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2014

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Articles 1 - 30 of 975

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Mechanisms Of Translational Repression Of The Sperm Mitochondria Associated-Cysteine Rich Protein (Smcp) Mrna In Round Spermatids, Danielle L. Cullinane Dec 2014

Mechanisms Of Translational Repression Of The Sperm Mitochondria Associated-Cysteine Rich Protein (Smcp) Mrna In Round Spermatids, Danielle L. Cullinane

Graduate Doctoral Dissertations

The sperm-mitochondria-associated cysteine-rich protein (SMCP) is a male germ cell-specific protein that localizes to the outer membranes of sperm mitochondria and increases sperm motility. The Smcp mRNA is transcribed in early spermatids, and stored in a translationally repressed state for ~7 days before translation is activated in late spermatids. Identifying the cis-elements and trans-factors that repress the Smcp mRNA in early spermatids is important because these factors and elements coordinate the translational activity of hundreds of mRNAs.

A mutation was studied in transgenic mice in which the 16 nucleotides downstream of the first poly(A) signal in the ...


Dna-Guided Establishment Of Canonical Nucleosome Patterns In A Eukaryotic Genome, Leslie Y. Beh, Noam Kaplan, Manuel M. Muller, Tom W. Muir, Laura F. Landweber Dec 2014

Dna-Guided Establishment Of Canonical Nucleosome Patterns In A Eukaryotic Genome, Leslie Y. Beh, Noam Kaplan, Manuel M. Muller, Tom W. Muir, Laura F. Landweber

University of Massachusetts Medical School Faculty Publications

A conserved hallmark of eukaryotic chromatin architecture is the distinctive array of well-positioned nucleosomes downstream of transcription start sites (TSS). Recent studies indicate that trans-acting factors establish this stereotypical array. Here, we present the first genome-wide in vitro and in vivo nucleosome maps for the ciliate Tetrahymena thermophila. In contrast with previous studies in yeast, we find that the stereotypical nucleosome array is preserved in the in vitro reconstituted map, which is governed only by the DNA sequence preferences of nucleosomes. Remarkably, this average in vitro pattern arises from the presence of subsets of nucleosomes, rather than the whole array ...


Real-Time Kinetic Studies Of Bacillus Subtilis Oxalate Decarboxylase And Ceriporiopsis Subvermispora Oxalate Oxidase Using Luminescent Oxygen Sensor, Laura Molina, Thomas Goodall, Umar Twahir, Ellen W. Moomaw Dec 2014

Real-Time Kinetic Studies Of Bacillus Subtilis Oxalate Decarboxylase And Ceriporiopsis Subvermispora Oxalate Oxidase Using Luminescent Oxygen Sensor, Laura Molina, Thomas Goodall, Umar Twahir, Ellen W. Moomaw

Faculty Publications

Oxalate decarboxylase (OxDC), an enzyme of the bicupin superfamily, catalyzes the decomposition of oxalate into carbon dioxide and formate at an optimal pH of 4.3 in the presence of oxygen. However, about 0.2% of all reactions occur through an oxidase mechanism that consumes oxygen while producing two equivalents of carbon dioxide and one equivalent of hydrogen peroxide. The kinetics of oxidase activity were studied by measuring the consumption of dissolved oxygen over time using a luminescent oxygen sensor. We describe the implementation of and improvements to the oxygen consumption assay. The oxidase activity of wild type OxDC was ...


Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett Dec 2014

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of ...


Mirage Dna Transposon Silencing By C. Elegans Condensin Ii Subunit Hcp-6: A Masters Thesis, Anna Malinkevich Dec 2014

Mirage Dna Transposon Silencing By C. Elegans Condensin Ii Subunit Hcp-6: A Masters Thesis, Anna Malinkevich

GSBS Dissertations and Theses

Mobile genetic elements represent a large portion of the genome in many species. Posing a danger to the integrity of genetic information, silencing and structural machinery has evolved to suppress the mobility of foreign and transposable elements within the genome. Condensin proteins – which regulate chromosome structure to promote chromosome segregation – have been demonstrated to function in repetitive gene regulation and transposon silencing in several species. In model system Caenorhabditis elegans, microarray analysis studies have implicated Condensin II subunit HCP-6 in the silencing of multiple loci, including DNA transposon MIRAGE. To address the hypothesis that HCP-6 has a direct function in ...


Mtorc2 Is Required For Rit-Mediated Oxidative Stress Resistance, Weikang Cai, Douglas A. Andres Dec 2014

Mtorc2 Is Required For Rit-Mediated Oxidative Stress Resistance, Weikang Cai, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Rit, a member of the Ras family of GTPases, has been shown to promote cell survival in response to oxidative stress, in part by directing an evolutionarily conserved p38 MAPK-Akt survival cascade. Aberrant Rit signaling has recently been implicated as a driver mutation in human cancer, adding importance to the characterization of critical Rit effector pathways. However, the mechanism by which Rit-p38 signaling regulated Akt activity was unknown. Here, we identify mTORC2 as a critical downstream mediator of Rit-dependent survival signaling in response to reactive oxygen species (ROS) stress. Rit interacts with Sin1 (MAPKAP1), and Rit loss compromises ROS-dependent mTORC2 ...


Investigating The Links Between Ozone And Organic Aerosol Chemistry In A Biomass Burning Plume From A Prescribed Fire In California Chaparral, M. J. Alvarado, C. R. Lonsdale, Robert Yokelson, S. K. Akagi, H. Coe, J. S. Craven, E. V. Fischer, G. R. Mcmeeking, J. H. Seinfeld, T. Soni, J. W. Taylor, D. R. Weise, C. E. Wold Dec 2014

Investigating The Links Between Ozone And Organic Aerosol Chemistry In A Biomass Burning Plume From A Prescribed Fire In California Chaparral, M. J. Alvarado, C. R. Lonsdale, Robert Yokelson, S. K. Akagi, H. Coe, J. S. Craven, E. V. Fischer, G. R. Mcmeeking, J. H. Seinfeld, T. Soni, J. W. Taylor, D. R. Weise, C. E. Wold

Chemistry and Biochemistry Faculty Publications

Within minutes after emission, rapid, complex photochemistry within a biomass burning smoke plume can cause large changes in the concentrations of ozone (O3) and organic aerosol (OA). Being able to understand and simulate this rapid chemical evolution under a wide variety of conditions is a critical part of forecasting the impact of these fires on air quality, atmospheric composition, and climate. Here we use version 2.1 of the Aerosol Simulation Program (ASP) to simulate the evolution of O3 and secondary organic aerosol (SOA) within a young biomass burning smoke plume from the Williams prescribed burn in chaparral ...


Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett Dec 2014

Chromatin Regulators And Dna Repair: A Dissertation, Gwendolyn M. Bennett

GSBS Dissertations and Theses

DNA double-strand break (DSB) repair is essential for maintenance of genome stability. However, the compaction of the eukaryotic genome into chromatin creates an inherent barrier to any DNA-mediated event, such as during DNA repair. This demands that there be mechanisms to modify the chromatin structure and thus access DNA. Recent work has implicated a host of chromatin regulators in the DNA damage response and several functional roles have been defined. Yet the mechanisms that control their recruitment to DNA lesions, and their relationship with concurrent histone modifications, remain unclear. We find that efficient DSB recruitment of many yeast chromatin regulators ...


A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu Dec 2014

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased ...


Regulation Of Phialide Morphogenesis In Aspergillus Nidulans, Hu Yin Dec 2014

Regulation Of Phialide Morphogenesis In Aspergillus Nidulans, Hu Yin

Dissertations and Theses in Biological Sciences

Filamentous fungi have two distinctive life cycles, vegetative growth and development for sexual or asexual spore formation. The asexual reproduction in development as conidiation in A. nidulans is the dominant form of producing spores effectively. A complex conidiophore structure is developed during asexual reproduction process. The conidiophore is formed from hyphal cell and consists of stalk, vesicle, metulae, phialide and conidial spores. Phialides are essential sporogenous cells in the conidiophore structure. The growth pattern is switched from acropetal to basipetal between phialide and spores, which makes phialide a unique cell type in A. nidulans and other phialide producing fungi. Study ...


Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach Dec 2014

Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach

Theses

Contaminated sediments in marine environments have been shown to be good indicators of ecological risk and a means to assess anthropogenic impacts on marine habitats and the animals that inhabit them (Long et al. 1995, Rattner 2009). Estuarine sediments are especially complex media with regard to physical, chemical, and biological characteristics that trap, store, modify and sometimes release contaminants to the biota (Long et al. 1995). Especially vulnerable are animals that are in constant contact with the sediments, such as flatfishes that partially bury themselves for camouflage (Costa et al. 2011). Impacts can be assessed in a number of ways ...


Direct Interactions Promote Eviction Of The Sir3 Heterochromatin Protein By The Swi/Snf Chromatin Remodeling Enzyme, Benjamin J. Manning, Craig L. Peterson Dec 2014

Direct Interactions Promote Eviction Of The Sir3 Heterochromatin Protein By The Swi/Snf Chromatin Remodeling Enzyme, Benjamin J. Manning, Craig L. Peterson

GSBS Student Publications

Heterochromatin is a specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. Despite its globally repressive role, heterochromatin must also be dynamic, allowing for its repair and replication. In budding yeast, heterochromatin formation requires silent information regulators (Sirs) Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating-type loci. Previously, we found that the SWI/SNF chromatin remodeling enzyme can catalyze the ATP-dependent eviction of Sir3p from recombinant nucleosomal arrays, and this activity enhances early steps of recombinational repair in vitro. Here, we show that the ATPase subunit of ...


Unbiased Chromatin Accessibility Profiling By Red-Seq Uncovers Unique Features Of Nucleosome Variants In Vivo, Poshen B. Chen, Lihua Julie Zhu, Sarah J. Hainer, Kurtis N. Mccannell, Thomas G. Fazzio Dec 2014

Unbiased Chromatin Accessibility Profiling By Red-Seq Uncovers Unique Features Of Nucleosome Variants In Vivo, Poshen B. Chen, Lihua Julie Zhu, Sarah J. Hainer, Kurtis N. Mccannell, Thomas G. Fazzio

Open Access Articles

BACKGROUND: Differential accessibility of DNA to nuclear proteins underlies the regulation of numerous cellular processes. Although DNA accessibility is primarily determined by the presence or absence of nucleosomes, differences in nucleosome composition or dynamics may also regulate accessibility. Methods for mapping nucleosome positions and occupancies genome-wide (MNase-seq) have uncovered the nucleosome landscapes of many different cell types and organisms. Conversely, methods specialized for the detection of large nucleosome-free regions of chromatin (DNase-seq, FAIRE-seq) have uncovered numerous gene regulatory elements. However, these methods are less successful in measuring the accessibility of DNA sequences within nucelosome arrays.

RESULTS: Here we probe the ...


Development Of An Immunodiagnostic Assay For Canine Tear Lacritin, Alison Mae Enghauser Dec 2014

Development Of An Immunodiagnostic Assay For Canine Tear Lacritin, Alison Mae Enghauser

Senior Honors Projects, 2010-current

Purpose: Lacritin is a naturally occurring human glycoprotein secreted from the lacrimal gland as a component of tears. Preliminary studies suggest that down-regulation of lacritin is associated with various ocular diseases, such as dry eye syndrome and blepharitis. Thus, lacritin shows potential as a new topical therapeutic for the treatment of ocular diseases. Previous studies have shown that recombinant human lacritin, when topically applied to rabbit eyes, promotes basal tearing. Antibodies produced against the terminal ends of human lacritin were used to develop a clinical immunodiagnostic assay that detect and quantify lacritin in human tear samples. In order to develop ...


Synthesis And Characterization Of Polymer (Sulfonated Poly-Ether-Ether-Ketone) Based Nanocomposite (H-Boron Nitride) Membrane For Hydrogen Storage, Naresh Muthu, S. Rajashabala, R. Kannan Dec 2014

Synthesis And Characterization Of Polymer (Sulfonated Poly-Ether-Ether-Ketone) Based Nanocomposite (H-Boron Nitride) Membrane For Hydrogen Storage, Naresh Muthu, S. Rajashabala, R. Kannan

Chemistry and Biochemistry Faculty Publications

The development of light weight and compact hydrogen storage materials is still prerequisite to fuel-cell technology to be fully competitive. The present experimental study reports the hydrogen storage capability of sulfonated poly-ether-ether-ketone (SPEEK)-hexagonal boron nitride (h-BN) (SPEEK-h-BN) nanocomposite membranes. The nanocomposite membranes are prepared by considering various amount of h-BN (0, 1, 3 and 5 wt. %) by phase inversion technique. The degree of sulfonation of the PEEK (SPEEK) is found to be 65% by Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. Hydrogen adsorption studies have been carried out using a Seiverts-like hydrogenation setup. The membranes are characterized by ...


Transcriptomic And Proteomic Dynamics In The Metabolism Of A Diazotrophic Cyanobacterium, Cyanothece Sp. Pcc 7822 During A Diurnal Light-Dark Cycle, Louis Sherman Dec 2014

Transcriptomic And Proteomic Dynamics In The Metabolism Of A Diazotrophic Cyanobacterium, Cyanothece Sp. Pcc 7822 During A Diurnal Light-Dark Cycle, Louis Sherman

Louis A Sherman

Background: Cyanothece sp. PCC 7822 is an excellent cyanobacterial model organism with great potential to be applied as a biocatalyst for the production of high value compounds. Like other unicellular diazotrophic cyanobacterial species, it has a tightly regulated metabolism synchronized to the light-dark cycle. Utilizing transcriptomic and proteomic methods, we were able to quantify the relationships between transcription and translation underlying central and secondary metabolism in response to nitrogen free, 12 hour light and 12 hour dark conditions.

Results: By combining mass-spectrometry based proteomics and RNA-sequencing transcriptomics, we quantitatively measured a total of 6766 mRNAs and 1322 proteins at four ...


Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker Dec 2014

Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Student Scholar Symposium Abstracts and Posters

The molecular chaperone protein Hsp70 is centrally involved in cellular homeostasis by assisting in the folding and degradation of protein substrates. Hsp70 is joined by co-chaperones, such as Hsp110, which contribute to specialized tasks of the Hsp70 complex. Imbalances of this heat shock protein system are believed to be involved with the deregulation of cancer pathways and other human diseases. Better understanding of how these heat shock proteins work at the molecular level, which has been investigated using molecular docking tools, will give more clues about biological function. Simulating the formation and function of Hsp70 based chaperone complexes could provide ...


Hcpe, A Potential Immuno-Modulatory Protein From Helicobacter Pylori That Is Dependent On The Disulfide Bond Protein Dsbhp, Jeff Lester Dec 2014

Hcpe, A Potential Immuno-Modulatory Protein From Helicobacter Pylori That Is Dependent On The Disulfide Bond Protein Dsbhp, Jeff Lester

Electronic Thesis and Dissertation Repository

H. pylori is a human gastric pathogen that colonizes ~ 50% of the world’s population. It can cause gastritis, gastric or duodenal ulcers and also gastric cancer. H. pylori produces Helicobacter cysteine rich protein HcpE, a secreted protein which may play a role in virulence. In this study we show that HcpE is secreted in the culture supernatant both as a soluble protein and in association with outer membrane vesicles, and may play a role in the modulation of H. pylori inflammatory responses. We identified that DsbHP is necessary for HcpE production and secretion in H. pylori, and demonstrated ...


[Alpha]-Amylase Action And 13c-Nmr Studies On Amylose-V Complexes And Retrograded Amylose, Jay-Lin Jane Dec 2014

[Alpha]-Amylase Action And 13c-Nmr Studies On Amylose-V Complexes And Retrograded Amylose, Jay-Lin Jane

Jay-Lin Jane

Aqueous amylodextrins form helical complexes with alcohol, halogenated hydrocarbons, and triiodide known as V-complexes. With the formation of these complexes, the ('13)C-nuclear magnetic resonance (n.m.r.) signals of carbons 1 and 4 are shifted substantially downfield due to rotations about the glycosidic bond necessary to form the helical conformation. ('13)C-N.m.r. studies with amylodextrin, (alpha)-methyl D-glucoside, and (alpha)-methyl maltoside complexes suggest a complexing mechanism in which pyranose ring strain, induced by binding of the complexing agent, is relieved by rotations about the glycosidic bonds.;Retrograded amylodextrin, gives ('1)H and ('13)C n.m ...


The Recombination Enhancer Modulates The Conformation Of Chr. Iii In Budding Yeast: A Dissertation, Jon-Matthew Belton Dec 2014

The Recombination Enhancer Modulates The Conformation Of Chr. Iii In Budding Yeast: A Dissertation, Jon-Matthew Belton

GSBS Dissertations and Theses

A hierarchy of different chromosome conformations plays a role in many biological systems. These conformations contribute to the regulation of gene expression, cellular development, chromosome transmission, and defects can lead to human disease. The highest functional level of this hierarchy is the partitioning of the genome into compartments of active and inactive chromatin domains (1’s -10’s Mb). These compartments are further partitioned into Topologically Associating Domains (TADs) that spatially cluster co-regulated genes (100’s kb – 1’s Mb). The final level that has been observed is long range loops formed between regulatory elements and promoters (10’s kb ...


Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), Michael Hoffmann Dec 2014

Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), Michael Hoffmann

Michael H.G. Hoffmann

This argument shows how the hypothesis that muscles are probably stimulated exclusively by chemical signals and not by electrical ones can be justified by Loewi's experimentum crucis.


Effect Of Intracellular Expression Of Antimicrobial Peptide Ll-37 On Growth Of Escherichia Coli Strain Top10 Under Aerobic And Anaerobic Conditions, Wei Liu, Shi Dong, Fei Xu, Xue Wang, T. Withers, Hongwei Yu, Xin Wang Dec 2014

Effect Of Intracellular Expression Of Antimicrobial Peptide Ll-37 On Growth Of Escherichia Coli Strain Top10 Under Aerobic And Anaerobic Conditions, Wei Liu, Shi Dong, Fei Xu, Xue Wang, T. Withers, Hongwei Yu, Xin Wang

Hongwei Yu

Antimicrobial peptides (AMPs) can cause lysis of target bacteria by directly inserting themselves into the lipid bilayer. This killing mechanism confounds the identification of the intracellular targets of AMPs. To circumvent this, we used a shuttle vector containing the inducible expression of a human cathelicidin-related AMP, LL-37, to examine its effect on Escherichia coli TOP10 under aerobic and anaerobic growth conditions. Induction of LL-37 caused growth inhibition and alteration in cell morphology to a filamentous phenotype. Further examination of the E. coli cell division protein FtsZ revealed that LL-37 did not interact with FtsZ. Moreover, intracellular expression of LL-37 results ...


Design, Assessment, And In Vivo Evaluation Of A Computational Model Illustrating The Role Of Cav1 In Cd4+ T-Lymphocytes, Brittany D. Conroy, Tyler A. Herek, Timonthy D. Shew, Matthew Latner, Joshua J. Larson, Laura Allen, Paul H. Davis, Tomáš Helikar, Christine E. Cutucache Dec 2014

Design, Assessment, And In Vivo Evaluation Of A Computational Model Illustrating The Role Of Cav1 In Cd4+ T-Lymphocytes, Brittany D. Conroy, Tyler A. Herek, Timonthy D. Shew, Matthew Latner, Joshua J. Larson, Laura Allen, Paul H. Davis, Tomáš Helikar, Christine E. Cutucache

Biochemistry -- Faculty Publications

Caveolin-1 (CAV1) is a vital scaffold protein heterogeneously expressed in both healthy and malignant tissue. We focus on the role of CAV1 when overexpressed in T-cell leukemia. Previously, we have shown that CAV1 is involved in cell-to-cell communication, cellular proliferation, and immune synapse formation; however, the molecular mechanisms have not been elucidated.We hypothesize that the role of CAV1 in immune synapse formation contributes to immune regulation during leukemic progression, thereby warranting studies of the role of CAV1 in CD4+ T-cells in relation to antigen-presenting cells. To address this need, we developed a computational model of a CD4+ immune effector ...


Gaip Interacting Protein C-Terminus Regulates Autophagy And Exosome Biogenesis Of Pancreatic Cancer Through Metabolic Pathways, Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay Dec 2014

Gaip Interacting Protein C-Terminus Regulates Autophagy And Exosome Biogenesis Of Pancreatic Cancer Through Metabolic Pathways, Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay

Open Dartmouth: Faculty Open Access Articles

GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular ...


Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan Dec 2014

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq ...


Novel Mechanisms In The Sorting Of Proglucagon To The Secretory Granules Of The Regulated Secretory Pathway, Leonard M. Guizzetti Dec 2014

Novel Mechanisms In The Sorting Of Proglucagon To The Secretory Granules Of The Regulated Secretory Pathway, Leonard M. Guizzetti

Electronic Thesis and Dissertation Repository

The prohormone proglucagon encodes for multiple peptide hormones, including glucagon, glucagon-like peptide-1 (GLP-1), and GLP-2, produced through tissue-specific processing by prohormone convertase (PC) 1/3 and PC2. In alpha cells, PC2 yields glucagon, the major counter-regulatory hormone to insulin, which together, control glucose homeostasis. In contrast, GLP-1 and GLP2 are mainly produced in intestinal L-cells by PC1/3. GLP-1 stimulates insulin secretion following a meal, and therefore has opposing function to glucagon regulating glucose homeostasis; in contrast, GLP-2 enhances gut nutrient absorption. Efficient sorting of proglucagon to secretory granules is required for nutrient-regulated secretion. The aim of this thesis is ...


Ethanol Modulation Of Mammalian Bk Channels In Excitable Tissues: Molecular Targets And Their Possible Contribution To Alcohol-Induced Altered Behavior, Alex M. Dopico, Anna N. Bukiya, Gilles E. Martin Dec 2014

Ethanol Modulation Of Mammalian Bk Channels In Excitable Tissues: Molecular Targets And Their Possible Contribution To Alcohol-Induced Altered Behavior, Alex M. Dopico, Anna N. Bukiya, Gilles E. Martin

University of Massachusetts Medical School Faculty Publications

In most tissues, the function of Ca(2+)- and voltage-gated K(+) (BK) channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naive preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of ...


Novel Protein Secretion And Chitin Utilization Machinery Of Flavobacterium Johnsoniae, Sampada Suresh Kharade Dec 2014

Novel Protein Secretion And Chitin Utilization Machinery Of Flavobacterium Johnsoniae, Sampada Suresh Kharade

Theses and Dissertations

Flavobacterium johnsoniae, a member of phylum Bacteroidetes, is a gliding bacterium that digests insoluble chitin. A novel protein secretion system, the Type IX secretion system (T9SS), secretes the motility adhesins SprB and RemA and is also required for chitin utilization. In order to understand F. johnsoniae chitin utilization and the role of the T9SS, Fjoh_4555 (chiA) was targeted for analysis. Disruption of chiA resulted in cells that failed to digest chitin and complementation restored this ability. Antisera raised against ChiA were used to characterize its secretion. ChiA was secreted in soluble form by wild-type cells but remained cell-associated in T9SS ...


Oligomerization Of The Sterile-2 G-Protein Coupled Receptor In Yeast Cells In The Presence And Absence Of Alpha-Factor Pheromone Using Fluorescence Spectroscopy And Forster Resonance Energy Transfer Analysis, Joel David Paprocki Dec 2014

Oligomerization Of The Sterile-2 G-Protein Coupled Receptor In Yeast Cells In The Presence And Absence Of Alpha-Factor Pheromone Using Fluorescence Spectroscopy And Forster Resonance Energy Transfer Analysis, Joel David Paprocki

Theses and Dissertations

G-protein-coupled receptors (GPCRs) are the largest family of receptors that respond to a wide variety of extracellular stimuli, including molecular ligands such as odorants, neurotransmitters, and hormones, as well as physical agents sigh as light and pressure. The stimulation event results in initiating conformational changes in the structure of the receptor, which further results in the release of the heterotrimeric G-protein; the latter has a variety of functions within signaling pathways in cellular biology. The GPCR explored in this investigation is the Sterile 2 α-factor receptor (Ste2), whose natural function is that of a yeast mating pheromone receptor. Its natural ...


Interaction Of Rhizobium Sp. Strain Irbg74 With A Legume (Sesbania Cannabina) And A Cereal (Oryza Sativa), Shubhajit Mitra Dec 2014

Interaction Of Rhizobium Sp. Strain Irbg74 With A Legume (Sesbania Cannabina) And A Cereal (Oryza Sativa), Shubhajit Mitra

Theses and Dissertations

Rhizobium sp. IRBG74 (IRBG74) develops a classical nitrogen-fixing symbiosis with the legume Sesbania cannabina and also promotes the growth of rice (Oryza sativa), but not much is known about the rhizobial determinants important for these interactions. We hypothesize that Rhizobium sp. IRBG74 utilizes similar mechanisms to endophytically colonize both legume and cereal hosts. In this study, we analyzed the colonization of rice and S. cannabina using a strain of IRBG74 marked with β-glucuronidase (GUS) and Green Fluorescent Protein (GFP). IRBG74 infected both of the host plants through crack entry under submerged conditions, but showed root hair mediated infection under aerobic ...