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Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah 2021 Seton Hall University

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy ...


Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline 2021 University of Nebraska at Omaha

Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline

Theses/Capstones/Creative Projects

Inflammatory Bowel Diseases (IBD) including ulcerative colitis, indeterminate colitis, and Crohn’s disease are increasingly common conditions that places a high physical and financial burden on individuals and global healthcare systems. Though many treatments exist for these conditions, their unpredictable nature and causation make them difficult to manage across the variety of IBD patients. Additionally, many of these treatments come with undesirable side effects or modes of delivery. Therefore, it is worthwhile to explore the use of Short Chain Fatty Acids (SCFAs) such as butyrate whose affects in the human gut include decreased inflammation and decreased risk of colorectal cancer ...


Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. McCormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe 2021 Virginia Commonwealth University, School of Pharmacy

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods ...


Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver 2020 Olivet Nazarene University

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Pence-Boyce STEM Student Scholarship

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus ...


The Lipid Handling Capacity Of Subcutaneous Fat Is Programmed By Mtorc2 During Development, Wen-Yu Hsiao, Su Myung Jung, Yuefeng Tang, John A. Haley, Rui Li, Huawei Li, Camila Martinez Calejman, Joan Sanchez-Gurmaches, Chien-Min Hung, Amelia K. Luciano, Victoria DeMambro, Kathryn E. Wellen, Clifford J. Rosen, Lihua Julie Zhu, David A. Guertin 2020 University of Massachusetts Medical School

The Lipid Handling Capacity Of Subcutaneous Fat Is Programmed By Mtorc2 During Development, Wen-Yu Hsiao, Su Myung Jung, Yuefeng Tang, John A. Haley, Rui Li, Huawei Li, Camila Martinez Calejman, Joan Sanchez-Gurmaches, Chien-Min Hung, Amelia K. Luciano, Victoria Demambro, Kathryn E. Wellen, Clifford J. Rosen, Lihua Julie Zhu, David A. Guertin

Open Access Publications by UMMS Authors

Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness ...


Upregulating Beta-Hexosaminidase Activity In Rodents Prevents Alpha-Synuclein Lipid Associations And Protects Dopaminergic Neurons From Alpha-Synuclein-Mediated Neurotoxicity, Oeystein R. Brekk, Joanna A. Korecka, Cecile C. Crapart, Mylene Huebecker, Zachary K. MacBain, Sara Ann Rosenthal, Miguel Sena-Esteves, David A. Priestman, Frances M. Platt, Ole Isacson, Penelope J. Hallett 2020 Harvard Medical School

Upregulating Beta-Hexosaminidase Activity In Rodents Prevents Alpha-Synuclein Lipid Associations And Protects Dopaminergic Neurons From Alpha-Synuclein-Mediated Neurotoxicity, Oeystein R. Brekk, Joanna A. Korecka, Cecile C. Crapart, Mylene Huebecker, Zachary K. Macbain, Sara Ann Rosenthal, Miguel Sena-Esteves, David A. Priestman, Frances M. Platt, Ole Isacson, Penelope J. Hallett

Open Access Publications by UMMS Authors

Sandhoff disease (SD) is a lysosomal storage disease, caused by loss of beta-hexosaminidase (HEX) activity resulting in the accumulation of ganglioside GM2. There are shared features between SD and Parkinson's disease (PD). alpha-synuclein (aSYN) inclusions, the diagnostic hallmark sign of PD, are frequently found in the brain in SD patients and HEX knockout mice, and HEX activity is reduced in the substantia nigra in PD. In this study, we biochemically demonstrate that HEX deficiency in mice causes formation of high-molecular weight (HMW) aSYN and ubiquitin in the brain. As expected from HEX enzymatic function requirements, overexpression in vivo of ...


Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech 2020 University of Massachusetts Medical School

Single-Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie A. Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

Open Access Publications by UMMS Authors

Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsalpha deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression ...


Exogenous Lipoid Pneumonia Complicated By Mineral Oil Asperation In A Patient With Chronic Constipation: A Case Report And Review, Hafiz Muhammad Jeelani, Muhammad Mubbashir Sheikh, Belaal Sheikh, Hafiz Mahboob, Anchit Bharat 2020 Rosalind Franklin University of Medicine and Science

Exogenous Lipoid Pneumonia Complicated By Mineral Oil Asperation In A Patient With Chronic Constipation: A Case Report And Review, Hafiz Muhammad Jeelani, Muhammad Mubbashir Sheikh, Belaal Sheikh, Hafiz Mahboob, Anchit Bharat

School of Medicine Faculty Publications

Exogenous lipoid pneumonia is a rare and frequently misdiagnosed lung disease. It occurs as an inflammatory reaction secondary to either aspiration or inhalation of lipids. Our patient had a history significant for recurrent pneumonia and the use of mineral oil for chronic constipation. A chest computed tomography showed multifocal consolidative opacities with areas of low attenuation, highly suspicious of exogenous lipid pneumonia. The diagnosis was confirmed with combined bronchoalveolar lavage and transbronchial lung biopsy that showed lipid-laden macrophages consistent with exogenous lipoid pneumonia. After thorough medication review, apart from mineral oil, no other contributing factors were found. A diagnosis of ...


Jnk-Mediated Disruption Of Bile Acid Homeostasis Promotes Intrahepatic Cholangiocarcinoma, Elisa Manieri, Tamera Barrett, Julie Cavanagh-Kyros, Roger J. Davis, Alfonso Mora, Guadalupe Sabio 2020 National Centre for Cardiovascular Research, Spain

Jnk-Mediated Disruption Of Bile Acid Homeostasis Promotes Intrahepatic Cholangiocarcinoma, Elisa Manieri, Tamera Barrett, Julie Cavanagh-Kyros, Roger J. Davis, Alfonso Mora, Guadalupe Sabio

University of Massachusetts Medical School Faculty Publications

Metabolic stress causes activation of the cJun NH2-terminal kinase (JNK) signal transduction pathway. It is established that one consequence of JNK activation is the development of insulin resistance and hepatic steatosis through inhibition of the transcription factor PPARalpha. Indeed, JNK1/2 deficiency in hepatocytes protects against the development of steatosis, suggesting that JNK inhibition represents a possible treatment for this disease. However, the long-term consequences of JNK inhibition have not been evaluated. Here we demonstrate that hepatic JNK controls bile acid production. We found that hepatic JNK deficiency alters cholesterol metabolism and bile acid synthesis, conjugation, and transport, resulting in ...


Acidic Ph Triggers Lipid Mixing Mediated By Lassa Virus Gp, Uriel Bulow, Ramesh Govindan, James B. Munro 2020 Tufts University

Acidic Ph Triggers Lipid Mixing Mediated By Lassa Virus Gp, Uriel Bulow, Ramesh Govindan, James B. Munro

Open Access Publications by UMMS Authors

Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever, a lethal disease endemic to Western Africa. LASV entry is mediated by the viral envelope glycoprotein (GP), a class I membrane fusogen and the sole viral surface antigen. Previous studies have identified components of the LASV entry pathway, including several cellular receptors and the requirement of endosomal acidification for infection. Here, we first demonstrate that incubation at a physiological temperature and pH consistent with the late endosome is sufficient to render pseudovirions, bearing LASV GP, non-infectious. Antibody binding indicates that this loss of infectivity is due to a conformational ...


Dgat1 Is A Lipid Metabolism Oncoprotein That Enables Cancer Cells To Accumulate Fatty Acid While Avoiding Lipotoxicity [Preprint], Daniel J. Wilcock, Melissa Kasheta, Craig J. Ceol 2020 University of Manchester

Dgat1 Is A Lipid Metabolism Oncoprotein That Enables Cancer Cells To Accumulate Fatty Acid While Avoiding Lipotoxicity [Preprint], Daniel J. Wilcock, Melissa Kasheta, Craig J. Ceol

University of Massachusetts Medical School Faculty Publications

Dysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone ...


Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis [Preprint], Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech 2020 University of Massachusetts Medical School

Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis [Preprint], Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4 ...


Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help ...


Are Dietary Fish Oil Supplements Appropriate For Dyslipidemia Management? A Review Of The Evidence, Samuel C. R. Sherratt, Michael Lero, R. Preston Mason 2020 Elucida Research LLC

Are Dietary Fish Oil Supplements Appropriate For Dyslipidemia Management? A Review Of The Evidence, Samuel C. R. Sherratt, Michael Lero, R. Preston Mason

Open Access Publications by UMMS Authors

PURPOSE OF REVIEW: The purpose of this review is to assess whether dietary fish oil supplements can be appropriate for patients with elevated triglycerides and cardiovascular risk based on a comprehensive analysis of their composition, and level of regulatory oversight.

RECENT FINDINGS: Approximately 19 million people in the United States take fish oil supplements, many for the purpose of treating or preventing heart disease. Unlike prescription products, fish oil supplements are classified as food by the Food and Drug Administration (FDA) and are not required to undergo manufacturing oversight or clinical testing. Analysis of widely used dietary fish oil supplements ...


Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech 2020 University of Massachusetts Medical School

Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech

Open Access Publications by UMMS Authors

BACKGROUND: The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance.

SCOPE OF REVIEW: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance ...


Serum Amyloid A Is Not Incorporated Into Hdl During Hdl Biogenesis, Ailing Ji, Xuebing Wang, Victoria P. Noffsinger, Drew Jennings, Maria C. de Beer, Frederick C. de Beer, Lisa R. Tannock, Nancy R. Webb 2020 University of Kentucky

Serum Amyloid A Is Not Incorporated Into Hdl During Hdl Biogenesis, Ailing Ji, Xuebing Wang, Victoria P. Noffsinger, Drew Jennings, Maria C. De Beer, Frederick C. De Beer, Lisa R. Tannock, Nancy R. Webb

Saha Cardiovascular Research Center Faculty Publications

Liver-derived serum amyloid A (SAA) is present in plasma where it is mainly associated with HDL and from which it is cleared more rapidly than are the other major HDL-associated apolipoproteins. Although evidence suggests that lipid-free and HDL-associated forms of SAA have different activities, the pathways by which SAA associates and disassociates with HDL are poorly understood. In this study, we investigated SAA lipidation by hepatocytes and how this lipidation relates to the formation of nascent HDL particles. We also examined hepatocyte-mediated clearance of lipid-free and HDL-associated SAA. We prepared hepatocytes from mice injected with lipopolysaccharide or an SAA-expressing adenoviral ...


Mtorc2-Akt Signaling To Atp-Citrate Lyase Drives Brown Adipogenesis And De Novo Lipogenesis, Camila Martinez Calejman, S. Trefely, S. W. Entwisle, Amelia K. Luciano, Su Myung. Jung, Wen-Yu Hsiao, A. Torres, C. M. Hung, H. Li, N. W. Snyder, J. Villen, K. E. Wellen, David A. Guertin 2020 University of Massachusetts Medical School

Mtorc2-Akt Signaling To Atp-Citrate Lyase Drives Brown Adipogenesis And De Novo Lipogenesis, Camila Martinez Calejman, S. Trefely, S. W. Entwisle, Amelia K. Luciano, Su Myung. Jung, Wen-Yu Hsiao, A. Torres, C. M. Hung, H. Li, N. W. Snyder, J. Villen, K. E. Wellen, David A. Guertin

Open Access Publications by UMMS Authors

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation ...


The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine 2020 Virginia Commonwealth University

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute ...


Does Enhancing Epidermal Barrier Function With Moisturizing Topical Products Improve Acne Vulgaris In Adult Patients Compared To Non-Moisturizing Products Or Non-Intervention?, Aziza Jadallah 2020 Arcadia University

Does Enhancing Epidermal Barrier Function With Moisturizing Topical Products Improve Acne Vulgaris In Adult Patients Compared To Non-Moisturizing Products Or Non-Intervention?, Aziza Jadallah

Capstone Showcase

Introduction: Acne is a common skin disorder with multifactorial causes that can persist beyond adolescence or appear for the first time in adulthood. Treatments of varying potency exist, ranging from over-the-counter face washes and creams to prescription topical and oral treatments. Current treatment guidelines target sebum production, exfoliation of excess skin cells, and the bacteria Propionibacterium acnes. Research as early as 1995 suggests dysfunctions of the skin barrier, such as abnormal ceramide levels and increased water loss, play a role in the pathophysiology of acne and are not addressed by current treatments. This review analyzes the role of moisturizing products ...


Influence Of Single And Multiple Histidine Residues And Their Ionization Properties On Transmembrane Helix Dynamics, Orientations And Fraying, Fahmida Afrose 2019 University of Arkansas, Fayetteville

Influence Of Single And Multiple Histidine Residues And Their Ionization Properties On Transmembrane Helix Dynamics, Orientations And Fraying, Fahmida Afrose

Theses and Dissertations

Since aromatic and charged residues are often present in various locations of transmembrane helices of integral membrane proteins, their impacts on the molecular properties of transmembrane proteins and their interactions with lipids are of particular interest in many studies. In this work, I used solid-state deuterium NMR spectroscopy in designed model peptide GWALP23 [GGALW(LA)6LWLAGA] with selective deuterium labels to addresses the pH dependence and influence of single and multiple “guest” histidine residues in the orientation and dynamic behaviors of transmembrane proteins. The mutations include Gly to His (G2/22 to H2/22), Trp to His (W5/19 to ...


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