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2004

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Full-Text Articles in Life Sciences

Modulating Hiv-1 Replication By Rna Interference Directed Against Human Transcription Elongation Factor Spt5, Yueh-Hsin Ping, Chia-Ying Chu, Hong Cao, Jean-Marc Jacque, Mario Stevenson, Tariq M. Rana Dec 2004

Modulating Hiv-1 Replication By Rna Interference Directed Against Human Transcription Elongation Factor Spt5, Yueh-Hsin Ping, Chia-Ying Chu, Hong Cao, Jean-Marc Jacque, Mario Stevenson, Tariq M. Rana

Open Access Articles

BACKGROUND: Several cellular positive and negative elongation factors are involved in regulating RNA polymerase II processivity during transcription elongation in human cells. In recruiting several of these regulatory factors to the 5' long terminal repeat (LTR) promoter during transcription elongation, HIV-1 modulates replication of its genome in a process mediated by the virus-encoded transactivator Tat. One particular cellular regulatory factor, DSIF subunit human SPT5 (hSpt5), has been implicated in both positively and negatively regulating transcriptional elongation but its role in Tat transactivation in vivo and in HIV-1 replication has not been completely elucidated. RESULTS: To understand the in vivo function ...


Regulation Of Cell Cycle By The Anaphase Spindle Midzone, Maki Murata-Hori, Greenfield Sluder, Yu-Li Wang Dec 2004

Regulation Of Cell Cycle By The Anaphase Spindle Midzone, Maki Murata-Hori, Greenfield Sluder, Yu-Li Wang

Open Access Articles

BACKGROUND: A number of proteins accumulate in the spindle midzone and midbody of dividing animal cells. Besides proteins essential for cytokinesis, there are also components essential for interphase functions, suggesting that the spindle midzone and/or midbody may play a role in regulating the following cell cycle.

RESULTS: We microsurgically severed NRK epithelial cells during anaphase or telophase, such that the spindle midzone/midbody was associated with only one of the daughter cells. Time-lapse recording of cells severed during early anaphase indicated that the cell with midzone underwent cytokinesis-like cortical contractions and progressed normally through the interphase, whereas the cell ...


Chromosomal Duplications And Cointegrates Generated By The Bacteriophage Lamdba Red System In Escherichia Coli K-12, Anthony R. Poteete, Anita C. Fenton, Ashwini Nadkarni Dec 2004

Chromosomal Duplications And Cointegrates Generated By The Bacteriophage Lamdba Red System In Escherichia Coli K-12, Anthony R. Poteete, Anita C. Fenton, Ashwini Nadkarni

Open Access Articles

BACKGROUND: An Escherichia coli strain in which RecBCD has been genetically replaced by the bacteriophage lambda Red system engages in efficient recombination between its chromosome and linear double-stranded DNA species sharing sequences with the chromosome. Previous studies of this experimental system have focused on a gene replacement-type event, in which a 3.5 kbp dsDNA consisting of the cat gene and flanking lac operon sequences recombines with the E. coli chromosome to generate a chloramphenicol-resistant Lac- recombinant. The dsDNA was delivered into the cell as part of the chromosome of a non-replicating lambda vector, from which it was released by ...


The Histone Fold Domain Of Cse4 Is Sufficient For Cen Targeting And Propagation Of Active Centromeres In Budding Yeast, Lisa Morey, Kelly Barnes, Yinhuai Chen, Molly Fitzgerald-Hayes, Richard E. Baker Dec 2004

The Histone Fold Domain Of Cse4 Is Sufficient For Cen Targeting And Propagation Of Active Centromeres In Budding Yeast, Lisa Morey, Kelly Barnes, Yinhuai Chen, Molly Fitzgerald-Hayes, Richard E. Baker

Open Access Articles

Centromere-specific H3-like proteins (CenH3s) are conserved across the eukaryotic kingdom and are required for packaging centromere DNA into a specialized chromatin structure required for kinetochore assembly. Cse4 is the CenH3 protein of the budding yeast Saccharomyces cerevisiae. Like all CenH3 proteins, Cse4 consists of a conserved histone fold domain (HFD) and a divergent N terminus (NT). The Cse4 NT contains an essential domain designated END (for essential N-terminal domain); deletion of END is lethal. To investigate the role of the Cse4 NT in centromere targeting, a series of deletion alleles (cse4DeltaNT) were analyzed. No part of the Cse4 NT was ...


Plag1 And Plagl2 Are Oncogenes That Induce Acute Myeloid Leukemia In Cooperation With Cbfb-Myh11, Sean F. Landrette, Ya-Huei Kuo, Karen Hensen, Sahar Barjesteh Van Waalwijk Van Doorn-Khosrovani, Paola N. Perrat, Wim J. M. Van De Ven, Ruud Delwel, Lucio H. Castilla Dec 2004

Plag1 And Plagl2 Are Oncogenes That Induce Acute Myeloid Leukemia In Cooperation With Cbfb-Myh11, Sean F. Landrette, Ya-Huei Kuo, Karen Hensen, Sahar Barjesteh Van Waalwijk Van Doorn-Khosrovani, Paola N. Perrat, Wim J. M. Van De Ven, Ruud Delwel, Lucio H. Castilla

Open Access Articles

Recurrent chromosomal rearrangements are associated with the development of acute myeloid leukemia (AML). The frequent inversion of chromosome 16 creates the CBFB-MYH11 fusion gene that encodes the fusion protein CBFbeta-SMMHC. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation, and induces leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBF beta-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBF beta-SMMHC in vivo to efficiently trigger leukemia with short latency in the mouse. In addition, Plag1 and Plagl2 increased ...


Translational Regulation Of Gene Expression, Stephanie Kervestin, Nadia Amrani Dec 2004

Translational Regulation Of Gene Expression, Stephanie Kervestin, Nadia Amrani

Open Access Articles

A report on the Cold Spring Harbor Laboratory meeting 'Translational Control', Cold Spring Harbor, USA, 7-12 September 2004.


Novel Role For A Sterol Response Element Binding Protein In Directing Spermatogenic Cell-Specific Gene Expression, Hong Wang, Jovenal T. San Agustin, George B. Witman, Daniel L. Kilpatrick Dec 2004

Novel Role For A Sterol Response Element Binding Protein In Directing Spermatogenic Cell-Specific Gene Expression, Hong Wang, Jovenal T. San Agustin, George B. Witman, Daniel L. Kilpatrick

Open Access Articles

Sperm are highly specialized cells, and their formation requires the synthesis of a large number of unique mRNAs. However, little is known about the transcriptional mechanisms that direct male germ cell differentiation. Sterol response element binding protein 2gc (SREBP2gc) is a spermatogenic cell-enriched isoform of the ubiquitous transcription factor SREBP2, which in somatic cells is required for homeostatic regulation of cholesterol. SREBP2gc is selectively enriched in spermatocytes and spermatids, and, due to its novel structure, its synthesis is not subject to cholesterol feedback control. This suggested that SREBP2gc has unique cell- and stage-specific functions during spermatogenesis. Here, we demonstrate that ...


Overexpression Of Glycine-Extended Gastrin Inhibits Parietal Cell Loss And Atrophy In The Mouse Stomach, Guanglin Cui, Theodore J. Koh, Duan Chen, Chun-Mei Zhao, Shigeo Takaishi, Graham J. Dockray, Andrea Varro, Arlin B. Rogers, James G. Fox, Timothy C. Wang Nov 2004

Overexpression Of Glycine-Extended Gastrin Inhibits Parietal Cell Loss And Atrophy In The Mouse Stomach, Guanglin Cui, Theodore J. Koh, Duan Chen, Chun-Mei Zhao, Shigeo Takaishi, Graham J. Dockray, Andrea Varro, Arlin B. Rogers, James G. Fox, Timothy C. Wang

Open Access Articles

Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Helicobacter infection. Transgenic mice overexpressing amidated gastrin (INS-GAS mice), G-gly (MTI/G-gly mice), and both peptides (INS-GAS/G-gly mice) were used for assessment of acid secretion and ulcer susceptibility and histologic examination and scoring of preneoplastic lesions in response to the 3 and 6 months Helicobacter felis (H. felis) infection. We found that MTI/G-gly ...


Inducible Changes In Cell Size And Attachment Area Due To Expression Of A Mutant Swi/Snf Chromatin Remodeling Enzyme, David A. Hill, Simion I. Chiosea, Saha Jamaluddin, Kanaklata Roy, Andrew H. Fischer, Douglas D. Boyd, Jeffrey A. Nickerson, Anthony N. Imbalzano Nov 2004

Inducible Changes In Cell Size And Attachment Area Due To Expression Of A Mutant Swi/Snf Chromatin Remodeling Enzyme, David A. Hill, Simion I. Chiosea, Saha Jamaluddin, Kanaklata Roy, Andrew H. Fischer, Douglas D. Boyd, Jeffrey A. Nickerson, Anthony N. Imbalzano

Open Access Articles

The SWI/SNF enzymes belong to a family of ATP-dependent chromatin remodeling enzymes that have been functionally implicated in gene regulation, development, differentiation and oncogenesis. BRG1, the catalytic core subunit of some of the SWI/SNF enzymes, can interact with known tumor suppressor proteins and can act as a tumor suppressor itself. We report that cells that inducibly express ATPase-deficient versions of BRG1 increase in cell volume, area of attachment and nuclear size upon expression of the mutant BRG1 protein. Examination of focal adhesions reveals qualitative changes in paxillin distribution but no difference in the actin cytoskeletal structure. Increases in ...


Mitochondrial Remodeling In Adipose Tissue Associated With Obesity And Treatment With Rosiglitazone, Leanne Wilson-Fritch, Sarah M. Nicoloro, My T. Chouinard, Mitchell A. Lazar, Patricia C. Chui, John D. Leszyk, Juerg R. Straubhaar, Michael P. Czech, Silvia Corvera Nov 2004

Mitochondrial Remodeling In Adipose Tissue Associated With Obesity And Treatment With Rosiglitazone, Leanne Wilson-Fritch, Sarah M. Nicoloro, My T. Chouinard, Mitchell A. Lazar, Patricia C. Chui, John D. Leszyk, Juerg R. Straubhaar, Michael P. Czech, Silvia Corvera

Open Access Articles

Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of ...


Intact Gram-Negative Helicobacter Pylori, Helicobacter Felis, And Helicobacter Hepaticus Bacteria Activate Innate Immunity Via Toll-Like Receptor 2 But Not Toll-Like Receptor 4, Leisa Mandell, Anthony P. Moran, Andrew Cocchiarella, Jeanmarie Houghton, Nancy Taylor, James G. Fox, Timothy C. Wang, Evelyn A. Kurt-Jones Nov 2004

Intact Gram-Negative Helicobacter Pylori, Helicobacter Felis, And Helicobacter Hepaticus Bacteria Activate Innate Immunity Via Toll-Like Receptor 2 But Not Toll-Like Receptor 4, Leisa Mandell, Anthony P. Moran, Andrew Cocchiarella, Jeanmarie Houghton, Nancy Taylor, James G. Fox, Timothy C. Wang, Evelyn A. Kurt-Jones

Open Access Articles

Molecular and genetic studies have demonstrated that members of the Toll-like receptor (TLR) family are critical innate immune receptors. TLRs are recognition receptors for a diverse group of microbial ligands including bacteria, fungi, and viruses. This study demonstrates that distinct TLRs are responsible for the recognition of Helicobacter lipopolysaccharide (LPS) versus intact Helicobacter bacteria. We show that the cytokine-inducing activity of Helicobacter LPS was mediated by TLR4; i.e., TLR4-deficient macrophages were unresponsive to Helicobacter pylori LPS. Surprisingly, the cytokine response to whole Helicobacter bacteria (H. pylori, H. hepaticus, and H. felis) was mediated not by TLR4 but rather by ...


Gel Shift Analysis Of The Empa Promoter Region In Vibrio Anguillarum, Steven M. Denkin, Pedja Sekaric, David R. Nelson Oct 2004

Gel Shift Analysis Of The Empa Promoter Region In Vibrio Anguillarum, Steven M. Denkin, Pedja Sekaric, David R. Nelson

Open Access Articles

BACKGROUND: The induction of metalloprotease encoded by empA in Vibrio anguillarum occurs at high cell density in salmon intestinal mucus. Previously we have shown that there are significant differences in empA expression in two strains of V. anguillarum, M93Sm and NB10. It is hypothesized that differences in empA regulation are due to differences in binding of regulatory elements.

RESULTS: Two strains of V. anguillarum, M93Sm and NB10, were examined and compared for the presence of DNA regulatory proteins that bind to and control the empA promoter region. Gel mobility shift assays, using a digoxigenin (DIG)-labeled oligomer containing a lux ...


Structural Basis For Coevolution Of A Human Immunodeficiency Virus Type 1 Nucleocapsid-P1 Cleavage Site With A V82a Drug-Resistant Mutation In Viral Protease, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Nancy M. King, Celia A. Schiffer Oct 2004

Structural Basis For Coevolution Of A Human Immunodeficiency Virus Type 1 Nucleocapsid-P1 Cleavage Site With A V82a Drug-Resistant Mutation In Viral Protease, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Nancy M. King, Celia A. Schiffer

Open Access Articles

Maturation of human immunodeficiency virus (HIV) depends on the processing of Gag and Pol polyproteins by the viral protease, making this enzyme a prime target for anti-HIV therapy. Among the protease substrates, the nucleocapsid-p1 (NC-p1) sequence is the least homologous, and its cleavage is the rate-determining step in viral maturation. In the other substrates of HIV-1 protease, P1 is usually either a hydrophobic or an aromatic residue, and P2 is usually a branched residue. NC-p1, however, contains Asn at P1 and Ala at P2. In response to the V82A drug-resistant protease mutation, the P2 alanine of NC-p1 mutates to valine ...


The 4q Subtelomere Harboring The Fshd Locus Is Specifically Anchored With Peripheral Heterochromatin Unlike Most Human Telomeres, Rose Tam, Kelly P. Smith, Jeanne B. Lawrence Oct 2004

The 4q Subtelomere Harboring The Fshd Locus Is Specifically Anchored With Peripheral Heterochromatin Unlike Most Human Telomeres, Rose Tam, Kelly P. Smith, Jeanne B. Lawrence

Open Access Articles

This paper investigates the nuclear localization of human telomeres and, specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside within the internal, euchromatic compartment. In contrast, 4q35 localizes at the peripheral heterochromatin with 4p more internal, generating a reproducible chromosome orientation that we relate to gene expression profiles. Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal ...


Mitochondrial Survivin Inhibits Apoptosis And Promotes Tumorigenesis, Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri Oct 2004

Mitochondrial Survivin Inhibits Apoptosis And Promotes Tumorigenesis, Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri

Open Access Articles

Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway ...


A Gateway-Compatible Yeast One-Hybrid System, Bart Deplancke, Denis Dupuy, Marc Vidal, Albertha J. M. Walhout Oct 2004

A Gateway-Compatible Yeast One-Hybrid System, Bart Deplancke, Denis Dupuy, Marc Vidal, Albertha J. M. Walhout

Open Access Articles

Since the advent of microarrays, vast amounts of gene expression data have been generated. However, these microarray data fail to reveal the transcription regulatory mechanisms that underlie differential gene expression, because the identity of the responsible transcription factors (TFs) often cannot be directly inferred from such data sets. Regulatory TFs activate or repress transcription of their target genes by binding to cis-regulatory elements that are frequently located in a gene's promoter. To understand the mechanisms underlying differential gene expression, it is necessary to identify physical interactions between regulatory TFs and their target genes. We developed a Gateway-compatible yeast one-hybrid ...


The Match Study Results In The Context Of Secondary Stroke Prevention, Marc Fisher, Antonio Davalos Oct 2004

The Match Study Results In The Context Of Secondary Stroke Prevention, Marc Fisher, Antonio Davalos

Open Access Articles

No abstract provided.


Structural And Thermodynamic Basis For The Binding Of Tmc114, A Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor, Nancy M. King, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Piet B. T. P. Wigerinck, Marie-Pierre De Bethune, Celia A. Schiffer Oct 2004

Structural And Thermodynamic Basis For The Binding Of Tmc114, A Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor, Nancy M. King, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Piet B. T. P. Wigerinck, Marie-Pierre De Bethune, Celia A. Schiffer

Open Access Articles

TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the basis for this potency, we solved crystal structures of TMC114 complexed with wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V) protease variant. In addition, we determined the corresponding binding thermodynamics by isothermal titration calorimetry. TMC114 binds approximately 2 orders of magnitude more tightly to the wt enzyme ...


Intraflagellar Transport And Cilia-Dependent Renal Disease: The Ciliary Hypothesis Of Polycystic Kidney Disease, Gregory J. Pazour Oct 2004

Intraflagellar Transport And Cilia-Dependent Renal Disease: The Ciliary Hypothesis Of Polycystic Kidney Disease, Gregory J. Pazour

Open Access Articles

Epithelial cells that line mammalian kidney nephrons have solitary nonmotile primary cilium projecting from their surface into the lumens of the ducts and tubules. Mutations that block the assembly of these cilia cause cystic kidney disease. The products of human autosomal dominant and recessive polycystic kidney disease genes and products of the nephronophthisis disease genes are at least partially localized to primary cilia. This suggests that the cilium serves as an organizing center for the early steps of the signal transduction pathway that is responsible for monitoring the integrity of the kidney nephron and controlling cell proliferation and differentiation.


Judging A Virus By Its Cover, Eva Szomolanyi-Tsuda, Raymond M. Welsh Oct 2004

Judging A Virus By Its Cover, Eva Szomolanyi-Tsuda, Raymond M. Welsh

Open Access Articles

The production of protective neutralizing antibodies occurs quickly in some viral infections but very slowly in others. In a new study, surface glycoproteins (the targets of neutralization) of 2 different viruses were genetically switched. Analysis of the neutralizing antibody response to each of the 2 parent and recombinant viruses in infected mice revealed that the speed of neutralizing antibody induction was intrinsically dependent on the surface glycoprotein and not the rest of the virus.


Phosphatidylinositol-4,5-Bisphosphate-Rich Plasma Membrane Patches Organize Active Zones Of Endocytosis And Ruffling In Cultured Adipocytes, Shaohui Huang, Lawrence M. Lifshitz, Varsha Patki, Richard A. Tuft, Kevin E. Fogarty, Michael P. Czech Oct 2004

Phosphatidylinositol-4,5-Bisphosphate-Rich Plasma Membrane Patches Organize Active Zones Of Endocytosis And Ruffling In Cultured Adipocytes, Shaohui Huang, Lawrence M. Lifshitz, Varsha Patki, Richard A. Tuft, Kevin E. Fogarty, Michael P. Czech

Open Access Articles

A major regulator of endocytosis and cortical F-actin is thought to be phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] present in plasma membranes. Here we report that in 3T3-L1 adipocytes, clathrin-coated membrane retrieval and dense concentrations of polymerized actin occur in restricted zones of high endocytic activity. Ultrafast-acquisition and superresolution deconvolution microscopy of cultured adipocytes expressing an enhanced green fluorescent protein- or enhanced cyan fluorescent protein (ECFP)-tagged phospholipase Cdelta1 (PLCdelta1) pleckstrin homology (PH) domain reveals that these zones spatially coincide with large-scale PtdIns(4,5)P2-rich plasma membrane patches (PRMPs). PRMPs exhibit lateral dimensions exceeding several micrometers, are relatively stationary ...


Comparisons Of The M1 Genome Segments And Encoded Mu2 Proteins Of Different Reovirus Isolates, Peng Yin, Natalie D. Keirstead, Teresa J. Broering, Michelle M. Arnold, John S. L. Parker, Max L. Nibert, Kevin M. Coombs Sep 2004

Comparisons Of The M1 Genome Segments And Encoded Mu2 Proteins Of Different Reovirus Isolates, Peng Yin, Natalie D. Keirstead, Teresa J. Broering, Michelle M. Arnold, John S. L. Parker, Max L. Nibert, Kevin M. Coombs

Open Access Articles

BACKGROUND: The reovirus M1 genome segment encodes the mu2 protein, a structurally minor component of the viral core, which has been identified as a transcriptase cofactor, nucleoside and RNA triphosphatase, and microtubule-binding protein. The mu2 protein is the most poorly understood of the reovirus structural proteins. Genome segment sequences have been reported for 9 of the 10 genome segments for the 3 prototypic reoviruses type 1 Lang (T1L), type 2 Jones (T2J), and type 3 Dearing (T3D), but the M1 genome segment sequences for only T1L and T3D have been previously reported. For this study, we determined the M1 nucleotide ...


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 ...


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 ...


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 ...