Medicine and Health Sciences Commons^™

Early Goal-Directed Therapy In Severe Sepsis And Septic Shock: Insights And Comparisons To Process, Promise, And Arise, H. Bryant Nguyen, Anja Kathrin Jaehne, Namita Jayaprakash, Matthew W. Semler, Sara Hegab, Angel Coz-Yataco, Geneva Tatem, Dhafer Salem, Steven Moore, Kamran Boka, Jasreen Kaur Gill, Jayna Gardner-Gray, Jacqueline Pflaum, Juan Pablo Domecq, Gina Hurst, Justin B Belsky, Raymond Fowkes, Ronald B. Elkin, Steven Q. Simpson, Jay L. Falk, Daniel J. Singer, Emanuel P. Rivers

Internal Medicine Faculty Publications

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was …

Immunoglobulin G4-Related Disease: A Rare Disease With An Unusual Presentation, Muhammad Waqas Khan, Terrance Hadley, Melissa Kesler, Zartash Gul

Internal Medicine Faculty Publications

IgG4-RD can also present in the skeletal muscle, mimicking several other diseases. It is unusual for this relatively new classification of diseases to present in the muscles and can be mistakenly diagnosed as other autoimmune diseases rendering a delay in the appropriate management and progression of the disease.

Structure And Functions Of Angiotensinogen, Hong Lu, Lisa A. Cassis, Craig W. Vander Kooi, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of …

Normal Lactate Dehydrogenase Does Not Exclude Pump Thrombosis In Left Ventricular Assist Devices, Julie Shelton Do, Bennet George Md, Amanda Hart Bsn, Rn, Maya Guglin Md

The VAD Journal

Left ventricular assist device (LVAD) pump thrombosis is a well-known complication of LVAD placement. Elevated lactate dehydrogenase (LDH) has classically been the first objective marker of pump thrombosis. In this case, we present a patient found to have normal serum LDH values but was ultimately found to have significant pump thrombosis.

Mtor: Alzheimer's Disease Prevention For Apoe4 Carriers, Ai-Ling Lin, D. Allan Butterfield, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Phylotoast: Bioinformatics Tools For Species-Level Analysis And Visualization Of Complex Microbial Datasets, Shareef M. Dabdoub, Megan L. Fellows, Akshay D. Paropkari, Matthew R. Mason, Sarandeep S. Huja, Alexandra A. Tsigarida, Purnima S. Kumar

Oral Health Science Faculty Publications

The 16S rRNA gene is widely used for taxonomic profiling of microbial ecosystems; and recent advances in sequencing chemistry have allowed extremely large numbers of sequences to be generated from minimal amounts of biological samples. Analysis speed and resolution of data to species-level taxa are two important factors in large-scale explorations of complex microbiomes using 16S sequencing. We present here new software, Phylogenetic Tools for Analysis of Species-level Taxa (PhyloToAST), that completely integrates with the QIIME pipeline to improve analysis speed, reduce primer bias (requiring two sequencing primers), enhance species-level analysis, and add new visualization tools. The code …

Outcomes Of External Repair Of Heartmate Ii™ Lvad Percutaneous Leads, Jay D. Pal, Claudius Mahr, Jason W. Smith, Todd F. Dardas, Jay Pinette, David J. Farrar, Nahush A. Mokadam

The VAD Journal

Background: The HeartMate II Left Ventricular Assist Device (LVAD) receives power via a percutaneous lead connected to an external controller and batteries. At times, this lead can be damaged during normal wear, as well as by traumatic fracture, which may jeopardize the functionality of the LVAD. If there is significant internal damage, surgical replacement of the LVAD is required. However it is possible to repair externally damaged leads by replacing the distal portion of the lead to avoid pump replacement. We report the overall experience and outcomes in patients with external lead repairs.

Methods: A procedure for full …

Affordable Care Act Implementation And Multi-Sector Contributions To Population Health, Glen P. Mays

Health Management and Policy Presentations

Research Objective: The Affordable Care Act established new resources and incentives for hospitals, insurers, public health agencies, and others to contribute to disease prevention and health promotion activities, potentially changing the structure of public health delivery systems and expanding the implementation of strategies that improve population health. This study uses data from the 1998-2014 National Longitudinal Survey of Public Health Systems to examine: (1) the degree and nature of change in multi-sectoral contributions to public health activities; and (2) the extent to which these system changes are attributable to key ACA provisions including coverage expansions, Prevention and Public Health funding, …

Integrating Delivery And Financing Systems Across Sectors To Build A Culture Of Health, Glen P. Mays

Health Management and Policy Presentations

The delivery and financing systems for medical care, public health, and social and community services are powerful determinants of health and wellbeing for families and communities across the U.S. Unfortunately, these systems interact in complex and often poorly understood ways through fragmented funding streams, organizational relationships, information flows, and governance and decision-making structures. This session will feature new studies underway through the Robert Wood Johnson Foundation’s Systems for Action (S4A) Research Program to test multi-sector strategies for integrating delivery and financing systems to improve population health.

Featured speakers:

David Meltzer, MD, PhD, University of Chicago Urban Labs. Expanding a Comprehensive …

Age- And Sex-Related Changes In Fasting Plasma Glucose And Lipoprotein In Cynomolgus Monkeys, Feng Yue, Guodong Zhang, Rongping Tang, Zhouquan Zhang, Liqiong Teng, Zhiming Zhang

Neuroscience Faculty Publications

Background: The age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including …

Cellular And Molecular Features Of Developmentally Programmed Genome Rearrangement In A Vertebrate (Sea Lamprey: Petromyzon Marinus), Vladimir A. Timoshevskiy, Joseph R. Herdy, Melissa C. Keinath, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

The sea lamprey (Petromyzon marinus) represents one of the few vertebrate species known to undergo large-scale programmatic elimination of genomic DNA over the course of its normal development. Programmed genome rearrangements (PGRs) result in the reproducible loss of ~20% of the genome from somatic cell lineages during early embryogenesis. Studies of PGR hold the potential to provide novel insights related to the maintenance of genome stability during the cell cycle and coordination between mechanisms responsible for the accurate distribution of chromosomes into daughter cells, yet little is known regarding the mechanistic basis or cellular context of PGR in this or …

A Cell Cycle-Regulated Toxoplasma Deubiquitinase, Tgotud3a, Targets Polyubiquitins With Specific Lysine Linkages, Animesh Dhara, Anthony P. Sinai

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The contribution of ubiquitin-mediated mechanisms in the regulation of the Toxoplasma gondii cell cycle has remained largely unexplored. Here, we describe the functional characterization of a T. gondii deubiquitinase (TGGT1_258780) of the ovarian-tumor domain-containing (OTU) family, which, based on its structural homology to the human OTUD3 clade, has been designated TgOTUD3A. The TgOTUD3A protein is expressed in a cell cycle-dependent manner mimicking its mRNA expression, indicating that it is regulated primarily at the transcriptional level. TgOTUD3A, which was found in the cytoplasm at low levels in G₁ parasites, increased in abundance with the progression of the …

Compositions And Methods For Treating Ischemia, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Patents

The presently-disclosed subject matter provides methods for preventing ischemia in a cell, treating ischemia in a subject, and preventing an infarction in a subject that utilize α5β1 integrin inhibitor. In some instances, α5β1 integrin inhibitor is administered to a subject prior to, during, or after the onset of ischemia to treat the ischemia and/or prevent infarction. In some instances the present methods prevent the occurrence of an infarction. In some instances the present methods restores perfusion to organs and tissues.

A Randomized, Double-Blind, Placebo-Controlled Phase Ii Trial Investigating The Safety And Immunogenicity Of Modified Vaccinia Ankara Smallpox Vaccine (Mva-Bn®) In 56-80-Year-Old Subjects, Richard N. Greenberg, Christine M. Hay, Jack T. Stapleton, Thomas C. Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred Von Krempelhuber, Philip Young, Richard Nichols, Thomas P. Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin

Internal Medicine Faculty Publications

Background Modified Vaccinia Ankara MVA-BN^® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN^® (MVA) was assessed in a 56–80 years old population.

Methods MVA with a virus titer of 1 x 10⁸ TCID₅₀/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated …

Feasibility Of Conducting A Web-Based Survey Of Patient-Reported Outcomes And Rehabilitation Progress, Jennifer S. Howard, Jenny L. Toonstra, Amanda R. Meade, Caitlin E. Whale Conley, Carl G. Mattacola

Physical Therapy Faculty Publications

Background: Web-based surveys provide an efficient means to track clinical outcomes over time without the use of clinician time for additional paperwork. Our purpose was to determine the feasibility of utilizing web-based surveys to capture rehabilitation compliance and clinical outcomes among postoperative orthopedic patients. The study hypotheses were that (a) recruitment rate would be high (> 90%), (b) patients receiving surveys every two weeks would demonstrate higher response rates than patients that receive surveys every four weeks, and (c) response rates would decrease over time.

Methods: The study design involved a longitudinal cohort. Surgical knee patients were recruited for study …

Duplication And Remolding Of Trna Genes In The Mitochondrial Genome Of Reduvius Tenebrosus (Hemiptera: Reduviidae), Pei Jiang, Hu Li, Fan Song, Yao Cai, Jianyun Wang, Jinpeng Liu, Wanzhi Cai

Markey Cancer Center Faculty Publications

Most assassin bugs are predators that act as important natural enemies of insect pests. Mitochondrial (mt) genomes of these insects are double-strand circular DNAs that encode 37 genes. In the present study, we explore the duplication and rearrangement of tRNA genes in the mt genome of Reduvius tenebrosus, the first mt genome from the subfamily Reduviinae. The gene order rearranges from CR (control region)-trnI-trnQ-trnM-ND2 to CR-trnQ-trnI2-trnI1-trnM-ND2. We identified 23 tRNA genes, including 22 tRNAs commonly found in insects and an additional trnI (trnI2), which has high sequence similarity to trnM. We found several …

New Directions In Public Health Systems Research: The U.S. Context, Glen P. Mays

Health Management and Policy Presentations

Public health services and delivery systems have the potential to improve population health and reduce health inequities by intervening on pathways that connect social and economic determinants to health outcomes. This session profiles the developing field of public health services and systems research (PHSSR) in the United States and new research directions to better understand the current and potential impact of public health delivery systems on social and economic drivers of health. We discuss emerging opportunities for cross-national comparative research on public health delivery systems in the U.S. and Canada.

Data Correlations Between Gender, Cytomegalovirus Infection And T Cells, Nk Cells, And Soluble Immune Mediators In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Charlotte A. Peterson, D. Travis Thomas, Charles T. Lutz

Pathology and Laboratory Medicine Faculty Publications

We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56^dim NK cell responses to a variety of stimuli and with CD56^bright/CD56^dim NK cell ratio. We also present the correlation of retinol binding protein (RBP)−4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56^dim NK cell responses. These data are discussed in Al-Attar et al. (2016)

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Pruning Or Tuning? Maturational Profiles Of Face Specialization During Typical Development, Xun Zhu, Ramesh S. Bhatt, Jane E. Joseph

Psychology Faculty Publications

Introduction: Face processing undergoes significant developmental change with age. Two kinds of developmental changes in face specialization were examined in this study: specialized maturation, or the continued tuning of a region to faces but little change in the tuning to other categories; and competitive interactions, or the continued tuning to faces accompanied by decreased tuning to nonfaces (i.e., pruning). Methods: Using fMRI, in regions where adults showed a face preference, a face- and object-specialization index were computed for younger children (5-8 years), older children (9-12 years) and adults (18-45 years). The specialization index was scaled to each subject's maximum activation …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S. Mhashilkar, Sai L. Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R. Palli, H. Lee Woodcock, Thomas R. Unnasch

Entomology Faculty Publications

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at …

Hexavalent Chromium Induces Malignant Transformation Of Human Lung Bronchial Epithelial Cells Via Ros-Dependent Activation Of Mir-21-Pdcd4 Signaling, Poyil Pratheeshkumar, Young-Ok Son, Sasidharan Padmaja Divya, Lilia Turcios, Ram Vinod Roy, John Andrew Hitron, Lei Wang, Donghern Kim, Jin Dai, Padmaja Asha, Zhuo Zhang, Xianglin Shi

Center for Research on Environmental Disease Faculty Publications

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with an increased risk of lung cancer. However, the mechanisms underlying Cr(VI)-induced carcinogenesis remain unclear. MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. Studies have shown that miR-21 exerts its oncogenic activity by targeting the tumor suppressor gene programmed cell death 4 (PDCD4). The present study examined the role of miR-21-PDCD4 signaling in Cr(VI)-induced cell transformation and tumorigenesis. Results showed that Cr(VI) induces ROS generation in human bronchial epithelial (BEAS-2B) cells. Chronic exposure to Cr(VI) is able to cause malignant transformation in BEAS-2B cells. Cr(VI) caused a significant increase of …

Fh535, A Β-Catenin Pathway Inhibitor, Represses Pancreatic Cancer Xenograft Growth And Angiogenesis, Lu Liu, Qiaoming Zhi, Meng Shen, Fei-Ran Gong, Binhua P. Zhou, Lian Lian, Bairong Shen, Kai Chen, Weiming Duan, Meng-Yao Wu, Min Tao, Wei Li

Markey Cancer Center Faculty Publications

The WNT/β-catenin pathway plays an important role in pancreatic cancer carcinogenesis. We evaluated the correlation between aberrant β-catenin pathway activation and the prognosis pancreatic cancer, and the potential of applying the β-catenin pathway inhibitor FH535 to pancreatic cancer treatment. Meta-analysis and immunohistochemistry showed that abnormal β-catenin pathway activation was associated with unfavorable outcome. FH535 repressed pancreatic cancer xenograft growth in vivo. Gene Ontology (GO) analysis of microarray data indicated that target genes responding to FH535 participated in stemness maintenance. Real-time PCR and flow cytometry confirmed that FH535 downregulated CD24 and CD44, pancreatic cancer stem cell (CSC) markers, suggesting FH535 …

Klf4 Deletion Alters Gastric Cell Lineage And Induces Muc2 Expression, Tianxin Yu, Xi Chen, T. Lin, J. Liu, M. Li, W. Zhang, X. Xu, W. Zhao, M. Liu, Dana L. Napier, Chi Wang, B. Mark Evers, Chunming Liu

Markey Cancer Center Faculty Publications

Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4^fl/fl and Lgr5-Cre;Klf4^fl/fl. KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous …

Exploring Body Mass Index Changes In Left Ventricular Assist Device Patients, Raquel E. Thomas, Corrine Hanson, Glenda Woscyna, Brian D. Lowes

The VAD Journal

Background: Current treatment options for end-stage heart failure, such as transplantation, can be limited by obesity guidelines. Mechanical devices such as Left Ventricular Assistive Devices (LVAD) can bridge heart failure patients to transplantation, however, after implantation; some patients may experience weight gain that precludes them from transplantation. Therefore, the objective of this study was to evaluate weight changes after the implantation of an LVAD.

Methods: A retrospective review of 130 patients receiving an LVAD were divided into two groups based on BMI at the time of implantation: obese (>30 kg/m²) and non-obese (/m²). Patients were …

Breast-Cancer-Specific Mortality In Patients Treated Based On The 21-Gene Assay: A Seer Population-Based Study, Valentina I. Petkov, Dave P. Miller, Nadia Howlader, Nathan Gliner, Will Howe, Nicola Schussler, Kathleen Cronin, Frederick L. Baehner, Rosemary Cress, Dennis Deapen, Sally L. Glaser, Brenda Y. Hernandez, Charles F. Lynch, Lloyd Mueller, Ann G. Schwartz, Stephen M. Schwartz, Antoinette Stroup, Carol Sweeney, Thomas C. Tucker, Kevin C. Ward, Charles Wiggins, Xiao-Cheng Wu, Lynne Penberthy, Steven Shak

Markey Cancer Center Faculty Publications

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results …

Multiorgan Chronic Inflammatory Hepatobiliary Pancreatic Murine Model Deficient In Tumor Necrosis Factor Receptors 1 And 2, Helieh S. Oz

Physiology Faculty Publications

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues.

METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological …

A Protocol For Collecting Human Cardiac Tissue For Research, Cheavar A. Blair, Premi Haynes, Stuart G. Campbell, Charles Chung, Mihail I. Mitov, Donna Dennis, Mark R. Bonnell, Charles W. Hoopes, Maya Guglin, Kenneth S. Campbell

The VAD Journal

This manuscript describes a protocol at the University of Kentucky that allows a translational research team to collect human myocardium that can be used for biological research. We have gained a great deal of practical experience since we started this protocol in 2008, and we hope that other groups might be able to learn from our endeavors. To date, we have procured ~4000 samples from ~230 patients. The tissue that we collect comes from organ donors and from patients who are receiving a heart transplant or a ventricular assist device because they have heart failure. We begin our manuscript by …

Role Of Histidine 547 Of Human Dopamine Transporter In Molecular Interaction With Hiv-1 Tat And Dopamine Uptake, Yaxia Yuan, Pamela M. Quizon, Wei-Lun Sun, Jianzhuang Yao, Jun Zhu, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

HIV-1 Tat plays an important role in HIV-associated neurocognitive disorders (HAND) by disrupting neurotransmission including dopamine uptake by human dopamine transporter (hDAT). Previous studies have demonstrated that HIV-1 Tat directly binds to hDAT and some amino-acid mutations that attenuate the hDAT-Tat binding also significantly decreased dopamine uptake activity of hDAT. This combined computational-experimental study demonstrates that histidine-547 (H547) of hDAT plays a crucial role in the hDAT-Tat binding and dopamine uptake by hDAT, and that the H547A mutation can not only considerably attenuate Tat-induced inhibition of dopamine uptake, but also significantly increase the V_max of hDAT for dopamine uptake. …

Modeling And Re-Engineering Of Azotobacter Vinelandii Alginate Lyase To Enhance Its Catalytic Efficiency For Accelerating Biofilm Degradation, Chul Ho Jang, Yu Lan Piao, Xiaoqin Huang, Eun Jeong Yoon, So Hee Park, Kyoung Lee, Chang-Guo Zhan, Hoon Cho

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Alginate is known to prevent elimination of Pseudomonas aeruginosa biofilms. Alginate lyase (AlgL) might therefore facilitate treatment of Pseudomonas aeruginosa-infected cystic fibrosis patients. However, the catalytic activity of wild-type AlgL is not sufficiently high. Therefore, molecular modeling and site-directed mutagenesis of AlgL might assist in enzyme engineering for therapeutic development. AlgL, isolated from Azotobacter vinelandii, catalyzes depolymerization of alginate via a β-elimination reaction. AlgL was modeled based on the crystal structure template of Sphingomonas AlgL species A1-III. Based on this computational analysis, AlgL was subjected to site-directed mutagenesis to improve its catalytic activity. The k_cat/K …