bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope Specificity and Clonality of EBV-Specific CTLs Used to Treat Posttransplant Lymphoproliferative Disease
Authors: McAulay Karen A. , Haque Tanzina , Urquhart Gillian , Bellamy Christopher , Guiretti Deisy , Crawford Dorothy H. 
Published: March 2009

Abstract
In a recent phase II clinical trial using banked allogeneic CTL lines to treat EBV-associated posttransplant lymphoproliferative disease, a response rate of 52% was recorded 6 mo posttreatment. Tumor response was associated with an increase in both CTL/recipient HLA matches and CD4+ T cells within the infused CTL lines. The present study was undertaken to correlate tumor response with CTL specificity. The majority of CTL lines infused recognized EBV-encoded nuclear Ag-3 proteins, but CTL protein specificity itself did not correlate with tumor response. Specificity in conjunction with donor/recipient functional HLA matching as opposed to HLA matching alone, however, was important for tumor response. CTL receptor TCR β-chain variable gene subfamilies were polyclonal, with no preferential use of a particular family. However, tumor response was improved in those receiving CTL lines with polyclonal vs clonal distribution for subfamilies 2, 3, and 9. Interestingly, in five of six tumors (five Hodgkin’s-like and one Burkitt’s-like posttransplant lymphoproliferative disease) with restricted viral gene expression a complete response was recorded, although in some cases the tumor cells did not express the proteins recognized by the infused CTL. Thus CTL were advantageous when functionally HLA matched but for certain tumor types complete responses occurred in the absence of detectable specific CTL/tumor recognition. We suggest that either the allogenic CTL contained small, undetectable, EBV-specific, HLA-matched T cell populations or perhaps they stimulated nonspecific inflammatory responses in vivo, which were beneficial for tumor regression. These observations should be considered when designing and implementing CTL therapies.
The mDial Formin Is Required for Neutrophil Polarization, Migration, and Activation of the LARG/RhoA/ROCK Signaling Axis during Chemotaxis
Authors: Shi Yongquan , Zhang Jinyi , Mullin Michael , Dong Baoxia , Alberts Arthur S. , Siminovitch Katherine A. 
Published: March 2009

Abstract
Neutrophil chemotaxis depends on actin dynamics, but the roles for specific cytoskeleton regulators in this response remain unclear. By analysis of mammalian diaphanous-related formin 1 (mDia1)-deficient mice, we have identified an essential role for this actin nucleator in neutrophil chemotaxis. Lack of mDia1 was associated with defects in chemoattractant-induced neutrophil actin polymerization, polarization, and directional migration, and also with impaired activation of RhoA, its downstream target p160-Rho-associated coil-containing protein kinase (ROCK), and the leukemia-associated RhoA guanine nucleotide exchange factor (LARG). Our data also revealed mDia1 to be associated with another cytoskeletal regulator, Wiskott-Aldrich syndrome protein (WASp), at the leading edge of chemotaxing neutrophils and revealed polarized morphology and chemotaxis to be more mildly impaired in WAS−/− than in mDia1−/− neutrophils, but essentially abrogated by combined mDia1/WASp deficiency. Thus, mDia1 roles in neutrophil chemotaxis appear to be subserved in concert with WASp and are realized at least in part by activation of the LARG/RhoA/ROCK signaling pathway.
Coordinate Regulation of TLR-Mediated Arachidonic Acid Mobilization in Macrophages by Group IVA and Group V Phospholipase A2s
Authors: Ruipérez Violeta , Astudillo Alma M. , Balboa María A. , Balsinde Jesús 
Published: March 2009

Abstract
Macrophages can be activated through TLRs for a variety of innate immune responses. In contrast with the wealth of data existing on TLR-dependent gene expression and resultant cytokine production, very little is known on the mechanisms governing TLR-mediated arachidonic acid (AA) mobilization and subsequent eicosanoid production. We have previously reported the involvement of both cytosolic group IVA phospholipase A2 (cPLA2) and secreted group V phospholipase A2 (sPLA2-V) in regulating the AA mobilization response of macrophages exposed to bacterial LPS, a TLR4 agonist. In the present study, we have used multiple TLR agonists to define the role of various PLA2s in macrophage AA release via TLRs. Activation of P388D1 and RAW2647.1 macrophage-like cells via TLR1/2, TLR2, TLR3, TLR4, TLR6/2, and TLR7, but not TLR5 or TLR9, resulted in AA mobilization that appears to involve the activation of both cPLA2 and sPLA2 but not of calcium-independent phospholipase A2. Furthermore, inhibition of sPLA2-V by RNA interference or by two cell-permeable compounds, namely scalaradial and manoalide, resulted in a marked reduction of the phosphorylation of ERK1/2 and cPLA2 via TLR1/2, TLR2, TLR3, and TLR4, leading to attenuated AA mobilization. Collectively, the results suggest a model whereby sPLA2-V contributes to the macrophage AA mobilization response via various TLRs by amplifying cPLA2 activation through the ERK1/2 phosphorylation cascade.
Antibiotics: Biosynthesis
Authors: Zotchev Sergey B 
Published: March 2009

AbstractAntibiotics are synthesized by many bacterial, fungal, plant, and animal species as secondary metabolites not required for normal growth of the producing organisms. Medical usefulness of some antibiotics in treatment of infections and cancer prompted investigations into their biosynthesis, which have revealed great complexity and variability of enzymes and reactions involved. Although antibiotics are represented by compounds that belong to diverse chemical classes, some common themes are observed in their biosynthesis. Those themes comprise assembly of antibiotic scaffolds from activated precursors that originate from primary metabolism, followed by modification of the scaffolds with different chemical moieties. In this review, generalized schemes of antibiotic biosynthesis are discussed, along with the common enzymology, genetics, and methods used for studying antibiotic biosynthesis pathways.
Proteins: Array‐Based Techniques
Authors: Tomizaki Kin‐ya , Usui Kenji , Mihara Hisakazu 
Published: March 2009

AbstractIn recent years, array‐based technologies, including DNA microarrays and protein‐detecting microarrays have been getting more attractive and promising as high‐throughput research/diagnostic tools. DNA microarrays comprise oligo‐DNA immobilized onto solid surfaces. Whereas protein‐detecting microarrays are categorized in several formats depending on classes of capturing agents that selectively bind to proteins of interest. Protein‐based capturing agents such as antibodies and fusion proteins are commonly immobilized onto solid surfaces. Alternatively, DNA/RNA aptamers, synthetic peptides, and small molecules including drugs and carbohydrates also act as capturing agents. In particular, peptides as capturing agents are very versatile, because they are chemically prepared according to the well‐established standard synthetic procedures and enable site‐specific and directed surface modifications. In this review, we describe the basic features of protein‐detecting microarray technologies (capturing agents, surface chemistry, and signal generation/readout); thereafter we suggest that the use of synthetic peptides is a very promising and powerful tool to monitor not only protein–peptide interactions but also enzymatic activities.
Chemotaxis
Authors: Eisenbach Michael 
Published: March 2009

AbstractChemotaxis is a basic guidance mechanism employed by cells and organisms to move toward beneficial targets or environments and to avoid undesired ones. This mechanism, which is prevalent from bacteria to human beings, consists of two basic processes. One is the formation by diffusion of a concentration gradient of a specific chemical. The other is the sensation of this gradient by a cell/organism and the modification of its direction of movement up or down the chemical gradient (the chemical being defined as chemoattractant or chemorepellent, respectively). Although chemotaxis is a universal mechanism and so are the steps that constitute it (gradient sensing by receptors, signal transduction and amplification, and movement response), the processes that underlie this mechanism are diverse.
Viral Cysteine Peptidases and Cysteine Peptidase Inhibitors
Authors: Yin Jiang , James Michael N. G. 
Published: March 2009

Abstract

Polyprotein processing is a controlled cascade of proteolytic events carried out by virally encoded cysteine proteinases. It plays a central role in the infectious life cycle of animal RNA viruses such as picornaviruses, caliciviruses, and coronaviruses. Furthermore, some of these viral enzymes are vitally important in viral RNA genome replication, virion assembly, and virus–host antagonism. The 3 C
pro
and 3 C‐like (3CL
pro
) peptidases are structurally related to the chymotrypsin branch of the serine proteinase family, but they have the catalytic serine residue replaced by a cysteine. Their uniquely designed yet structurally conserved S1 substrate binding pocket strongly favors a P1‐Glutamine in the substrate. The high level of structural conservation in the active sites of 3 C
pro
and 3CL
pro
and the lack of a mammalian homolog make these enzymes hotly pursued targets for antiviral drug design. The structures of these viral cysteine peptidases in complex with various inhibitors have shed light not only on how different inhibitors work but also on the catalytic mechanisms underlying the hydrolysis of normal peptidyl substrates. Most importantly, the results from the structural studies on Hepatitis A virus (HAV) 3 C
pro
point out possible new directions in the design of therapeutic intervention in a variety of diseases caused by members of these large RNA virus families.
Metals in Medicine: Therapeutic Agents
Authors: Mukherjee Arindam , Sadler Peter J. 
Published: March 2009

AbstractWithin the emerging field of medicinal inorganic chemistry, the realization that metal complexes can be designed as both therapeutic and diagnostic agents with novel mechanisms of action is increasing. Some recent advances are highlighted in this review, beginning with the success of platinum anticancer complexes and attempts to extend such activity to other transition metals, even to arsenic. Lithium is widely used for bipolar affective disorders, and gold is used for the treatment of rheumatoid arthritis. Metal ions also play crucial roles in contrast agents for magnetic resonance imaging and in radiopharmaceuticals used for imaging and therapy. Metal complexes offer flexible design platforms as enzyme inhibitors, and metals in enzyme active sites can be key drug targets. The antimicrobial and antiviral activities of certain metal complexes may prove useful in the fight against antibiotic resistance. Metals play key roles, too, in the control of small signaling molecules such as nitric oxide and carbon monoxide. Control of the uptake and distribution of the essential metals also presents a challenge, which is aided by modern genomic knowledge.
Micro
RNA
Authors: Visone Rosa , Croce Carlo M. 
Published: March 2009

Abstract

miRNAs (microRNAs) are single‐stranded noncoding RNAs 18–29 nucleotides long that were first discovered as critical regulators of developmental timing events in
Caenorhabditis elegans
. Several studies collectively identified ∼3000 mature miRNAs highly conserved in species that range from plants to humans, which suggests that they are ancient players. Recently, poor or not conserved miRNAs were identified by using new software program for miRNAs prediction. miRNAs are processed through a multistep process and confer their regulation at a posttranscriptional level by blocking and causing degradation of target miRNAs. The processing steps are performed by members of the RNAse III enzyme family, whereas gene‐silencing events are mediated by members of the highly conserved Argonaute (AGO) protein family. In mammals, miRNAs are predicted to control the activity of more than 30% of all protein‐coding genes, and they have been shown to participate in the regulation of almost every cellular process investigated so far. Improved bioinformatic programs now can predict the miRNAs targets in a more‐efficient manner, thus facilitating the identification of miRNA function. Recently, new insights have been provided into the role of miRNAs in various biological events, which include development, aging and cancer.
Mass Spectrometry to Identify Posttranslational Modifications
Authors: Eyers Claire E. , Gaskell Simon J. 
Published: March 2009

AbstractThe analysis of posttranslational modifications using mass spectrometric‐based strategies is a rapidly growing area of postgenome science. This article describes an overview of the techniques currently used in the analysis of some common protein modifications. Strategies are described for the selective enrichment of modified peptides to facilitate mass spectrometric analysis. Techniques are also described for the identification of peptides that carry specific modifications by detection of characteristic fragment ions following collision‐induced dissociation.
Protein– Protein Interactions
Authors: Sundberg Eric J. 
Published: March 2009

Abstract
Although proteins have numerous capabilities, one of their most important functions is to bind other proteins. These protein–protein interactions are critical for nearly every cellular process, and when they become corrupted, they often result in a diseased state. Because of the importance of protein–protein interactions in nearly all aspects of biology, efforts to decipher the rules that govern these associations have been underway for many decades. This review provides an overview of the evolution of the study of protein–protein interactions with an emphasis on recent developments in the field that concern the modular architecture of protein–protein interfaces and the networked communications within these binding sites that serve as a driving force for protein complex specificity and affinity. Relationships between biophysical studies performed to quantify the myriad factors that contribute to protein molecular recognition and computational analysis and interaction prediction algorithm development, as well as drug discovery and development, are also highlighted.
Ubiquitin Proteasome Pathway
Authors: Navon Ami , Ciechanover Aaron 
Published: March 2009

AbstractThe 26S proteasome is responsible for the rapid destruction of damaged polypeptides and the controlled removal of critical regulatory proteins. This ATP‐dependent system is highly regulated and generally recognizes and processes substrates covalently attached to polyubiquitin chains. In eukaryotes, the proteasome is also essential for the cellular immune response as it generates most of the peptides used for class 1 MHC presentation. We review herein; the ubiquitin tagging system, the general architecture of the 26S proteasome, as well as some none canonical functions of the 26S proteasome.
ATPSynthesis, Chemistry of
Authors: Wilkens Stephan 
Published: March 2009

AbstractThe universal carrier of free energy in all living organisms is adenosine triphosphate (ATP). Virtually all energy‐requiring biological processes are coupled to the enzymatic hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi). The enzyme complex that synthesizes the bulk of the cellular ATP is called F1F0–ATP synthase. F1F0–ATP synthase is found in energy‐converting membranes, such as the inner membrane of mitochondria, the plasma membrane of bacteria, and the thylakoid membrane of chloroplasts, where it harnesses the potential energy of a transmembrane electrochemical gradient that is generated during oxidation of foodstuffs or photosynthesis. F1F0–ATP synthase is a rotary molecular motor enzyme: The energy released in the membrane‐bound part (F0) of the enzyme during ion translocation is transmitted to the catalytic sites on the membrane extrinsic part (F1) via rotation of a central domain made of polypeptides from both F0and F1. This specialized topics review summarizes our current understanding of the biological process of ATP synthesis and emphasizes recent insights into the atomic structure of ATP synthase and the fascinating mechanism of subunit‐rotation‐induced energy coupling.
Biocatalysis and Biotransformation
Authors: Roberts Stan , Turner Nicholas John 
Published: March 2009

Abstract
Biocatalysis and biotransformations are two expressions that relate to the use of enzymes as catalysts for reactions that introduce or modify functional groups in organic compounds. Enzymes are proteins that consist of one or more chains of condensed amino acids. Because all 20 natural amino acids (with the exception of glycine) are chiral, these biological catalysts are also chiral; as such, they are often used to prepare optically active organic molecules, which may be difficult to obtain by chemical means. The biocatalyst can be used as isolated, partially purified protein or as a constituent of a cell, usually a bacterium or fungus. Moreover, isolated enzymes can be used in free, soluble form or more often they are immobilized by conjugation to an insoluble support, for example an ion‐exchange resin. Immobilization of enzymes is often found to improve their stability when used under process‐related conditions. It also facilitates recovery and reuse of the biocatalyst.
Second Messengers in Cellular Signaling
Authors: DiPilato Lisa M. , Zhang Jin 
Published: March 2009

AbstractSecond messengers are a class of highly ubiquitous signaling molecules, which play important roles in nearly all cellular processes, which range from fertilization and development to cell death. These signaling molecules include the cyclic nucleotides cAMP and cGMP, calcium, and lipid‐derived second messengers, such as diacylglycerol, IP3, and PIP3. Although biochemically different in structure and activity, these signaling molecules share key features that are required for second‐messenger action and necessary for efficient and specific signaling. The use of fluorescent sensors to monitor second messengers in real time as well as small molecules to manipulate and perturb signaling has greatly advanced our understanding of these dynamic signaling molecules. These tools and methods should continue to provide insights into the nuances of cell signaling and their related diseases as well as aid the development of new therapeutics. This article reviews the molecular mechanisms that govern second‐messenger action and the current approaches to studying them.
14‐3‐3 Proteins
Authors: Cockrell Lisa M. , Du Yuhong , Acker Timothy M. , Fu Haian 
Published: March 2009

AbstractThe 14‐3‐3 proteins are a family of multifunctional regulators in eukaryotic organisms. Through binding to over 200 client proteins, 14‐3‐3 proteins regulate numerous cellular functions, which include metabolic pathways, molecular trafficking, and cell‐cycle progression. Most 14‐3‐3 interactions are mediated by defined phosphoserine/threonine motifs within the target protein sequence. The presence of these phosphorylated motifs allows for integration of 14‐3‐3 interactions with client proteins into a diverse cellular signaling network, through the actions of various protein kinases and phosphatases. As evidence of its vital role in cell function, 14‐3‐3 has been implicated in human diseases, such as cancer and neuronal disorders. Thus, development of small‐molecule 14‐3‐3 modulators will allow the continued discovery of the critical importance of 14‐3‐3 in normal physiology and lead to future use as targeted therapies in human disease.
Integrated and Organized Cellular Energetic Systems
Authors: Saks Valdur , Monge Claire , Guzun Rita , Dzeja Petras , Wallimann Theo 
Published: March 2009

AbstractBioenergetics as a part of biophysical chemistry and biophysics is a quantitative science that is based on several fundamental theories. The definition of energy itself is given by the first law of thermodynamics, and application of the second law of thermodynamics shows that the living cells can only function as open systems in which internal order (low entropy state) is maintained by increasing the entropy in surrounding medium (Schrödinger's principle of negentropy). For this mechanism, exchange of mass is needed that yields metabolism as the sum of catabolism and anabolism. The free‐energy changes taking place during metabolic reactions obey rules of chemical thermodynamics, which deals with Gibbs free energy of chemical reactions and with electrochemical potentials. For application of these theories to the integrated systemsin vivo, complex cellular organization should be accounted for: macromolecular crowding, metabolic channeling and functional coupling mechanisms caused by close and tight protein–protein interactions, compartmentation of enzymes, as well as both macrocompartmentation and microcompartmentation of substrates and metabolites in cells should be considered. For integration of these system components, effective methods of communication, including compartmentalized energy transfer systems, are required. These systems are represented in muscle cells by phosphotransfer networks, mostly by creatine kinase and adenylate kinase systems. System analysis of these networks shows their central role both in energy transfer and metabolic feedback regulation of mitochondrial function, in regulation of ion fluxes and cellular energetics during increased workload by synchronizing the cellular electrical and mechanical activities with energy supply and substrate oxidation.
Alberti's Paradigm
Authors: Garber Richard 
Published: March 2009

AbstractCould the advent of building information modelling (BIM) see the architect's status return to that of his medieval counterpart, the master builder? Guest‐editor Richard Garber examines the work of Filippo Brunelleschi, who did the seemingly impossible in early 15th‐century Florence by spanning the massive opening of the dome of Santa Maria del Fiore, the city's cathedral, through an adept use of physical models. Copyright © 2009 John Wiley & Sons, Ltd.
McLean's Nuggets
Authors: McLean Will 
Published: March 2009

AbstractThe development of a clean, plentiful and low‐cost alternative energy source is the holy grail of the 21st century. Ken Yeang looks into his crystal ball and asks whether the future could lie in nanoenergy and the proliferation of numerous personal nanogenerators ‐ attached to buildings, individuals or under bridges. Copyright © 2009 John Wiley & Sons, Ltd.
Nanoparticle formation through solid‐fed flame synthesis: Experiment and modeling
Authors: Widiyastuti W. , Purwanto Agus , Wang Wei‐Ning , Iskandar Ferry , Setyawan Heru , Okuyama Kikuo 
Published: March 2009

AbstractThe preparation of silica nanoparticles through solid‐fed flame synthesis was investigated experimentally and theoretically. Monodispersed submicrometer‐ and micrometer‐sized silica powders were selected as solid precursors for feeding into a flame reactor. The effects of flame temperature, residence time, and precursor particle size were investigated systematically. Silica nanoparticles were formed by the nucleation, coagulation, and surface growth of the generated silica vapors due to the solid precursor evaporation. Numerical modeling was conducted to describe the mechanism of nanoparticle formation. Evaporation of the initial silica particles was considered in the modeling, accounting for its size evolution. Simultaneous mass transfer modeling due to the silica evaporation was solved in combination with a general dynamics equation solution. The modeling and experimental results were in agreement. Both results showed that the methane flow rate, carrier gas flow rate, and initial particle size influenced the effectiveness of nanoparticle formation in solid‐fed flame synthesis. © 2009 American Institute of Chemical Engineers AIChE J, 2009