bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apo‐Hsp90 coexists in two open conformational states in solution
Authors: Bron Patrick , Giudice Emmanuel , Rolland Jean‐Paul , Buey Rubén M. , Barbier Pascale , Díaz J. Fernando , Peyrot Vincent , Thomas Daniel , Garnier Cyrille 
Published: May 2008

Background information. Hsp90 (90 kDa heat‐shock protein) plays a key role in the folding and activation of many client proteins involved in signal transduction and cell cycle control. The cycle of Hsp90 has been intimately associated with large conformational rearrangements, which are nucleotide‐binding‐dependent. However, up to now, our understanding of Hsp90 conformational changes derives from structural information, which refers to the crystal states of either recombinant Hsp90 constructs or the prokaryotic homologue HtpG (Hsp90 prokaryotic homologue).Results and discussion. Here, we present the first nucleotide‐free structures of the entire eukaryotic Hsp90 (apo‐Hsp90) obtained by small‐angle X‐ray scattering and single‐particle cryo‐EM (cryo‐electron microscopy). We show that, in solution, apo‐Hsp90 is in a conformational equilibrium between two open states that have never been described previously. By comparing our cryo‐EM maps with HtpG and known Hsp90 structures, we establish that the structural changes involved in switching between the two Hsp90 apo‐forms require large movements of the NTD (N‐terminal domain) and MD (middle domain) around two flexible hinge regions.Conclusions. The present study shows, for the first time, the structure of the entire eukaryotic apo‐Hsp90, along with its intrinsic flexibility. Although large structural rearrangements, leading to partial closure of the Hsp90 dimer, were previously attributed to the binding of nucleotides, our results reveal that they are in fact mainly due to the intrinsic flexibility of Hsp90 dimer. Taking into account the preponderant role of the dynamic nature of the structure of Hsp90, we reconsider the Hsp90 ATPase cycle.
Toxoplasma gondii Hsp20 is a stripe‐arranged chaperone‐like protein associated with the outer leaflet of the inner membrane complex
Authors: de Miguel Natalia , Lebrun Maryse , Heaslip Aoife , Hu Ke , Beckers Con J. , Matrajt Mariana , Dubremetz Jean F. , Angel Sergio O. 
Published: May 2008

Background information. Toxoplasma gondii is among the most successful parasites, with nearly half of the human population chronically infected. T. gondii has five sHsps [small Hsps (heat‐shock proteins)] located in different subcellular compartments. Among them, Hsp20 showed to be localized at the periphery of the parasite body. sHsps are widespread, constituting the most poorly conserved family of molecular chaperones. The presence of sHsps in membrane structures is unusual.Results. The localization of Hsp20 was further analysed using high‐resolution fluorescent light microscopy as well as electron microscopy, which revealed that Hsp20 is associated with the outer surface of the IMC (inner membrane complex), in a set of discontinuous stripes following the same spiralling trajectories as the subpellicular microtubules. The detergent extraction profile of Hsp20 was similar to that of GAP45 [45 kDa GAP (gliding‐associated protein)], a glideosome protein associated with the IMC, but was different from that of IMC1 protein. Although we were unable to detect interacting protein partners of Hsp20 either in normal or stressed tachyzoites, an interaction of Hsp20 with phosphatidylinositol 4‐phosphate and phosphatidylinositol 4,5‐bisphosphate phospholipids could be observed.Conclusions. Hsp20 was shown to be associated with a specialized membranous structure of the parasite, the IMC. This discontinuous striped‐arrangement is unique in T. gondii, indicating that the topology of the outer leaflet of the IMC is not homogeneous.
Comparable potency of IFNα2 and IFNβ on immediate JAK/STAT activation but differential down-regulation of IFNAR2
Authors: Marijanovic Zrinka , Ragimbeau Josiane , van der Heyden José , Uzé Gilles , Pellegrini Sandra 
Published: May 2008

Type I IFNs (interferons) (IFNα/β) form a family of related cytokines that control a variety of cellular functions through binding to a receptor composed of IFNAR (IFNα receptor subunit) 1 and 2. Among type I IFNs, the α2 and β subtypes exhibit a large difference in their binding affinities to IFNAR1, and it was suggested that high concentrations of IFNAR1 may compensate for its low intrinsic binding affinity for IFNα2. We tested whether receptor-proximal signalling events are sensitive to IFNAR1 surface concentration by investigating the relationship between relative IFNAR1/IFNAR2 surface levels and IFNα2 and IFNβ signalling potencies in several cell lines. For this, we monitored the activation profile of JAK (Janus kinase)/STAT (signal transducer and activator of transcription) proteins, measured basal and ligand-induced surface decay of each receptor subunit and tested the effect of variable IFNAR1 levels on IFNα2 signalling potency. Our data show that the cell-surface IFNAR1 level is indeed a limiting factor for assembly of the functional complex, but an increased concentration of it does not translate into an IFNα/β differential JAK/STAT signalling nor does it change the dynamics of the engaged receptor. Importantly, however, our data highlight a differential effect upon routing of IFNAR2. Following binding of IFNα2, IFNAR2 is internalized, but, instead of being routed towards degradation as it is when complexed to IFNβ, it recycles back to the cell surface. These observations suggest strongly that the stability and the intracellular lifetime of the ternary complex account for the differential control of IFNAR2. Moreover, the present study opens up the attractive possibility that endosomal-initiated signalling may contribute to IFNα/β differential bioactivities.
Effect of branched-chain amino acids on muscle atrophy in cancer cachexia
Authors: Eley Helen L. , Russell Steven T. , Tisdale Michael J. 
Published: May 2008

In the present study, the BCAAs (branched-chain amino acids) leucine and valine caused a significant suppression in the loss of body weight in mice bearing a cachexia-inducing tumour (MAC16), producing a significant increase in skeletal muscle wet weight, through an increase in protein synthesis and a decrease in degradation. Leucine attenuated the increased phosphorylation of PKR (double-stranded-RNA-dependent protein kinase) and eIF2α (eukaryotic initiation factor 2α) in skeletal muscle of mice bearing the MAC16 tumour, due to an increased expression of PP1 (protein phosphatase 1). Weight loss in mice bearing the MAC16 tumour was associated with an increased amount of eIF4E bound to its binding protein 4E-BP1 (eIF4E-binding protein 1), and a progressive decrease in the active eIF4G–eIF4E complex due to hypophosphorylation of 4E-BP1. This may be due to a reduction in the phosphorylation of mTOR (mammalian target of rapamycin), which may also be responsible for the decreased phosphorylation of p70S6k (70 kDa ribosomal S6 kinase). There was also a 5-fold increase in the phosphorylation of eEF2 (eukaryotic elongation factor 2), which would also decrease protein synthesis through a decrease in translation elongation. Treatment with leucine increased phosphorylation of mTOR and p70S6k, caused hyperphosphorylation of 4E-BP1, reduced the amount of 4E-BP1 associated with eIF4E and caused an increase in the eIF4G–eIF4E complex, together with a reduction in phosphorylation of eEF2. These changes would be expected to increase protein synthesis, whereas a reduction in the activation of PKR would be expected to attenuate the increased protein degradation.
Human copper transporter 2 is localized in late endosomes and lysosomes and facilitates cellular copper uptake
Authors: van den Berghe Peter V. E. , Folmer Dineke E. , Malingré Helga E. M. , van Beurden Ellen , Klomp Adriana E. M. , van de Sluis Bart , Merkx Maarten , Berger Ruud , Klomp Leo W. J. 
Published: May 2008

High-affinity cellular copper uptake is mediated by the CTR (copper transporter) 1 family of proteins. The highly homologous hCTR (human CTR) 2 protein has been identified, but its function in copper uptake is currently unknown. To characterize the role of hCTR2 in copper homoeostasis, epitope-tagged hCTR2 was transiently expressed in different cell lines. hCTR2–vsvG (vesicular-stomatitis-virus glycoprotein) predominantly migrated as a 17 kDa protein after imunoblot analysis, consistent with its predicted molecular mass. Chemical cross-linking resulted in the detection of higher-molecular-mass complexes containing hCTR2–vsvG. Furthermore, hCTR2–vsvG was co-immunoprecipitated with hCTR2–FLAG, suggesting that hCTR2 can form multimers, like hCTR1. Transiently transfected hCTR2–eGFP (enhanced green fluorescent protein) was localized exclusively to late endosomes and lysosomes, and was not detected at the plasma membrane. To functionally address the role of hCTR2 in copper metabolism, a novel transcription-based copper sensor was developed. This MRE (metal-responsive element)–luciferase reporter contained four MREs from the mouse metallothionein 1A promoter upstream of the firefly luciferase open reading frame. Thus the MRE–luciferase reporter measured bioavailable cytosolic copper. Expression of hCTR1 resulted in strong activation of the reporter, with maximal induction at 1 μM CuCl2, consistent with the Km of hCTR1. Interestingly, expression of hCTR2 significantly induced MRE–luciferase reporter activation in a copper-dependent manner at 40 and 100 μM CuCl2. Taken together, these results identify hCTR2 as an oligomeric membrane protein localized in lysosomes, which stimulates copper delivery to the cytosol of human cells at relatively high copper concentrations. This work suggests a role for endosomal and lysosomal copper pools in the maintenance of cellular copper homoeostasis.
The role of computer‐aided psychotherapy within an NHS CBT specialist service
Authors: Learmonth Despina , Trosh Jo , Rai Sadik , Sewell Janet , Cavanagh Kate 
Published: May 2008

AbstractTo date, the feasibility of computer‐aided psychotherapy as an intervention has only been recognised in primary care practice. The present study sought to evaluate the impact of ‘Beating the Blues’ (BtB), an established computerised cognitive behaviour therapy (CCBT) self‐help programme for the management of anxiety and depression, within an NHS CBT specialist healthcare centre. Of the 555 service users who used BtB as part of routine care, with follow‐up assessment at six to eight weeks, 71% completed all eight sessions. Statistically significant differences on the Beck Depression Inventory‐II (BDI‐II) and Beck Anxiety Inventory (BAI) were found in completer and intention‐to‐treat analyses; 50% of completers achieved reliable change on the BDI‐II and approximately 25% of completers achieved reliable and clinically significant change on both measures. Outcomes were benchmarked against outcomes in studies of routine face‐to‐face CBT. These findings provide evidence that BtB may be of value to service users in secondary mental healthcare centres, alleviating current burdens on public health and therapeutic resources. Future research directions should include examining which factors influence individuals’ decisions to try computer‐aided psychotherapy, which individuals are best suited to using these interventions, and why some users drop out prior to programme completion.
An analysis of complaints to the British Association for Counselling and Psychotherapy, 1996–2006
Authors: Khele Suky , Symons Clare , Wheeler Sue 
Published: May 2008

AbstractIn autumn 2006 the British Association for Counselling and Psychotherapy approved a proposal to conduct an independent audit of complaints submitted. This article represents the first stage of that audit. Case information from the professional conduct files was accessed and a total of 84 cases, considered by a pre‐hearing assessment panel to require a full hearing, were identified for this audit. The cases cover the period from October 1996 to January 2006. The information obtained was entered into a database for numerical analysis. Key findings suggest that accredited members are disproportionately complained against, as are male members of the association. The majority of complaints are made by people who are themselves involved in counselling.
Instabilities and Self-Organization in Materials
Authors: Ghoniem Nasr , Walgraef Daniel 
Published: May 2008

Abstract
In materials, critical phenomena such as phase transitions, plastic deformation and fracture are intimately related to self-organization. Understanding the origin of spatio-temporal order in systems far from thermal equilibrium and the selection mechanisms of spatial structures and their symmetries is a major theme of present day research on the structure of continuous matter. Furthermore, the development of methods for producing spatially-ordered and self-assembled microstructure in solids by non-equilibrium methods opens the door to many technological applications. In order to describe and understand the behaviour of such materials, dynamical concepts related to non-equilibrium phenomena, irreversible thermodynamics, nonlinear dynamics, and bifurcation theory, are required. The generic presence of defects and their crucial influence on pattern formation and critical phenomena in extended systems is now well-established. Similar to observations in hydrodynamical, liquid crystal, and laser systems, defects in materials have a profound effect. This book is divided into two volumes. The first volume is devoted to the most basic concepts of the physics, mechanics, and mathematical theory utilized in the analysis of non-equilibrium materials. The book presents a background on material deformation, defect theory, transport processes, and the statistical mechanics and thermodynamics of phase transitions. Mathematical concepts of non-linear dynamics, such as bifurcation and instability theory, the dynamics of complex systems near pattern forming instabilities, the generic aspects of pattern formation, selection and stability are presented. Stochastic and numerical methods used in this field are also introduced. The methods and techniques developed in the first volume are applied in the second volume to specific problems in various advanced technologies.
NONEQUILIBRIUM PHASE TRANSITIONS
Authors: Ghoniem Nasr M. , Walgraef Daniel D. 
Published: May 2008

Abstract
This chapter presents theoretical developments in the treatment of atomic clustering. The theory is applicable to atomic species, which broadly include lattice or surface atoms, molecules, impurities or point defects. The theory is applied in two general areas: on studies of nucleation and growth of precipitates during solidification of metallic alloys, and on atomic clustering on surfaces during deposition of vapour or energetic atoms.
BIFURCATIONS AND INSTABILITIES
Authors: Ghoniem Nasr M. , Walgraef Daniel D. 
Published: May 2008

Abstract
This chapter focuses on the mathematical structures underlying the notions of stability, bifurcation, and instabilities in complex nonlinear dynamical systems described by sets of ordinary or partial differential equations. It begins by presenting the basic ideas of stability analysis in systems described by ordinary differential equations, introducing Lyapunov functions and their utilization in stability analysis. The stability of systems described by partial differential equations is discussed, emphasizing some of the basic ideas that allow quantitative descriptions of patterns. Specific models illustrating the concepts behind Hopf and Turing instabilities are also discussed.
PHASE INSTABILITIES AND PATTERNS
Authors: Ghoniem Nasr M. , Walgraef Daniel D. 
Published: May 2008

Abstract
This chapter begins with a discussion of phase transformations and the design of materials. It then presents a case study on the art of steel-making. This is followed by a discussion of precipitate evolution and structure, phase instabilities, stress effects on spinodal decomposition, and martensitic phase transformations.
MECHANICAL INSTABILITIES
Authors: Ghoniem Nasr M. , Walgraef Daniel D. 
Published: May 2008

Abstract
This chapter is focused on mechanical instabilities, which give rise to microstructure pattern formation and eventual failure of stressed solids. Plastic instabilities are described in detail because of their importance in understanding the mechanical behaviour of materials, and because of the strong link between mechanical instabilities and failure. The problem of fracture and damage is also discussed within the present framework. Finally, some aspects of the mechanics of granular materials and associated instabilities are considered.
SYCAMORE—a

sy

stems biology

c

omputational

a

nalysis and

mo

deling

r

esearch

e

nvironment
Authors: Weidemann Andreas , Richter Stefan , Stein Matthias , Sahle Sven , Gauges Ralph , Gabdoulline Razif , Surovtsova Irina , Semmelrock Nils , Besson Bruno , Rojas Isabel , Wade Rebecca , Kummer Ursula 
Published: May 2008

Abstract
Summary: SYCAMORE is a browser-based application that facilitates construction, simulation and analysis of kinetic models in systems biology. Thus, it allows e.g. database supported modelling, basic model checking and the estimation of unknown kinetic parameters based on protein structures. In addition, it offers some guidance in order to allow non-expert users to perform basic computational modelling tasks.
Availability: SYCAMORE is freely available for academic use at http://sycamore.eml.org. Commercial users may acquire a license.
Contact: ursula.kummer@bioquant.uni-heidelberg.de
Postglacial dispersal limitation of widespread forest plant species in nemoral Europe
Authors: Svenning Jens‐Christian , Normand Signe , Skov Flemming 
Published: May 2008

Climate is often singled out as the primary range limiting factor at large scales, while other environmental factors, notably soil, are thought to predominate at smaller scales. However, the postglacial migrational lag hypothesis controversially suggests that many species are strongly dispersal‐limited and still expanding from their ice age refugia. We investigated the importance of postglacial migrational lag, climate, and soil as range determinants for 47 widespread forest plant species across nemoral Europe (47.0–60.0°N, west of 24.0°E) using regression modeling, information‐theoretic model selection, multi‐model inference, and variation partitioning. Migrational lag was represented by a measure of accessibility to recolonization from ice age refugia.Twelve species were largely ubiquitous and not analyzed further. For the remaining species, there was strong support for climate, soil, and accessibility to postglacial recolonization. Accessibility accounted for a small to moderate amount of variation, but its model‐averaged regression coefficient was stronger than those for climate or soil for 11 species and the second or third strongest coefficient for an additional 10 species. The resulting odds ratios were greater than one for 33 out of 35 species, i.e. adjusted for climate and soil, prevalence for the far majority of the 35 non‐ubiquitous species increased with increasing accessibility. There were no differences among growth forms in the importance of accessibility. In contrast, compared to non‐boreal species, accessibility had little importance for species with wide boreal distributions, as expected from their more widespread, northern glacial distributions.In conclusion, even the ranges of many widespread forest plant species are probably still moderately to strongly limited by postglacial migrational lag. Therefore, although species ranges are also strongly influenced by climate, we cannot expect most forest plant species to closely track the expected 21st century climatic changes.
Migration across the sinusoidal endothelium regulates neutrophil mobilization in response to ELR + CXC chemokines
Authors: Burdon Peter C. E. , Martin Coralie , Rankin Sara M. 
Published: May 2008

SummaryAn increase in circulating neutrophils is a characteristic feature of many inflammatory reactions and is a result of the rapid mobilization of neutrophils from the bone marrow, driven by inflammatory mediators, including the ELR + CXC chemokines. In this paper, using a combination of light and electron microscopy and anin situperfusion system of the rat femoral bone marrow, we examined this mobilization process in detail. We show that mobilization of neutrophils stimulated by the CXC chemokine, rat MIP‐2, involves neutrophil migration from the haematopoietic compartment of the bone marrow across the bone marrow sinusoidal endothelium via a transcellular route. The critical role of the bone marrow sinusoidal endothelium in regulating neutrophil mobilization was demonstrated by artificially disrupting the bone marrow endothelial barrier by treatment with cytochalasin D, which results in the non‐selective release of leucocytes from the bone marrow. In contrast, inhibiting the activity of p38 mitogen‐activated protein kinase, inhibited both MIP‐2 stimulated chemotaxis of bone marrow neutrophilsin vitroand neutrophil mobilizationin situwhile, a broad spectrum matrix metalloproteinase inhibitor, BB94, had no effect on neutrophil mobilization. These results support the hypothesis that neutrophil migration drives their mobilization and highlights the function of the sinusoidal endothelium in regulating this process.
Haploinsufficiency of RPS14 in 5q− syndrome is associated with deregulation of ribosomal‐ and translation‐related genes
Authors: Pellagatti Andrea , Hellström‐Lindberg Eva , Giagounidis Aristoteles , Perry Janet , Malcovati Luca , Della Porta Matteo G. , Jädersten Martin , Killick Sally , Fidler Carrie , Cazzola Mario , Wainscoat James S. , Boultwood Jacqueline 
Published: May 2008

SummaryWe have previously demonstrated haploinsufficiency of the ribosomal gene RPS14, which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q− syndrome. Patients with Diamond‐Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal‐ and translation‐related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal‐ and translation‐related genes in the CD34+ cells of 15 myelodysplastic syndrome (MDS) patients with 5q− syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three‐way comparison, 55 of 579 ribosomal‐ and translation‐related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q− syndrome patient group. Using hierarchical clustering, patients with the 5q− syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal‐ and translation‐related genes. Patients with the 5q− syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q− syndrome represents a disorder of aberrant ribosome biogenesis.