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Articles 1 - 30 of 47

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

Some Of The Most Interesting Casp11 Targets Through The Eyes Of Their Authors, Andriy Kryshtafovych, John Moult, Arnaud Basle, Alex Burgin, Timonthy K. Craig, Robert A. Edwards, Deborah Fass, Marcus D. Hartmann, Mateusz Korycinski, Richard J. Lewis, Donald Lorimer, Andrei N. Lupas, Janet Newman, Thomas S. Peat, Kurt H. Piepenbrink, Janani Prahlad, Mark J. Van Raaij, Forest Rohwer, Anca M. Segall, Victor Seguritan, Eric J. Sundberg, Abhimanyu K. Singh, Mark A. Wilson, Torsten Schwede Jun 2019

Some Of The Most Interesting Casp11 Targets Through The Eyes Of Their Authors, Andriy Kryshtafovych, John Moult, Arnaud Basle, Alex Burgin, Timonthy K. Craig, Robert A. Edwards, Deborah Fass, Marcus D. Hartmann, Mateusz Korycinski, Richard J. Lewis, Donald Lorimer, Andrei N. Lupas, Janet Newman, Thomas S. Peat, Kurt H. Piepenbrink, Janani Prahlad, Mark J. Van Raaij, Forest Rohwer, Anca M. Segall, Victor Seguritan, Eric J. Sundberg, Abhimanyu K. Singh, Mark A. Wilson, Torsten Schwede

Kurt Piepenbrink

The Critical Assessment of protein Structure Prediction (CASP) experiment would not have been possible without the prediction targets provided by the experimental structural biology community. In this article, selected crystallographers providing targets for the CASP11 experiment discuss the functional and biological significance of the target proteins, highlight their most interesting structural features, and assess whether these features were correctly reproduced in the predictions submitted to CASP11.


Dna Uptake By Type Iv Filaments, Kurt H. Piepenbrink Jun 2019

Dna Uptake By Type Iv Filaments, Kurt H. Piepenbrink

Kurt Piepenbrink

Bacterial uptake of DNA through type IV filaments is an essential component of natural competence in numerous gram-positive and gram-negative species. Recent advances in the field have broadened our understanding of the structures used to take up extracellular DNA. Here, we review seminal experiments in the literature describing DNA binding by type IV pili, competence pili and the flp pili of Micrococcus luteus; collectively referred to here as type IV filaments. We compare the current state of the field on mechanisms of DNA uptake for these three appendage systems and describe the current mechanistic understanding of both DNA-binding and …


Phenotypic Screening Identifies Brefeldin A/Ascotoxin As An Inducer Of Lipid Storage In The Algae Chlamydomonas Reinhardtii, Nishikant Wase, Boqiang Tu, Paul N. Black, Concetta C. Dirusso Sep 2018

Phenotypic Screening Identifies Brefeldin A/Ascotoxin As An Inducer Of Lipid Storage In The Algae Chlamydomonas Reinhardtii, Nishikant Wase, Boqiang Tu, Paul N. Black, Concetta C. Dirusso

Nishikant Wase

The use of microalgae as a biofuel feedstock is highly desired, but current methods to induce lipid accumulation cause severe stress responses that limit biomass and, thus oil yield. To address these issues, a high throughput screening (HTS) method was devised to identify chemical inducers of growth and lipid accumulation. Optimization was performed to determine the most effective cell density, DMSO and Nile Red (NR) concentrations to monitor growth and lipid accumulation. The method was tested using 1717 compounds from National Cancer Institute (NCI) Diversity Set III and Natural Products Set II in Chlamydomonas reinhardtii. Cells were inoculated at …


Correction For Sandai Et Al., The Evolutionary Rewiring Of Ubiquitination Targets Has Reprogrammed The Regulation Of Carbon Assimilation In The Pathogenic Yeast Candida Albicans, Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown Jul 2017

Correction For Sandai Et Al., The Evolutionary Rewiring Of Ubiquitination Targets Has Reprogrammed The Regulation Of Carbon Assimilation In The Pathogenic Yeast Candida Albicans, Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Janet Walker

No abstract provided.


The Evolutionary Rewiring Of Ubiquitination Targets Has Reprogrammed The Regulation Of Carbon Assimilation In The Pathogenic Yeast Candida Albicans, Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown Jul 2017

The Evolutionary Rewiring Of Ubiquitination Targets Has Reprogrammed The Regulation Of Carbon Assimilation In The Pathogenic Yeast Candida Albicans, Doblin Sandai, Zhikang Yin, Laura Selway, David Stead, Janet Walker, Michelle D. Leach, Iryna Bohovych, Iuliana V. Ene, Stavroula Kastora, Susan Budge, Carol A. Munro, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Janet Walker

Microbes must assimilate carbon to grow and colonize their niches. Transcript profiling has suggested that Candida albicans, a major pathogen of humans, regulates its carbon assimilation in an analogous fashion to the model yeast Saccharomyces cerevisiae, repressing metabolic pathways required for the use of alterative nonpreferred carbon sources when sugars are available. However, we show that there is significant dislocation between the proteome and transcriptome in C. albicans. Glucose triggers the degradation of the ICL1 and PCK1 transcripts in C. albicans, yet isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are stable and are retained. Indeed, numerous enzymes required for the …


Isotopic Discrimination In The Double-Crested Cormorant (Phalacrocorax Auritus), Elizabeth C. Craig, Brian S. Dorr, Katie C. Hanson-Dorr, Jed P. Sparks, Paul D. Curtis Oct 2015

Isotopic Discrimination In The Double-Crested Cormorant (Phalacrocorax Auritus), Elizabeth C. Craig, Brian S. Dorr, Katie C. Hanson-Dorr, Jed P. Sparks, Paul D. Curtis

Brian S Dorr

The diet-tissue discrimination factor is the amount by which a consumer’s tissue varies isotopically from its diet, and is therefore a key element in models that use stable isotopes to estimate diet composition. In this study we measured discrimination factors in blood (whole blood, red blood cells and plasma), liver, muscle and feathers of Double- crested Cormorants (Phalacrocorax auritus) for stable isotope ratios of carbon, nitrogen and sulfur. Cormorants exhibited discrimination factors that differed significantly among tissue types (for carbon and nitrogen), and differed substantially (in the context of the isotopic variation among relevant prey species) from those observed in …


The Effects Of Acute And Chronic Hypoxia On Cortisol, Glucose And Lactate Concentrations In Different Populations Of Three-Spined Stickleback, E. A. O'Connor, T. G. Pottinger, L. U. Sneddon Apr 2015

The Effects Of Acute And Chronic Hypoxia On Cortisol, Glucose And Lactate Concentrations In Different Populations Of Three-Spined Stickleback, E. A. O'Connor, T. G. Pottinger, L. U. Sneddon

Lynne Sneddon, PhD

The response of individuals from three different populations of three-spined sticklebacks to acute and chronic periods of hypoxia (4.4 kPa DO, 2.2 mg l-1) were tested using measures of whole-body (WB) cortisol, glucose and lactate. Although there was no evidence of a neuroendocrine stress response to acute hypoxia, fish from the population least likely to experience hypoxia in their native habitat had the largest response to low oxygen, with significant evidence of anaerobic glycolysis after two hours of hypoxia. However, there was no measurable effect of a more prolonged period (seven days) of hypoxia on any of the fish in …


A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars Jun 2013

A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars

Yulia Dementieva

The effects of the polyunsaturated omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) on hematopoiesis are complex in that both FA forms are processed into leukotrienes, eicosanoids, and prostaglandins, which can have independent effects. These FA have antagonistic effects in that n-6 FA prostaglandins tend to be pro-proliferative and pro-inflammatory, while the effects of n-3 FA prostaglandins are the opposite. We have previously shown that diets high in n-3 FA reduce the size of the middle to later stage myeloid progenitor compartment in FVB X sv129 F1hybrid mice. To assay the effects of high n-3 FA diets on earlier stages …


Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles Jun 2013

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Goran Boskovic

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …


Functions And Future Applications Of F1 Atpase As Nanobioengine - Powering The Nanoworld!, Sandip S. Magdum Jan 2013

Functions And Future Applications Of F1 Atpase As Nanobioengine - Powering The Nanoworld!, Sandip S. Magdum

Sandip S. Magdum

Recent nanotechnological revolution mandates astonishing imagination about future nanoworld. Nature has ability to create nanobiomolecules which can function in extraordinary way which can be used to produce nano hybrid systems. The opportunity to use such nanobiomolecules in combination of nanomechanical systems for development of novel nano hybrid systems for their various applications needs to explore in further nanotechnological development. F1 ATPase is a subunit of ATP synthase, which is one of the biomolecular structure works on the plasma membrane of the living cell. The reversible function of F1 ATPase gives a counterclockwise rotation of γ shaft by hydrolyzing ATP and …


Structural Adaptations Of Proteins To Different Biological Membranes, Prof. Stephanie Tristram-Nagle, Irina Pogozheva, Harold Mosberg, Andrei Lomize Dec 2012

Structural Adaptations Of Proteins To Different Biological Membranes, Prof. Stephanie Tristram-Nagle, Irina Pogozheva, Harold Mosberg, Andrei Lomize

Prof. Stephanie Tristram-Nagle Ph.D.

To gain insight into adaptations of proteins to their membranes, intrinsic hydrophobic thicknesses, distributions of different chemical groups and profiles of hydrogen-bonding capacities (α and β) and the dipolarity/ polarizability parameter (π*) were calculated for lipid-facing surfaces of 460 integral α-helical, β-barrel and peripheral proteins from eight types of biomembranes. For comparison, polarity profiles were also calculated for ten artificial lipid bilayers that have been previously studied by neutron and X-ray scattering. Estimated hydrophobic thicknesses are 30–31 Å for proteins from endoplasmic reticulum, thylakoid, and various bacterial plasma membranes, but differ for proteins from outer bacterial, inner mitochondrial and eukaryotic …


Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman Oct 2012

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …


Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman Oct 2012

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods: Female SV 129 mice were divided into two groups and placed on …


Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman Oct 2012

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …


Morphology And Fracture Of Enamel, Sangwon Myoung, James Lee, Paul Constantino, Peter Lucas, Herzl Chai, Brian Law Sep 2012

Morphology And Fracture Of Enamel, Sangwon Myoung, James Lee, Paul Constantino, Peter Lucas, Herzl Chai, Brian Law

Paul J. Constantino

This study examines the inter-relation between enamel morphology and crack resistance by sectioning extracted human molars after loading to fracture. Cracks appear to initiate from tufts, hypocalcified defects at the enamel–dentin junction, and grow longitudinally around the enamel coat to produce failure. Microindentation corner cracks placed next to the tufts in the sections deflect along the tuft interfaces and occasionally penetrate into the adjacent enamel. Although they constitute weak interfaces, the tufts are nevertheless filled with organic matter, and appear to be stabilized against easy extension by self-healing, as well as by mutual stress-shielding and decussation, accounting at least in …


Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman Sep 2012

Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman

Susan H. Jackman

Objective: To determine the prevalence and site of isolation of different serotypes of group B streptococcus (GBS) colonization or infection at a small community hospital. Methods: GBS isolates were obtained from a small community hospital and were then serotyped as la, Ib, II, III, IV, V or non-typeable. Hospital records were reviewed for patient sex, age and pregnancy status as well as the site of GBS isolation. Results: GBS serotypes Ia, III and V were most common and accounted for over 60% of the total number of isolates. Serotype Ia was most prevalent in reproductive-age females, while serotypes V and …


Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry Sep 2012

Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry

Susan H. Jackman

While pathogenic T cells have been identified for several diseases with epithelial cell damage, an autoimmune T cell-mediated response targeted against a known keratinocyte antigen has not been reported. Previously we described an autoimmune response directed to the mouse epidermal cell antigens, Skn. For our murine model, primed Skn-immune lymphocytes are adoptively transferred to recipients, which develop lesions at the site of mild skin trauma. In this study we investigated the nature of the autoimmune component of the Skn response. A time-course study demonstrated a relationship between the number of primed Sknimmune cells injected and the severity of skin lesions …


Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman Sep 2012

Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman

David G. Chaffin

Objective: To determine the prevalence and site of isolation of different serotypes of group B streptococcus (GBS) colonization or infection at a small community hospital. Methods: GBS isolates were obtained from a small community hospital and were then serotyped as la, Ib, II, III, IV, V or non-typeable. Hospital records were reviewed for patient sex, age and pregnancy status as well as the site of GBS isolation. Results: GBS serotypes Ia, III and V were most common and accounted for over 60% of the total number of isolates. Serotype Ia was most prevalent in reproductive-age females, while serotypes V and …


Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles Sep 2012

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles

James Denvir

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …


Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman Aug 2012

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Elaine Hardman Ph.D.

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods: Female SV 129 mice were divided into two groups and placed on …


Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman Aug 2012

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Elaine Hardman Ph.D.

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …


Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman Aug 2012

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Elaine Hardman Ph.D.

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …


A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars Aug 2012

A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars

Elaine Hardman Ph.D.

The effects of the polyunsaturated omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) on hematopoiesis are complex in that both FA forms are processed into leukotrienes, eicosanoids, and prostaglandins, which can have independent effects. These FA have antagonistic effects in that n-6 FA prostaglandins tend to be pro-proliferative and pro-inflammatory, while the effects of n-3 FA prostaglandins are the opposite. We have previously shown that diets high in n-3 FA reduce the size of the middle to later stage myeloid progenitor compartment in FVB X sv129 F1hybrid mice. To assay the effects of high n-3 FA diets on earlier stages …


Epigenetic Modification As An Enabling Mechanism For Leukemic Transformation, Vincent Sollars Aug 2012

Epigenetic Modification As An Enabling Mechanism For Leukemic Transformation, Vincent Sollars

Vincent E Sollars

Cancer is now thought of as a fundamentally genetic disease, in that changes in the genome result in aberrant gene expression of oncogenes and tumor suppressor genes to promote oncogenesis. However, with our increasing knowledge of gene regulation, it is becoming obvious that changes in nucleotide sequence are not the sole mechanism for eliciting changes in transcription. An additional layer of regulation of gene expression, called epigenetics, is now being realized as increasingly important in oncogenesis. Epigenetics is defined as non-sequence based changes in chromatin that elicit changes in gene expression that are propagated through mitosis and/or meiosis. The alleles …


Membrane Fusion Proteins Are Required For Oskar Mrna Localization In The Drosophila Egg Chamber, Douglas Ruden, Vincent Sollars, Xiaoyan Wang, Daisuke Mori, Marina Alterman, Xiangyi Lu Aug 2012

Membrane Fusion Proteins Are Required For Oskar Mrna Localization In The Drosophila Egg Chamber, Douglas Ruden, Vincent Sollars, Xiaoyan Wang, Daisuke Mori, Marina Alterman, Xiangyi Lu

Vincent E Sollars

We used a genetic screen in Drosophila to identify mutations which disrupt the localization of oskar mRNA during oogenesis. Based on the hypothesis that some cytoskeletal components which are required during the mitotic divisions will also be required for oskar mRNA localization during oogenesis, we designed the following genetic screen. We screened for P-element insertions in genes which slow down the blastoderm mitotic divisions. A secondary genetic screen was to generate female germ-line clones of these potential cell division cycle genes and to identify those which cause the mislocalization of oskar mRNA. We identified mutations in ter94 which disrupt the …


Diversity In Secreted Pla2-Iia Activity Among Inbred Mouse Strains That Are Resistant Or Susceptible To Apcmin/+ Tumorigenesis, Marina Markova, Revati Koratkar, Karen Silverman, Vincent Sollars, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur Buchberg, Linda Siracusa, Steven Farber Aug 2012

Diversity In Secreted Pla2-Iia Activity Among Inbred Mouse Strains That Are Resistant Or Susceptible To Apcmin/+ Tumorigenesis, Marina Markova, Revati Koratkar, Karen Silverman, Vincent Sollars, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur Buchberg, Linda Siracusa, Steven Farber

Vincent E Sollars

The secreted phospholipase A2 type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in ApcMin/+ mice. To determine if intestinal secreted phospholipase A2 (sPLA2) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA2 activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA2 enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA …


A Drosophila Kinesin-Like Protein, Klp38b, Functions During Meiosis, Mitosis, And Segmentation, Douglas Ruden, Wei Cui, Vincent Sollars, Marina Alterman Aug 2012

A Drosophila Kinesin-Like Protein, Klp38b, Functions During Meiosis, Mitosis, And Segmentation, Douglas Ruden, Wei Cui, Vincent Sollars, Marina Alterman

Vincent E Sollars

We show that klp38B, isolated as a mutation that dominantly prolongs blastoderm mitotic cycles in Drosophila, encodes a Drosophila kinesin-like protein. Further genetic analyses show that Klp38B not only functions during mitosis, but is also required for meiosis and abdominal segmentation. Sequence comparisons suggest that Klp38B encodes an aminoterminal microtubule motor domain, a central a-helical coiled-coil domain, and a C-terminal globular domain. Evidence that Klp38B is required during meiosis is that flies transheterozygous for mutations in both klp38B and nod have a high frequency of 4th chromosome meiotic nondisjunction. Nod is a chromokinesin, a chromosome binding kinesin, that is believed …


17-N-Allylamino-17-Demethoxygeldanamycin Induces A Diverse Response In Human Acute Myelogenous Cells, Jennifer Napper, Vincent Sollars Aug 2012

17-N-Allylamino-17-Demethoxygeldanamycin Induces A Diverse Response In Human Acute Myelogenous Cells, Jennifer Napper, Vincent Sollars

Vincent E Sollars

The goal of this study was to ascertain the specific effects of 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) treatment in human acute myelogenous leukemia (AML). Four human leukemia cell lines were treated with varying doses of 17-AAG followed by analysis of toxicity, apoptosis, proliferation, and cell cycle. Cell cycle analysis revealed that the cells accumulate in G2/M phase within 96 hours of treatment, although the effect was not equivalent among the cell lines. p21, p53 expression and MDR1 activity were among the possible mechanisms uncovered for the differing responses. Exploiting these differences may allow for more effective combinatory treatments in patients with AML.


Evidence For An Epigenetic Mechanism By Which Hsp90 Acts As A Capacitor For Morphological Evolution, Vincent E. Sollars, Xiangyi Lu, Li Xiao, Xiaoyan Wang, Mark D. Garfinkel, Douglas M. Ruden Aug 2012

Evidence For An Epigenetic Mechanism By Which Hsp90 Acts As A Capacitor For Morphological Evolution, Vincent E. Sollars, Xiangyi Lu, Li Xiao, Xiaoyan Wang, Mark D. Garfinkel, Douglas M. Ruden

Vincent E Sollars

Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 0-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90’s capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression of the morphogen …


The Epigenomic Viewpoint On Cellular Differentiation Of Myeloid Progenitor Cells As It Pertains To Leukemogenesis, Vincent E. Sollars Aug 2012

The Epigenomic Viewpoint On Cellular Differentiation Of Myeloid Progenitor Cells As It Pertains To Leukemogenesis, Vincent E. Sollars

Vincent E Sollars

The new millennium has brought with it a surge of research in the field of epigenetics. This has included advances in our understanding of stem cell characteristics and mechanisms of commitment to cell lineages prior to differentiation. The nature of stem cells is similar to that of malignant cells in that they have unlimited self-renewal and protection from apoptosis, leading researchers to suspect that stem cells are the target of oncogenesis. This review will explore the idea of how epigenetic control of gene expression may contribute to mechanisms controlling differentiation of myeloid progenitor cells and its importance to our understanding …