bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology
Authors: Wu Hao , Arron Joseph R. 
Published: October 2003

AbstractTumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is a crucial signaling molecule regulating a diverse array of physiological processes, including adaptive immunity, innate immunity, bone metabolism and the development of several tissues including lymph nodes, mammary glands, skin and the central nervous system. It is a member of a group of six closely related TRAF proteins, which serve as adapter molecules, coupling the TNF receptor (TNFR) superfamily to intracellular signaling events. Among the TRAF proteins, TRAF6 is unique in that, in addition to mediating TNFR family signaling, it is also essential for signaling downstream of an unrelated family of receptors, the interleukin‐1 (IL‐1) receptor/Toll‐like receptor (IL‐1R/TLR) superfamily. Gene targeting experiments have identified several indispensable physiological functions of TRAF6, and structural and biochemical studies have revealed the potential mechanisms of its action. By virtue of its many signaling roles, TRAF6 represents an important target in the regulation of many disease processes, including immunity, inflammation and osteoporosis. BioEssays 25:1096–1105, 2003. © 2003 Wiley Periodicals, Inc.
Small GTPases and the evolution of the eukaryotic cell
Authors: Jékely Gáspár 
Published: October 2003

AbstractThe origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras‐family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during eukaryote evolution had secretory, and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented. BioEssays 25:1129–1138, 2003. © 2003 Wiley Periodicals, Inc.
Pathogenic archaea: do they exist?
Authors: Cavicchioli Ricardo , Curmi Paul M.G. , Saunders Neil , Thomas Torsten 
Published: October 2003

AbstractArchaea are microorganisms that are distinct from bacteria and eukaryotes. They are prevalent in extreme environments, and yet found in most ecosystems. They are a natural component of the microbiota of most, if not all, humans and other animals. Despite their ubiquity and close association with humans, animals and plants, no pathogenic archaea have been identified. Because no archaeal pathogens have yet been identified, there is a general assumption that archaeal pathogens do not exist. This review examines whether this is a good assumption by investigating the potential for archaea to be or become pathogens. This is achieved by addressing: the diversity of archaea versus known pathogens, opportunities for archaea to demonstrate pathogenicity and be detected as pathogens, reports linking archaea with disease, and immune responses to archaea. In addition, molecular and genomic data are examined for the presence of systems utilised in pathogenesis. The view of this report is that, although archaea can presently be described as non‐pathogenic, they have the potential to be (discovered as) pathogens. The present optimistic view that there are no archaeal pathogens is tainted by a severe lack of relevant knowledge, which may have important consequences in the future. BioEssays 25:1119–1128, 2003. © 2003 Wiley Periodicals, Inc.
PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease
Authors: Vossenaar Erik R. , Zendman Albert J.W. , van Venrooij Walther J. , Pruijn Ger J.M. 
Published: October 2003

AbstractPeptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of protein‐bound arginine to citrulline. This post‐translational modification may have a big impact on the structure and function of the target protein. In this review, we will discuss the effects of citrullination and its involvement in several human diseases, including rheumatoid arthritis and multiple sclerosis. So far, four isotypes of PAD have been described in mammals. We describe the existence of PAD in non‐mammalian vertebrates and the existence of a fifth mammalian PAD. In addition, tissue‐specific expression, genomic organization and evolutionary conservation of the different PAD isotypes will be discussed in detail. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265‐9247/suppmat/2003/25/v25.1106.html. BioEssays 25:1106–1118, 2003. © 2003 Wiley Periodicals, Inc.
Anti‐cancer selection as a source of developmental and evolutionary constraints
Authors: Galis Frietson , Metz Johan A.J. 
Published: October 2003

AbstractRecently at least two papers1,2have appeared that look at cancer from an evolutionary perspective. That cancer has a negative effect on fitness needs no argument. However, cancer origination is not an isolated process, but the potential for it is linked in diverse ways to other genetically determined developmental events, complicating the way selection acts on it, and through it on the evolution of development. The two papers take a totally different line. Kavanagh argues that anti‐cancer selection has led to developmental constraints. Leroi et al. argue that cancer is a side‐effect of recent evolutionary changes that usually will disappear over time through anti‐cancer selection. Here we place the papers in a wider perspective, and in so doing discuss various alternative developmental links cancer may have together with their evolutionary implications. BioEssays 25:1035–1039, 2003. © 2003 Wiley Periodicals, Inc.
Alternative splicing and evolution
Authors: Boue Stephanie , Letunic Ivica , Bork Peer 
Published: October 2003

AbstractAlternative splicing is a critical post‐transcriptional event leading to an increase in the transcriptome diversity. Recent bioinformatics studies revealed a high frequency of alternative splicing. Although the extent of AS conservation among mammals is still being discussed, it has been argued that major forms of alternatively spliced transcripts are much better conserved than minor forms.1 It suggests that alternative splicing plays a major role in genome evolution allowing new exons to evolve with less constraint. BioEssays 25:1031–1034, 2003. © 2003 Wiley Periodicals, Inc.
Mechanism‐based protein design: Attempted “nucleation–condensation” approach to a possible minimal helix‐bundle protein
Authors: Mohanraja K. , Dhanasekaran M. , Kundu B. , Durani S. 
Published: October 2003

AbstractIn an intended mechanism‐based de novo approach, a 22‐mer peptide was so designed as to make it both a stereochemically nucleatable and hydrophobically condensable minimal globular protein. Framework‐like nucleation of a triple‐helix bundle was targeted by employing as folding nucleators composite β‐turns that could both nucleate helices and place them in close juxtaposition for possible interhelical interaction. To promote the targeted triple‐helix bundle to condense as a globular protein, an amphipathic sequence pattern was adopted for possible hydrophobic interhelical interaction. A predominantly helicogenic 22‐mer amphipathic peptide was thus designed, punctuating it with composite type II′–III and type II–Asx type β‐turns as the helix nucleators cum chain reversal elements. The peptide made by solid‐phase synthesis was shown by NMR and CD to be a nascent and distorted triple‐helix bundle in a trifluoroethanol (TFE)–water mixture, but more or less a random coil in water. A fold nucleation effect is evident in the TFE–water mixture, but apparently the hydrophobic effect cannot sustain the peptide conformational order in water. A lack of synergy between folding nucleation and hydrophobic condensation of the peptide is possible. Indeed, a mismatch between the sequential H,P pattern of the peptide and its nascent‐type globular fold in a TFE–water mixture is evident based on a simulated annealing study guided by NMR. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 355–363, 2003
DNA deformation energetics and protein binding
Authors: Zakrzewska K. 
Published: October 2003

AbstractThe formation of protein‐DNA complexes often involves deformation of the DNA double helix. We have calculated the energy necessary to produce this deformation in 71 crystallographically determined complexes, using internal coordinate energy optimization with the JUMNA program and a generalized Born continuum solvent treatment. An analysis of the data allows deformation energy to be interpreted in terms of both local and global structural changes. We find that, in the majority of complexes, roughly 60% of the deformation energy corresponds to backbone distortion. It is also found that large changes in stacking and pairing energies are often compensated for by other, longer range, stabilizing factors. Some deformations, such as base opening, can be large, but only‐produce local energetic effects. In terms of backbone distortions, the angle α, most often involved in αγ transitions, makes the most significant energetic contribution. This type of transition is twice as costly as those involving β, or coupled εζ changes. Sugar amplitude changes are also energetically significant, in contrast to changes in phase angles. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 414–423, 2003
Binding of copper(II) ions to the polyproline II helices of PEVK modules of the giant elastic protein titin as revealed by ESI‐MS, CD, and NMR
Authors: Ma Kan , Wang Kuan 
Published: October 2003

AbstractTitin, a family of giant elastic proteins, constitutes an elastic sarcomere matrix in striated muscle. In the I‐band region of the sarcomere, the titin PEVK segment acts as a molecular spring to generate elasticity as well as sites of adhesion with parallel thin filaments. Previously, we reported that PEVK consists of tandem repeats of 28 residue modules and that the “polyproline II‐coil” motif is the fundamental conformational motif of the PEVK module. In order to characterize the factors that may affect and alter the PPII‐coil conformational motifs, we have initiated a systematic study of the interaction with divalent cations (Cu2+, Ca2+, Zn2+, and Ni2+) and a conformational profile of PEVK peptides (a representative 28‐mer peptide PR: PEPPKEVVPEKKAPVAPPKKPEVPPVKV and its subfragments PR1: kvPEPPKEVVPE, PR2: VPEKKAPVAPPK, PR3: KPEVPPVKV). UV‐Vis absorption difference spectra and CD spectra showed that Cu2+ bound to PR1 with high affinity (20 μM), while its binding to PR2 and PR3 as well as the binding of other cations to all four peptides were of lower affinity (>100 μM). Conformational studies by CD revealed that Cu2+ binding to PR1 resulted in a polyproline II to turn transition up to a 1:2 PR1/Cu2+ ratio and a coil to turn transition at higher Cu2+ concentration. ESI‐MS provided the stoichiometry of PEVK peptide‐Cu2+ complexes at both low and high ion strength, confirming the specific high affinity binding of Cu2+ to PR1 and PR. Furthermore, NMR and ESI‐MS/MS fragmentation analysis elucidated the binding sites of the PEVK peptide‐Cu2+ complexes at −2KVPE2, 8VPE10, 13APV15, and 22EVP24. A potential application of Cu2+ binding in peptide sequencing by mass spectrometry was also revealed. We conclude that Cu2+ binds and bends PEVK peptides to a beta‐turn‐like structure at specific sites. The specific targeting of Cu2+ towards PPII is likely to be of significant value in elucidating the roles of PPII in titin elasticity as well as in interactions of proline‐rich proteins. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 297–309, 2003
Spectroscopic investigation on gel‐forming β‐sheet assemblage of peptide derivatives
Authors: Ganesh S. , Prakash S. , Jayakumar R. 
Published: October 2003

AbstractThe conformational studies of peptide derivatives A and B in a gel state were studied by using circular dichroism (CD), Fourier transformed infrared (FTIR), and fluorescence spectroscopic techniques. Birefringence and electron microscopic studies were carried out to characterize the morphological aspects of the fibrils in the gel. The FTIR spectra of the peptides show the absence of free NH in the gel state, implying that the intermolecular hydrogen‐bond formation is the driving force for the aggregation. The CD spectrum of the peptide gels shows the presence of antiparallel and parallel β‐sheet conformation for peptide derivatives A and B, respectively. Electron microscopic studies (EM) of the peptide derivatives A and B reveal that peptide A formed rigid, rod‐like structures without cross‐linking and peptide B formed loose fibrils organized into highly noncovalently cross‐linked mesh‐like structural aggregates. Peptide A was much more soluble in alcoholic solvents than peptide B, and no birefringence was observed with Congo red (CR) staining in the temperature range of 0–80°C. The spectroscopic studies indicate that peptide B consists of domains having a significant amount of β‐sheet structure and exhibiting golden yellow birefringence between 53 and 56°C when stained with Congo red. On the other hand, peptide A gives no evidence of birefringence under polarized light. Fluorescence probe binding studies with pyrene in gel state with peptides A and B indicates the polarity in the interior of the aggregates. The data presented in the present work indicate that peptide B forms fibrils, which is similar to amyloid aggregates that are present in biological systems. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 346–354, 2003
Physicochemical characterization of branched chain polymeric polypeptide carriers based on a poly‐lysine backbone
Authors: Nagy I. B. , Hudecz F. , Alsina M. A. , Reig F. 
Published: October 2003

AbstractA systematic study is reported on the physicochemical characteristics of two branched chain polymers (based on a poly‐L‐lysine backbone) with a general formula poly[Lys‐(DL‐Alam‐Xi)], where X = Orn (OAK) or N‐acetyl‐Glu (Ac‐EAK) and m ≅ 3, using surface pressure and fluorescence polarization methods. These data are compared with those of the linear poly(L‐Lys) from which OAK and Ac‐EAK are derived. These two polymers show a moderate surface activity, able to form stable monomolecular layers at the air‐water interface. Poly(L‐Lys), the most hydrophilic, has the lowest surface activity. The interaction of these polymers with phospholipid bilayers either neutral or negatively charged was studied with vesicles labeled with two fluorescent probes: ANS and DPH. Results indicate that these polymers are able to accommodate in their internal structure, mainly through electrostatic interactions, a certain amount of ANS marker molecules, but fluorescence increases of the ANS‐polypeptide complexes were so low that its influence in further polarization measurements could be discarded. After interaction with liposomes, these polymers induce an increase in the polarization of the probes, thus indicating a rigidification of the bilayers. Electrostatic forces seem to be very important in this interaction; cationic polymers are clearly more active, with PG‐containing liposomes, than Ac‐EAK. Moreover, in these assays poly(L‐Lys) behaves as the more active compound. This fact is probably due to its major ability to form α‐helical structures that could insert easily in the bilayers. These results indicate that the polymeric structures studied can be used as carriers for biologically active molecules, because their interactions with bilayers remain soft and have a positive effect on the stability of the membranes. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 323–335, 2003
Speed‐up of DNA melting algorithm with complete nearest neighbor properties
Authors: Tøstesen Eivind , Liu Fang , Jenssen Tor‐Kristian , Hovig Eivind 
Published: October 2003

AbstractWe describe an optimized algorithm, which is faster and more accurate compared to previously described algorithms, for computing the statistical mechanics of denaturation of nucleic acid sequences according to the classical Poland‐Scheraga type of model. Nearest neighbor thermodynamics has been included in a complete and general way, by rigorously treating nearest neighbor interactions, helix end interactions, and isolated base‐pairs. This avoids the simplifications of previous approaches and achieves full generality and controllability with respect to thermodynamic modeling. The algorithm computes subchain partition functions by recursion, from which various quantitative aspects of the melting process are easily derived, for example the base‐pairing probability profiles. The algorithm represents an optimization with respect to algorithmic complexity of the partition function algorithm of Yeramian et al. (Biopolymers 1990, 30, 481–497): we reduce the computation time for a base‐pairing probability profile from O(N2) to O(N), where N is the sequence length. This speed‐up comes in addition to the speed‐up due to a multiexponential approximation of the loop entropy factor as introduced by Fixman and Freire22 and applied by Yeramian et al.25 The speed‐up, however, is independent of the multiexponential approximation and reduces time from O(N3) to O(N2) in the exact case. A method for representing very large numbers is described, which avoids numerical overflow in the partition functions for genomic length sequences. In addition to calculating the standard base‐pairing probability profiles, we propose to use the algorithm to calculate various other probabilities (loops, helices, tails) for a more direct view of the melting regions and their positions and sizes. This can provide a better understanding of the physics of denaturation and the biology of genomes. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 364–376, 2003
Structure–activity relationships in the hydrophobic interactions of polyphenols with cellulose and collagen
Authors: Tang H. R. , Covington A. D. , Hancock R. A. 
Published: October 2003

AbstractPolyphenol interactions with both cellulose and collagen in the solid state have been studied by using chromatography on cellulose and by evaluating the hydrothermal stability of the polyphenol treated sheepskin collagen. Twenty‐four polyphenolic compounds were studied, including seven glucose‐based gallotannins, five polyalcohol‐based gallotannins, and twelve ellagitannins. In the cellulose–polyphenols systems, the polyphenol's affinity to cellulose is positively correlated with their molecular masses, the number of galloyl groups, and their hydrophobicity (logP). The polyphenol treatment increased the hydrothermal stability of collagen samples, and such effects are also positively correlated with the molecular masses, total number of galloyl groups and the hydrophobicity of polyphenols. Ellagitannins showed much weaker interactions with both biopolymers than gallotannins having similar molecular mass, the same number of galloyl groups, and the same number of phenolic hydroxyl groups. It is concluded that, for the polyphenol interactions with both cellulose and collagen, (1) the galloyl group of polyphenols is the functional group; (2) the strength of interactions are positively correlated with molecular size, the number of galloyl groups and the hydrophobicity of polyphenols; (3) the hydrophobic interactions are of great significance; and (4) the interactions are strongly dependent on the flexibility of galloyl groups. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 403–413, 2003
The solution structure of frenatin 3, a neuronal nitric oxide synthase inhibitor from the giant tree frog,Litoria infrafrenata
Authors: Brinkworth Craig S. , Carver John A. , Wegener Kate L. , Doyle Jason , Llewellyn Lyndon E. , Bowie John H. 
Published: October 2003

AbstractThe peptide frenatin 3 is a major component of the skin secretion of the Australian giant tree frog,Litoria infrafrenata. Frenatin 3 is 22 amino acids in length, and shows neither antimicrobial nor anticancer activity. It inhibits the production of nitric oxide by the enzyme neuronal nitric oxide synthase at a micromolar concentration by binding to its regulatory protein, Ca2+calmodulin, a protein known to recognize and bind amphipathic α‐helices. The solution structure of frenatin 3 has been investigated using NMR spectroscopy and restrained molecular dynamics calculations. In trifluoroethanol/water mixtures, the peptide forms an amphipathic α‐helix over residues 1–14 while the C‐terminal eight residues are more flexible and less structured. The flexible region may be responsible for the lack of antimicrobial activity. In water, frenatin 3 exhibits some α‐helical character in its N‐terminal region. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 424–434, 2003
Meeting Highlights: Genome Informatics
Authors: Wixon Jo , Ashurst Jennifer 
Published: October 2003

AbstractWe bring you the highlights of the second Joint Cold Spring Harbor Laboratory and Wellcome Trust ‘Genome Informatics’ Conference, organized by Ewan Birney, Suzanna Lewis and Lincoln Stein. There were sessions on in silico data discovery, comparative genomics, annotation pipelines, functional genomics and integrative biology. The conference included a keynote address by Sydney Brenner, who was awarded the 2002 Nobel Prize in Physiology or Medicine (jointly with John Sulston and H. Robert Horvitz) a month later. Copyright © 2003 John Wiley & Sons, Ltd.
Post‐normalization quality assessment visualization of microarray data
Authors: McClure John , Wit Ernst 
Published: October 2003

AbstractPost‐normalization checking of microarrays rarely occurs, despite the problems that using unreliable data for inference can cause. This paper considers a number of different ways to check microarrays after normalization for a variety of potential problems. Four types of problem with microarray data that these checks can identify are: clerical mistakes, array‐wide hybridization problems, problems with normalization and mishandling problems. Any of these can seriously affect the results of any analysis. The three main techniques used to identify these problems are dimension reduction techniques, false array plots and correlograms. None of the techniques are computationally very intensive and all can be carried out in the R statistical package. Once discovered, problems can either be rectified or excluded from the data. Copyright © 2003 John Wiley & Sons, Ltd.
Proteins interacting with Caenorhabditis elegans Gα subunits
Authors: Cuppen Edwin , van der Linden Alexander M. , Jansen Gert , Plasterk Ronald H. A. 
Published: October 2003

AbstractTo identify novel components in heterotrimeric G‐protein signalling, we performed an extensive screen for proteins interacting with Caenorhabditis elegans Gα subunits. The genome of C. elegans contains homologues of each of the four mammalian classes of Gα subunits (Gs, Gi/o, Gq and G12), and 17 other Gα subunits. We tested 19 of the Gα subunits and four constitutively activated Gα subunits in a large‐scale yeast two‐hybrid experiment. This resulted in the identification of 24 clones, representing 11 different proteins that interact with four different Gα subunits. This set includes C. elegans orthologues of known interactors of Gα subunits, such as AGS3 (LGN/PINS), CalNuc and Rap1Gap, but also novel proteins, including two members of the nuclear receptor super family and a homologue of human haspin (germ cell‐specific kinase). All interactions were found to be unique for a specific Gα subunit but variable for the activation status of the Gα subunit. We used expression pattern and RNA interference analysis of the G‐protein interactors in an attempt to substantiate the biological relevance of the observed interactions. Furthermore, by means of a membrane recruitment assay, we found evidence that GPA‐7 and the nuclear receptor NHR‐22 can interact in the animal. Copyright © 2003 John Wiley & Sons, Ltd.