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Articles 1 - 13 of 13
Full-Text Articles in Life Sciences
Understanding How Camkii Holoenzyme Dynamics Facilities Activation-Triggered Subunit Exchange, Ana P. Torres-Ocampo
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 …
Structure-Function Studies Of The Trypanosome Mitochondrial Replication Protein Polib, Raveen Armstrong
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 …
Utilizing Fluorescence Microscopy To Characterize The Subcellular Distribution Of The Novel Protein Acheron, Varun Sheel
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 …
Hsp70 Phosphorylation: A Case Study Of Serine Residues 385 And 400, Sashrika Saini
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, …
Exploring Knockdown Phenotypes And Interactions Between Atad3 Proteins In Arabidopsis Thaliana, Eli S. Gordon
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. …
Novel Approaches Towards Improved Purity In High Yield Transcription Reactions, Elvan Cavac
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 …
Pharmacological Chaperoning Of Human Lysosomal Neuraminidase 1, Di Chu
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 …
The Lipid Peroxidation Product Ekode Exacerbates Colonic Inflammation And Colon Tumorigenesis, Lei Lei, Jun Yang, Jianan Zhang, Guodong Zhang
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 …
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
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 …
How The Protein Data Bank Changed Biology: An Introduction To The Jbc Reviews Thematic Series, Part 1, Helen M. Berman, Lila M. Gierasch
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. …
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
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 …
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
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. …
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
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 …