Caltech Authors
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Repository of works by Caltech published authors.
Mostrando recursos 1 - 20 de 23
1.
Kinetics of phase transformations in the peridynamic formulation of continuum mechanics - Dayal, Kaushik; Bhattacharya, Kaushik
We study the kinetics of phase transformations in solids using the peridynamic formulation of continuum mechanics. The peridynamic theory is a nonlocal formulation that does not involve spatial derivatives, and is a powerful tool to study defects such as cracks and interfaces.
We apply the peridynamic formulation to the motion of phase boundaries in one dimension. We show that unlike the classical continuum theory, the peridynamic formulation does not require any extraneous constitutive laws such as the kinetic relation (the relation between the velocity of the interface and the thermodynamic driving force acting across it) or the nucleation criterion (the...
2.
Connectivity in the Yeast Cell Cycle Transcription Network: Inferences from Neural Networks - Hart, Christopher Edward; Mjolsness, Erik; Wold, Barbara J.
A current challenge is to develop computational approaches to infer gene network regulatory relationships based on multiple types of large-scale functional genomic data. This work shows that single-layer feedforward Artificial Neural Network (ANN) models can effectively discover gene network structure by integrating global in vivo protein:DNA interaction data (ChIP/Array) with genome-wide microarray RNA data. We model the yeast cell cycle transcription network, which is composed of several hundred genes with phase specific RNA expression outputs plus their cognate activating and repressing transcription factors. The resulting ANNs were robust to noise in the data and to a variety of perturbations. They...
3.
WormBook: the online review of Caenorhabditis elegans biology - Girard, Lisa R.; Fiedler, Tristan J.; Harris, Todd W.; Carvalho, Felicia; Antoshechkin, Igor; Han, Michael; Sternberg, Paul W.; Stein, Lincoln D.; Chalfie, Martin
WormBook (www.wormbook.org) is an open-access, online collection of original, peer-reviewed chapters on the biology of Caenorhabditis elegans and related nematodes. Since WormBook was launched in June 2005 with 12 chapters, it has grown to over 100 chapters, covering nearly every aspect of C.elegans research, from Cell Biology and Neurobiology to Evolution and Ecology. WormBook also serves as the text companion to WormBase, the C.elegans model organism database. Objects such as genes, proteins and cells are linked to the relevant pages in WormBase, providing easily accessible background information. Additionally, WormBook chapters contain links to other relevant topics in WormBook, and the...
4.
The Drosophila IAP DIAP2 is dispensable for cell survival, required for the innate immune response to Gram-negative bacterial infection, and can be negatively regulated by the Reaper/Hid/Grim family of IAP-binding apoptosis inducers - Huh, Jun R.; Foe, Ian; Muro, Israel; Chen, Chun Hong; Seol, Jae Hong; Yoo, Soon Ji; Guo, Ming; Park, Jin Mo; Hay, Bruce A.
Many IAP family proteins inhibit apoptosis. IAPs contain N-terminal BIR domains and a C-terminal RING ubiquitin ligase domain. Drosophila IAP DIAP1 is essential for the survival of many cells, protecting them from apoptosis by inhibiting active caspases. Apoptosis initiates when proteins such as Reaper, Hid and Grim bind a surface groove in DIAP1 BIR domains via an N-terminal IAP-binding motif (IBM). This evolutionarily conserved interaction disrupts DIAP1-caspase interactions, unleashing apoptosis-inducing caspase activity. A second Drosophila IAP, DIAP2, also binds Rpr and Hid, and inhibits apoptosis in multiple contexts when overexpressed. However, due to a lack of mutants little is known...
5.
Directed evolution of Vibrio fischeri LuxR for improved response to butanoyl-homoserine lactone - Hawkins, Andrew C.; Arnold, Frances H.; Stuermer, Rainer; Hauer, Bernhard; Leadbetter, Jared R.
LuxR is the 3-oxohexanoyl-homoserine lactone (3OC6HSL) dependent transcriptional activator of the prototypical acyl-homoserine lactone (AHL) quorum sensing system of Vibrio fischeri. Wild-type LuxR exhibits no response to butanoyl-HSL (C4HSL) in quantitative bioassays at concentrations of up to 1 µM; a previously described LuxR variant (LuxR-G2E) exhibits a broadened response to diverse AHLs, including pentanoyl-HSL (C5HSL), but not to C4HSL. Here, two rounds of directed evolution of LuxR-G2E generated variants of LuxR that responded to C4HSL at concentrations as low as 10 nM. One variant, LuxR-G4E, had only one change, I45F, relative to the parent LuxR-G2E, which itself differs from wild-type...
6.
Conformational variability of the glycine receptor M2 domain in response to activation by different agonists - Pless, Stephan A.; Dibas, Mohammed I.; Lester, Henry A.; Lynch, Joseph W.
Models describing the structural changes mediating cys-loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric ?1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19 or 22 positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19C increased by ~20% and the emission peak shifted...
7.
Mechanisms of base selection by the E.coli mispaired uracil glycosylase, MUG - Liu, Pingfang; Theruvathu, Jacob A.; Darwanto, Agus; Valinluck Lao, Victoria; Pascal, Tod; Goddard, William, III; Sowers, Lawrence C.
The repair of the multitude of single-base lesions formed daily in the cells of all living organisms is accomplished primarily by the base-excision repair (BER) pathway that initiates repair through a series of lesion-selective glycosylases. In this paper, single-turnover kinetics have been measured on a series of oligonucleotide substrates containing both uracil and purine analogs for the E. coli mispaired uracil glycosylase, MUG. The relative rates of glycosylase cleavage have been correlated with the free energy of helix formation, and with the size and electronic inductive properties of a series of uracil 5-substituents. Data is presented that MUG can exploit...
8.
Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plamsa membrane - Zhang, An-Sheng; Yang, Fan; Meyer, Kathrin; Hernandez, Catalina; Chapman-Arvedson, Tara; Bjorkman, Pamela J.; Enns, Caroline A.
Hemochromatosis type 2 gene (HFE2) is highly expressed in skeletal muscle and liver hepatocytes. Its encoded protein, hemojuvelin (HJV), is a co-receptor for the bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and enhances the BMP-induced hepcidin expression. Hepcidin is a central iron regulatory hormone predominantly secreted from hepatocytes. HJV also binds neogenin, a membrane protein widely expressed in many tissues. Neogenin is required for the processing and release of HJV from cells. The role that neogenin plays in HJV trafficking was investigated, using HepG2 cells, a human hepatoma cell line. Knockdown of endogenous neogenin markedly suppresses HJV release,...
9.
Signaling and crosstalk by C5a and UDP in macrophages selectively use PLCbeta 3 to regulate intracellular free calcium - Roach, Tamara I. A.; Rebres, Robert A.; Fraser, Iain D. C.; DeCamp, Dianne L.; Lin, Keng-Mean; Sternweis, Paul C.; Simon, Mel I.; Seaman, William E.
Studies in fibroblasts, neurons, and platelets have demonstrated the integration of signals from different G-protein coupled receptors (GPCRs) in raising intracellular free Ca2+. To study signal integration in macrophages, we screened RAW264.7 cells and bone marrow-derived macrophages (BMDM) for their Ca2+ response to GPCR ligands. We found a synergistic response to complement component 5a (C5a) in combination with uridine 5-diphosphate (UDP), platelet activating factor (PAF) or lysophosphatidic acid (LPA). The C5a response was Gai-dependent, while the UDP, PAF, and LPA responses were Gaqdependent. Synergy between C5a and UDP, mediated by the C5a and P2Y6 receptors, required dual receptor occupancy, and...
10.
Lattice thermal conductivity of self-assembled PbTe-Sb2Te3 composites with nanometer lamellae - Ikeda, Teruyuki; Toberer, Eric S,; Ravi, Vilupanur; Haile, Sossina; Snyder, G. Jeffrey
In the system of PbTe and Sb2Te3, a metastable compound Pb2Sb6Te11 appears by solidification processing. It has been reported that this compound is decomposed into the two immiscible thermoelectric materials forming nanosized lamellar structure by heat treatments. The fraction transformed and the inter-lamellar spacing was systematically investigated. In this work, the thermal conductivities and the electrical resistivities have been measured as functions of annealing time through the transformation and the coarsening processes to clarify the effect of the fraction transformed and the inter-lamellar spacing. The thermal conductivity of Pb2Sb6Te11 is lower than that after the decomposition. The lattice part of...
11.
A survey of models of network formation: stability and efficiency - Jackson, Matthew O.
I survey the recent literature on the formation of networks. I provide definitions of network games, a number of examples of models from the literature, and discuss some of what is known about the (in)compatibility of overall societal welfare with individual incentives to form and sever links.
12.
Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine transferase - Hwang, Cheol-Sang; Shemorry, Anna; Varshavsky, Alexander
O6-methylguanine (O6meG) and related modifications of guanine in double-stranded DNA are functionally severe lesions that can be produced by many alkylating agents, including N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), a potent carcinogen. O6meG is repaired through its demethylation by the O6-alkylguanine-DNA alkyltransferase (AGT). This protein is called Mgmt (or MGMT) in mammals and Mgt1 in the yeast Saccharomyces cerevisiae. AGT proteins remove methyl and other alkyl groups from an alkylated O6 in guanine by transferring the adduct to an active-site cysteine residue. The resulting S-alkyl-Cys of AGT is not restored back to Cys, so repair proteins of this kind can act only once. We...
13.
Core binding factors are necessary for natural killer cell development, and cooperate with Notch signaling during T cell specification - Guo, Yalin; Maillard, Ivan; Chakraborti, Sankhamala; Rothenberg, Ellen V.; Speck, Nancy A.
CBF{beta} is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBF{beta} levels display profound, early defects in T but not B cell development. Here we show that CBF{beta} is also required at very early stages of natural killer (NK) cell development. We also demonstrate that T cell development aborts during specification, as the expression of Gata3 and Tcf7, which encode key regulators of T lineage specification, is substantially reduced, as are functional thymic progenitors. Constitutively active Notch or IL-7 signaling cannot restore T cell expansion or differentiation of CBF{beta} insufficient cells, nor can overexpression of...
14.
Processing of G4 DNA by Dna2 Helicase/nuclease and RPA provides insights into the mechanism of Dna2/RPA substrate recognition - Masuda-Sasa, Taro; Polaczek, Piotr; Peng, Xiao P.; Chen, Lu; Campbell, Judith L.
The polyguanine-rich DNA sequences commonly found at telomeres and in rDNA arrays have been shown to assemble into structures known as G quadruplexes, or G4 DNA, stabilized by base-stacked G quartets, an arrangement of four hydrogen-bonded guanines. G4 DNA structures are resistant to the many helicases and nucleases that process intermediates arising in the course of DNA replication and repair. The lagging strand DNA replication protein, Dna2, has demonstrated a unique localization to telomeres and a role in de novo telomere biogenesis, prompting us to study the activities of Dna2 on G4 DNA-containing substrates. We find that yeast Dna2 binds...
15.
Design and Expression of a Dimeric Form of the Human Immunodeficiency Virus Type 1 Antibody 2G12 with Increased Neutralization Potency - West, Anthony P., Jr.; Galimidi, Rachel P.; Foglesong, Christopher P.; Gnanapragasam, Priyanthi N. P.; Huey-Tubman, Kathryn E.; Klein, Joshua S.; Suzuki, Maria D.; Tiangco, Noreen E.; Vielmetter, Jost; Bjorkman, Pamela J.
The antigen-binding fragment of the broadly neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) antibody 2G12 has an unusual 3D domain-swapped structure with two aligned combining sites that facilitates recognition of its carbohydrate epitope on gp120. When expressed as an intact IgG, 2G12 formed typical IgG monomers containing two combining sites and a small fraction of a higher molecular weight species, which showed a significant increase in neutralization potency (50- to 80-fold compared to 2G12 monomer) across a range of clade A and B strains of HIV-1. Here we show that the higher molecular weight species corresponds to a 2G12 dimer...
16.
An intersubunit hydrogen bond in the nicotinic acetylcholine receptor that contributes to channel gating - Gleitsman, Kristin Rule; Kedrowski, Sean M. A.; Lester, Henry A.; Dougherty, Dennis A.
The muscle nicotinic acetylcholine receptor (nAChR) is a large, allosteric, ligand-gated ion channel with the subunit composition ?2???. Though much is now known about the structure of the binding site, relatively little is understood about how the binding event is communicated to the channel gate, causing the pore to open. Here we identify a key hydrogen bond near the binding site that is involved in the gating pathway. Using mutant cycle analysis with the novel unnatural residue ?-hydroxyserine (Sah), we find that the backbone N-H of ?S191 in loop C makes a hydrogen bond to an anionic side chain of...
17.
An intersubunit hydrogen bond in the nicotinic acetylcholine receptor that contributes to channel gating - Gleitsman, Kristin Rule; Kedrowski, Sean M. A.; Lester, Henry A.; Dougherty, Dennis A.
The muscle nicotinic acetylcholine receptor (nAChR) is a large, allosteric, ligand-gated ion channel with the subunit composition α2βγδ. Though much is now known about the structure of the binding site, relatively little is understood about how the binding event is communicated to the channel gate, causing the pore to open. Here we identify a key hydrogen bond near the binding site that is involved in the gating pathway. Using mutant cycle analysis with the novel unnatural residue α-hydroxyserine (Sah), we find that the backbone N-H of αS191 in loop C makes a hydrogen bond to an anionic side chain of...
18.
Probing the role of PrP repeats in conformational conversion and amyloid assembly of chimeric yeast prions - Dong, Jijun; Bloom, Jesse D.; Goncharov, Vladimir; Chattopadhyay, Madhuri; Millhauser, Glenn L.; Lynn, David G.; Schiebel, Thomas; Lindquist, Susan
Oligopeptide repeats appear in many proteins that undergo conformational conversions to form amyloid, including the mammalian prion protein PrP and the yeast prion protein Sup35. While the repeats in PrP have been studied more exhaustively, interpretation of these studies is confounded by the fact that many details of the PrP prion conformational conversion are not well understood. On the other hand, there is now a relatively good understanding of the factors that guide the conformational conversion of the Sup35 prion protein. In order to provide a general model for studying the role of oligopeptide repeats in prion conformational conversion and...
19.
Cellular expression and crystal structure of the murine cytomegalovirus MHC-Iv glycoprotein, m153 - Mans, Janet; Natarajan, Kannan; Balbo, Andrea; Schuck, Peter; Eikel, Daniel; Hess, Sonja; Robinson, Howard; Šimić, Hrvoje; Jonjić, Stipan; Tiemessen, Caroline T.; Margulies, David H.
Mouse cytomegalovirus (MCMV), a β-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. MCMV encodes the m145 family of putative immunoevasins with predicted MHC-I structure. Functions attributed to some family members include downregulation of host MHC-I (m152) and NKG2D ligands (m145, m152, m155) and interaction with inhibitory or activating NK receptors (m157). We present the cellular, biochemical and structural characterization of m153, which is a heavily glycosylated homodimer, that does not require β2m or peptide, and is expressed at the surface of MCMV-infected cells. Its 2.4 Å crystal structure confirms that...
20.
Planktonic and sediment-associated aerobic methanotrophs in two seep systems along the North American margin - Tavormina, Patricia L.; Ussler, William, III; Orphan, Victoria J.
Methane vents are of significant geochemical and ecological importance. Notable progress has been made towards understanding anaerobic methane oxidation in marine sediments, however, the diversity and distribution of aerobic methanotrophs in the water column are poorly characterized. Both environments play an essential role in regulating methane release from the oceans to the atmosphere. In this study, the diversity of particulate methane monooxygenase (pmoA) and 16S rRNA genes from two methane vent environments along the California continental margin was characterized. The pmoA phylotypes recovered from methane-rich sediments and the overlying water column differed. Sediments harbored the greatest number of unique pmoA...
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