Biochemistry, Biophysics, and Structural Biology Commons^™

The Landscape Of Renal Replacement Therapy In Veterans Affairs Medical Center Intensive Care Units, Chandan Vangala, Maulin Shah, Natasha N Dave, Layth Al Attar, Sankar D Navaneethan, Venkat Ramanathan, Susan Crowley, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

BACKGROUND: Outpatient dialysis is standardized with several evidence-based measures of adequacy and quality that providers aim to meet while providing treatment. By contrast, in the intensive care unit (ICU) there are different types of prolonged and continuous renal replacement therapies (PIRRT and CRRT, respectively) with varied strategies for addressing patient care and a dearth of nationally accepted quality parameters. To eventually describe appropriate quality measures for ICU-related renal replacement therapy (RRT), we first aimed to capture the variety and prevalence of basic strategies and equipment utilized in the ICUs of Veteran Affairs (VA) medical facilities with inpatient hemodialysis capabilities.

METHODS: …

Transient Ascaris Suum Larval Migration Induces Intractable Chronic Pulmonary Disease And Anemia In Mice, Yifan Wu, Evan Li, Morgan Knight, Grace Adeniyi-Ipadeola, Li-Zhen Song, Alan R Burns, Ana Clara Gazzinelli-Guimaraes, Ricardo Fujiwara, Maria Elena Bottazzi, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host's lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through the host lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that …

Genetic Testing In Ambulatory Cardiology Clinics Reveals High Rate Of Findings With Clinical Management Implications, David R Murdock, Eric Venner, Donna M Muzny, Ginger A Metcalf, Mullai Murugan, Trevor D Hadley, Varuna Chander, Paul S De Vries, Xiaoming Jia, Aliza Hussain, Ali M Agha, Aniko Sabo, Shoudong Li, Qingchang Meng, Jianhong Hu, Xia Tian, Michelle Cohen, Victoria Yi, Christie L Kovar, Marie-Claude Gingras, Viktoriya Korchina, Chad Howard, Daniel L Riconda, Stacey Pereira, Hadley S Smith, Zohra A Huda, Alexandria Buentello, Patricia R Marino, Lee Leiber, Ashok Balasubramanyam, Christopher I Amos, Andrew B Civitello, Mihail G Chelu, Ronald Maag, Amy L Mcguire, Eric Boerwinkle, Xander H T Wehrens, Christie M Ballantyne, Richard A Gibbs

Faculty, Staff and Students Publications

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted.

METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record.

RESULTS: Notably, 32% of patients had a genetic finding with clinical …

Bicuspid Aortic Valve In Pregnancy Complicated By Aortic Valve Vegetation, Aortic Root Abscess, And Aortic Insufficiency, Shan He, Christopher A Huynh, Yi Deng, Sandeep Markan, Anvinh Nguyen

Faculty, Staff and Students Publications

A 39-year-old patient presented to our Labor and Delivery unit with fever and nausea in the context of recent bacteriuria. She was found to be in sepsis due to an incidental bicuspid aortic valve (BAV) complicated by aortic valvular vegetations, severe aortic insufficiency, and aortic root abscess, requiring an emergent cesarean section. Three days after delivery, the patient successfully underwent a mechanical aortic valve replacement and root reconstruction. In this case report, medical, surgical, and anesthetic management of parturient patients with BAV are discussed. The management of this congenital valvulopathy and vasculopathy is complicated by the extensive hemodynamic and cardiovascular …

Predicted Vitamin D Status And Colorectal Cancer Incidence In The Black Women's Health Study, Lauren E Barber, Kimberly A Bertrand, Jessica L Petrick, Hanna Gerlovin, Laura F White, Lucile L Adams-Campbell, Lynn Rosenberg, Hemant K Roy, Julie R Palmer

Faculty, Staff and Students Publications

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of …

Associations Of High-Sensitivity Troponin And Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From The Sprint Randomized Clinical Trial, Jarett D Berry, Vijay Nambi, Walter T Ambrosius, Haiying Chen, Anthony A Killeen, Addison Taylor, Robert D Toto, Elsayed Z Soliman, John W Mcevoy, Ambarish Pandey, Parag H Joshi, Stefan Blankenberg, Dalane W Kitzman, Christie M Ballantyne, James A De Lemos

Faculty, Staff and Students Publications

IMPORTANCE: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

OBJECTIVE: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

DESIGN, SETTING, AND PARTICIPANTS: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

The Flavoprotein Rcla Is A Hypothiocyanous Acid Reductase, Irina Chapman

Masters Theses

Reactive chlorine species (RCS) - hypochlorous acid (HOCl), hypothiocyanous acid (HOSCN), and chloramines - are powerful antimicrobial oxidants generated by the innate immune system. Bacteria developed defense mechanisms against RCS, which are highly toxic for invading pathogens. One such defense system involves RclA, an enzyme from the flavin disulfide reductase family, which is massively upregulated upon exposure of Escherichia coli to RCS. Recent research suggests that RclA functions as a Cu(II) reductase to provide resistance against RCS. However, the exact mechanism used by RclA was subject to debate. In this study, we demonstrate that RclA is unlikely to function as …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello

Graduate Theses and Dissertations

Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …

Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase, Hao Chen

Graduate Theses and Dissertations

Aminoacyl-tRNA synthetases (AARSs) are an ancient and highly conserved family of enzymes which can catalyze a two-steps aminoacylation reaction to charge tRNAs with their cognate amino acids, thus playing crucial roles in ribosomal protein synthesis. Naturally, the accurate amino acids and tRNA recognition of these synthetases are essential to the fidelity of translation process. To assure the correct recognition, some of these synthetases have evolved with an editing function to help remove the mischarged tRNAs. In addition to these functions, AARSs are also involved in various biological processes ranging from transcription to translation. Currently, a series of proteomic studies have …

Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones

Chemistry & Biochemistry Theses & Dissertations

According to the International Energy Outlook 2019, released by the U.S. Energy Information Administration, it is projected that the energy consumption will increase up to 50% between 2018 and 2050 worldwide. As fossil fuel being a finite source of energy with the risk of depletion, many countries are now facing an energy security crisis. Therefore, it is important to develop other renewable and sustainable energy sources that will allow countries to shift away from depending on fossil fuels. Among several types of renewable energy, biofuel production using genetically engineered cyanobacteria is capturing much interest due to its many advantages. Different …

Mechanisms Of Stress Survival In Gram Positive Bacterial Pathogens, Asia Poudel

Chemistry & Biochemistry Theses & Dissertations

Anaerobic Gram-positive bacteria are not a well-characterized group but include many human pathogens that are resilient against stresses caused by the human immune system or by antibiotic treatment. This dissertation investigated the survival mechanisms of two clinically relevant Gram-positive organisms, Clostridioides difficile and Cutibacterium acnes under extracellular stresses. The response of the opportunistic skin pathogen Cutibacterium acnes to nanosecond electric pulses is characterized and found that growth in a biofilm, which usually protects bacteria from stress, renders this species more killable by this treatment. In addition, the stringent response (SR), a conserved bacterial stress survival mechanism, is studied in the …

V-Myb Avian Myel Oblast Viral Oncogene Homolog Like 1 (Mybl1) Knockdown And Its Role In A Triple Negative Breast Cancer, Nabras Mahmoud Abdulrahman

Theses (2016-Present)

Triple Negative Breast Cancer (TNBC) is defined as negative for three genes, estrogen receptor (ESR), progesterone receptor (PR) and Human epidermal growth factor receptor (HER2-neu) genes. Previous data show the V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) gene is over-expressed in Triple negative breast cancer cell line (MDA-MB231). MYBL1 belongs to the MYB family of genes which are transcription factors and proto-oncogenes which are associated with cell cycle regulation, apoptosis, and differentiation, all of which are key events associated with cancers. It could be that MYBL1 contributes to these same processes in TNBC. Instead of studying MYBL1’s …

Living With A Giant, Flowering Parasite: Metabolic Differences Between Tetrastigma Loheri Gagnep. (Vitaceae) Shoots Uninfected And Infected With Rafflesia (Rafflesiaceae) And Potential Applications For Propagation, Jeanmaire Molina, Dejan Nikolic, Jashvanth Raaj Jeevarathanam, Rinat Abzalimov, Eun‑Jung Park, Ronniel Pedales, Elmer‑Rico E. Mojica, Danilo Tandang, William Mclaughlin, Kyle Wallick, James Adams, Ari Novy, Susan K. Pell, Richard B. Van Breemen, John M. Pezzuto

Advanced Science Research Center

Main conclusion: Metabolites in Rafflesia-infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia-infected shoots, oxylipins, which mediate immune response, were elevated.

Endemic to the forests of Southeast Asia, Rafflesia (Rafflesiaceae) is a genus of holoparasitic plants producing the largest flowers in the world, yet completely dependent on its host, the tropical grape vine, Tetrastigma. Rafflesia species are threatened with extinction, making them an iconic symbol of plant conservation. Thus …

Case Report: Molecular Diagnosis Of Cystoisospora Belli In A Severely Immunocompromised Patient With Hiv And Kaposi Sarcoma, Roumen Borilov Iordanov, Lauren M Leining, Meng Wu, Galant Chan, Andrew R Dinardo, Rojelio Mejia

Faculty, Staff and Students Publications

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting …

Hematopoiesis Under Telomere Attrition At The Single-Cell Resolution, Natthakan Thongon, Feiyang Ma, Andrea Santoni, Matteo Marchesini, Elena Fiorini, Ashley Rose, Vera Adema, Irene Ganan-Gomez, Emma M Groarke, Fernanda Gutierrez-Rodrigues, Shuaitong Chen, Pamela Lockyer, Sarah Schneider, Carlos Bueso-Ramos, Guillermo Montalban-Bravo, Caleb A Class, Kelly A Soltysiak, Matteo Pellegrini, Ergun Sahin, Alison A Bertuch, Courtney D Dinardo, Guillermo Garcia-Manero, Neal S Young, Karen Dwyer, Simona Colla

Faculty, Staff and Students Publications

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion. …

Recovery Of Altered Diabetic Myofibroblast Heterogeneity And Gene Expression Associated With Cd301b+ Macrophages, Maryellen R. Haas, Darlene V. Nguyen, Brett A. Shook

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.

Analysis Of Hendra Virus Fusion Protein N-Terminal Transmembrane Residues, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, J. Lizbeth Reyes Zamora, Carole L. Moncman, Andreea Popa, Everett Clinton Smith, Stacy R. Webb, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Hendra virus (HeV) is a zoonotic enveloped member of the family Paramyoxviridae. To successfully infect a host cell, HeV utilizes two surface glycoproteins: the attachment (G) protein to bind, and the trimeric fusion (F) protein to merge the viral envelope with the membrane of the host cell. The transmembrane (TM) region of HeV F has been shown to have roles in F protein stability and the overall trimeric association of F. Previously, alanine scanning mutagenesis has been performed on the C-terminal end of the protein, revealing the importance of β-branched residues in this region. Additionally, residues S490 and Y498 have …

Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant

Publications and Research

Far-red light (FRL) photoacclimation in cyanobacteria provides a selective growth advantage for some terrestrial cyanobacteria by expanding the range of photosynthetically active radiation to include far-red/near-infrared light (700–800 nm). During this photoacclimation process, photosystem II (PSII), the water:plastoquinone photooxidoreductase involved in oxygenic photosynthesis, is modified. The resulting FRL-PSII is comprised of FRL-specific core subunits and binds chlorophyll (Chl) d and Chl f molecules in place of several of the Chl a molecules found when cells are grown in visible light. These new Chls effectively lower the energy canonically thought to define the “red limit” for light required to drive photochemical …