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Articles 1 - 30 of 88
Full-Text Articles in Molecular Biology
Development Of Novel Small Molecule Therapeutics For Myotonic Dystrophy, Xhesika Azis
Development Of Novel Small Molecule Therapeutics For Myotonic Dystrophy, Xhesika Azis
Biological Sciences
Myotonic Dystrophy type 1 (DM1) results from expanded CUG repeat RNA that sequesters MBNL proteins and disrupts alternative splicing. Small molecules that bind toxic repeat RNA and release MBNL proteins represent a promising therapeutic strategy. This thesis examines newly synthesized modified polycyclic compounds (MPCs) engineered to target CUG RNA with enhanced specificity and efficacy. Through Suzuki–Miyaura coupling and benzoquinone-mediated cyclization, MPC03 was synthesized and characterized by NMR and LC–MS.
The biological activity of these compounds was assessed in DM1 patient-derived myotubes and fibroblasts. MPC03 consistently produced dose-dependent rescue of multiple MBNL-regulated exons, restoring splicing patterns toward those observed in healthy …
Technological Development Of In-Cell Nmr: Microfluidic, Metabolomic, And Fluxomic Approaches, Nicholas Sciolino
Technological Development Of In-Cell Nmr: Microfluidic, Metabolomic, And Fluxomic Approaches, Nicholas Sciolino
Electronic Theses & Dissertations (2024 - present)
In the fields of structural biology, metabolomics, and fluxomics, there is a driving, technique-based concern when it comes to high-resolution spectrometry and its marriage to biological and physiological relevance. Sample preparation often involves cellular perturbation, lysate separation schemes, combinations with non-biological reagents, and timeline slack. Conceptually, the farther we get from the cell, the greater the potential disparity between what exists in vivo and our in vitro manipulations. This is particularly true when seeking to collect data on transfected targets of interest, and on sensitive metabolic equilibria that occur on the order of minutes. The question remains: if we are …
Characterization Of Adaptive Quorum Sensing In Pseudomonas Aeruginosa, Kayla Simanek
Characterization Of Adaptive Quorum Sensing In Pseudomonas Aeruginosa, Kayla Simanek
Electronic Theses & Dissertations (2024 - present)
Pseudomonas aeruginosa is an opportunistic pathogen that is highly antibiotic resistant and causes tens of thousands of infections each year. It persists in hospitals by forming biofilms on medical equipment like ventilators and catheters, making it difficult to eradicate. Biofilm formation, among other virulence factors of P. aeruginosa, is regulated through quorum sensing, a mechanism of bacterial communication. Quorum sensing is primarily coordinated through LuxI-R type systems comprised of an autoinducer synthase and receptor, respectively. Canonically, the first system to be expressed is LasI-R, and LasR upregulates the second arm of the quorum sensing network, the RhlI-R system. Research …
Conserved A-Rich Regions In The 3’ Utr Of Zika Virus Differentially Affect Viral Gene Expression, Kristen Kaytes
Conserved A-Rich Regions In The 3’ Utr Of Zika Virus Differentially Affect Viral Gene Expression, Kristen Kaytes
Electronic Theses & Dissertations (2024 - present)
Following its discovery in 1947, Zika virus garnered little attention in the global stage until a rapidly spreading epidemic brough the virus to the global stage in 2015. Continuous advances in research have begun to further the understanding of the molecular biology of Zika virus, however much is still unknown. Much of our understanding of the virus comes from cross reference to other viruses within the same family, such as Dengue virus and West Nile virus. A commonality of these viruses is that they resemble cellular mRNAs and have a single-stranded positive-sense RNA genome that contains a 5’-cap but lacks …
Investigating Rna Dysfunction Of Inherited Neuromuscular And Neurodevelopmental Disease, Jacob H. Schroader
Investigating Rna Dysfunction Of Inherited Neuromuscular And Neurodevelopmental Disease, Jacob H. Schroader
Electronic Theses & Dissertations (2024 - present)
ITPase deficiency is a rare but fatal, autosomal recessive enzyme deficiency involving encephalopathy, microcephaly, congenital cataracts, hypotonia, developmental delay, and dilated cardiomyopathy. Within a decade since the original description of the severe form in humans, there are huge gaps in the field regarding the underlying molecular mechanisms driving pathogenesis resulting from ITPase deficiency. Past studies have focused on characterization of the organism level ITPase-deficient phenotype, but the molecular and cellular characterization remains to be fully described. Due to the biochemical function and established biological role of the ITPase enzyme, investigation into the consequences of inosine accumulation and misincorporation into RNA …
Identifying Novel Therapeutics And Modifiers Of Myotonic Dystrophy Type 1, Jesus Alberto Frias
Identifying Novel Therapeutics And Modifiers Of Myotonic Dystrophy Type 1, Jesus Alberto Frias
Legacy Theses & Dissertations (2009 - 2024)
The expansion of microsatellite repeats within the human genome has been identified as the cause of numerous hereditary diseases, including myotonic dystrophy (DM). DM is an autosomal dominant disease with a worldwide prevalence of ~1:8000 individuals. DM presents multisystemic symptoms such as myotonia, cardiac conduction defects, muscle wasting and weakness, insulin resistance, and cataracts. There are two genetically distinct, yet clinically similar types of DM: DM type 1 (DM1), caused by CTG repeat expansions in the 3’ UTR of the dystrophia myotonica protein kinase (DMPK) gene and DM type 2 (DM2), resulting from CCTG repeat expansions in the first intron …
Identification Of Genes Conferring Resistance To 2-Amino-3-Methylimidazo [4,5-F] Quinoline Genotoxicity In Budding Yeast Using High-Throughput And Targeted Approaches, Michael J. Dolan
Legacy Theses & Dissertations (2009 - 2024)
Heterocyclic aromatic amines (HAAs) are potent carcinogenic agents found in charred read meat and cigarette smoke. We hypothesize that HAAs may contribute to red meat being a risk factor for colorectal cancer (CRC). At present, few eukaryotic genes conferring resistance to HAAs have been identified. In this research, the genome of Saccharomyces cerevisiae (budding yeast) was profiled using next-generation sequencing to identify genes conferring resistance to one such HAA, 2-amino-3-methylimidazo[4,5-f] quinoline (IQ).CYP1A2 and NAT2 activate IQ to become a mutagenic nitrenium compound. Deletion libraries expressing human CYP1A2 and NAT2 or no human genes were exposed to either 400 or 800 …
Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion
Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion
Legacy Theses & Dissertations (2009 - 2024)
The main purpose of pharmaceutical production is to produce safe effective medicine for patient use. In an effort to ensure patient safety constant surveillance for viruses takes place. The detection of a viral nucleic acid in a pharmaceutical production setting results in investigations to assess its infectious potential. This is an intensive, expensive process that entails many tests such as the observation of hemadsorption, cytopathic effects (CPE), and more. These tests are typically specific and only capture certain viruses, as factors like CPE can only be observed in some viral species. A new investigational method that is effective on all …
Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery
Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery
Legacy Theses & Dissertations (2009 - 2024)
Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …
N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado
N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado
Legacy Theses & Dissertations (2009 - 2024)
Myogenesis involves skeletal muscle stem cells (MuSCs) that produce and regenerate skeletal muscle during regular growth and repair. However, when this system fails to function normally, it can lead to musculoskeletal diseases like Duchenne Muscular Dystrophy (DMD). Therefore, it is important to study the molecular mechanisms behind this developmental process in order to seek therapies and solutions for these types of diseases. Our interest lies in the field of epitranscriptomics, which focuses on post-transcriptional ribonucleic acid (RNA) modifications, particularly N6-methyladenosine (m6A), which involves the addition of a methyl group to the adenosine nucleotide, a process that is mediated by the …
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Legacy Theses & Dissertations (2009 - 2024)
The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …
Inhibition Of Lysine Acetyltransferases Kat 3a/3b And Its Effect On Poliovirus Proliferation, Eduards Norkvests
Inhibition Of Lysine Acetyltransferases Kat 3a/3b And Its Effect On Poliovirus Proliferation, Eduards Norkvests
Legacy Theses & Dissertations (2009 - 2024)
Ribosomes have been traditionally viewed as invariable machinery, but in recent years more and more evidence for their heterogeneity has emerged. Core ribosomal proteins, ribosomal-associated proteins, and post-translational modifications all contribute to the variations found within these crucial subcellular components.In our research, we focused on lysine acetylation – a post translational modification found on many ribosomal proteins. We used a chemical inhibitor of acetyltransferases KAT 3A and KAT 3B to observe the effect that inhibiting acetylation may have in the context of translation. By using poliovirus to shut off conventional cellular translation, we were able to look at a narrow …
Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa
Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa
Legacy Theses & Dissertations (2009 - 2024)
Organogenesis is the process organs go through where cellular communications coordinate all a developing organ needs. What organs need are more cells, in the right place, doing the right job. In the salivary gland, we know that stromal cells are important for organogenesis and that they coordinate the epithelium’s form and functions. However, specific stromal contributions have focused on epithelial quantity and placement. There is less information about how the stroma directs the epithelium towards certain functions. Here we used organoids as a model for understanding what stromal signaling directs epithelial cell fate. We found that stromal cell state is …
Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian
Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian
Legacy Theses & Dissertations (2009 - 2024)
Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …
Modulation Of Rho Termination : Expectation Vs Reality, Kavya Sri Sai Chegireddy
Modulation Of Rho Termination : Expectation Vs Reality, Kavya Sri Sai Chegireddy
Legacy Theses & Dissertations (2009 - 2024)
Transcription termination factor Rho is an essential protein in many bacteria. Rho is an ATP-dependent RNA helicase that accounts for 20-50% of termination events in Escherichia coli and plays an important role in preventing pervasive transcription that otherwise might be lethal to bacteria. Rho termination usually occurs in the 3’ UTRs and non-coding regions of the DNA, and the actively transcribing RNA is believed to be protected by translating ribosomes from Rho termination since both transcription and translation are a simultaneous process in prokaryotes. However, in reality, Rho terminates transcription of some protein-coding genes, and fails to terminate transcription of …
Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena
Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena
Legacy Theses & Dissertations (2009 - 2024)
Mycobacterium abscessus (Mab), a non-tuberculous environmental mycobacterium is one of the emerging pathogens. The number of Mab infections has doubled in the past decade. It is also an opportunistic pathogen usually infecting immunocompromised individuals and causing numerous skin and soft tissue infections. It commonly causes lung infections in people who are already infected with one or other lung infections such as tuberculosis. The treatment of Mab infections is difficult because of its intrinsic resistance to most of the antibiotics available. This project studies Rifampicin (RIF) resistance in Mab, as RIF is a well-established treatment for other mycobacterial infections including tuberculosis, …
Host Factors Affecting Group Ii Intron Retrotransposition, Justin Michael Waldern
Host Factors Affecting Group Ii Intron Retrotransposition, Justin Michael Waldern
Legacy Theses & Dissertations (2009 - 2024)
Group II introns are self-splicing mobile elements that are thought to be the evolutionary ancestors of eukaryotic retrotransposons, the spliceosome, and spliceosomal introns. Yet, little is known about how group II introns have coevolved within their native hosts or about the corresponding host biology.Using the Ll.LtrB intron in its native host, Lactococcus lactis, I first sought to identify host factors that influence retrotransposition. Since retrotransposition can be costly to the host organism, group II introns must achieve a delicate balance between self-proliferation and host preservation. By utilizing the native host organism, my goal was to unearth retrotransposition-related mechanisms that have …
Retrotransposon-Mediated Transduction Of An Environmental Cue To Regulate Centrosome Fate, Shawn Patrick Murphy
Retrotransposon-Mediated Transduction Of An Environmental Cue To Regulate Centrosome Fate, Shawn Patrick Murphy
Legacy Theses & Dissertations (2009 - 2024)
In 1969, the enrichment of mobile element repeat sequences led Britton and Davidson to propose the hypothesis that gene expression in higher eukaryotes is regulated through the exaptation of mobile elements. In this work, I have explored the hypothesis that mobile elements can also be harnessed by the host to regulate asymmetric cell division, thereby determining cell fate. Retrotransposons are ubiquitous eukaryotic mobile elements that transpose through an RNA intermediate. They are often active in cell types that divide asymmetrically to yield daughter cells with different fates, such as embryonic stem cells, germline stem cells, neuronal stem cells and the …
The Phosphodiesterase, Rv0805, Is An Unheralded Component Of Tb Complex Mycobacterial Physiology In And Beyond Camp Homeostasis, James R. Mcdowell
The Phosphodiesterase, Rv0805, Is An Unheralded Component Of Tb Complex Mycobacterial Physiology In And Beyond Camp Homeostasis, James R. Mcdowell
Legacy Theses & Dissertations (2009 - 2024)
Phosphodiesterases (PDEs) are integral components of 3’,5’-cyclic adenosine monophosphate (cAMP) signaling pathways by degrading cAMP to modulate the concentration, duration, and localization of the cAMP signal which maintains the specificity of cAMP pathways. The human pathogen, Mycobacterium tuberculosis (Mtb) has a unique cAMP network architecture with at least 15 adenylyl cyclases (ACs) that generate cAMP, but only one characterized PDE, Rv0805, which is found exclusively in pathogenic mycobacteria. Rv0805 can influence Mtb cAMP levels but the absence of Rv0805 orthologs in non-pathogenic mycobacteria and apparent separation of Rv0805 from cAMP directed roles led to numerous questions surrounding PDE function in …
Identification Of Ires Activity In Cellular Mrnas And Viral Rna Using A Circular Rna Construct, Priyanka Sehta
Identification Of Ires Activity In Cellular Mrnas And Viral Rna Using A Circular Rna Construct, Priyanka Sehta
Legacy Theses & Dissertations (2009 - 2024)
Translation initiation is a critical step in the process of protein synthesis. The canonical way of translation initiation involves ribosomes being recruited to the 7-methyl guanosine cap present at the 5’end of the untranslated region (5’ UTR) of the RNAs. However, viral RNAs and some cellular mRNAs lack this 5’ cap structure and thus deploy an alternate non-canonical translation initiation mechanism. In non-canonical translation initiation, ribosome recruitment is facilitated by the RNA secondary structures called Internal Ribosome Entry Site (IRES) present most often in the 5’ UTR. To measure IRES-mediated translation, the dual luciferase assay has been the gold standard. …
Role Of Rna Helicases In The Drosophila Germline, Patrick Blatt
Role Of Rna Helicases In The Drosophila Germline, Patrick Blatt
Legacy Theses & Dissertations (2009 - 2024)
Gametogenesis, the process of creating egg or sperm, is required for launching successive generations of sexually reproducing organisms. The developmental milestones that occur during gamete production have been studied for decades and are of critical interest to gain insight to conserved features of human fertility. Drosophila has been used for over a century as an efficient research model and remains pivotal in uncovering fundamental biological paradigms. During Drosophila egg production, or oogenesis, several developmental transitions must be traversed to ensure completion of oogenesis including: Germline Stem Cell (GSC) maintenance and differentiation, mitotic and meiotic cell divisions, and production of maternally …
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Legacy Theses & Dissertations (2009 - 2024)
The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Legacy Theses & Dissertations (2009 - 2024)
The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …
The Stromal Response In Salivary Gland Injury, Kevin O'Keefe
The Stromal Response In Salivary Gland Injury, Kevin O'Keefe
Legacy Theses & Dissertations (2009 - 2024)
Abstract
Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy
Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy
Legacy Theses & Dissertations (2009 - 2024)
Germ cells give rise to gametes and link generations by passing genetic information from parent to offspring. Gametes arise from, in many sexually reproducing organisms, germline stem cells (GSCs) which are set aside early during development. GSCs have an amazing capacity to undergo self-renewal to give rise to a pool of undifferentiated cells, while also differentiating to generate specialized germ cells such as haploid gametes. Upon female GSC differentiation, mitotically dividing germ cells can initiate meiosis, and mature within a follicle. During maturation, the specified oocyte is provided with a trust fund of RNAs and proteins for the next generation …
Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau
Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau
Legacy Theses & Dissertations (2009 - 2024)
Diabetes is a global health epidemic that can be devastating to those afflicted,
The Guardian Of The Genome : Regulation Of The Enhancer Networks Governing The P53-Mediated Stress Response, Allison Catizone
The Guardian Of The Genome : Regulation Of The Enhancer Networks Governing The P53-Mediated Stress Response, Allison Catizone
Legacy Theses & Dissertations (2009 - 2024)
After fertilization in vertebrates, cells work to build organs, tissues and begin to rapidly differentiate and proliferate. This process is the orchestration of finely tuned signals and perfectly timed gene expression patterns. The first step in gene expression, transcription, is governed by proteins known as transcription factors (TF). TFs are responsible for binding to DNA, altering chromatin structure, and driving activation of other genes based on the organism’s needs. Once the process of development is complete, organisms shift their resources to maintaining homeostasis. Humans regularly encounter outside stressors such as UV radiation, pollution, allergens, and drugs. Cells also accumulate mutations …
Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller
Regulation Of Gene Expression Through Ribosome-Associated Proteins, Clare Margaret Miller
Legacy Theses & Dissertations (2009 - 2024)
Translation is a crucial mechanism for generating proteins to carry out cellular processes and for ensuring proper cell functions. Ribosomes are at the center of translation and are complex pieces of machinery. They consist of at least 80 core eukaryotic ribosomal proteins, which are conserved from prokaryotes, and four ribosomal RNAs (rRNAs): 18S, 28S, 5,8A 5S. In addition, numerous translation factors aid the ribosome in protein production. While ribosomes are typically described by these core features, they are known to exist in a heterogenous pool with variations in protein composition, modifications of rRNA, and an assortment of non-ribosomal proteins that …
The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer
The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer
Legacy Theses & Dissertations (2009 - 2024)
Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …
Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama
Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama
Biological Sciences
Hypoglycemia is a state of abnormally low blood glucose. Many patients who use insulin, primarily for the treatment of diabetes, experience multiple bouts of hypoglycemia, termed recurrent hypoglycemia (RH). Because RH impairs cognitive function and ability to appropriately respond to a subsequent episode of hypoglycemia, it is critical to develop treatments. One approach, which we have taken here, is to attempt to preserve neuronal fuel supply during a hypoglycemic episode. Medium-chain triglycerides are medium-chain fatty acid (MCT) esters of glycerol that can provide an alternative fuel source to the brain via ketones; the hippocampus is known to express transporters for …