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2004

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University of Massachusetts Medical School

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Articles 31 - 60 of 84

Full-Text Articles in Life Sciences

Quantitative Signature For Architectural Organization Of Regulatory Factors Using Intranuclear Informatics, Daniel W. Young, Sayyed K. Zaidi, Paul S. Furcinitti, Amjad Javed, Andre J. Van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein Sep 2004

Quantitative Signature For Architectural Organization Of Regulatory Factors Using Intranuclear Informatics, Daniel W. Young, Sayyed K. Zaidi, Paul S. Furcinitti, Amjad Javed, Andre J. Van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein

GSBS Student Publications

Regulatory machinery for replication and gene expression is punctately organized in supramolecular complexes that are compartmentalized in nuclear microenvironments. Quantitative approaches are required to understand the assembly of regulatory machinery within the context of nuclear architecture and to provide a mechanistic link with biological control. We have developed 'intranuclear informatics' to quantify functionally relevant parameters of spatially organized nuclear domains. Using this informatics strategy we have characterized post-mitotic reestablishment of focal subnuclear organization of Runx (AML/Cbfa) transcription factors in progeny cells. By analyzing point mutations that abrogate fidelity of Runx intranuclear targeting, we establish molecular determinants for the spatial ...


Using Total Fluorescence Increase (Signal Mass) To Determine The Ca2+ Current Underlying Localized Ca2+ Events, Hui Zou, Lawrence M. Lifshitz, Richard A. Tuft, Kevin E. Fogarty, Joshua J. Singer Sep 2004

Using Total Fluorescence Increase (Signal Mass) To Determine The Ca2+ Current Underlying Localized Ca2+ Events, Hui Zou, Lawrence M. Lifshitz, Richard A. Tuft, Kevin E. Fogarty, Joshua J. Singer

Open Access Articles

The feasibility of determining localized Ca(2+) influx using only wide-field fluorescence images was explored by imaging (using fluo-3) single channel Ca(2+) fluorescence transients (SCCaFTs), due to Ca(2+) entry through single openings of Ca(2+)-permeable ion channels, while recording unitary channel currents. Since the image obtained with wide-field optics is an integration of both in-focus and out-of-focus light, the total fluorescence increase (DeltaF(total) or "signal mass") associated with a SCCaFT can be measured directly from the image by adding together the fluorescence increase due to Ca(2+) influx in all of the pixels. The assumptions necessary ...


Regulation Of Muscle Fiber Type And Running Endurance By Ppardelta, Yong-Xu Wang, Chung-Li Zhang, Ruth T. Yu, Helen K. Cho, Michael C. Nelson, Corinne R. Bayuga-Ocampo, Jungyeob Ham, Heonjoong Kang, Ronald M. Evans Aug 2004

Regulation Of Muscle Fiber Type And Running Endurance By Ppardelta, Yong-Xu Wang, Chung-Li Zhang, Ruth T. Yu, Helen K. Cho, Michael C. Nelson, Corinne R. Bayuga-Ocampo, Jungyeob Ham, Heonjoong Kang, Ronald M. Evans

Program in Gene Function and Expression Publications and Presentations

Endurance exercise training can promote an adaptive muscle fiber transformation and an increase of mitochondrial biogenesis by triggering scripted changes in gene expression. However, no transcription factor has yet been identified that can direct this process. We describe the engineering of a mouse capable of continuous running of up to twice the distance of a wild-type littermate. This was achieved by targeted expression of an activated form of peroxisome proliferator-activated receptor delta (PPARdelta) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers. Treatment of wild-type mice with PPARdelta agonist elicits a similar type ...


A Mechanical Basis For Chromosome Function, Nancy Kleckner, Denise Zickler, Gareth H. Jones, Job Dekker, Ruth Padmore, Jim Henle, John N. Hutchinson Aug 2004

A Mechanical Basis For Chromosome Function, Nancy Kleckner, Denise Zickler, Gareth H. Jones, Job Dekker, Ruth Padmore, Jim Henle, John N. Hutchinson

Program in Gene Function and Expression Publications and Presentations

We propose that chromosome function is governed by internal mechanical forces generated by programmed tendencies for expansion of the DNA/chromatin fiber against constraining features.


Flagellin Acting Via Tlr5 Is The Major Activator Of Key Signaling Pathways Leading To Nf-Kappa B And Proinflammatory Gene Program Activation In Intestinal Epithelial Cells, Thomas Tallant, Amitabha Deb, Niladri Kar, Joseph Lupica, Michael J. De Veer, Joseph A. Didonato Aug 2004

Flagellin Acting Via Tlr5 Is The Major Activator Of Key Signaling Pathways Leading To Nf-Kappa B And Proinflammatory Gene Program Activation In Intestinal Epithelial Cells, Thomas Tallant, Amitabha Deb, Niladri Kar, Joseph Lupica, Michael J. De Veer, Joseph A. Didonato

Open Access Articles

BACKGROUND: Infection of intestinal epithelial cells by pathogenic Salmonella leads to activation of signaling cascades that ultimately initiate the proinflammatory gene program. The transcription factor NF-kappa B is a key regulator/activator of this gene program and is potently activated. We explored the mechanism by which Salmonella activates NF-kappa B during infection of cultured intestinal epithelial cells and found that flagellin produced by the bacteria and contained on them leads to NF-kappa B activation in all the cells; invasion of cells by the bacteria is not required to activate NF-kappa B.

RESULTS: Purified flagellin activated the mitogen activated protein kinase ...


Bone Marrow Microenvironmental Changes Underlie Reduced Rag-Mediated Recombination And B Cell Generation In Aged Mice, Joseph E. Labrie, Alex P. Sah, David M. Allman, Michael P. Cancro, Rachel M. Gerstein Aug 2004

Bone Marrow Microenvironmental Changes Underlie Reduced Rag-Mediated Recombination And B Cell Generation In Aged Mice, Joseph E. Labrie, Alex P. Sah, David M. Allman, Michael P. Cancro, Rachel M. Gerstein

Open Access Articles

During aging, adaptive immunity is severely compromised, due in part to decreased production of B lymphocytes and loss of immunoglobulin (Ig) diversity. However, the molecular mechanisms that underlie age-associated diminished B cell production remain unclear. Using in vivo labeling, we find that this reduction in marrow pre-B cells reflects increased attrition during passage from the pro-B to pre-B cell pool. Analyses of reciprocal bone marrow chimeras reveal that the magnitude and production rates of pre-B cells are controlled primarily by microenvironmental factors, rather than intrinsic events. To understand changes in pro-B cells that could diminish production of pre-B cells, we ...


Selective Modulation Of Type 1 Insulin-Like Growth Factor Receptor Signaling And Functions By Beta1 Integrins, Hira Lal Goel, Mara Fornaro, Loredana Moro, Natalia Teider, Johng S. Rhim, Michael King, Lucia R. Languino Aug 2004

Selective Modulation Of Type 1 Insulin-Like Growth Factor Receptor Signaling And Functions By Beta1 Integrins, Hira Lal Goel, Mara Fornaro, Loredana Moro, Natalia Teider, Johng S. Rhim, Michael King, Lucia R. Languino

Open Access Articles

We show here that beta1 integrins selectively modulate insulin-like growth factor type I receptor (IGF-IR) signaling in response to IGF stimulation. The beta1A integrin forms a complex with the IGF-IR and insulin receptor substrate-1 (IRS-1); this complex does not promote IGF-I mediated cell adhesion to laminin (LN), although it does support IGF-mediated cell proliferation. In contrast, beta1C, an integrin cytoplasmic variant, increases cell adhesion to LN in response to IGF-I and its down-regulation by a ribozyme prevents IGF-mediated adhesion to LN. Moreover, beta1C completely prevents IGF-mediated cell proliferation and tumor growth by inhibiting IGF-IR auto-phosphorylation in response to IGF-I stimulation ...


Deletion Of The Nucleotide Excision Repair Gene Ercc1 Reduces Immunoglobulin Class Switching And Alters Mutations Near Switch Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Erin K. Linehan, Michael Z. Twarog, Laura J. Niedernhofer, Jan H. J. Hoeijmakers, Janet Stavnezer Aug 2004

Deletion Of The Nucleotide Excision Repair Gene Ercc1 Reduces Immunoglobulin Class Switching And Alters Mutations Near Switch Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Erin K. Linehan, Michael Z. Twarog, Laura J. Niedernhofer, Jan H. J. Hoeijmakers, Janet Stavnezer

Women’s Health Research Faculty Publications

The structure-specific endonuclease ERCC1-XPF is an essential component of the nucleotide excision DNA repair pathway. ERCC1-XPF nicks double-stranded DNA immediately adjacent to 3' single-strand regions. Substrates include DNA bubbles and flaps. Furthermore, ERCC1 interacts with Msh2, a mismatch repair (MMR) protein involved in class switch recombination (CSR). Therefore, ERCC1-XPF has abilities that might be useful for antibody CSR. We tested whether ERCC1 is involved in CSR and found that Ercc1(-)(/)(-) splenic B cells show moderately reduced CSR in vitro, demonstrating that ERCC1-XPF participates in, but is not required for, CSR. To investigate the role of ERCC1 in CSR, the nucleotide ...


Compartment-Specific Perturbation Of Protein Handling Activates Genes Encoding Mitochondrial Chaperones, Takunari Yoneda, Cristina Benedetti, Fumihiko Urano, Scott G. Clark, Heather P. Harding, David Ron Jul 2004

Compartment-Specific Perturbation Of Protein Handling Activates Genes Encoding Mitochondrial Chaperones, Takunari Yoneda, Cristina Benedetti, Fumihiko Urano, Scott G. Clark, Heather P. Harding, David Ron

Program in Gene Function and Expression Publications and Presentations

Protein folding in the mitochondria is assisted by nuclear-encoded compartment-specific chaperones but regulation of the expression of their encoding genes is poorly understood. We found that the mitochondrial matrix HSP70 and HSP60 chaperones, encoded by the Caenorhabditis elegans hsp-6 and hsp-60 genes, were selectively activated by perturbations that impair assembly of multi-subunit mitochondrial complexes or by RNAi of genes encoding mitochondrial chaperones or proteases, which lead to defective protein folding and processing in the organelle. hsp-6 and hsp-60 induction was specific to perturbed mitochondrial protein handling, as neither heat-shock nor endoplasmic reticulum stress nor manipulations that impair mitochondrial steps in ...


Intranuclear Trafficking: Organization And Assembly Of Regulatory Machinery For Combinatorial Biological Control, Sayyed K. Zaidi, Daniel W. Young, Je-Yong Choi, Jitesh Pratap, Amjad Javed, Martin A. Montecino, Janet L. Stein, Jane B. Lian, Andre J. Van Wijnen, Gary S. Stein Jul 2004

Intranuclear Trafficking: Organization And Assembly Of Regulatory Machinery For Combinatorial Biological Control, Sayyed K. Zaidi, Daniel W. Young, Je-Yong Choi, Jitesh Pratap, Amjad Javed, Martin A. Montecino, Janet L. Stein, Jane B. Lian, Andre J. Van Wijnen, Gary S. Stein

GSBS Student Publications

The molecular logistics of nuclear regulatory processes necessitate temporal and spatial regulation of protein-protein and protein-DNA interactions in response to physiological cues. Biochemical, in situ, and in vivo genetic evidence demonstrates the requirement for intranuclear localization of regulatory complexes that functionally couple cellular responses to signals that mediate combinatorial control of gene expression. We have summarized evidence that subnuclear targeting of transcription factors mechanistically links gene expression with architectural organization and assembly of nuclear regulatory machinery for biological control. The compromised intranuclear targeting of regulatory proteins under pathological conditions provides options for the diagnosis and treatment of disease.


Somatic Localization Of A Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity In The Nucleus Accumbens, Gilles E. Martin, Sylvie I. Puig, Andrzej Z. Pietrzykowski, Paula L. Feinberg-Zadek, Patrick Emery, Steven N. Treistman Jul 2004

Somatic Localization Of A Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity In The Nucleus Accumbens, Gilles E. Martin, Sylvie I. Puig, Andrzej Z. Pietrzykowski, Paula L. Feinberg-Zadek, Patrick Emery, Steven N. Treistman

Open Access Articles

Alcohol is an addictive drug that targets a variety of ion channels and receptors. To address whether the effects of alcohol are compartment specific (soma vs dendrite), we examined the effects of ethanol (EtOH) on large-conductance calcium-activated potassium channels (BK) in cell bodies and dendrites of freshly isolated neurons from the rat nucleus accumbens (NAcc), a region known to be critical for the development of addiction. Compartment-specific drug action was indeed observed. Clinically relevant concentrations of EtOH increased somatic but not dendritic BK channel open probability. Electrophysiological single-channel recordings and pharmacological analysis of the BK channel in excised patches from ...


A Novel Phosphatidylinositol(3,4,5)P3 Pathway In Fission Yeast, Prasenjit Mitra, Yingjie Zhang, Lucia E. Rameh, Mariya P. Ivshina, Dannel Mccollum, John J. Nunnari, Gregory M. Hendricks, Monica L. Kerr, Seth J. Field, Lewis C. Cantley, Alonzo H. Ross Jul 2004

A Novel Phosphatidylinositol(3,4,5)P3 Pathway In Fission Yeast, Prasenjit Mitra, Yingjie Zhang, Lucia E. Rameh, Mariya P. Ivshina, Dannel Mccollum, John J. Nunnari, Gregory M. Hendricks, Monica L. Kerr, Seth J. Field, Lewis C. Cantley, Alonzo H. Ross

Open Access Articles

The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at ...


Microarray Profiling Of Progesterone-Regulated Endometrial Genes During The Rhesus Monkey Secretory Phase, Christopher I. Ace, William C. Okulicz Jul 2004

Microarray Profiling Of Progesterone-Regulated Endometrial Genes During The Rhesus Monkey Secretory Phase, Christopher I. Ace, William C. Okulicz

Open Access Articles

BACKGROUND: In the endometrium the steroid hormone progesterone (P), acting through its nuclear receptors, regulates the expression of specific target genes and gene networks required for endometrial maturation. Proper endometrial maturation is considered a requirement for embryo implantation. Endometrial receptivity is a complex process that is spatially and temporally restricted and the identity of genes that regulate receptivity has been pursued by a number of investigators. METHODS: In this study we have used high density oligonucleotide microarrays to screen for changes in mRNA transcript levels between normal proliferative and adequate secretory phases in Rhesus monkey artificial menstrual cycles. Biotinylated cRNA ...


The Single-Strand Dna Binding Activity Of Human Pc4 Prevents Mutagenesis And Killing By Oxidative Dna Damage, Jen-Yeu Wang, Altaf Hossain Sarker, Priscilla K. Cooper, Michael R. Volkert Jun 2004

The Single-Strand Dna Binding Activity Of Human Pc4 Prevents Mutagenesis And Killing By Oxidative Dna Damage, Jen-Yeu Wang, Altaf Hossain Sarker, Priscilla K. Cooper, Michael R. Volkert

Open Access Articles

Human positive cofactor 4 (PC4) is a transcriptional coactivator with a highly conserved single-strand DNA (ssDNA) binding domain of unknown function. We identified PC4 as a suppressor of the oxidative mutator phenotype of the Escherichia coli fpg mutY mutant and demonstrate that this suppression requires its ssDNA binding activity. Saccharomyces cerevisiae mutants lacking their PC4 ortholog Sub1 are sensitive to hydrogen peroxide and exhibit spontaneous and peroxide-induced hypermutability. PC4 expression suppresses the peroxide sensitivity of the yeast sub1Delta mutant, suggesting that the human protein has a similar function. A role for yeast and human proteins in DNA repair is suggested ...


Biological Analysis Of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified From Brain And Lymph Node Tissues Of Aids Patients With Neuropathology Reveals Two Distinct Tropism Phenotypes And Identifies Envelopes In The Brain That Confer An Enhanced Tropism And Fusigenicity For Macrophages, Paul J. Peters, Jayanta Bhattacharya, Samantha Hibbitts, Matthias T. Dittmar, Graham Simmons, Jeanne E. Bell, Peter Simmonds, Paul R. Clapham Jun 2004

Biological Analysis Of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified From Brain And Lymph Node Tissues Of Aids Patients With Neuropathology Reveals Two Distinct Tropism Phenotypes And Identifies Envelopes In The Brain That Confer An Enhanced Tropism And Fusigenicity For Macrophages, Paul J. Peters, Jayanta Bhattacharya, Samantha Hibbitts, Matthias T. Dittmar, Graham Simmons, Jeanne E. Bell, Peter Simmonds, Paul R. Clapham

Open Access Articles

Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4(+) CCR5(+) cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue ...


Life, Death And E2f: Linking Proliferation Control And Dna Damage Signaling Via E2f1, Harry A. Rogoff, Timothy F. Kowalik Jun 2004

Life, Death And E2f: Linking Proliferation Control And Dna Damage Signaling Via E2f1, Harry A. Rogoff, Timothy F. Kowalik

Open Access Articles

Proper regulation of cellular proliferation is critical for normal development and cancer prevention. Most, if not all, cancer cells contain mutations in the Rb/E2F pathway, which controls cellular proliferation. Inactivation of the retinoblastoma (Rb) family of proteins can occur through Rb loss, mutation, or inactivation by cellular or viral oncoproteins leading to unrestrained proliferation and, often times, results in apoptosis. The loss of growth control occurs primarily by derepression and activation of the E2F transcription factors. E2F1 in particular, serves as the primary link between loss of Rb function and activation of p53-dependent apoptosis. E2F1 function is crucial for ...


Cell Cycle Progression After Cleavage Failure: Mammalian Somatic Cells Do Not Possess A "Tetraploidy Checkpoint", Yumi Uetake, Greenfield Sluder Jun 2004

Cell Cycle Progression After Cleavage Failure: Mammalian Somatic Cells Do Not Possess A "Tetraploidy Checkpoint", Yumi Uetake, Greenfield Sluder

Open Access Articles

Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a "tetraploidy checkpoint" that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 microM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed ...


The Effect Of Epidural Anesthesia On Oncologic Outcomes After Surgery For Colon And Rectal Cancer, Jaimee Demone Jun 2004

The Effect Of Epidural Anesthesia On Oncologic Outcomes After Surgery For Colon And Rectal Cancer, Jaimee Demone

Senior Scholars Program

Background: Surgical trauma induces a physiologic stress response that is well documented in the literature (Kehlet, 1999; Ordemann, 2001; Ozawa, 2000). The surgical stress response comprises alterations in the endocrine, metabolic, inflammatory and immune systems with important clinical ramifications on patient morbidity and recovery in the post-operative period. Consequences have been identified in multiple organ systems. Emphasis has therefore been placed on the identification of practices and techniques that may reduce the invasiveness of the surgical procedure and hence the resultant deleterious surgical stress response. Minimally invasive surgery, i.e. laparoscopy, is one innovation that has been shown to reduce ...


The Effect Of Facial Fractures On The Treatment And Outcome Of Trauma Patients Presenting With Acute Cervical Spine Fractures, Andrea Marvin Jun 2004

The Effect Of Facial Fractures On The Treatment And Outcome Of Trauma Patients Presenting With Acute Cervical Spine Fractures, Andrea Marvin

Senior Scholars Program

Background: While there have been a few reports involving identification of trauma patients with combined facial and cervical spine fractures, no study has specifically addressed the effects of a coexistent facial injury on evaluation and treatment of a significant cervical spine injury. The purpose of this study was to investigate whether coexisting facial fractures affect the timing, method, or rate of complications for treatment of acute cervical spine fractures.

Methods: A prospectively collected institutional trauma registry containing 50 patient records from the years 1998 to 2002 was reviewed for patients with combination facial and cervical spine fractures. Thirty seven patients ...


Positive And Negative Regulation Of Poly(A) Nuclease, David A. Mangus, Matthew C. Evans, Nathan S. Agrin, Mandy M. Smith, Preetam Gongidi, Allan Jacobson Jun 2004

Positive And Negative Regulation Of Poly(A) Nuclease, David A. Mangus, Matthew C. Evans, Nathan S. Agrin, Mandy M. Smith, Preetam Gongidi, Allan Jacobson

Open Access Articles

PAN, a yeast poly(A) nuclease, plays an important nuclear role in the posttranscriptional maturation of mRNA poly(A) tails. The activity of this enzyme is dependent on its Pan2p and Pan3p subunits, as well as the presence of poly(A)-binding protein (Pab1p). We have identified and characterized the associated network of factors controlling the maturation of mRNA poly(A) tails in yeast and defined its relevant protein-protein interactions. Pan3p, a positive regulator of PAN activity, interacts with Pab1p, thus providing substrate specificity for this nuclease. Pab1p also regulates poly(A) tail trimming by interacting with Pbp1p, a factor ...


Unconventional Myosin Myo1c Promotes Membrane Fusion In A Regulated Exocytic Pathway, Avirup Bose, Stacey I. Robida, Paul S. Furcinitti, Anil Chawla, Kevin E. Fogarty, Silvia Corvera, Michael P. Czech Jun 2004

Unconventional Myosin Myo1c Promotes Membrane Fusion In A Regulated Exocytic Pathway, Avirup Bose, Stacey I. Robida, Paul S. Furcinitti, Anil Chawla, Kevin E. Fogarty, Silvia Corvera, Michael P. Czech

Open Access Articles

Glucose homeostasis is controlled in part by regulation of glucose uptake into muscle and adipose tissue. Intracellular membrane vesicles containing the GLUT4 glucose transporter move towards the cell cortex in response to insulin and then fuse with the plasma membrane. Here we show that the fusion step is retarded by the inhibition of phosphatidylinositol (PI) 3-kinase. Treatment of insulin-stimulated 3T3-L1 adipocytes with the PI 3-kinase inhibitor LY294002 causes the accumulation of GLUT4-containing vesicles just beneath the cell surface. This accumulation of GLUT4-containing vesicles near the plasma membrane prior to fusion requires an intact cytoskeletal network and the unconventional myosin motor ...


Functional Mri Of Rat And Monkey Models Of Absence Epilepsy: A Dissertation, Jeffrey R. Tenney May 2004

Functional Mri Of Rat And Monkey Models Of Absence Epilepsy: A Dissertation, Jeffrey R. Tenney

GSBS Dissertations and Theses

A seizure is defined as an abnormal electrical discharge from the brain that results in the affected area losing its normal function and reacting uncontrollably. A particular subset of seizures, known as absence seizures, are characterized by brief, paroxysmal losses of consciousness that are associated with bilaterally synchronous 3 Hz spike and wave discharges (SWDs) on electroencephalography (EEG). The optimal way to understand any disease state is to study it within the human. Unfortunately, well controlled experiments in humans are difficult due to small patient populations, treatment medications which alter the seizure, and the ethical problems associated with invasive experimental ...


Nuclear Microenvironments: An Architectural Platform For The Convergence And Integration Of Transcriptional Regulatory Signals, Gary S. Stein, Janet L. Stein, Jane B. Lian, Andre J. Van Wijnen, Martin A. Montecino, Amjad Javed, Sayyed K. Zaidi, Daniel W. Young, Je-Yong Choi, Shirwin M. Pockwinse May 2004

Nuclear Microenvironments: An Architectural Platform For The Convergence And Integration Of Transcriptional Regulatory Signals, Gary S. Stein, Janet L. Stein, Jane B. Lian, Andre J. Van Wijnen, Martin A. Montecino, Amjad Javed, Sayyed K. Zaidi, Daniel W. Young, Je-Yong Choi, Shirwin M. Pockwinse

GSBS Student Publications

Functional interrelationships between the intranuclear organization of nucleic acids and regulatory proteins are obligatory for fidelity of transcriptional activation and repression. In this article, using the Runx/AML/Cbfa transcription factors as a paradigm for linkage between nuclear structure and gene expression we present an overview of growing insight into the dynamic organization and assembly of regulatory machinery for gene expression at microenvironments within the nucleus. We address contributions of nuclear microenvironments to the convergence and integration of regulatory signals that mediate transcription by supporting the combinatorial assembly of regulatory complexes.


Prevalence And Antimicrobial Susceptibilities Of Bacteria Isolated From Blood Cultures Of Hospitalized Patients In The United States In 2002, James A. Karlowsky, Mark E. Jones, Deborah C. Draghi, Clyde Thornsberry, Daniel F. Sahm, Gregory A. Volturo May 2004

Prevalence And Antimicrobial Susceptibilities Of Bacteria Isolated From Blood Cultures Of Hospitalized Patients In The United States In 2002, James A. Karlowsky, Mark E. Jones, Deborah C. Draghi, Clyde Thornsberry, Daniel F. Sahm, Gregory A. Volturo

Open Access Articles

BACKGROUND: Bloodstream infections are associated with significant patient morbidity and mortality. Antimicrobial susceptibility patterns should guide the choice of empiric antimicrobial regimens for patients with bacteremia.

METHODS: From January to December of 2002, 82,569 bacterial blood culture isolates were reported to The Surveillance Network (TSN) Database-USA by 268 laboratories. Susceptibility to relevant antibiotic compounds was analyzed using National Committee for Clinical Laboratory Standards guidelines.

RESULTS: Coagulase-negative staphylococci (42.0%), Staphylococcus aureus (16.5%), Enterococcus faecalis (8.3%), Escherichia coli (7.2%), Klebsiella pneumoniae (3.6%), and Enterococcus faecium (3.5%) were the most frequently isolated bacteria from blood cultures ...


Identification Of Factors Regulating Poly(A) Tail Synthesis And Maturation, David A. Mangus, Mandy M. Smith, Jennifer M. Mcsweeney, Allan Jacobson May 2004

Identification Of Factors Regulating Poly(A) Tail Synthesis And Maturation, David A. Mangus, Mandy M. Smith, Jennifer M. Mcsweeney, Allan Jacobson

Open Access Articles

Posttranscriptional maturation of the 3' end of eukaryotic pre-mRNAs occurs as a three-step pathway involving site-specific cleavage, polymerization of a poly(A) tail, and trimming of the newly synthesized tail to its mature length. While most of the factors essential for catalyzing these reactions have been identified, those that regulate them remain to be characterized. Previously, we demonstrated that the yeast protein Pbp1p associates with poly(A)-binding protein (Pab1p) and controls the extent of mRNA polyadenylation. To further elucidate the function of Pbp1p, we conducted a two-hybrid screen to identify factors with which it interacts. Five genes encoding putative ...


Characterization Of Restrictions To Human Immunodeficiency Virus Type 1 Infection Of Monocytes, Karine Triques, Mario Stevenson Apr 2004

Characterization Of Restrictions To Human Immunodeficiency Virus Type 1 Infection Of Monocytes, Karine Triques, Mario Stevenson

Open Access Articles

Tissue macrophages are an important cellular reservoir for replication of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. In vitro, the ability of macrophages to support viral replication is differentiation dependent in that precursor monocytes are refractory to infection. There is, however, no consensus as to the exact point at which infection is restricted in monocytes. We have revisited this issue and have compared the efficiencies of early HIV-1 replication events in monocytes and in differentiated macrophages. Although virus entry in monocytes was comparable to that in differentiated macrophages, synthesis of full-length viral cDNAs was very inefficient. Relative ...


Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact On Association With Membrane Lipid Rafts And Incorporation Onto Budding Virus Particles, Jayanta Bhattacharya, Paul J. Peters, Paul R. Clapham Apr 2004

Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact On Association With Membrane Lipid Rafts And Incorporation Onto Budding Virus Particles, Jayanta Bhattacharya, Paul J. Peters, Paul R. Clapham

Open Access Articles

The human immunodeficiency virus type 1 (HIV-1) envelope comprises a surface gp120 and a transmembrane gp41. The cytoplasmic domain of gp41 contains cysteine residues (C764 and C837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (I. Rousso, M. B. Mixon, B. K. Chen, and P. S. Kim, Proc. Natl. Acad. Sci. USA 97:13523-13525, 2000). Several infectious HIV-1 clones contain envelopes that have no gp41 cytoplasmic cysteines. Since no other gp41 amino acid is a target for palmitoylation, these clones imply that palmitoylation is not essential ...


Mutated Form Of The Newcastle Disease Virus Hemagglutinin-Neuraminidase Interacts With The Homologous Fusion Protein Despite Deficiencies In Both Receptor Recognition And Fusion Promotion, Jianrong Li, Edward J. Quinlan, Anne M. Mirza, Ronald M. Iorio Apr 2004

Mutated Form Of The Newcastle Disease Virus Hemagglutinin-Neuraminidase Interacts With The Homologous Fusion Protein Despite Deficiencies In Both Receptor Recognition And Fusion Promotion, Jianrong Li, Edward J. Quinlan, Anne M. Mirza, Ronald M. Iorio

Open Access Articles

The Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein mediates attachment to cellular receptors. The fusion (F) protein promotes viral entry and spread. However, fusion is dependent on a virus-specific interaction between the two proteins that can be detected at the cell surface by a coimmunoprecipitation assay. A point mutation of I175E in the neuraminidase (NA) active site converts the HN of the Australia-Victoria isolate of the virus to a form that can interact with the F protein despite negligible receptor recognition and fusion-promoting activities. Thus, I175E-HN could represent a fusion intermediate in which HN and F are associated and primed ...


Zip Kinase Is Responsible For The Phosphorylation Of Myosin Ii And Necessary For Cell Motility In Mammalian Fibroblasts, Satoshi Komatsu, Mitsuo Ikebe Apr 2004

Zip Kinase Is Responsible For The Phosphorylation Of Myosin Ii And Necessary For Cell Motility In Mammalian Fibroblasts, Satoshi Komatsu, Mitsuo Ikebe

Open Access Articles

Reorganization of actomyosin is an essential process for cell migration and myosin regulatory light chain (MLC20) phosphorylation plays a key role in this process. Here, we found that zipper-interacting protein (ZIP) kinase plays a predominant role in myosin II phosphorylation in mammalian fibroblasts. Using two phosphorylation site-specific antibodies, we demonstrated that a significant portion of the phosphorylated MLC20 is diphosphorylated and that the localization of mono- and diphosphorylated myosin is different from each other. The kinase responsible for the phosphorylation was ZIP kinase because (a) the kinase in the cell extracts phosphorylated Ser19 and Thr18 of MLC20 with similar potency ...


The C-Terminus Of Rat L-Histidine Decarboxylase Specifically Inhibits Enzymic Activity And Disrupts Pyridoxal Phosphate-Dependent Interactions With L-Histidine Substrate Analogues, John V. Fleming, Ignacio Fajardo, Michael R. Langlois, Francisca Sanchez-Jimenez, Timothy C. Wang Apr 2004

The C-Terminus Of Rat L-Histidine Decarboxylase Specifically Inhibits Enzymic Activity And Disrupts Pyridoxal Phosphate-Dependent Interactions With L-Histidine Substrate Analogues, John V. Fleming, Ignacio Fajardo, Michael R. Langlois, Francisca Sanchez-Jimenez, Timothy C. Wang

Open Access Articles

Full-length rat HDC (L-histidine decarboxylase) translated in reticulocyte cell lysate reactions is inactive, whereas C-terminally truncated isoforms are capable of histamine biosynthesis. C-terminal processing of the approximately 74 kDa full-length protein occurs naturally in vivo, with the production of multiple truncated isoforms. The minimal C-terminal truncation required for the acquisition of catalytic competence has yet to be defined, however, and it remains unclear as to why truncation is needed. Here we show that approximately 74 kDa HDC monomers can form dimers, which is the conformation in which the enzyme is thought to be catalytically active. Nevertheless, the resulting dimer is ...