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Articles 1 - 23 of 23
Full-Text Articles in Molecular Biology
Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff
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 …
Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee
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 …
Tracking And Modulating Circadian Rhythms In Cell Culture Models, Sujeewa Sampath Lellupitiyage Don
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 …
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 …
Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois
Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois
Doctoral Dissertations
Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …
Involvement Of Calcium-Dependent Protein Kinases And Phosphatases In Sperm Capacitation-Associated Events, Bidur Paudel
Involvement Of Calcium-Dependent Protein Kinases And Phosphatases In Sperm Capacitation-Associated Events, Bidur Paudel
Doctoral Dissertations
ABSTRACT To acquire fertilizing ability, mammalian sperm undergo a series of biochemical and physiological changes collectively known as capacitation1,2. At the molecular level, capacitation is associated with a fast bicarbonate (HCO3-)-dependent activation of a unique type of soluble adenyl cyclase (sAC) and a consequent increase in cyclic AMP (cAMP) levels and PKA activation3. Activation of a cAMP/PKA pathway results in the phosphorylation of PKA substrates, which in turn initiates activation of several signaling cascades ultimately leading to an increase in phosphorylation on tyrosine residues (P-Tyr) of sperm axonemal proteins4,5. Increase in …
Tpr-Containing Proteins Control Protein Organization And Homeostasis For The Endoplasmic Reticulum, Jill Bradley-Graham
Tpr-Containing Proteins Control Protein Organization And Homeostasis For The Endoplasmic Reticulum, Jill Bradley-Graham
Doctoral Dissertations
The endoplasmic reticulum (ER) is a complex, multifunctional organelle comprised of a continuous membrane and lumen that is organized into several functional regions. It plays various roles including protein translocation, folding, quality control, secretion, calcium signaling, and lipid biogenesis. Cellular protein homeostasis is maintained by a complicated chaperone network, and the largest functional family within this network consists of proteins containing tetratricopeptide repeats (TPRs). TPRs are well-studied structural motifs that mediate intermolecular protein-protein interactions, supporting interactions with a wide range of ligands or substrates. Nine TPR-containing proteins have been shown to localize to the ER and control protein organization and …
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben
Doctoral Dissertations
The ER Degradation-Enhancing Mannosidase-Like protein 1 (EDEM1) is a critical endoplasmic reticulum (ER) quality control factor involved in identifying and directing non-native proteins to the ER-associated protein degradation (ERAD) pathway. However, its recognition and binding properties have remained enigmatic since its discovery. Here we provide evidence for an additional redox-sensitive interaction between EDEM1 and Z/NHK that requires the presence of the single Cys on the α-1 antitrypsin ERAD clients. Moreover, this Cys-dependent interaction is necessary when the proteins are isolated under stringent detergent conditions, ones in which only strong covalent interactions can be sustained. This interaction is inherent to the …
The Interplay Between Polarity Regulators, Calcium, And The Actin Cytoskeleton During Tip Growth, Carlisle Bascom Jr
The Interplay Between Polarity Regulators, Calcium, And The Actin Cytoskeleton During Tip Growth, Carlisle Bascom Jr
Doctoral Dissertations
Plant cell growth is a meticulously regulated process whereby the cell wall is selectively loosened to allow for turgor-pressure driven expansion. The rate of expansion must equal delivery of new material, or the cell will lyse. In many plant cells, this process happens diffusely around the cell. However, a number of plant cells have anisotropic shapes that require exquisite spatial control of secretion. One simple example of anisotropic patterning is tip growth; highly polarized cell expansion utilized by pollen tubes, root hairs, and moss protonemata. Investigating the role various molecules have in tip growth sheds light on how plant cells …
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Doctoral Dissertations
During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …
Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard
Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard
Doctoral Dissertations
Small heat shock proteins (sHSPs) and related α-crystallins are virtually ubiquitous, ATP-independent molecular chaperones linked to protein misfolding diseases. They comprise a conserved core α-crystallin domain (ACD) flanked by an evolutionarily variable N-terminal domain (NTD) and semi-conserved C-terminal extension/domain (CTD). They are capable of binding up to an equal mass of unfolding protein, forming large, heterogeneous sHSP-substrate complexes that coordinate with ATP-dependent chaperones for refolding. To derive common features of sHSP-substrate recognition, I compared the chaperone activity and specific sHSP-substrate interaction sites for three different sHSPs from Arabidopsis (At17.6B), pea (Ps18.1) and wheat (Ta16.9), for which the atomic solution-state structures …
Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass
Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass
Doctoral Dissertations
Proteolysis shapes many aspects of cellular survival, including protein quality control and cellular signaling. Powered proteolysis couples ATP hydrolysis with a degradation force that actively probes and interrogates the protein population. ClpXP, exemplifies a conserved two-part protease system charged with powered proteolysis. This protease exists as a regulatory element (ClpX), and a compartmentalized, self-contained peptidase element (ClpP). In Caulobacter crescentus, ClpXP degradation plays a crucial role maintaining proteins that exhibit proper activity, and also triggers the start of cellular differentiation. Substrate elimination requires shared aspects of the protease from both quality control and precision protein destruction functions. Here, the regulatory …
Dissecting Molecular Pathways That Ensure Proper Chromosome Segregation And Cell Division, Anna Ye
Dissecting Molecular Pathways That Ensure Proper Chromosome Segregation And Cell Division, Anna Ye
Doctoral Dissertations
Equal segregation of the genome is a prerequisite for cell survival. During cell division the duplicated DNA is compacted into chromosomes and a multi-protein macrostructure, known as the kinetochore (Kt), is assembled on each copy of compacted DNA. Simultaneously, the mitotic spindle, which is made up of microtubules (MTs), is built to facilitate the equal distribution of the chromosomes between the resulting daughter cells. Kinetochores mediate the interaction between the MTs and the chromosomes, properly positioning them for segregation. To ensure that the DNA is equally divided in every cell division, cells have built a surveillance system to detect any …
Regulated Proteolysis Of Dnaa Coordinates Cell Growth With Stress Signals In Caulobacter Crescentus, Jing Liu
Regulated Proteolysis Of Dnaa Coordinates Cell Growth With Stress Signals In Caulobacter Crescentus, Jing Liu
Doctoral Dissertations
DNA replication is an essential process in all domains of life. Replication must be precisely regulated, especially at the step of initiation. In bacteria, the replication initiator DnaA is regulated by multiple post-translational regulations to ensure timely replication. Caulobacter crescentus has the most strict replication regulation that DNA only replicates once per cell cycle, and proteolysis of DnaA identified in this species is the only irreversible way to inhibit DnaA, suggesting it might be pivotal to restricting DNA replication. However, the responsible protease(s) and mechanism for its degradation remain unclear since its first discovery in 2005. In this thesis, I …
The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas
The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas
Doctoral Dissertations
The fact that plants cannot use nitrogen in the gaseous form makes them dependent on the levels of usable nitrogen forms in the soil. Legumes overcome nitrogen limitation by entering a symbiotic association with rhizobia, soil bacteria that convert atmospheric nitrogen into usable ammonia. In root nodules, bacteria are internalized by host plant cells inside an intracellular compartment called the symbiosome where they morphologically differentiate into nitrogen-fixing forms by symbiosome-secreted host proteins. In this project, I explained the host proteins required to maintain bacterial symbionts and described their delivery to the symbiosome. I showed that the SYNTAXIN 132 (SYP132) gene …
Effect Of A 10 Day Decrease In Physical Activity On Circulating Angiogenic Cells, Gayatri Guhanarayan
Effect Of A 10 Day Decrease In Physical Activity On Circulating Angiogenic Cells, Gayatri Guhanarayan
Masters Theses 1911 - February 2014
Circulating angiogenic cells (CACs) are early predictors of cardiovascular health and are inversely proportional to related outcomes. Increased number and function of CACs is seen in healthy individuals compared with individuals with cardiovascular disease (CVD). Exercise increases CAC number and function in CVD populations, through a nitric oxide-mediated mechanism. Inactivity is a growing concern in industrialized nations; it is an independent risk factor for CVD and is linked to increased mortality. The purpose of this study was to understand the effect of reduced physical activity (rPA) on two CAC populations (CFU-Hill and CD34+) in highly active individuals. We …
The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone
The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone
Open Access Dissertations
Glioblastoma Multiforme (GBM) is the most common brain cancer and one of the most fatal forms of cancer overall. The average survival time is 10-14 months, and less than 10% of patients survive more than 5 years after diagnosis. It is characterized by extreme vasculature, chemo/radioresistance, and invasiveness into the normal brain. The current standard of care, which includes surgical removal of tumor, radiation, and the chemotherapeutic agent temozolomide, initially stunt tumor growth. Nevertheless, the tumor invariably rebounds and the patient succumbs to the disease. Therefore, there is an urgent need to develop new therapies for this devastating disease.
YKL-40 …
Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes
Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes
Open Access Dissertations
The root of the Tibetan plant Rhodiola crenulata is part of eastern traditional medicine. Studies have suggested that members of the Rhodiola genus display anticancer properties. In this study we examine the effect of R. crenulata in a cellular model of invasive breast cancer, this disease being the second cause of cancer death among women in the US. Deregulation of the Wnt/β-catenin pathway has been frequently observed in breast cancers and appears to have a key role in the transformation of benign cells to a malignant form. Although mutations of the Wnt growth factor are rarely observed in cancer, the …
Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich
Identification And Functional Characterization Of The Zebrafish Gene Quetschkommode (Que), Timo Friedrich
Open Access Dissertations
Locomotion in vertebrates depends on proper formation and maintenance of neuronal networks in the hind-brain and spinal cord. Malformation or loss of factors required for proper maintenance of these networks can lead to severe neurodegenerative diseases limiting or preventing locomotion. A powerful tool to investigate the genetic and cellular requirements for development and/or maintenance of these networks is a collection of zebrafish mutants with defects in motility. The zebrafish mutant quetschkommode (que) harbors a previously unknown gene defect leading to abnormal locomotor behavior. Here I show that the que mutants display a seizure-like behavior starting around four days post fertilization …
Transient Pharmacologic Lowering Of Aβ Production Prior To Deposition Results In Sustained Reduction Of Amyloid Plaque Pathology, Pritam Das, Christophe Verbeeck, Lisa Minter, Paramita Chakrabarty, Kevin Felsenstein, Thomas Kukar, Ghulam Maharvi, Abdul Fauq, Barbara A. Osborne, Todd E. Golde
Transient Pharmacologic Lowering Of Aβ Production Prior To Deposition Results In Sustained Reduction Of Amyloid Plaque Pathology, Pritam Das, Christophe Verbeeck, Lisa Minter, Paramita Chakrabarty, Kevin Felsenstein, Thomas Kukar, Ghulam Maharvi, Abdul Fauq, Barbara A. Osborne, Todd E. Golde
Barbara A. Osborne
Background: Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Disease modifying therapies targeting Aβ that are in development have been proposed to be more effective if treatment was initiated prior to significant accumulation of Aβ in the brain, but optimal timing of treatment initiation has not been clearly established in the clinic. We compared the efficacy of transient pharmacologic reduction of brain Aβ with a γ-secretase inhibitor (GSI ) for 1–3 months (M) treatment windows in APP Tg2576 mice and subsequent aging of the mice to either 15M or 18M. Results: These data show that reducing …
Xenopus Adam13 And Adam19 Are Important For Proper Convergence And Extension Of The Notochord, Russell David Neuner
Xenopus Adam13 And Adam19 Are Important For Proper Convergence And Extension Of The Notochord, Russell David Neuner
Open Access Dissertations
Gastrulation is a fundamental process that reorganizes the primary germ layers to shape the internal and external features of an early embryo. Morphogenetic movements underlying this process can be classified into a variety of different types of cellular movements. I will focus on investigating in this thesis two types of cell movements in the dorsal mesoderm; mediolateral cell intercalation and convergence and extension. During gastrulation, mesoderm cells send protrusions to gain traction on neighboring cells and the surrounding extracellular matrix; a process called mediolateral cell intercalation. Mesoderm cells use this type of cell movement to converge and extend the dorsal …
Connecting Motors And Membranes: A Quantitative Investigation Of Dynein Pathway Components And In Vitro Characterization Of The Num1 Coiled Coil Domain, Bryan J. St. Germain
Connecting Motors And Membranes: A Quantitative Investigation Of Dynein Pathway Components And In Vitro Characterization Of The Num1 Coiled Coil Domain, Bryan J. St. Germain
Masters Theses 1911 - February 2014
In the budding yeast, Saccharomyces Cerevisiae, dynein, a minus-end directed motor, is involved in nuclear migration and proper orientation of the mitotic spindle during mitosis. Our lab has developed a model that involves the loading of cytoplasmic dynein onto the plus-end of astral microtubules through interactions with Pac1/LIS1 and Bik1/CLIP-170. Dynein is then delivered to the cell cortex and anchored through a cortical receptor protein, Num1. Num1 is a 313KDa protein that localizes to the cell cortex and is an essential component of dynein mediated nuclear migration.
Using quantitative fluorescence techniques I was able to create a molecular inventory of …
Sex Difference In Calbindin Cell Number In The Mouse Preoptic Area: Effects Of Neonatal Estradiol And Bax Gene Deletion, Richard F. Gilmore Iii
Sex Difference In Calbindin Cell Number In The Mouse Preoptic Area: Effects Of Neonatal Estradiol And Bax Gene Deletion, Richard F. Gilmore Iii
Masters Theses 1911 - February 2014
The sexually dimorphic nucleus of the preoptic area (SDN-POA) was first discovered in rats and is one of the most famous and best studied sex differences in the field of neuroscience. Though well documented in rats (larger in males than females), this sex difference was only recently able to be observed in mice due to the discovery of the protein calbindin-D28k as a marker. Recent studies have shown a larger, more distinct calbindin-immunoreactive (ir) cell cluster in male mice compared to females. However, the exact location of the cluster and whether the sex difference is one of total cell number …