

Hypersensitivity reactions can be sudden and are often fatal. Many of these reactions occur as a result of allergies to prescribed medication. Adverse drug reactions or (ADR’s) were show in a recent study to affect over 6% of hospitalized patients and resulted in over 100,000 deaths a year in the US alone. This poster will review the importance of understanding genetic predisposition, through articles about possible genetic causes of allergies to penicillin and other beta-lactams. Changes in a specific HLA gene located on chromosome 6 showed a correlation to penicillin reactions in over 600,000 participants. Another study found a conclusive …


Nih Funding For Vaccine Readiness Before The Covid-19 Pandemic, Anthony E. Kiszewski, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley Mar 2021

Nih Funding For Vaccine Readiness Before The Covid-19 Pandemic, Anthony E. Kiszewski, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000–2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000–2019. During this period, NIH funding for published vaccine research against specific pandemic threats …


Transcutaneous Energy Transmission: Can We Do It Now?, Yuriy Pya Oct 2020

Transcutaneous Energy Transmission: Can We Do It Now?, Yuriy Pya

The VAD Journal

The percutaneous driveline used in contemporary LVADs presents a continuous risk of infection for the duration of support. Minimizing infection in durable mechanical circulatory support systems requires total implantation of all components and energy transfer by means other than percutaneous drivelines. A novel coplanar energy transfer (CET) system, similar to the original transcutaneous energy transfer (TET) design, is unique by incorporating two large rings with coil-within-the-coil topology to ensure strong resonance power. The CET system consists of an internal integrated controller, a battery coupled with an internal thoracic coil ring, and the LVAD pump. External equipment includes a power transmission …


Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane Jan 2020

Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane

Department of Biological Sciences Publications

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development …


The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue Apr 2019

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …


Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs Oct 2018

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …


Nanoparticles As Multimodal Photon Transducers Of Ionizing Radiation, Edwin C. Pratt, Travis M. Shaffer, Qize Zhang, Charles Michael Drain, Jan Grimm Sep 2018

Nanoparticles As Multimodal Photon Transducers Of Ionizing Radiation, Edwin C. Pratt, Travis M. Shaffer, Qize Zhang, Charles Michael Drain, Jan Grimm

Publications and Research

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies, and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be explained by only Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles, and γ radiation. We demonstrate that β scintillation contributes appreciably to excitation and reactivity in certain …


Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller Sep 2018

Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller

Bioelectrics Publications

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …


Endometrial Response To Conceptus-Derived Estrogen And Interleukin-1Β At The Time Of Implantation In Pigs, Hakhyun Ka, Heewon Seo, Yohan Choi, Inkyu Yoo, Jisoo Han Jun 2018

Endometrial Response To Conceptus-Derived Estrogen And Interleukin-1Β At The Time Of Implantation In Pigs, Hakhyun Ka, Heewon Seo, Yohan Choi, Inkyu Yoo, Jisoo Han

Obstetrics and Gynecology Faculty Publications

The establishment of pregnancy is a complex process that requires a well-coordinated interaction between the implanting conceptus and the maternal uterus. In pigs, the conceptus undergoes dramatic morphological and functional changes at the time of implantation and introduces various factors, including estrogens and cytokines, interleukin-1β2 (IL1B2), interferon-γ (IFNG), and IFN-δ (IFND), into the uterine lumen. In response to ovarian steroid hormones and conceptus-derived factors, the uterine endometrium becomes receptive to the implanting conceptus by changing its expression of cell adhesion molecules, secretory activity, and immune response. Conceptus-derived estrogens act as a signal for maternal recognition of pregnancy by changing the …


Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li Jan 2018

Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li

Faculty & Staff Scholarship

Quantum confined materials have been extensively studied for photoluminescent applica- tions. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio- imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for …


Macrophage Sensing Of Single- Walled Carbon Nanotubes Via Toll- Like Receptors, Sourav P. Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T. Andon, Tana Brzicova, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Ritta Lahesmaa, Bengt Fadeel Jan 2018

Macrophage Sensing Of Single- Walled Carbon Nanotubes Via Toll- Like Receptors, Sourav P. Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T. Andon, Tana Brzicova, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Ritta Lahesmaa, Bengt Fadeel

Faculty & Staff Scholarship

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger

inflammation. However, how these materials are ‘sensed’ by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. …


Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer Jan 2018

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …


Upregulation Of Dna Sensors In B16.F10 Melanoma Spheroid Cells After Electrotransfer Of Pdna, Katarina Znidar, Masa Bosnjak, Tanja Jesenko, Loree C. Heller, Maja Cemazar Jan 2018

Upregulation Of Dna Sensors In B16.F10 Melanoma Spheroid Cells After Electrotransfer Of Pdna, Katarina Znidar, Masa Bosnjak, Tanja Jesenko, Loree C. Heller, Maja Cemazar

Bioelectrics Publications

Increased expression of cytosolic DNA sensors, a category of pattern recognition receptor, after control plasmid DNA electrotransfer was observed in our previous studies on B16.F10 murine melanoma cells. This expression was correlated with the upregulation of proinflammatory cytokines and chemokines and was associated with cell death. Here, we expanded our research to include the influence of features of cells in a 3-dimensional environment, which better represents the tumors’ organization in vivo. Our results show that lower number of cells were transfected in spheroids compared to 2-dimensional cultures, that growth was delayed after electroporation alone or after electrotransfer of plasmid …


Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe Jan 2018

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …


Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar Jan 2018

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …


A Comparison Of Three Diagnostic Platforms For The Detection Of Influenza A And B In Children, Furqan Kabir, Marvi Tariq, Fatima Aziz, Syed Imran Rizvi, Shahida Qureshi, Syed Asad Ali, Najeeha Talat Iqbal Jan 2018

A Comparison Of Three Diagnostic Platforms For The Detection Of Influenza A And B In Children, Furqan Kabir, Marvi Tariq, Fatima Aziz, Syed Imran Rizvi, Shahida Qureshi, Syed Asad Ali, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Background: Viral flu is the predominant cause of hospitalization in young children, which invariably leads to enhanced morbidity and mortality in children in developing countries. Initial treatment of viral flu is based on presumptive diagnosis. Bedside testing is not common in clinical settings because of variable sensitivity and specificity of rapid tests in different settings.
Methods: To address this issue, we evaluated the performance of Binax influenza A/B rapid testing kit against two robust molecular platforms (quantitative real-time polymerase chain reaction [qRT-PCR] and TaqMan array card [TAC]) in 24 nasopharyngeal (NP) swabs, collected from children under 5 years of age. …


Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro Nov 2017

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …


Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel Nov 2017

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …


Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim Sep 2017

Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim

Journal of Bioresource Management

Typhoid is caused by Salmonella enterica serovar Typhi that is usually diagnosed by using serologic and immuno-chromatographic techniques in developing counties including Pakistan, which is thought to be an unreliable diagnostic method. For accurate diagnosis we used molecular techniques to amplify 204 bp StyR-36 and 498 bp flagellin gene for the identification of Salmonella enterica serovar Typhi. This study was done on 58 individuals diagnosed positive of typhoid via serologic tests and 50 healthy individuals as a control group. Success rate of amplification for flagellin gene was 77.58% while that for StyR-36 gene was 68.97% showing that flagellin gene primer …


Dusquetide: Reduction In Oral Mucositis Associated With Enduring Ancillary Benefits In Tumor Resolution And Decreased Mortality In Head And Neck Cancer Patients, Mahesh Kudrimoti, Amarinthia Curtis, Samar Azawi, Francis Worden, Sanford Katz, Douglas Adkins, Marcelo Bonomi, Zack Scott, Jenna Elder, Stephen T. Sonis, Richard Straube, Oreola Donini Sep 2017

Dusquetide: Reduction In Oral Mucositis Associated With Enduring Ancillary Benefits In Tumor Resolution And Decreased Mortality In Head And Neck Cancer Patients, Mahesh Kudrimoti, Amarinthia Curtis, Samar Azawi, Francis Worden, Sanford Katz, Douglas Adkins, Marcelo Bonomi, Zack Scott, Jenna Elder, Stephen T. Sonis, Richard Straube, Oreola Donini

Radiation Medicine Faculty Publications

Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified.


Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor Jul 2017

Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor

Department of Paediatrics and Child Health

Background: We present our experience with optimization and diagnostic use of quantitative real-time polymerase chain reaction (PCR) targeting the lytA gene of Streptococcus pneumoniae for the detection of S. pneumoniae in whole blood of children ≥5 CFU/10 μl or 1 copy of DNA/2 μl of blood.
Methods: This assay was applied on 1912 whole blood specimens collected from children pneumonia, of which 35 specimens were lytA positive. The bacterial loads were determined through categorization of load into five different categories, i.e., very high load, high load, moderate load, low load, and very low load.
Results: Of the 35 lytA-positive …


Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez May 2016

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …


A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin Mar 2016

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …


Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann Jan 2016

Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann

Athletic Training Collection

Background: A continued interest in concussion biomarkers makes the eventual implementation of identified biomarkers into routine concussion assessment an eventual reality. We sought to develop and test an interdisciplinary approach that could be used to integrate blood-based biomarkers into the established concussion management program for a collegiate football team.

Methods: We used a CLIA-certified laboratory for all testing and chose biomarkers where clinically validated testing was available as would be required for results used in clinical decision making. We summarized the existing methods and results for concussion assessment across an entire season to identify and demonstrate the challenges with the …


Background Differences In Baseline And Stimulated Mmp Levels Influence Abdominal Aortic Aneurysm Susceptibility, Matthew A. Dale, Melissa K. Suh, Shijia Zhao, Trevor Meisinger, Linxia Gu, Vicki J. Swier, Devendra K. Agrawal, Timothy Greiner, Jeffrey S. Carson, B. Timothy Baxter, Wanfen Xiong Dec 2015

Background Differences In Baseline And Stimulated Mmp Levels Influence Abdominal Aortic Aneurysm Susceptibility, Matthew A. Dale, Melissa K. Suh, Shijia Zhao, Trevor Meisinger, Linxia Gu, Vicki J. Swier, Devendra K. Agrawal, Timothy Greiner, Jeffrey S. Carson, B. Timothy Baxter, Wanfen Xiong

Department of Mechanical and Materials Engineering: Faculty Publications

Objective: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.

Methods: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction …


The Mouse That Trolled: The Long And Tortuous History Of A Gene Mutation Patent That Became An Expensive Impediment To Alzheimer's Research, Tania M. Bubela, Saurabh Vishnubhakat, Robert Cook-Deegan Jul 2015

The Mouse That Trolled: The Long And Tortuous History Of A Gene Mutation Patent That Became An Expensive Impediment To Alzheimer's Research, Tania M. Bubela, Saurabh Vishnubhakat, Robert Cook-Deegan

Office of the Provost

This case study presents the tale of the academic discovery of a rare mutation for early-onset Alzheimer's disease that was patented by a sole inventor and licensed to a non-practicing entity (NPE), the Alzheimer's Institute of America (AIA). Our aims are (1) to relate this story about patents, research tools, and impediments to medical progress, and (2) to inform ongoing debates about how patents affect research, disposition of university inventions, and the distribution of benefits from publicly funded research. We present an account of the hunt for Alzheimer's genes, their patenting, assignment, and enforcement based on literature, litigation records and …


Draft Genome Sequences Of Six Different Staphylococcus Epidermidis Clones, Isolated Individually From Preterm Neonates Presenting With Sepsis At Edinburgh's Royal Infirmary, Paul Walsh, M. Bekaert, J. Carroll, T. Manning, B. Kelly, A. O'Driscoll, X. Lu, C. Smith, P. Dickinson, K. Templeton, P. Ghazal, Roy D. Sleator May 2015

Draft Genome Sequences Of Six Different Staphylococcus Epidermidis Clones, Isolated Individually From Preterm Neonates Presenting With Sepsis At Edinburgh's Royal Infirmary, Paul Walsh, M. Bekaert, J. Carroll, T. Manning, B. Kelly, A. O'Driscoll, X. Lu, C. Smith, P. Dickinson, K. Templeton, P. Ghazal, Roy D. Sleator

Department of Biological Sciences Publications

Herein, we report the draft genome sequences of six individual Staphylococcus epidermidis clones, cultivated from blood taken from different preterm neonatal sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom.