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Articles 1 - 30 of 189

Full-Text Articles in Molecular Biology

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff Nov 2023

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff

Doctoral Dissertations

The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …

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Combining Simulation And The Mspa Nanopore To Study P53 Dynamics And Interactions, Samantha A. Schultz Nov 2023

Combining Simulation And The Mspa Nanopore To Study P53 Dynamics And Interactions, Samantha A. Schultz

Masters Theses

p53 is a transcription factor and an important tumor suppressor protein that becomes activated due to DNA damage. Because of its role as a tumor suppressor, mutations in the gene that encodes it are found in over 50% of human cancers. The N-terminal transactivation domain (NTAD) of p53 is intrinsically disordered and modulates the function and interactions of p53 in the cell. Its disordered structure allows it to be controlled closely by post-translation modifications that regulate p53’s ability to bind DNA and interact with regulatory binding partners. p53 is an attractive target for developing cancer therapeutics, but its intrinsically disordered …

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A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr. Aug 2023

A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr.

Doctoral Dissertations

During viral infection, virus and host clash for control of the cell in a conflict that ultimately drives the evolution of both sides and has lasting consequences in the form of pathogenesis. At the heart of this struggle is a contest for control of cellular gene expression, a struggle epitomized by an evolutionary tug-of-war for supremacy over RNA fate. During lytic replication, Kaposi’s sarcoma-associated herpesvirus (KSHV) triggers a massive RNA decay event known as viral “Host Shutoff” which decimates greater than 70% of the host transcriptome, simultaneously suppressing the cellular anti-viral response and freeing host resources for viral replication. However, …

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Modulation Of Plant Immunity During The Establishment Of The Nitrogen-Fixing Symbiosis, Miriam Hernandez-Romero Apr 2023

Modulation Of Plant Immunity During The Establishment Of The Nitrogen-Fixing Symbiosis, Miriam Hernandez-Romero

Doctoral Dissertations

Nitrogen is essential for plant tissue growth but is often a limited resource in soils. Many legumes overcome this limitation by entering a symbiotic association with soil microbes, called rhizobia, which provide nitrogen to the plant while rhizobia receive fixed carbon. To successfully form a symbiosis, the host and symbiont exchange a series of molecular signals. One major obstacle during this interaction is the host's innate immune system, which becomes active upon rhizobial detection. It is therefore the main focus of this thesis to identify the mechanisms that modulate host immunity. In the subsequent chapters, we focus on a rhizobial …

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Changes In Gene Expression From Long-Term Warming Revealed Using Metatranscriptome Mapping To Fac-Sorted Bacteria, Christopher A. Colvin Oct 2022

Changes In Gene Expression From Long-Term Warming Revealed Using Metatranscriptome Mapping To Fac-Sorted Bacteria, Christopher A. Colvin

Masters Theses

Soil microbiomes play pivotal roles to the health of the environment by maintaining metabolic cycles. One question is how will climate change affect soil bacteria over time and what could the repercussions be. To answer these questions, the Harvard Forest Long-Term Warming Experiment was established to mimic predicted climate change by warming plots of land 5℃ above ambient conditions. In 2017, 14 soil core samples were collected from Barre Woods warming experiment to mark 15 years since the establishment of the soil warming in that location. These samples underwent traditional metatranscriptomics to generate an mRNA library as well as a …

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Characterization Of The Poly (Adp-Ribose) Polymerase Family In The Fusarium Oxysporum Species Complex, Daniel Norment Oct 2022

Characterization Of The Poly (Adp-Ribose) Polymerase Family In The Fusarium Oxysporum Species Complex, Daniel Norment

Masters Theses

Fusarium oxysporum is a filamentous fungus that is known to invade over a hundred different hosts and poses a major threat to the economy and food supply world-wide. Poly (Adenosine diphosphate-Ribose) Polymerase (PARP) is a family of regulatory proteins that affect change in the cell through transfer of ADP-Ribose moieties onto target molecules. The most well-studied PARP protein is the human PARP1, a PARylating nuclear protein that serves as our model PARP protein. F. oxysporum was found to contain a large expansion of PARP catalytic-domain-containing proteins compared to other filamentous fungi. We utilized in silico multiple sequence alignments and domain …

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Chemosensory Receptors In Berghia Stephanieae: Bioinformatics And Localization, Kelsi L. Watkins Oct 2022

Chemosensory Receptors In Berghia Stephanieae: Bioinformatics And Localization, Kelsi L. Watkins

Masters Theses

Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A …

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The Sos Response In Escherichia Coli K12: An Exploration Of Mutations In Lexa And Reca Using Fluorescence Microscopy, Steven Van Alstine Oct 2022

The Sos Response In Escherichia Coli K12: An Exploration Of Mutations In Lexa And Reca Using Fluorescence Microscopy, Steven Van Alstine

Doctoral Dissertations

Faithful replication of the genome is paramount for maintaining the fitness of an organism. Therefore, life has evolved inducible mechanisms to be able to repair damaged DNA and maintain evolutionary fitness. The SOS response is a highly conserved DNA damage inducible response that is tightly regulated. Multiple factors contribute to the ability of the cell to perform proper DNA repair and induction of the SOS response including the amount of RecA, mutations in RecA that affect competition for DNA, and other proteins that interact with the RecA filament. The complex relationship between RecA and LexA is the subject of this …

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Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario Oct 2022

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …

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Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee Oct 2022

Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee

Doctoral Dissertations

Cellular protein pools are maintained through the biological processes of synthesis, degradation and quality control. As the dysregulation of these processes has been implicated in diseases such as neurodegeneration and cancer, understanding their functions is critical for drug development. Modification of proteins with ubiquitin may direct them to the proteasome, a large cellular protease complex, for degradation. Yet, the proteasome contains three deubiquitinating enzymes (DUBs) which remove ubiquitin from proteins, potentially altering their fate. As each DUB recognizes specific ubiquitin linkages and architectures, their activity may regulate how the proteasome handles substrates in dynamic cellular contexts. In this work, we …

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Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward Sep 2022

Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward

Doctoral Dissertations

Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …

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Investigating Structures And Functions Of Apoptotic Caspases, Ishankumar V. Soni Jun 2022

Investigating Structures And Functions Of Apoptotic Caspases, Ishankumar V. Soni

Doctoral Dissertations

Caspases are cysteine aspartate proteases involved in various cellular pathways including apoptosis, inflammation, and neurodegeneration. Caspase-9 is classified as an initiator apoptotic caspase that is activated upon intrinsic stress. Caspase-9 is composed of two domains: an N- terminal CARD domain and a catalytic core domain. We have employed hydrogen deuterium exchange mass spectrometry (H/DX-MS) to determine the 1) dynamics of the full-length caspase- 9, 2) dynamic impacts on caspase-9 upon substrate-induced dimerization, and 3) regions involved in the CARD: catalytic core domains interactions. Upon intrinsic stress, caspase-9 activates executioners, procaspase-3 and -7 but not procaspase-6. We have employed site-directed mutagenesis …

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Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don Jun 2022

Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don

Doctoral Dissertations

Circadian rhythms are 24–hour activity cycles that exist for all organisms, from yeast and bacteria to mammals. Epidemiological data has shown that disruptions to circadian rhythms are associated with various diseases, including cancers. Circadian rhythms are regulated at the cellular level by a "molecular clock,” whose oscillations in protein transcription and translation control a range of downstream pathways. However, the connections between altered rhythms and diseases at the molecular level is unclear. Therefore, in this project, I tracked circadian rhythms in a high-resolution manner and thoroughly analyzed them to more completely reflect circadian behaviors and clock functioning at the molecular …

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Screening For Binding Partners And Protein-Protein Interactions Of A Fungal Transcription Factor- Xdr1, Nishadi Punsara Gallala Gamage Mar 2022

Screening For Binding Partners And Protein-Protein Interactions Of A Fungal Transcription Factor- Xdr1, Nishadi Punsara Gallala Gamage

Masters Theses

Clarireedia spp. (formerly Sclerotinia homoeocarpaF.T. Bennett) is the causal agent dollar spot, the most economically important turfgrass disease impacting golf courses in North America. The most effective strategy for dollar spot control is repeated application of multiple classes of fungicides. However, reliance on chemical application has led to resistance to four classes of fungicides as well as multidrug resistance (MDR). Fungi are known to detoxify xenobiotics, like fungicides, through transcriptional regulation of three detoxification phases: modification, conjugation and secretion. Little is known, however, of the protein-protein interactions that facilitate these pathways. Following next-generation RNA sequencing of Clarireedia spp., a …

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Characterizing Mechanical Regulation Of Bone Metastatic Breast Cancer Cells, Boyuan Liu Mar 2022

Characterizing Mechanical Regulation Of Bone Metastatic Breast Cancer Cells, Boyuan Liu

Doctoral Dissertations

Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical stimuli in the skeleton are an important microenvironmental parameter that modulates tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. This work focused on bone matrix deformation and interstitial fluid flow based on their well-known roles in bone remodeling and in primary breast cancer. The goal of our research was to establish a platform that could define the relationship between …

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Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri Feb 2022

Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri

Doctoral Dissertations

Mechanical forces are an integral part in biology, they regulate several cellular properties, such as morphology, proliferation, migration. These forces are also involved in receptor signaling and the differentiation of different cell types. Different proteins and biomolecules such as cadherin, integrin, notch proteins are essential elements of these processes. Measuring these intercellular forces are challenging considering the minimal intensity (piconewton-level) of these molecular forces. In our lab, we have developed a membrane DNA tension probe (MDTP) that uses a DNA hairpin module to sense tensile forces and has a lipid anchor to modify onto live-cell membranes. The programmability of DNA …

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Plants, Pipettes And Pcr, Elizabeth Vierling Jan 2022

Plants, Pipettes And Pcr, Elizabeth Vierling

Science and Engineering Saturday Seminars

Plants are amazing organisms that provide us with food, building materials, the pleasure of gardens, as well as providing the foundation of critical world ecosystems. Although they may look like they are just stuck in one place and doing not more than growing, they have many, many complex ways in which they respond to the environment. The goal of this STEM Ed session will be to discuss ways that plants can respond to the environment with hands on exercises and exploration of possible classroom activities. Participants will engage in state-of-the art methods of testing plant DNA composition using the polymerase …

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Understanding How Camkii Holoenzyme Dynamics Facilities Activation-Triggered Subunit Exchange, Ana P. Torres-Ocampo Oct 2021

Understanding How Camkii Holoenzyme Dynamics Facilities Activation-Triggered Subunit Exchange, Ana P. Torres-Ocampo

Doctoral Dissertations

Long-term memory and learning are still poorly understood from a molecular and cellular standpoint. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is an oligomeric kinase that is involved in this remarkable process. However, the molecular details of its specific roles in these processes remains elusive. CaMKII activation-triggered subunit exchange presents a novel possible mechanism involved in long-term memory and learning by exchanging active subunits with other CaMKIIs. CaMKII subunit exchange also shows that exchanged CaMKIIs spread their phosphorylation state to newly synthesized CaMKIIs. This provides a long-lasting signal that might possibly be involved in long-term memory by escaping a cell’s …

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Structure-Function Studies Of The Trypanosome Mitochondrial Replication Protein Polib, Raveen Armstrong Oct 2021

Structure-Function Studies Of The Trypanosome Mitochondrial Replication Protein Polib, Raveen Armstrong

Masters Theses

Trypanosoma brucei and related protists are distinguished from all other eukaryotes by an unusual mitochondrial genome known as kinetoplast DNA (kDNA) that is a catenated network composed of minicircles and maxicircles. Replication of this single nucleoid involves a release, replicate, and reattach mechanism for the thousands of catenated minicircles and requires at least three DNA polymerase (POLIB, POLIC and POLID) with similarity to E. coli DNA polymerase I. Like other proofreading replicative DNA polymerases, POLIB has both an annotated polymerase domain and an exonuclease domain. Predictive modelling of POLIB indicates that it has the canonical right hand …

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Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel Oct 2021

Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel

Masters Theses

All cells carry the genetic machinery required to commit cell suicide; a process known as programmed cell death (PCD). While the ability to initiate PCD serves a number of useful purposes during development and homeostasis, misregulation of PCD is the underlying basis of most human diseases, including cancer, autoimmunity disorders and neurodegeneration. Using the tobacco hawkmoth Manduca sexta as a model organism, the Schwartz lab at UMass has demonstrated that PCD requires de novo gene expression and has cloned many death-associated genes. One of these genes encodes a novel protein that was named Acheron after one of the rivers of …

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Hsp70 Phosphorylation: A Case Study Of Serine Residues 385 And 400, Sashrika Saini Oct 2021

Hsp70 Phosphorylation: A Case Study Of Serine Residues 385 And 400, Sashrika Saini

Masters Theses

Molecular chaperones play a key role in maintaining a healthy cellular proteome by performing protein quality control. Heat shock protein 70s (Hsp70s) are a diverse class of evolutionarily conserved chaperones that interact with short hydrophobic sequences presented in unfolded proteins, promoting productive folding, and preventing proteins from aggregation. Most of the extensive research on chaperone examines mechanism, substrate promiscuity, and engagement with many co-chaperones. Only recently were chaperones recognized to be frequent targets of post-translational modifications (PTMs). Despite the recent rise in PTMs identified, the impact of these modifications on chaperone function, whether singular or in concert with other modifications, …

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Exploring Knockdown Phenotypes And Interactions Between Atad3 Proteins In Arabidopsis Thaliana, Eli S. Gordon Oct 2021

Exploring Knockdown Phenotypes And Interactions Between Atad3 Proteins In Arabidopsis Thaliana, Eli S. Gordon

Masters Theses

Mitochondria are required for a diverse array of cellular functions and processes. ATAD3 (ATPase family AAA domain containing protein 3) proteins are newly discovered mitochondrial membrane proteins in Arabidopsis thaliana. Homologous to ATAD3A in metazoans, Co-Immunoprecipitation/Mass spectrometry and genomic analysis identified a four ATAD3A homologues in A. thaliana. The four A. thaliana proteins are referred to as ATAD3A1 (At3g03060), ATAD3A2 (At5g16930), ATAD3B1 (At2g18330), and ATAD3B2 (At4g36580). Studies in metazoans indicate that ATAD3A localizes to Mitochondria-ER contact sites and is involved in a variety of processes required for proper mitochondrial function, but ATAD3A proteins are poorly defined in plants. …

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Novel Approaches Towards Improved Purity In High Yield Transcription Reactions, Elvan Cavac Jun 2021

Novel Approaches Towards Improved Purity In High Yield Transcription Reactions, Elvan Cavac

Doctoral Dissertations

High yields of RNA (e.g., mRNA, gRNA, lncRNA) are routinely prepared following a two-step approach: high yield in vitro transcription using T7 RNA polymerase, followed by extensive purification using gel or chromatic methods. In high yield transcription reactions, as RNA accumulates in solution, T7 RNA polymerase rebinds and extends the encoded RNA (using the RNA as a template), resulting in a product pool contaminated with longer than desired, (partially) double stranded impurities. Current purification methods often fail to fully eliminate these impurities which, if present in therapeutics, can stimulate the innate immune response with potentially fatal consequences. This study establishes …

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Pharmacological Chaperoning Of Human Lysosomal Neuraminidase 1, Di Chu May 2021

Pharmacological Chaperoning Of Human Lysosomal Neuraminidase 1, Di Chu

Doctoral Dissertations

Human lysosomal neuraminidase 1 (hNEU1) is an exo-a-sialidase which cleaves a(2-3) and a(2-6) linked sialic acids on glycoproteins in the lysosome. Deficiency of hNEU1 in the lysosome results in sialidosis, a lysosomal storage disease. Currently there is no effective treatment for sialidosis, which leads to a rising interest in discovering potential therapies. Here we presented a small molecule, α-D-N-acetylneuraminic acid (NANA), increases the protein amount and activity of both wild-type hNEU1 and three different hNEU1 mutations found in sialidosis patients in our mammalian cell system, suggesting that NANA works as a potential pharmacological chaperone for hNEU1 and provides …

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The Lipid Peroxidation Product Ekode Exacerbates Colonic Inflammation And Colon Tumorigenesis, Lei Lei, Jun Yang, Jianan Zhang, Guodong Zhang Jan 2021

The Lipid Peroxidation Product Ekode Exacerbates Colonic Inflammation And Colon Tumorigenesis, Lei Lei, Jun Yang, Jianan Zhang, Guodong Zhang

Food Science Department Faculty Publication Series

Oxidative stress is emerging as an important contributor to the pathogenesis of colorectal cancer (CRC), however, the molecular mechanisms by which the disturbed redox balance regulates CRC development remain undefined. Using a liquid chromatography?tandem mass spectrometry-based lipidomics, we found that epoxyketooctadecenoic acid (EKODE), which is a lipid peroxidation product, was among the most dramatically increased lipid molecules in the colon of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. This is, at least in part, due to increased oxidative stress in colon tumors, as assessed by analyzing gene expression of oxidative markers in AOM/DSS-induced CRC mice and human CRC patients in …

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Evidence For The Role Of Cyp51a And Xenobiotic Detoxification In Differential Sensitivity To Azole Fungicides In Boxwood Blight Pathogens, Stefanos Stravoravdis, Robert E. Marra, Nicholas R. Leblanc, Joanne Crouch, Jonathan P. Hulvey Jan 2021

Evidence For The Role Of Cyp51a And Xenobiotic Detoxification In Differential Sensitivity To Azole Fungicides In Boxwood Blight Pathogens, Stefanos Stravoravdis, Robert E. Marra, Nicholas R. Leblanc, Joanne Crouch, Jonathan P. Hulvey

Microbiology Department Faculty Publication Series

Boxwood blight, a fungal disease of ornamental plants (Buxus spp.), is caused by two sister species, Calonectria pseudonaviculata (Cps) and C. henricotiae (Che). Compared to Cps, Che is documented to display reduced sensitivity to fungicides, including the azole class of antifungals, which block synthesis of a key fungal membrane component, ergosterol. A previous study reported an ergosterol biosynthesis gene in Cps, CYP51A, to be a pseudogene, and RNA-Seq data confirm that a functional CYP51A is expressed only in Che. The lack of additional ergosterol biosynthesis genes showing significant differential expression suggests that the functional CYP51A in Che could contribute to …

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How The Protein Data Bank Changed Biology: An Introduction To The Jbc Reviews Thematic Series, Part 1, Helen M. Berman, Lila M. Gierasch Jan 2021

How The Protein Data Bank Changed Biology: An Introduction To The Jbc Reviews Thematic Series, Part 1, Helen M. Berman, Lila M. Gierasch

Biochemistry & Molecular Biology Department Faculty Publication Series

This collection of articles celebrates the 50th anniversary of the Protein Data Bank (PDB), the single global digital archive of biological macromolecular structures. The impact of the PDB is immense; we have invited a number of top researchers in structural biology to illustrate its influence on an array of scientific fields. What emerges is a compelling picture of the synergism between the PDB and the explosive progress witnessed in many scientific areas. Availability of reliable, openly accessible, well-archived structural information has arguably had more impact on cell and molecular biology than even some of the enabling technologies such as PCR. …

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The Thermogenic Characteristics Of Adipocytes Are Dependent On The Regulation Of Iron Homeostasis, Jin-Seon Yook, Mikyoung You, Yongeun Kim, Mi Zhou, Zhenhua Liu, Young-Cheul Kim, Jaekwon Lee, Soonkyu Chung Jan 2021

The Thermogenic Characteristics Of Adipocytes Are Dependent On The Regulation Of Iron Homeostasis, Jin-Seon Yook, Mikyoung You, Yongeun Kim, Mi Zhou, Zhenhua Liu, Young-Cheul Kim, Jaekwon Lee, Soonkyu Chung

Nutrition Department Faculty Publication Series

The development of thermogenic adipocytes concurs with mitochondrial biogenesis, an iron-dependent pathway. Iron regulatory proteins (IRP) 1 and 2 are RNA-binding proteins that regulate intracellular iron homeostasis. IRPs bind to the iron-response element (IRE) of their target mRNAs, balancing iron uptake and deposition at the posttranscriptional levels. However, IRP/IRE-dependent iron regulation in adipocytes is largely unknown. We hypothesized that iron demands are higher in brown/beige adipocytes than white adipocytes to maintain the thermogenic mitochondrial capacity. To test this hypothesis, we investigated the IRP/IRE regulatory system in different depots of adipose tissue. Our results revealed that 1) IRP/IRE interaction was increased …

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Polymeric Nanoparticles Active Against Dual-Species Bacterial Biofilms, Jessa Marie V. Makabenta, Jungmi Park, Cheng-Hsuan Li, Aritra Nath Chattopadhyay, Ahmed Nabawy, Ryan F. Landis, Akash Gupta, Suzannah Schmidt-Malan, Robin Patel, Vincent M. Rotello Jan 2021

Polymeric Nanoparticles Active Against Dual-Species Bacterial Biofilms, Jessa Marie V. Makabenta, Jungmi Park, Cheng-Hsuan Li, Aritra Nath Chattopadhyay, Ahmed Nabawy, Ryan F. Landis, Akash Gupta, Suzannah Schmidt-Malan, Robin Patel, Vincent M. Rotello

Chemistry Department Faculty Publication Series

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. …

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Modulating Glutathione Thiol Status Alters Pancreatic Β-Cell Morphogenesis In The Developing Zebrafish (Danio Rerio) Embryo, Archit Rastogi, Emily G. Severance, Haydee M. Jacobs, Sarah M. Conlin, Sadia T. Islam, Alicia R. Timme-Laragy Jan 2021

Modulating Glutathione Thiol Status Alters Pancreatic Β-Cell Morphogenesis In The Developing Zebrafish (Danio Rerio) Embryo, Archit Rastogi, Emily G. Severance, Haydee M. Jacobs, Sarah M. Conlin, Sadia T. Islam, Alicia R. Timme-Laragy

Environmental Health Sciences Faculty Publication Series

Emerging evidence suggests that redox-active chemicals perturb pancreatic islet development. To better understand potential mechanisms for this, we used zebrafish (Danio rerio) embryos to investigate roles of glutathione (GSH; predominant cellular redox buffer) and the transcription factor Nrf2a (Nfe2l2a; zebrafish Nrf2 coortholog) in islet morphogenesis. We delineated critical windows of susceptibility to redox disruption of beta-cell morphogenesis, interrogating embryos at 24, 48 and 72 h post fertilization (hpf) and visualized Nrf2a expression in the pancreas using whole-mount immunohistochemistry at 96 hpf. Chemical GSH modulation at 48 hpf induced significant islet morphology changes at 96 hpf. Pro-oxidant exposures to tert-butylhydroperoxide (77.6 …

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