bluuebunny/crossref_metadata_2025_split huggingface dataset:
The layered fold of the TSR domain of P. falciparum TRAP contains a heparin binding site
Authors: Tossavainen Helena , Pihlajamaa Tero , Huttunen Toni K. , Raulo Erkki , Rauvala Heikki , Permi Perttu , Kilpeläinen Ilkka 
Published: June 2006

AbstractThrombospondin‐related anonymous protein, TRAP, has a critical role in the hepatocyte invasion step of Plasmodium sporozoites, the transmissible form of the parasite causing malaria. The extracellular domains of this sporozoite surface protein interact with hepatocyte surface receptors whereas its intracellular domain acts as a link to the sporozoite actomyosin motor system. Liver heparan sulfate proteoglycans have been identified as potential ligands for TRAP. Proteoglycan binding has been associated with the A‐ and TSR domains of TRAP. We present the solution NMR structure of the TSR domain of TRAP and a chemical shift mapping study of its heparin binding epitope. The domain has an elongated structure stabilized by an array of tryptophan and arginine residues as well as disulfide bonds. The fold is very similar to those of thrombospondin type‐1 (TSP‐1) and F‐spondin TSRs. The heparin binding site of TRAP‐TSR is located in the N‐terminal half of the structure, the layered side chains forming an integral part of the site. The smallest heparin fragment capable of binding to TRAP‐TSR is a tetrasaccharide.
Crystal structure of trehalose‐6‐phosphate phosphatase–related protein: Biochemical and biological implications
Authors: Rao Krishnamurthy N. , Kumaran Desigan , Seetharaman Jayaraman , Bonanno Jeffrey B. , Burley Stephen K. , Swaminathan Subramanyam 
Published: June 2006

AbstractWe report here the crystal structure of a trehalose‐6‐phosphate phosphatase–related protein (T6PP) from Thermoplasma acidophilum, TA1209, determined by the dual‐wavelength anomalous diffraction (DAD) method. T6PP is a member of the haloacid dehalogenase (HAD) superfamily with significant sequence homology with trehalose‐6‐phosphate phosphatase, phosphoserine phosphatase, P‐type ATPases and other members of the family. T6PP possesses a core domain of known α/β‐hydrolase fold, characteristic of the HAD family, and a cap domain, with a tertiary fold consisting of a four‐stranded β‐sheet with two α‐helices on one side of the sheet. An active‐site magnesium ion and a glycerol molecule bound at the interface between the two domains provide insight into the mode of substrate binding by T6PP. A trehalose‐6‐phosphate molecule modeled into a cage formed by the two domains makes favorable interactions with the protein molecule. We have confirmed that T6PP is a trehalose phosphatase from amino acid sequence, three‐dimensional structure, and biochemical assays.
Lessons in stability from thermophilic proteins
Authors: Razvi Abbas , Scholtz J. Martin 
Published: June 2006

AbstractStudies that compare proteins from thermophilic and mesophilic organisms can provide insights into ability of thermophiles to function at their high habitat temperatures and may provide clues that enable us to better define the forces that stabilize all proteins. Most of the comparative studies have focused on thermal stability and show, as expected, that thermophilic proteins have higher Tm values than their mesophilic counterparts. Although these comparisons are useful, more detailed thermodynamic analyses are required to reach a more complete understanding of the mechanisms thermophilic protein employ to remain folded over a wider range of temperatures. This complete thermodynamic description allows one to generate a stability curve for a protein that defines how the conformational stability (ΔG) varies with temperature. Here we compare stability curves for many pairs of homologous proteins from thermophilic and mesophilc organisms. Of the basic methods that can be employed to achieve enhanced thermostability, we find that most thermophilic proteins use the simple method that raises the ΔG at all temperatures as the principal way to increase their Tm. We discuss and compare this thermodynamic method with the possible alternatives. In addition we propose ways that structural alterations and changes to the amino acid sequences might give rise to varied methods used to obtain thermostability.
Cooperativity and the origins of rapid, single‐exponential kinetics in protein folding
Authors: Faísca Patrícia F.N. , Plaxco Kevin W. 
Published: June 2006

AbstractThe folding of naturally occurring, single‐domain proteins is usually well described as a simple, single‐exponential process lacking significant trapped states. Here we further explore the hypothesis that the smooth energy landscape this implies, and the rapid kinetics it engenders, arises due to the extraordinary thermodynamic cooperativity of protein folding. Studying Miyazawa‐Jernigan lattice polymers, we find that, even under conditions where the folding energy landscape is relatively optimized (designed sequences folding at their temperature of maximum folding rate), the folding of protein‐like heteropolymers is accelerated when their thermodynamic cooperativity is enhanced by enhancing the nonadditivity of their energy potentials. At lower temperatures, where kinetic traps presumably play a more significant role in defining folding rates, we observe still greater cooperativity‐induced acceleration. Consistent with these observations, we find that the folding kinetics of our computational models more closely approximates single‐exponential behavior as their cooperativity approaches optimal levels. These observations suggest that the rapid folding of naturally occurring proteins is, in part, a consequence of their remarkably cooperative folding.
Bacteriorhodopsin chimeras containing the third cytoplasmic loop of bovine rhodopsin activate transducin for GTP/GDP exchange
Authors: Geiser Andrew H. , Sievert Michael K. , Guo Lian‐Wang , Grant Jennifer E. , Krebs Mark P. , Fotiadis Dimitrios , Engel Andreas , Ruoho Arnold E. 
Published: June 2006

AbstractThe mechanisms by which G‐protein‐coupled receptors (GPCRs) activate G‐proteins are not well understood due to the lack of atomic structures of GPCRs in an active form or in GPCR/G‐protein complexes. For study of GPCR/G‐protein interactions, we have generated a series of chimeras by replacing the third cytoplasmic loop of a scaffold protein bacteriorhodopsin (bR) with various lengths of cytoplasmic loop 3 of bovine rhodopsin (Rh), and one such chimera containing loop 3 of the human β2‐adrenergic receptor. The chimeras expressed in the archaeon Halobacterium salinarum formed purple membrane lattices thus facilitating robust protein purification. Retinal was correctly incorporated into the chimeras, as determined by spectrophotometry. A 2D crystal (lattice) was evidenced by circular dichroism analysis, and proper organization of homotrimers formed by the bR/Rh loop 3 chimera Rh3C was clearly illustrated by atomic force microscopy. Most interestingly, Rh3C (and Rh3G to a lesser extent) was functional in activation of GTPγ35S/GDP exchange of the transducin α subunit (Gαt) at a level 3.5‐fold higher than the basal exchange. This activation was inhibited by GDP and by a high‐affinity peptide analog of the Gαt C terminus, indicating specificity in the exchange reaction. Furthermore, a specific physical interaction between the chimera Rh3C loop 3 and the Gαt C terminus was demonstrated by cocentrifugation of transducin with Rh3C. This Gαt‐activating bR/Rh chimera is highly likely to be a useful tool for studying GPCR/G‐protein interactions.
Discrepancy between impedance and immunofluorescence platelet counting has implications for clinical decision making in patients with idiopathic thrombocytopenia purpura
Authors: Bowles Kristian M. , Bloxham David M. , Perry David J. , Baglin Trevor P. 
Published: June 2006

SummaryThis study investigated whether differences occur between the impedance and immunofluorescence methods for platelet quantification in idiopathic thrombocytopenia purpura (ITP). Immunofluorescence gave a platelet count >50% higher than the impedance test in 9/35 (26%) patients, of which 4/35 (11%) were >100% higher. The clinical severity of thrombocytopenia was changed as a result of the immunofluorescence test in 14/35 (40%) patients. Neither mean platelet volume nor platelet distribution width predicted impedance/immunofluorescence method discrepancy. It is suggested that immunofluorescence platelet counts should be performed on all ITP patients when the implementation of a therapeutic or diagnostic intervention is being considered.
Minimal residual disease directed therapy for childhood acute myeloid leukaemia: the time is now
Authors: Goulden Nick , Virgo Paul , Grimwade David 
Published: June 2006

SummaryThe continued improvement in the prognosis of childhood acute myeloid leukaemia (AML) has been paralleled by the use of increasingly intensive therapy. This has led to attempts to develop risk‐directed strategies in which the most intensive treatment is reserved for those at highest risk of relapse. Unfortunately, current approaches, which rely on cytogenetic sub‐grouping and morphological assessment of response to therapy, are inaccurate. New prognostic factors are needed. This annotation proposes that the introduction of protocols based on the measurement of minimal residual disease (MRD) holds the key to progression from an era of ‘cure at all costs’ to a more individualised approach. However, the full potential of MRD technologies will only be realised through properly designed studies with scrupulous attention to logistics and quality assurance. The article illustrates which children may benefit most from MRD analysis in AML and explores practical issues that should be addressed in the design of clinical trials.
Natural killer T cells and haemopoiesis
Authors: Karadimitris Anastasios , Patterson Scott , Spanoudakis Emmanouil 
Published: June 2006

SummaryInvariant natural killer T (iNKT) cells are a small but powerful subset of regulatory T cells involved in the modulation of a variety of normal and pathological immune responses. In contrast to conventional or other types of regulatory T cells, they are activated by glycolipid and phospholipid ligands that are presented to them by the non‐polymorphic, major histocompatibility complex class I‐like molecule CD1d. The in‐depth understanding of their function has resulted in successful, iNKT cell‐centred experimental therapeutic interventions including prevention of graft‐versus‐host disease and anti‐leukaemia effects. Extending these successes into the clinical arena will require better understanding of their contribution to the pathogenesis of human, including haematological, diseases.
Diagnosis of Burkitt lymphoma in due time: a practical approach
Authors: Cogliatti Sergio B. , Novak Urban , Henz Samuel , Schmid Ulrico , Möller Peter , Barth Thomas F. E. 
Published: June 2006

SummaryThe quick diagnosis of Burkitt lymphoma (BL) and its clear‐cut differentiation from diffuse large B‐cell lymphoma (DLBCL) is of great clinical importance because treatment strategies for these two disease entities differ markedly. As these two lymphomas are difficult to distinguish using the current World Health Organization classification, we studied 39 cases of highly proliferative peripheral blastic B‐cell lymphoma (HPBCL) to establish a practical differential‐diagnostic algorithm. Characteristics set for BL were a typical morphology, a mature B‐cell phenotype of CD10+, Bcl‐6+ and Bcl‐2− tumour cells, a proliferation rate of >95%, and the presence of C‐MYC rearrangements in the absence of t(14;18)(q32;q21). Altogether, these characteristics were found in only five of 39 cases, whereas the majority of tumours revealed mosaic features. We then followed a pragmatic stepwise approach for a classification algorithm that included the assessment of C‐MYC status to stratify HPBCL into four predefined diagnostic categories (DC), namely DC I (5/39, 12.8%): ‘classical BL’, DC II (11/39, 28.2%): ‘atypical BL’, DC III (9/39, 23.1%): ‘C‐MYC+ DLBCL’ and DC IV (14/39, 35.9%): ‘C‐MYC− HPBCL’. This proposal may serve as a robust and objective operational basis for therapeutic decisions for HPBCL within 1 week and is applicable to be evaluated for its prognostic relevance in clinical trials with uniformly treated patients.
Seed‐borne fungi detected in consignments of soybean seeds (Glycine max) imported into India
Authors: Agarwal P. C. , Dev U. , Singh B. , Indra R. , Khetarpal R. K. 
Published: July 2006

Inspection of 16 017 samples of soybean seeds imported into India from 1978 to 2004 resulted in the detection of 21 pathogens, including Peronospora manshurica which is not present in India. Seed‐borne fungi of high economic significance included: Ascochyta sojicola, Botryotinia fuckeliana, Cercospora kikuchii, Colletotrichum dematium, Corynespora cassicola, Diaporthe phaseolorum var. sojae, Fusarium oxysporum, Glomerella cingulata, Glomerella glycines, Macrophomina phaseolina, Nectria haematococca, Passalora sojina, Thanatephorus cucumeris as well as other fungal pathogens for which soybean is not a host such as Alternaria padwickii, Cochliobolus sativus, Fusarium culmorum, Fusarium poae, Glomerella graminicola, Setosphaeria rostrata, Verticillium albo‐atrum, etc. Some of the fungi detected have very wide host range. Details are presented on the fungi detected, the countries from which the imported consignments originated, and phytosanitary significance.
Fast‐decaying IP in frozen unconsolidated rocks and potentialities for its use in permafrost‐related TEM studies
Authors: Kozhevnikov N.O. , Antonov E.Y. 
Published: June 2006

ABSTRACTWe investigate the early time induced polarization (IP) phenomenon in frozen unconsolidated rocks and its association with transient electromagnetic (TEM) signals measured in northern regions. The distinguishing feature of these signals is the distortion of the monotony or sign reversals in the time range from a few tens to a few hundreds of microseconds. In simulating TEM data, the IP effects in frozen ground were attributed to the dielectric relaxation phenomenon rather than to the frequency‐dependent conductivity. This enabled us to use laboratory experimental data available in the literature on dielectric spectroscopy of frozen rocks. In our studies we focused on simulating the transient response of a coincident‐loop configuration in three simple models: (i) a homogeneous frozen earth (half‐space); (ii) a two‐layered earth with the upper layer frozen; (iii) a two‐layered earth with the upper layer unfrozen. The conductivities of both frozen and unfrozen ground were assumed to exhibit no frequency dispersion, whereas the dielectric permittivity of frozen ground was assumed to be described by the Debye model. To simplify the presentation and the comparison analysis of the synthetic data, the TEM response of a frozen polarizable earth was normalized to that of a non‐polarizable earth having the same structure and resistivities as the polarizable earth. The effect of the dielectric relaxation on a TEM signal is marked by a clearly defined minimum. Its time coordinate tmin is approximately three times larger than the dielectric relaxation time constant τ. This suggests the use of tmin for direct estimation of τ, which, in turn, is closely associated with the temperature of frozen unconsolidated rock. The ordinate of the minimum is directly proportional to the static dielectric permittivity of frozen earth. Increasing the resistivity of a frozen earth and/or decreasing the loop size results in a progressively stronger effect of the dielectric relaxation on the TEM signal. In the case of unfrozen earth, seasonal freezing is not likely to have an appreciable effect on the TEM signal. However, for the frozen earth, seasonal thawing of a near‐surface layer may result in a noticeable attenuation of the TEM signal features associated with dielectric relaxation in a frozen half‐space. Forward calculations show that the dielectric relaxation of frozen unconsolidated rocks may significantly affect the transient response of a horizontal loop laid on the ground. This conclusion is in agreement with a practical example of inversion of the TEM data measured over the permafrost.
Vector attenuation: elliptical polarization, raypaths and the Rayleigh‐window effect
Authors: Carcione José M. 
Published: June 2006

ABSTRACTWaves in dissipative media exhibit elliptical polarization. The direction of the major axis of the ellipse deviates from the propagation direction. In addition, Snell's law does not give the raypath, since the propagation (wavevector) direction does not coincide with the energy‐flux direction. Each of these physical characteristics depends on the properties of the medium and on the inhomogeneity angle of the wave. The calculations are relevant for multicomponent surveys, where the receivers are placed on the ocean‐floor. An example of the role played by inhomogeneous waves is given by the Rayleigh‐window effect, which implies a significant amplitude reduction of the reflection coefficient of the ocean‐bottom.
Correlation of Susceptibility and Cytostatic Factor‐Inducing Activity of Tumour Cells to Peritoneal Macrophages
Authors: HASHIMOTO S. , NAGAOKA M. , YOKOKURA T. , MUTAI M. 
Published: June 2006

L929, 3T12‐3, B16, 3LL, and YAC1 cells with cytostatic factor (CF)‐inducing activity from Lactobacillus casei‐elicited murine peritoneal macrophages (LCEPM) were susceptible to the cytostatic activity of LCEPM and to LCEPM‐produced CF, but L1210, P388D1, and Colon 26 cells, which have no CF‐inducing activity, were resistant to that of LCEPM and to the CF. The resistance of P815 cells to that of LCEPM was stronger than that of 3T12‐3 cells, but the CF‐inducing activity of P815 cells was about 5098 weaker than that of 3T12‐3 cells. Release of CF from LCEPM was also caused by heat‐killed (100°C, 10 min) 3T12‐3 or P813 cells, and this release was inhibited by d‐mannose. The CF‐inducing activity of heat‐killed 3T12‐3 or PK15 cells was reduced by mild trypsin digestion (37°C for 10 min). A d‐mannose‐containing glycopeptide or glycoprotein (GP) was separated from 3T12‐3 or P815 cells by concanavalin A (Con A) or wheat germ agglutinini (WGA) affinity chromatography. The CF were released from LCEPM by stimulation with the Con A‐binding GP of the tumour cells, but the WGA‐binding GP had little activity.It is suggested that tumour cells with CF‐inducing activity may he susceptible to the cytostatic activity of LCEPM, and those without CF‐inducing activity may be resistant to the cytostatic activity of LCEPM and the release of CF from activated macrophages may be caused by the Con A‐binding GP of the tumour cell surface.
Activation of Human T Lymphocytes by Phorbol‐12,13‐Dibutyrate and Ionomycin
Authors: LARSEN C. S. 
Published: June 2006

The calcium ionophore ionomycin and the phorbol ester phorbol‐12,13‐dibutyrate (PDBu) are shown to have a synergistic effect upon interleukin 2 (IL‐2) production, interleukin 2 receptor expression, and T‐lymphocyte proliferation.The proliferative response was inhibited by addition of a monoclonal antibody directed against the IL‐2R (Tac antigen) demonstrating that PDBu and ionomycin induce T‐cell growth through an IL‐2‐dependent autocrine pathway.Sequential stimulation with PDBu and ionomycin failed to induce IL‐2 production, IL‐2R expression, and consequently proliferation of the T cells, indicating that T‐cell activation requires simultaneous activation of protein kinase C (PKC) and elevation of cytosolic calcium.Exposure of T cells to both agents for different times resulted in IL‐2 production, IL‐2R expression, and proliferation in proportion to the duration of incubation with at least 4 h required for maximal T‐cell activation. Further, in the presence of PDBu maximal T‐cell activation was found to require stimulation with ionomycin for 4 h, indicating that a sustained increase in free cytoplasmic calcium of several hours' duration is essential for T‐cell activation. In contrast T cells incubated with ionomycin were induced to produce IL‐2 and express IL‐2Rs upon brief exposure to PDBu with a 2‐h incubation period being sufficient for maximal T‐cell activation. Thus transient activation of PKC seems to be sufficient for activation of the IL‐2 gene and IL‐2R gene. However, maximal T‐cell activation requires activation of PKC for at least 2 h.
Whole Cholera Toxin and B Subunit Act Synergistically as an Adjuvant for the Mucosal Immune Response of Mice to Keyhole Limpet Haemocyanin
Authors: WILSON A. D. , CLARKE C. J. , STOKES C. R. 
Published: June 2006

Cholera toxin (CT) is a potent stimulator of IgA responses when adtninistered orally and has been shown to promote IgA responses to a second protein such as keyhole limpet haemocyanin (KLH) if this is fed simultaneously. ln this paper we show that whilst feeding 5 mg KLH with either 0.5 μg CT or 10 μg B subunit fails to stimulate a mucosal IgA response to KLH, feeding 0.5μg CT and 10 μg B subunit together with 5 mg KLH produces a local IgA anti‐KLH response as greal as that produced by 10 μg of whole CT. ln addition to stimulating IgA responses in the lamina propria, preliminary results indicate that cellular responses are also stimulated, as we have demonstrated KLH antigen‐driven proliferation of cells isolated from groups of mice fed either 10 μg CT + 5 mg KLH or O.5 μg CT + 10 μg CTB + 5 mg KLH but not mice fed KLH alone or with either 10 μg CTB or O.5 μg CT.These results indicate that the mucosal adjuvant action of CT is due to a synergistic effect involving both the GMl binding of the B subunit and adenylate cyelase activation by the A subunit.
A New Surface Antigen on Human Lymphocytes Defined by the Murine Monoclonal Antibody IVF7
Authors: GRUNEWALD J. , JANSON C. H. , TEHRANI M. J. , MATSUO Y. , MELLSTEDT H. , WIGZELL H. 
Published: June 2006

The murine monoclonal antibody (MoAb) IVF7 was produced against tumour cells from a patient with a CD 3+, CD4+, CD8− T‐cell chronic lymphatic leukaemia (T‐CLL). The MoAb IVF7 showed reactivity with subpopulations of normal peripheral blood lymphocytes (PBL), as well as with a few cell lines of haematopoietic origin. Thirty‐six percent of PBL were stained with IVF7. Analysing subpopulations, we found that 80% of NK cells, 25% of T cells, and 10–20% of B cells were positive. The myelomonocytic cell line KG‐1 was also stained. The molecular weight of the molecule was 40 kDa under reducing conditions. The antigen was found to be trypsinsensitive.MoAb IVF7 could modulate the antigen from the cell surface. The antibody did not stimulate PBL to DNA synthesis, nor did it significantly lnfluence NK cell‐mediaied kilting.