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2016

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Articles 1 - 30 of 183

Full-Text Articles in Molecular Biology

Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones Dec 2016

Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones

UMass Metabolic Network Publications

The p53 tumor suppressor acts as a guardian of the genome by preventing the propagation of DNA damage-induced breaks and mutations to subsequent generations of cells. We have previously shown that phosphorylation of the Mdm2 oncoprotein at Ser394 by the ATM kinase is required for robust p53 stabilization and activation in cells treated with ionizing radiation, and that loss of Mdm2 Ser394 phosphorylation leads to spontaneous tumorigenesis and radioresistance in Mdm2S394A mice. Previous in vitro data indicate that the c-Abl kinase phosphorylates Mdm2 at the neighboring residue (Tyr393) in response to DNA damage to regulate p53-dependent apoptosis. In this present ...


Wzb117 (2-Fluoro-6-(M-Hydroxybenzoyloxy) Phenyl M-Hydroxybenzoate) Inhibits Glut1-Mediated Sugar Transport By Binding Reversibly At The Exofacial Sugar Binding Site, Ogooluwa A. Ojelabi, Kenneth P. Lloyd, Andrew Simon, Julie K. De Zutter, Anthony Carruthers Dec 2016

Wzb117 (2-Fluoro-6-(M-Hydroxybenzoyloxy) Phenyl M-Hydroxybenzoate) Inhibits Glut1-Mediated Sugar Transport By Binding Reversibly At The Exofacial Sugar Binding Site, Ogooluwa A. Ojelabi, Kenneth P. Lloyd, Andrew Simon, Julie K. De Zutter, Anthony Carruthers

UMass Metabolic Network Publications

WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 mum but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with Ki(app) = 0.3 mum but is a competitive inhibitor of sugar exit indicating that WZB117 and CB ...


New Open Conformation Of Smyd3 Implicates Conformational Selection And Allostery, Nicholas Spellmon, Xiaonan Sun, Wen Xue, Joshua Holcomb, Srinivas Chakravarthy, Weifeng Shang, Brian Fp Edwards, Nualpun Sirinupong, Chunying Li, Zhe Yang Dec 2016

New Open Conformation Of Smyd3 Implicates Conformational Selection And Allostery, Nicholas Spellmon, Xiaonan Sun, Wen Xue, Joshua Holcomb, Srinivas Chakravarthy, Weifeng Shang, Brian Fp Edwards, Nualpun Sirinupong, Chunying Li, Zhe Yang

Biochemistry and Molecular Biology Faculty Publications

SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational ...


High Epstein-Barr Virus Load And Genomic Diversity Are Associated With Generation Of Gp350-Specific Neutralizing Antibodies Following Acute Infectious Mononucleosis, Eric R. Weiss, Galit Alter, Javier Gordon Ogembo, Jennifer L. Henderson, Barbara Tabak, Yasin Bakis, Mohan Somasundaran, Manuel Garber, Liisa K. Selin, Katherine Luzuriaga Dec 2016

High Epstein-Barr Virus Load And Genomic Diversity Are Associated With Generation Of Gp350-Specific Neutralizing Antibodies Following Acute Infectious Mononucleosis, Eric R. Weiss, Galit Alter, Javier Gordon Ogembo, Jennifer L. Henderson, Barbara Tabak, Yasin Bakis, Mohan Somasundaran, Manuel Garber, Liisa K. Selin, Katherine Luzuriaga

Garber Lab Publications

The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 ...


Ctcf-Mediated Topological Boundaries During Development Foster Appropriate Gene Regulation, Varun Narendra, Milica Bulajic, Job Dekker, Esteban O. Mazzoni, Danny Reinberg Dec 2016

Ctcf-Mediated Topological Boundaries During Development Foster Appropriate Gene Regulation, Varun Narendra, Milica Bulajic, Job Dekker, Esteban O. Mazzoni, Danny Reinberg

Program in Systems Biology Publications and Presentations

The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains ...


Pgc-1alpha Dictates Endothelial Function Through Regulation Of Enos Expression, Siobhan M. Craige, Swenja Kroller-Schon, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M. Contractor, Yongmei Pei, Eberhard Schulz, John F. Keaney Jr. Dec 2016

Pgc-1alpha Dictates Endothelial Function Through Regulation Of Enos Expression, Siobhan M. Craige, Swenja Kroller-Schon, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M. Contractor, Yongmei Pei, Eberhard Schulz, John F. Keaney Jr.

UMass Metabolic Network Publications

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1alpha (PGC-1alpha) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1alpha in vascular function using mice with endothelial specific loss of function (PGC-1alpha EC KO) and endothelial specific gain of function (PGC-1alpha EC TG). Here we report that endothelial PGC-1alpha is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1alpha sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1alpha EC TG mice were ...


The Effects Of High Concentrations Of Ionic Liquid On Gb1 Protein Structure And Dynamics Probed By High-Resolution Magic-Angle-Spinning Nmr Spectroscopy, Lisa Warner, Erica Gjersing, Shelby E. Follett, K. Wade Elliott, Sergei V. Dzyuba, Krisztina Varga Dec 2016

The Effects Of High Concentrations Of Ionic Liquid On Gb1 Protein Structure And Dynamics Probed By High-Resolution Magic-Angle-Spinning Nmr Spectroscopy, Lisa Warner, Erica Gjersing, Shelby E. Follett, K. Wade Elliott, Sergei V. Dzyuba, Krisztina Varga

Biomolecular Research Center Publications and Presentations

Ionic liquids have great potential in biological applications and biocatalysis, as some ionic liquids can stabilize proteins and enhance enzyme activity, while others have the opposite effect. However, on the molecular level, probing ionic liquid interactions with proteins, especially in solutions containing high concentrations of ionic liquids, has been challenging. In the present work the 13C, 15N-enriched GB1 model protein was used to demonstrate applicability of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy to investigate ionic liquid–protein interactions. Effect of an ionic liquid (1-butyl-3- methylimidazolium bromide, [C4-mim]Br) on GB1was studied over a wide range of the ...


Freeze Tolerance Of Cyphoderris Monstrosa (Orthoptera: Prophalangopsidae), Jantina Toxopeus, Jacqueline Lebenzon, Alexander H. Mckinnon, Brent J. Sinclair Dec 2016

Freeze Tolerance Of Cyphoderris Monstrosa (Orthoptera: Prophalangopsidae), Jantina Toxopeus, Jacqueline Lebenzon, Alexander H. Mckinnon, Brent J. Sinclair

Biology Publications

The great grig, Cyphoderris monstrosa Uhler (Orthoptera: Prophalangopsidae), is a large (20-30 mm, >1 g), nocturnal ensiferan that in habits montane coniferous forests in northwestern North America. C. monstrosa overwinters as a late-instar nymph, but its cold tolerance strategy has not previously been reported. We collected nymphs from near Kamloops, British Columbia, in late spring to determine their cold tolerance strategy. C. monstrosa nymphs were active at low temperatures until they froze at -4.6 ± 0.3 °C. The nymphs survived internal ice formation (i.e. are freeze tolerant), had a lethal temperature between -9 and -12 °C, and could ...


Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim Dec 2016

Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim

UMass Metabolic Network Publications

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates ...


Structural Basis For The Recognition Of Spliceosomal Smn/B/B' Proteins By The Rbm5 Ocre Domain In Splicing Regulation, André Mourão, Sophie Bonnal, Komal Soni, Lisa Warner, Rémy Bordonné, Juan Valcárcel, Michael Sattler Nov 2016

Structural Basis For The Recognition Of Spliceosomal Smn/B/B' Proteins By The Rbm5 Ocre Domain In Splicing Regulation, André Mourão, Sophie Bonnal, Komal Soni, Lisa Warner, Rémy Bordonné, Juan Valcárcel, Michael Sattler

Biomolecular Research Center Publications and Presentations

The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for alternative splicing regulation and mediates interactions with components of the U4/U6.U5 tri-snRNP. We show that the RBM5 OCRE domain adopts a unique β–sheet fold. NMR and biochemical experiments demonstrate that the OCRE domain directly binds to the proline-rich C-terminal tail of the essential snRNP core proteins SmN/B/B’. The NMR structure of an OCRE-SmN peptide complex reveals a specific recognition of poly-proline ...


Direct Characterization Of The Maize Starch Synthase Iia Product Shows Maltodextrin Elongation Occurs At The Non-Reducing End, Mark E. Larson, Daniel J. Falconer, Alan M. Myers, Adam W. Barb Nov 2016

Direct Characterization Of The Maize Starch Synthase Iia Product Shows Maltodextrin Elongation Occurs At The Non-Reducing End, Mark E. Larson, Daniel J. Falconer, Alan M. Myers, Adam W. Barb

Biochemistry, Biophysics and Molecular Biology Publications

A comprehensive description of starch biosynthesis and granule assembly remains undefined despite the central nature of starch as an energy storage molecule in plants and as a fundamental calorie source for many animals. Multiple theories regarding the starch synthase (SS)-catalyzed assembly of (α1–4)-linked D-glucose molecules into maltodextrins generally agree that elongation occurs at the non-reducing terminus based on the degradation of radiolabeled maltodextrins, although recent reports challenge this hypothesis. Surprisingly, a direct analysis of the SS catalytic product has not been reported, to our knowledge. We expressed and characterized recombinant Zea mays SSIIa and prepared pure ADP- ...


Digitor/Dasciz Has Multiple Roles In Drosophila Development, Saheli Sengupta, Uttama Rath, Changfu Yao, Michael Zavortink, Chao Wang, Jack Girton, Kristen M. Johansen, Jorgen Johansen Nov 2016

Digitor/Dasciz Has Multiple Roles In Drosophila Development, Saheli Sengupta, Uttama Rath, Changfu Yao, Michael Zavortink, Chao Wang, Jack Girton, Kristen M. Johansen, Jorgen Johansen

Biochemistry, Biophysics and Molecular Biology Publications

In this study we provide evidence that the spindle matrix protein Skeletor in Drosophila interacts with the human ASCIZ (also known as ATMIN and ZNF822) ortholog, Digitor/dASCIZ. This interaction was first detected in a yeast two-hybrid screen and subsequently confirmed by pull-down assays. We also confirm a previously documented function of Digitor/dASCIZ as a regulator of Dynein light chain/Cut up expression. Using transgenic expression of a mCitrine-labeled Digitor construct, we show that Digitor/dASCIZ is a nuclear protein that is localized to interband and developmental puff chromosomal regions during interphase but redistributes to the spindle region during ...


Pld-Specific Small-Molecule Inhibitors Decrease Tumor-Associated Macrophages And Neutrophils Infiltration In Breast Tumors And Lung And Liver Metastases, Karen M. Henkels, Naveen Reddy Muppani, Julian Gomez-Cambronero Nov 2016

Pld-Specific Small-Molecule Inhibitors Decrease Tumor-Associated Macrophages And Neutrophils Infiltration In Breast Tumors And Lung And Liver Metastases, Karen M. Henkels, Naveen Reddy Muppani, Julian Gomez-Cambronero

Biochemistry and Molecular Biology Faculty Publications

Phospholipase D-2 (PLD2) has a key role in breast cancer formation and metastasis formation with PLD small inhibitors reducing primary tumor growth. This study aimed to evaluate the importance of targeting PLD on the tumor microenvironment. We provide evidence about the beneficial effect of PLD inhibitors [FIPI (dual PLD1/PLD2) or VU0155072-2 (PLD2 inhibitor)] on avoiding infiltration of tumor-helping macrophages and neutrophils. Tumor growth and metastasis within the primary tumors had low (<20% over controls) PLD enzyme activity. Unexpectedly, we found that the inhibitors also affected PLD2 gene expression and protein albeit at a lesser extent. The later could indicate that targeting both the actual PLD enzyme and its activity could be beneficial for potential cancer treatments in vivo. F4/80 and Ly6G staining of macrophages and neutrophils, respectively, and Arg1 staining data were consistent with M2 and N2 polarization. NOS2 staining increased in xenotransplants ...


Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio Nov 2016

Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio

Open Access Articles

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that ...


Co2-Fixing One-Carbon Metabolism In A Cellulose-Degrading Bacterium Clostridium Thermocellum, Wei Xiong, Paul P. Lin, Lisa Warner, James C. Liao, Pin-Ching Maness, Katherine J. Chou Nov 2016

Co2-Fixing One-Carbon Metabolism In A Cellulose-Degrading Bacterium Clostridium Thermocellum, Wei Xiong, Paul P. Lin, Lisa Warner, James C. Liao, Pin-Ching Maness, Katherine J. Chou

Biomolecular Research Center Publications and Presentations

Clostridium thermocellum can ferment cellulosic biomass to formate and other end products, including CO2. This organism lacks formate dehydrogenase (Fdh), which catalyzes the reduction of CO2 to formate. However, feeding the bacterium 13C-bicarbonate and cellobiose followed by NMR analysis showed the production of 13C-formate in C. thermocellum culture, indicating the presence of an uncharacterized pathway capable of converting CO2 to formate. Combining genomic and experimental data, we demonstrated that the conversion of CO2 to formate serves as a CO2 entry point into the reductive one-carbon (C1) metabolism, and internalizes CO2 via two ...


Intraflagellar Transport Protein Ift20 Is Essential For Male Fertility And Spermiogenesis In Mice, Zhengang Zhang, Wei Li, Yong Zhang, Ling Zhang, Maria E. Teves, Hong Liu, Jerome F. Strauss 3rd, Gregory J. Pazour, James A. Foster, Rex A. Hess, Zhibing Zhang Nov 2016

Intraflagellar Transport Protein Ift20 Is Essential For Male Fertility And Spermiogenesis In Mice, Zhengang Zhang, Wei Li, Yong Zhang, Ling Zhang, Maria E. Teves, Hong Liu, Jerome F. Strauss 3rd, Gregory J. Pazour, James A. Foster, Rex A. Hess, Zhibing Zhang

University of Massachusetts Medical School Faculty Publications

Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and a decrease in mature lysosomes. The few developed sperm had ...


Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim Nov 2016

Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim

University of Massachusetts Medical School Faculty Publications

Skeletal muscle insulin resistance is a major characteristic of obesity and type 2 diabetes. Although obesity-mediated inflammation is causally associated with insulin resistance, the underlying mechanism is unclear. Here, we examined the effects of chronic obesity in mice with muscle-specific overexpression of interleukin-10 (MIL10). After 16 weeks of a high-fat diet (HFD), MIL10 mice became markedly obese but showed improved insulin action compared to that of wild-type mice, which was largely due to increased glucose metabolism and reduced inflammation in skeletal muscle. Since leptin regulates inflammation, the beneficial effects of interleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice ...


Screening Of Plants For Antibacterial Properties: Growth Inhibition Of Staphylococcus Aureus By Artemisia Tridentata, Steven Ross Eichelbaum Nov 2016

Screening Of Plants For Antibacterial Properties: Growth Inhibition Of Staphylococcus Aureus By Artemisia Tridentata, Steven Ross Eichelbaum

FIU Electronic Theses and Dissertations

Drug-resistant pathogenic and opportunistic bacteria are increasing in occurrence and prevalence, and pose a dangerous threat to human health. In the search for novel antibiotics with which to combat this threat, plants, specifically those used in traditional medicine with ascribed antibacterial properties, offer a promising and potentially vast source of such therapeutic compounds. The purpose of this study was therefore to screen chemical extracts created from various plant species for antibacterial properties versus pathogenic bacterial species. In the course of these antibacterial assays, we successfully identified a methanol extract derived from Artemisia tridentata tridentata plant material as capable of inhibiting ...


Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo Nov 2016

Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo

GSBS Student Publications

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT ...


Microbial Functional Diversity And The Associated Biogeochemical Interactions Across Miami-Dade County, Florida Soils, Priyanka Kushwaha Nov 2016

Microbial Functional Diversity And The Associated Biogeochemical Interactions Across Miami-Dade County, Florida Soils, Priyanka Kushwaha

FIU Electronic Theses and Dissertations

Decomposition of soil organic matter by microbial processes results in carbon sequestration within soils and/or carbon loss via atmospheric emission of carbon dioxide and methane. Natural as well as anthropogenic factors have been documented to impact soil microbial diversity and the associated biogeochemical functions. The soil microbial communities co-inhabiting Miami-Dade County soils, Florida are under threat because of the ongoing restoration efforts in the adjoining Florida Everglades Parks, predicted climatic changes such as sea-level rise and high rainfall, as well as urbanization. Therefore, an improved understanding of the current microbial functional communities is essential to better assess the impact ...


Assessing The Risk Of Resistance Evolution, Adult And Larval Susceptibility, And Sublethal Effects After Exposure Of Corn Rootworms To Vacuolar Atpase-A And Snf7 Dsrnas, Adriano Elias Pereira Nov 2016

Assessing The Risk Of Resistance Evolution, Adult And Larval Susceptibility, And Sublethal Effects After Exposure Of Corn Rootworms To Vacuolar Atpase-A And Snf7 Dsrnas, Adriano Elias Pereira

Dissertations and Student Research in Entomology

Corn rootworms are Diabroticite beetles from the genus Diabrotica and include the western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, and the northern corn rootworm, D. barberi Smith & Lawrence, as the most important pests in the U.S. Corn Belt. The southern corn rootworm (SCR), D. undecimpunctata howardi Barber, is considered a polyphagous plant pest and feeds in a wide variety of plants including peanuts, cucurbits, soybeans, and especially corn. Resistance to control methods including behavioral resistance to crop rotation and to corn hybrids expressing Bacillus thuringiensis Berliner toxins in WCR has frequently been reported. SCR has been considered a ...


Extending A Single Residue Switch For Abbreviating Catalysis In Plant Ent-Kaurene Synthases, Meirong Jia, Reuben J. Peters Nov 2016

Extending A Single Residue Switch For Abbreviating Catalysis In Plant Ent-Kaurene Synthases, Meirong Jia, Reuben J. Peters

Biochemistry, Biophysics and Molecular Biology Publications

Production of ent-kaurene as a precursor for important signaling molecules such as the gibberellins seems to have arisen early in plant evolution, with corresponding cyclase(s) present in all land plants (i.e., embryophyta). The relevant enzymes seem to represent fusion of the class II diterpene cyclase that produces the intermediate ent-copalyl diphosphate (ent-CPP) and the subsequently acting class I diterpene synthase that produces ent-kaurene, although the bifunctionality of the ancestral gene is only retained in certain early diverging plants, with gene duplication and sub-functionalization leading to distinct ent-CPP synthases and ent-kaurene synthases (KSs ...


Identification Of A Dolabellane Type Diterpene Synthase And Other Root-Expressed Diterpene Synthases In Arabidopsis, Qiang Wang, Meirong Jia, Jung-Hyun Huh, Andrew Muchlinski, Reuben J. Peters, Dorothea Tholl Nov 2016

Identification Of A Dolabellane Type Diterpene Synthase And Other Root-Expressed Diterpene Synthases In Arabidopsis, Qiang Wang, Meirong Jia, Jung-Hyun Huh, Andrew Muchlinski, Reuben J. Peters, Dorothea Tholl

Biochemistry, Biophysics and Molecular Biology Publications

Arabidopsis thaliana maintains a complex metabolism for the production of secondary or specialized metabolites. Such metabolites include volatile and semivolatile terpenes, which have been associated with direct and indirect defensive activities in flowers and leaves. In comparison, the structural diversity and function of terpenes in Arabidopsis roots has remained largely unexplored despite a substantial number of root-expressed genes in the Arabidopsis terpene synthase (TPS) gene family. We show that five root-expressed TPSs of an expanded subfamily-a type clade in the Arabidopsis TPS family function as class I diterpene synthases that predominantly convert geranylgeranyl diphosphate (GGPP) to different semi-volatile diterpene products ...


Structural And Genetic Analyses Of The Mycobacterium Tuberculosis Protein Kinase B Sensor Domain Identify A Potential Ligand-Binding Site, Daniil M. Prigozhin, Kadamba Papavinasasundaram, Christina E. Baer, Kenan C. Murphy, Alisa Moskaleva, Tony Y. Chen, Tom Alber, Christopher M. Sassetti Oct 2016

Structural And Genetic Analyses Of The Mycobacterium Tuberculosis Protein Kinase B Sensor Domain Identify A Potential Ligand-Binding Site, Daniil M. Prigozhin, Kadamba Papavinasasundaram, Christina E. Baer, Kenan C. Murphy, Alisa Moskaleva, Tony Y. Chen, Tom Alber, Christopher M. Sassetti

UMass Metabolic Network Publications

Monitoring the environment with serine/threonine protein kinases is critical for growth and survival of Mycobacterium tuberculosis, a devastating human pathogen. Protein kinase B (PknB) is a transmembrane serine/threonine protein kinase that acts as an essential regulator of mycobacterial growth and division. The PknB extracellular domain (ECD) consists of four repeats homologous to penicillin-binding protein and serine/threonine kinase associated (PASTA) domains, and binds fragments of peptidoglycan. These properties suggest that PknB activity is modulated by ECD binding to peptidoglycan substructures, however, the molecular mechanisms underpinning PknB regulation remain unclear. In this study, we report structural and genetic characterization ...


Crystal Structure Of The Dna Binding Domain Of The Transcription Factor T-Bet Suggests Simultaneous Recognition Of Distant Genome Sites, Ce Feng Liu, Gabriel S. Brandt, Quyen Q. Hoang, Natalia Naumova, Vanja Lazarevic, Eun Sook Hwang, Job Dekker, Laurie H. Glimcher, Dagmar Ringe, Gregory A. Petsko Oct 2016

Crystal Structure Of The Dna Binding Domain Of The Transcription Factor T-Bet Suggests Simultaneous Recognition Of Distant Genome Sites, Ce Feng Liu, Gabriel S. Brandt, Quyen Q. Hoang, Natalia Naumova, Vanja Lazarevic, Eun Sook Hwang, Job Dekker, Laurie H. Glimcher, Dagmar Ringe, Gregory A. Petsko

Program in Systems Biology Publications and Presentations

The transcription factor T-bet (Tbox protein expressed in T cells) is one of the master regulators of both the innate and adaptive immune responses. It plays a central role in T-cell lineage commitment, where it controls the TH1 response, and in gene regulation in plasma B-cells and dendritic cells. T-bet is a member of the Tbox family of transcription factors; however, T-bet coordinately regulates the expression of many more genes than other Tbox proteins. A central unresolved question is how T-bet is able to simultaneously recognize distant Tbox binding sites, which may be located thousands of base pairs away. We ...


A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout Oct 2016

A Gene-Centered C. Elegans Protein-Dna Interaction Network Provides A Framework For Functional Predictions, Juan Fuxman Bass, Carles Pons, Lucie Kozlowski, John S. Reece-Hoyes, Shaleen Shrestha, Amy D. Holdorf, Akihiro Mori, Chad L. Myers, Albertha J. M. Walhout

Open Access Articles

Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90 ...


Cxcr4 Identifies Transitional Bone Marrow Premonocytes That Replenish The Mature Monocyte Pool For Peripheral Responses, Shu Zhen Chong, Maximilien Evrard, John E. Harris, Lai Guan Ng Oct 2016

Cxcr4 Identifies Transitional Bone Marrow Premonocytes That Replenish The Mature Monocyte Pool For Peripheral Responses, Shu Zhen Chong, Maximilien Evrard, John E. Harris, Lai Guan Ng

UMass Metabolic Network Publications

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the ...


Cxcr4 Identifies Transitional Bone Marrow Premonocytes That Replenish The Mature Monocyte Pool For Peripheral Responses, Shu Zhen Chong, John E. Harris, Lai Guan Ng Oct 2016

Cxcr4 Identifies Transitional Bone Marrow Premonocytes That Replenish The Mature Monocyte Pool For Peripheral Responses, Shu Zhen Chong, John E. Harris, Lai Guan Ng

UMass Metabolic Network Publications

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the ...


The Rna-Binding Protein Atx-2 Regulates Cytokinesis Through Par-5 And Zen-4, Megan M. Gnazzo, Eva-Maria E. Uhlemann, Alex R. Villarreal, Masaki Shirayama, Eddie G. Dominguez, Ahna R. Skop Oct 2016

The Rna-Binding Protein Atx-2 Regulates Cytokinesis Through Par-5 And Zen-4, Megan M. Gnazzo, Eva-Maria E. Uhlemann, Alex R. Villarreal, Masaki Shirayama, Eddie G. Dominguez, Ahna R. Skop

Open Access Articles

The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5-GFP, and ultimately a reduction of ...


Ataluren Stimulates Ribosomal Selection Of Near-Cognate Trnas To Promote Nonsense Suppression, Bijoyita Roy, Westley J. Friesen, Yuki Tomizawa, John D. Leszyk, Jin Zhuo, Briana Johnson, Jumana Dakka, Christopher R. Trotta, Xiaojiao Xue, Venkateshwar Mutyam, Kim M. Keeling, James A. Mobley, Steven M. Rowe, David M. Bedwell, Ellen M. Welch, Allan Jacobson Oct 2016

Ataluren Stimulates Ribosomal Selection Of Near-Cognate Trnas To Promote Nonsense Suppression, Bijoyita Roy, Westley J. Friesen, Yuki Tomizawa, John D. Leszyk, Jin Zhuo, Briana Johnson, Jumana Dakka, Christopher R. Trotta, Xiaojiao Xue, Venkateshwar Mutyam, Kim M. Keeling, James A. Mobley, Steven M. Rowe, David M. Bedwell, Ellen M. Welch, Allan Jacobson

Microbiology and Physiological Systems Publications and Presentations

A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in ...