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Articles 61 - 90 of 1022
Full-Text Articles in Medical Sciences
Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang
Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang
All ETDs from UAB
Understanding the molecular features underlying cancer health differences is crucial for developing effective therapeutic strategies. Multi-omics data analysis, integrating various molecular layers such as genomics, transcriptomics, epigenomics, proteomics, and metabolomics, provides a comprehensive approach to characterize the molecular landscape of cancer differences. By integrating diverse omics data, researchers can identify genetic variations, gene expression patterns, epigenetic modifications, and protein alterations that contribute to differences in cancer progression, and treatment response. These molecular features can serve as potential biomarkers for predicting patient outcomes and guiding personalized treatment strategies. Furthermore, multi-omics data analysis enables the identification of molecular subtypes specific to different …
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
All ETDs from UAB
In the United States, acute kidney injury (AKI) affects nearly 20% of all intensive care unit patients. Additionally, over a third of Americans aged 50 or older suffer from stage 3 chronic kidney disease (CKD) or higher. AKI and CKD are encompassing terms for many etiologies and pathological processes that affect different regions of the kidney but converge at tissue inflammation and fibrosis. Macrophages perform vital homeostatic functions and can initiate or ameliorate inflammation and fibrosis. As the largest component of the kidney immune system, kidney resident macrophages (KRMs) have been implicated in both disease propagation and mitigation, yet the …
Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher
Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher
All ETDs from UAB
Only ten percent of drugs in clinical trials are ultimately approved by the Food and Drug Administration (FDA). With many diseases and disorders needing therapeutic options, computational drug repurposing methodologies are great alternatives to some drug discovery methods due to quicker FDA approval and lower cost. We sought to gain insights to improve the identification of drug repurposing candidates that will be safe and effective to increase the success of computational drug repurposing approaches. In regards to identifying safe drug candidates, pharmacovigilance studies of adverse event case reports identified that women are more likely to experience an adverse event, and …
Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico
Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico
All ETDs from UAB
RNA binding proteins (RBPs) are critical regulators of gene expression as they are responsible for the chaperoning and processing of every nascent RNA transcript. Many studies have investigated mechanisms of specificity of RBP function and have identified factors such as cell-specific expression of RBPs and differential preferences for RNA secondary structure. However, RBPs are often multi-domain proteins that contain repeats of various RNA binding domains (e.g., RNA recognition motif) and little work in the genomic era of transcriptomic interrogation has been done to define the contribution of individual domains to the overall protein function. Polypyrimidine tract binding protein 1 (PTBP1) …
Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle
Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle
All ETDs from UAB
Frontotemporal dementia (FTD) is a leading cause of early-onset dementia and has a significant socioeconomic burden due to difficulties in diagnosis and delay to diagnosis. FTD is a clinically, pathologically, and genetically heterogeneous disorder. The pathological changes associated with FTD are termed frontotemporal lobar degeneration (FTLD). Protein aggregates are always present in FTLD, with >90% of cases presenting with either TDP-43 or tau pathology. Most cases of FTD are sporadic, but familial cases account for up to 25% of FTD. All familial FTD is inherited in an autosomal dominant fashion with most cases being caused by mutations in tau (MAPT), …
Investigation Into The Structure And Function Of Tyrosyl-Dna Phosphodiesterase I'S N-Terminal Domain, Evan J. Brettrager
Investigation Into The Structure And Function Of Tyrosyl-Dna Phosphodiesterase I'S N-Terminal Domain, Evan J. Brettrager
All ETDs from UAB
Tyrosyl-DNA phosphodiesterase I (Tdp1) is a eukaryotic DNA repair enzyme that removes adducts from DNA ends via hydrolysis of a phosphodiester bond. These adducts consist of damaged nucleotides or trapped protein-DNA complexes. Tdp1 hydrolyzes the phosphodiester bond utilizing two catalytic histidines and forming a Tdp1-DNA covalent intermediate. Mutations of these catalytic histidines have been shown to increase the stability of the Tdp1-DNA covalent intermediate and cause Topoisomerase I dependent toxicity in cells. We use these toxic Tdp1 mutant enzymes to study the function of Tdp1’s N-terminal domain (NTD). Full-length Tdp1 has proven difficult to purify due to degradation of the …
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
All ETDs from UAB
During the process of malignant transformation, cells have striking changes in their cell surface glycosylation. One of these changes is an enrichment for α2,6 sialic acid which is added by the sialyltransferase, ST6GAL1. ST6GAL1 is upregulated in numerous malignancies and acts by adding an α2,6 sialic acid onto receptors bound for the plasma membrane. This sialic acid, in turn, modulates the activity of the receptor by regulating conformation, clustering, and cell surface retention. The work presented in this dissertation focuses on how ST6GAL1-mediated sialylation of a specific cell surface receptor, epidermal growth factor receptor (EGFR), regulates many of its properties. …
Macrophage Ipla2ss-Derived Lipid Signaling Contributes To Type 1 Diabetes Development, Abdulaziz Saad Almutairi
Macrophage Ipla2ss-Derived Lipid Signaling Contributes To Type 1 Diabetes Development, Abdulaziz Saad Almutairi
All ETDs from UAB
Type 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-secreting pancreatic β-cells that leads to hyperglycemia; however, the mechanism of β-cells destruction remains elusive. Ca2+-independent phospholipase A2β (iPLA2β), which hydrolyzes membrane phospholipids at the sn-2 position and releases bioactive lipids, modulates polarization of macrophages (M ). Data from our lab suggests that selective iPLA2β-derived lipid signals (iDLs) (i.e., PGs, HETEs, DHETs, LTB4) produced by M from spontaneous-T1D prone nonobese diabetic mice (NOD) are high during the pre-diabetic phase. However, the impact of macrophage-derived iDLs in T1D remains unclear. Therefore, we generated a NOD mouse model with …
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
All ETDs from UAB
Streptococcus parasanguinis is an oral commensal bacterium that produces hydrogen peroxide. Hydrogen peroxide can react with endogenous molecules such as nitrite to form reactive nitrogen intermediates (RNI). These S. parasanguinis-mediated RNI have been shown to inhibit oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Aggregatibacter actinomycetemcomitans. As such, S. parasanguinis plays a protective role in the oral microbial ecosystem by antagonizing and preventing colonization by oral pathogens. In addition to being an important organism for the health of the oral cavity, S. parasanguinis has also been associated with improved outcomes for people with cystic fibrosis. There are two explanations …
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
All ETDs from UAB
Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …
Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano
Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano
All ETDs from UAB
The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays a critical role in nervous system processes. This includes the maintenance of cellular homeostasis in neurons (1). It also includes synaptic efficacy and plasticity as well as protein turnover, presynaptic vesicle transport, and neuronal protesostasis. Proteasome function is impaired as a consequence of aging, which is aggravated by conditions like Alzheimer's Disease and Related-Dementias (AD, ADRD) (2). According to earlier work from our lab the proteasome is critical to how quickly AD progresses. In Drosophila, human cells, and …
Molecular Determinants Of Retroviral Gag Targeting To The Plasma Membrane For Assembly, Dominik Herrmann
Molecular Determinants Of Retroviral Gag Targeting To The Plasma Membrane For Assembly, Dominik Herrmann
All ETDs from UAB
Human T-cell leukemia virus 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. Several serious diseases have been linked to HTLV-1 infection, such as Adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Between 10-20 million people are infected with HTLV-1 making it a major cause of morbidity and mortality worldwide. A comprehensive understanding of the factors that govern retroviral replication precludes the development of efficient antiretroviral therapies (ARTs). In the example of HIV-1, atomic level structural data was paramount to developing and improving upon many of the ARTs used today, underscoring the need for structure …
Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir
Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir
All ETDs from UAB
Inflammatory bowel disease (IBD) results from the interplay of genetic susceptibility, environmental influences, the microbiota, and aberrant immune responses. Despite the fact that over 200 genetic susceptibility loci have been identified, the genetic contribution to disease onset is believed to be less than 50%. Environmental factors have arisen as key drivers of disease. Early life stress (ELS) is an understudied environmental trigger linked to IBD susceptibility. Utilizing 2 separate models of ELS, we show that ELS results in diminished colonic corticosterone and prolonged intestinal inflammation upon colitogenic insult. ELS-exposed animals consistently demonstrated high levels of colonic Tnf, concurrently with decreased …
Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter
Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter
All ETDs from UAB
Gout is a common inflammatory arthritis that is increasing in prevalence globally. It has clear sex differences, being more common among men, though comorbidities appear to be more common among women. It also varies in prevalence between populations, driven by a combination of genetic and socioeconomic factors. Genetic studies have identified gout-associated genetic variants, several of which are shared between different populations. Here, I combined gout-associated genetic variants into a gout polygenic risk score. This score was then used to elucidate the genetic underpinning of gout severity and presence of comorbidities, comparing its effects in different sexes and populations. I …
Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress
Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress
All ETDs from UAB
Neurological injuries occur in epidemic proportions worldwide. Neuronal injuries are events resulting in damage to the central nervous system (CNS) that impair neurological function. Subsequent impairments in neuronal function can be rapid, existing immediately after injury, or progressive and chronic impairments that persist for the lifetime of the survivor. CNS injury constitutes a broad class of environmental and pathophysiological insults ranging from blunt-force trauma to the brain or spinal cord, to acute ischemic and hemorrhagic strokes, and insults resultant from neurotoxic agents. While divergent in initial cause, many of these insults share underlying pathophysiological outcomes including excitotoxic cell signaling, neuroinflammation, …
Molecular Mechanisms Of Amphetamine Abuse, Samuel James Mabry
Molecular Mechanisms Of Amphetamine Abuse, Samuel James Mabry
All ETDs from UAB
Amphetamine (AMPH), a psychostimulant commonly prescribed for the treatment of neuropsychiatric and neurological disorders, has a high liability for abuse. The stimulant properties of AMPH are primarily associated with its ability to increase dopamine (DA) neurotransmission. This increase is mediated by non-vesicular DA release (DA efflux). This DA efflux is the result of the reversal of the DA transporter (DAT), which is promoted by AMPH. Syntaxin 1 (Stx1), a SNARE protein, interacts with the DAT N-terminus. Stx1 is phosphorylated at Ser14 by casein kinase II (CK2). This phosphorylation site contributes to the DAT/Stx1 interaction and is critical for allowing DAT …
Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme
Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme
All ETDs from UAB
Breast cancer is one of the most common and deadly cancers diagnosed in women each year. The HER2-positive subtype of breast cancer is associated with poor prognosis and lower progression-free survival. Early identification of HER2 expression is extremely important for the effective treatment of the disease. Current methods to diagnose HER2-positive breast cancer involve invasive biopsies to semi-quantitatively determine the amount of HER2 expression. However, many lesions are often unavailable for biopsy due to their location and there may be variable HER2 expression between the primary tumor and metastasis. Positron emission tomography (PET) can give a full-body, non-invasive evaluation of …
Investigating Regulatory Mechanisms Of Transcription By Rna Polymerase I, Abigail Kate Huffines
Investigating Regulatory Mechanisms Of Transcription By Rna Polymerase I, Abigail Kate Huffines
All ETDs from UAB
There are at least three eukaryotic RNA polymerases (Pols), Pols I, II, and III. These Pols are essential for transcription, where RNA is synthesized from various DNA templates. While transcription has been well-studied for decades, there are still many questions that remain unanswered about how this process is regulated for each of the three Pols. Transcription is highly regulated and complex, therefore, many different mechanisms exist to tightly control it in the cell. Some of these mechanisms include regulation by transcription factors and co-transcriptional RNA processing. While these regulatory mechanisms are of great interest, they have not yet been fully …
Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs
Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs
All ETDs from UAB
In contrast to Bacteria and Archaea that express a single DNA-dependent RNA polymerase (RNAP), eukaryotes express at least three structurally distinct, nuclear, DNA-dependent RNA polymerases (Pols I, II, and III) that are responsible for synthesizing all the genome-encoded RNA required by the cell. Despite the discovery of the Pols over 50 years ago, there remains a knowledge gap concerning their enzymatic properties. Over the course of evolution, we know that Pols I, II, and III have diverged in structure and function. They share a 10-subunit core and are each responsible for transcribing unique genetic loci. What remains to be understood …
Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly
Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly
All ETDs from UAB
Neutrophils, the most abundant type of circulating leukocyte, represent a heterogeneous population with distinct roles in immune regulation and disease pathogenesis. A major obstacle to our understanding of neutrophil biology is that neutrophils are readily activated during preparation. The lack of standardized methodology for neutrophil characterization makes the comparison of results across studies challenging. Here we provide a careful comparison of eight characterization methods and present a novel, optimized protocol for the characterization of whole blood neutrophils minimizing activationinduced phenotypic alterations during processing. Despite successful virological control, HIV-1-infected individuals maintain an increased risk of life-threatening comorbidities including liver, cardiovascular, and …
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
All ETDs from UAB
The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint …
Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews
Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews
All ETDs from UAB
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen with a staggering potential for multi-drug resistance. Because of this, the Centers for Disease Control and Prevention and the World Health Organization monitor the spread of MRSA and encourage antibiotic development efforts targeting this pathogen. Despite this, few antibiotics have been developed and brought to market in recent decades. To continue treating infections caused by this organism, we must identify novel antibiotic molecules with different mechanisms of action from known antibiotics. Bacterial copper-dependent inhibitors (CDIs), molecules that become antibacterial in the presence of copper (Cu), have been studied as a novel …
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
All ETDs from UAB
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global morbidity and mortality since late 2019. Many infections result in self-limited disease and recovery in 1-2 weeks. However, a subset of individuals experience more severe illness, associated with hospitalization, ventilation, and potential mortality. HIV infection is a proposed risk factor for more severe illness due to people living with HIV (PLWH) experiencing chronic immune activation and inflammation despite effective antiretroviral therapy. While there is supporting evidence showing worsened clinical outcomes in PLWH experiencing acute COVID-19, the immune response driving these outcomes is less explored. We analyzed markers of immune activation …
Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis
All ETDs from UAB
RNA Polymerases are the molecular machines responsible for the synthesis of RNA from the DNA template. The presence of these machines is an absolute requirement for the function and replication of all cellular organisms. In eukaryotic organisms, there are a minimum of three RNA polymerases (Pols I, II, II). Despite shared subunits and homology, these three protein complexes are functionally distinct, with many unique sub-units and additional trans-acting factors. Pol I is responsible for the synthesis of three of the four ribosomal RNA species which is the first and rate limiting step of ribosome biogenesis. Pol I synthesizes the majority …
Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka
Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka
All ETDs from UAB
Opioid-related overdose deaths have increased drastically in the past three decades, and especially since the beginning of the COVID-19 pandemic, due to the addictive, analgesic, and euphoric properties of the drugs. To produce these effects, opioids bind to the mu opioid receptor (MOR) in GABAergic neurons. The MOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Previous studies of Oprm1 knockdown in medium spiny neurons (MSNs) of the mouse NAc have shown that these neuronal populations are involved in reinforcing reward-context pairing as well …
Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier
Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier
All ETDs from UAB
A broad spectrum of human birth defects arise from the disruption of morphogenesis, the critical process through which tissues and organs acquire their proper shape. Convergent extension (CE) is a universal morphogenetic engine that promotes polarized extension of diverse tissues and organs by regulating directional cell behavior, such as oriented cell intercalation. In vertebrates, CE is regulated by non-canonical Wnt/Planar Cell Polarity (PCP) pathway, an ancient signaling pathway that was originally discovered to coordinate the cellular polarity in the plane of the epithelium. Non-canonical Wnt/PCP signaling shares the Frizzled (Fz) receptor and cytoplasmic signal transducer Dishevelled (Dvl) with the canonical …
Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz
Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz
All ETDs from UAB
T follicular helper (Tfh) cells constitute a distinct subset of CD4 T cells that reside within B cell follicles, playing an indispensable role in orchestrating the Germinal Center (GC) response. In response to polarizing environments, such as Influenza A virus infection (IAV), Tfh cells secrete effector cytokines, including IFN-γ and IL-4. Nevertheless, the specific functions of cytokine-producing Tfh cell subsets, beyond their involvement in driving class switch recombination (CSR), remain largely unexplored. Here, we demonstrate that, following IAV infection, Tfh cell cytokine production undergoes a dynamic shift, transitioning from early IFN-γ dominance to later predominance of IL-4. The initial IFN-γ …
Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine Benjamin
Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine Benjamin
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Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. …
Novel Role For St6gal1 Sialyltransferase As A Tumor Driver In Pancreatic Ductal Adenocarcinoma, Nikita Umakant Bhalerao
Novel Role For St6gal1 Sialyltransferase As A Tumor Driver In Pancreatic Ductal Adenocarcinoma, Nikita Umakant Bhalerao
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ST6Gal1 sialyltransferase adds negatively charged sialic acid in an α2,6 linkage to N-glycans on glycoproteins bound for the cell surface/secretion thus altering receptor structure, function and downstream signaling pathways. ST6Gal1 is upregulated in multiple cancers, including pancreatic, and imparts cancer stem cell-like phenotype. Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a survival rate of ~10%. Acinar to ductal metaplasia (ADM), the tumor initiation stage of PDAC, occurs in response to insults like pancreatitis, when acinar cells dedifferentiate and form ductal-like cells with stem and ductal gene upregulation. These cells, on acquiring mutations such as in KRAS gene, can …
Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin
Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin
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Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …