bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc ions bind to and inhibit activated protein C
Authors: Zhu Tianqing , Ubhayasekera Wimal , Nickolaus Noëlle , Sun Wei , Tingsborg Susanne , Mowbray Sherry , Schedin-Weiss Sophia 
Published: July 2010

SummaryZn2+ ions were found to efficiently inhibit activated protein C (APC), suggesting a potential regulatory function for such inhibition. APC activity assays employing a chromogenic peptide substrate demonstrated that the inhibition was reversible and the apparent K
I was 13 ± 2 μM. k
cat was seven fold decreased whereas K
M was unaffected in the presence of 10 μM Zn2+. The inhibitory effect of Zn2+ on APC activity was also observed when factor Va was used as a substrate in an assay coupled to a prothrombinase assay. The interaction of Zn2+ with APC was accompanied by a reversible ~40% decrease in tryptophan fluorescence, consistent with the ion inducing a conformational change in the protein. The apparent K
D was 7.4 ± 1.5 μM and thus correlated well with the apparent K
I. In the presence of physiological Ca2+ concentration the K
I and K
D values were three to four fold enhanced, presum-ably due to the Ca2+-induced conformational change affecting the conformation of the Zn2+-binding site. The inhibition mechanism was non-competitive both in the absence and presence of Ca2+. Comparisons of sequences and structures suggested several possible sites for zinc binding. The magnitude of the apparent KI in relation to the blood and platelet concentrations of Zn2+ supports a physiological role for this ion in the regulation of anticoagulant activity of APC. These findings broaden the understanding of this versatile serine protease and enable the future development of potentially more efficient anticoagulant APC variants for treatments of thrombotic diseases.
Selective activation of the prostaglandin E2 receptor subtype EP2 or EP4 leads to inhibition of platelet aggregation
Authors: Yuhki Koh-ichi , Kojima Fumiaki , Yamada Takehiro , Fujino Takayuki , Hara Akiyoshi , Takayama Koji , Maruyama Takayuki , Yoshida Akitoshi , Narumiya Shuh , Kuriyama Shuhko , Kashiwagi Hitoshi , Ushikubi Fumitaka 
Published: July 2010

SummaryThe effect of selective activation of platelet prostaglandin (PG) E2 receptor subtype EP2 or EP4 on platelet aggregation remains to be determined. In platelets prepared from wild-type mice (WT platelets), high concentrations of PGE2 inhibited platelet aggregation induced by U-46619, a thromboxane receptor agonist. However, there was no significant change in the inhibitory effect of PGE2 on platelets lacking EP2 (EP2
–/– platelets) and EP4 (EP4
–/– platelets) compared with the inhibitory effect on WT platelets. On the other hand, AE1–259 and AE1–329, agonists for EP2 and EP4, respectively, potently inhibited U-46619 -induced aggregation with respective IC50 values of 590 ± 14 and 100 ± 4.9 nM in WT platelets, while the inhibition was significantly blunted in EP2
–/– and EP4
–/– platelets. In human platelets, AE1–259 and AE1–329 inhibited U-46619-induced aggregation with respective IC50 values of 640 ± 16 and 2.3 ± 0.3 nM. Notably, the inhibitory potency of AE1–329 in human platelets was much higher than that in murine platelets, while such a difference was not observed in the inhibitory potency of AE1–259. AE1–329 also inhibited adenosine diphosphate-induced platelet aggregation, and the inhibition was almost completely blocked by AE3–208, an EP4 antagonist. In addition, AE1–329 increased intracellular cAMP concentrations in a concentration- and EP4-dependent manner in human platelets. These results indicate that selective activation of EP2 or EP4 can inhibit platelet aggregation and that EP4 agonists are particularly promising as novel anti-platelet agents.
Incidence and predictors of venous thromboembolism in post-acute care patients
Authors: Ageno Walter , Airoldi Andrea , Bonizzoni Erminio , Campanini Mauro , Gussoni Gualberto , Silingardi Mauro , Valerio Antonella , Zilli Chiara , Iori Ido , Scannapieco Gianluigi ,   for the TERSICORE Study Group
Published: July 2010

SummaryFew studies have addressed the topic of venous thromboembolism (VTE) in patients hospitalised in rehabilitation facilities. This patient population is rapidly growing, and data aimed to better define VTE risk in this setting are needed. Primary aim of this prospective observational study was to evaluate the frequency of symptomatic, objectively confirmed VTE in a cohort of unselected consecutive patients admitted to rehabilitation facilities, after medical diseases or surgery. Further objectives were to assess overall mortality, to identify risk factors for VTE and mortality, and to assess the attitude of physicians towards thromboprophylaxis. A total of 3,039 patients were included in the study, and the median duration of hospitalisation was 26 days. Seventy-two patients (2.4%) had symptomatic VTE. The median time to VTE from admission to the long-term care unit was 13 days. According to multivariable analysis, previous VTE (hazard ratio 5.67, 95% confidence interval 3.30–9.77) and cancer (hazard ratio 2.26, 95% confidence interval 1.36–3.75) were significantly associated to the occurrence of VTE. Overall in-hospital mortality was 15.1%. Age over 75 years, male gender, disability, cancer, and the absence of thromboprophylaxis were significantly associated to an increased risk of death (multivariable analysis). In-hospital antithrombotic prophylaxis was administered to 75.1% of patients, and low-molecular-weight heparin was the most widely used agent. According to our study, patients admitted to rehabilitation facilities remain at substantially increased risk for VTE. Because this applies to the majority of these patients, there is a great need for clinical trials assessing optimal prophylactic strategies.
A New Tool for the Risk Stratification of Patients With Complex Coronary Artery Disease
Authors: Garg Scot , Sarno Giovanna , Garcia-Garcia Hector M. , Girasis Chrysafios , Wykrzykowska Joanna , Dawkins Keith D. , Serruys Patrick W. ,   on behalf of the ARTS-II Investigators
Published: July 2010

Background—

Presently, no effective risk model exists to predict long-term mortality or other major adverse cardiovascular and cerebrovascular events (MACCE) in those patients undergoing percutaneous coronary intervention (PCI). This study aimed to assess whether the Clinical SYNTAX Score (CSS) calculated by multiplying the SYNTAX Score to a modified ACEF score (age/ejection fraction +1 for each 10 mL the creatinine clearance <60 mL/min per 1.73 m
2
) would improve the ability of either score to predict mortality and MACCE.

Methods and Results—

The CSS was calculated in 512 patients enrolled in the ARTS-II study who had serum creatinine levels, ejection fraction, and body weight recorded at baseline. Clinical outcomes in terms of MACCE and mortality at 1- and 5-year follow-up were stratified according to CSS tertiles: CSS
LOW
≤15.6 (n=170), 15.6<CSS
MID
≤27.5 (n=171), and CSS
HIGH
>27.5 (n=171). At 1-year follow-up, rates of repeat revascularization and MACCE were significantly higher in the highest tertile group. At 5-year follow-up, CSS
HIGH
had a comparable rate of myocardial infarction, a trend toward a significantly higher rate of death, and significantly higher rates of repeat revascularization and overall MACCE compared with patients in the lower 2 tertiles. The respective C-statistics for the CSS, SYNTAX Score, and ACEF score for 5-year mortality were 0.69, 0.62, and 0.65 and for 5-year MACCE were 0.62, 0.59, and 0.57.

Conclusions—
An improvement in the ability of the SYNTAX Score to predict MACCE and mortality can be achieved by combining the SYNTAX Score with a simple clinical risk score incorporating age, ejection fraction, and creatinine clearance to produce the Clinical SYNTAX score.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00235170.
A hydrothermal clay mineral assemblage at the Late Proterozoic unconformity in the Buenos Aires Complex – La Tinta Formation, Barker area, Tandilia Ranges (Argentina)
Authors: Martínez J. C. , Dristas J. A. , Massonne H.-J. , Theye T. 
Published: July 2010

AbstractA general alteration pattern of two transitional clay mineral assemblages was determined by petrography and X-ray diffractometry studies at the Tandilia Late Proterozoic unconformity zone, around the Barker locality: (1) K-white mica + chlorite + calcite ± anatase-rutile ± secondary quartz (farther from the unconformity) and (2) pyrophyllite + K-white mica + Ti-rich hematite ± aluminium phosphate-sulphate minerals ± tourmaline ± anatase-rutile (closer to the unconformity). The local occurrence of Na in K-white micas and K-Na in pyrophyllite is described for the first time. Possible interlayering with intermediate K-Na mica and paragonite is indicated by detailed X-ray diffraction analyses. A negative Eu anomaly (Eu/Eu* = 0.24), strongly positive Eu anomaly (Eu/Eu* =11.7) and positive Ce anomaly characterized rapid changes from an unaltered basement to the most altered basement and sedimentary rocks at the unconformity. Aluminium phosphate-sulphate minerals dominate patterns of LREE. A model of hydrothermal alteration comparable to that of unconformity-related uranium deposits is presented.
Fluoroleakeite, NaNa2(Mg2Fe3+2Li)Si8O22F2, a new mineral of the amphibole group from the Verkhnee Espe deposit, Akjailyautas Mountains, Eastern Kazakhstan District, Kazakhstan: description and crystal structure
Authors: Cámara F. , Hawthorne F. C. , Ball N. A. , Bekenova G. , Stepanov A. V. , Kotel'nikov P. E. 
Published: July 2010

AbstractFluoroleakeite, NaNa2(Mg2Fe3+2Li)Si8O22F2 is a new mineral of the amphibole group from the Verkhnee Espe deposit, Akjailyautas mountains, eastern Kazakhstan district, Kazakhstan. The granites and their host rocks have been intensely reworked by post-magmatic and host-rock fluids, resulting in intense recrystallization, enrichment in F, Li and rare elements, and replacement of primary biotite and sodic-calcic amphiboles by Li-bearing riebeckite, aegirine, astrophyllite and other sodic minerals including fluoroleakeite. Crystals are prismatic parallel to [001] with {100} and {110} faces and cleavage surfaces, and the prism direction is terminated by irregular fractures. Grains are up to 3 mm long, and occur as isolated crystals, as small aggregates, and as inclusions in cámaraite. Crystals are black with a very pale grey to colourless streak. Fluoroleakeite is brittle, has a Mohs hardness of 6 and a splintery fracture; it is non-fluorescent with perfect {110} cleavage, no observable parting, and has a calculated density of 3.245 g cm–3. In plane-polarized light, it is pleochroic, X = pale grey-green, Y = medium grey, Z = grey-brown; X^a = 14.1° (in β obtuse), Y ‖ b, Z^c = 75.9° (in β acute). Fluoroleakeite is biaxial negative, α = 1.663(2), β = 1.673(2), γ = 1.680(2); 2Vobs = 80.9(6)°, 2Vcalc = 79.4°Fluoro-leakeite is monoclinic, space group C2/m, a = 9.8927(3), b = 17.9257(6), c = 5.2969(2) Å, β = 103.990(1)°, V = 905.7(1) Å3, Z = 2. The strongest ten X-ray diffraction lines in the powder pattern are [d in Å(I)(hkl)]: 2.718(100)(151), 8.434(40)(110), 4.464(30)(021), 3.405(30)(131), 3.137(20)(310), 2.541(20)(), 2.166(20)(261), 2.325(15)(), 2.275(15)() and 2.806(10)(330). Analysis by a combination of electron microprobe and crystal-structure refinement gives SiO2 53.34, Al2O3 0.62, TiO2 1.27, V2O3 0.05, Fe2O3 15.10, FeO 6.00, MnO 2.04, ZnO 0.18, MgO 6.40, CaO 0.13, Na2O 9.08, K2O 1.98, Li2O 1.10, F 3.33, H2Ocalc 0.16, sum 99.39 wt.%. The formula unit, calculated on the basis of 23 O, is A(Na0.64K0.38)(Na1.98Ca0.02)(Li0.66Mg1.42Fe0.752+Mn0.262+Zn0.02Fe1.693+V0.013+Ti0.144+Al0.03) (Si7.93Al0.07)O22(F1.57OH0.16O0.27). Crystal-structure refinement shows Li to be completely ordered at the M(3) site. Fluoroleakeite, ideally NaNa2(Mg2Fe23+Li)Si8O22F2, is related to end-member leakeite, NaNa2(Mg2Fe23+Li)Si8O22(OH)2 by the substitution F → (OH).
Thermal behaviour of libethenite from room temperature up to dehydration
Authors: Zema M. , Tarantino S. C. , Callegari A. M. 
Published: July 2010

AbstractThe structural modifications with temperature of libethenite, Cu2(PO4)(OH), were determined by single-crystal X-ray diffraction up to dehydration and consequent decomposition of the crystal under investigation. In the temperature range 25–475°C, libethenite shows positive and linear expansion. The axial thermal expansion coefficients, determined over this temperature range, are: αa = 6.6(1)·10–6 K–1, αb = 1.21(2)·10–5 K–1, αc = 9.0(2)·10–6 K–1, αv = 2.78(3)·10–5 K–1. Axial expansion is then anisotropic with αa:αb:αc = 1:1.83:1.33.Structure refinements of X-ray diffraction data collected at different temperatures allowed us to characterize the mechanisms by which the libethenite structure accommodates variations in temperature. Increasing temperature induces expansion of both Cu polyhedra and no significant variation of the PO4 tetrahedron, which acts as a rigid unit. Cu(1) octahedra expand mostly as a consequence of the increase of the axial bonds, and become more distorted. Starting from T = 500°C, precursor signs of incoming dehydration are visible: two adjacent OH groups approach each other and cause dramatic changes in the whole structure. Concomitantly, the libethenite crystal begins to deteriorate and, at T = 600°C, broad and weak diffraction effects of polycrystalline material are observed.
A protease-resistant PML-RARα has increased leukemogenic potential in a murine model of acute promyelocytic leukemia
Authors: Uy Geoffrey L. , Lane Andrew A. , Welch John S. , Grieselhuber Nicole R. , Payton Jacqueline E. , Ley Timothy J. 
Published: July 2010

Abstract
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves promyelocytic leukemia–retinoic acid receptor (PML-RAR)α (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild-type PR, but with significantly reduced latency (median leukemia-free survival of 274 days vs 473 days for wild-type PR, P < .001). Resistance to proteolysis may increase the abundance of full-length PR protein in early myeloid cells, and our previous data suggested that noncleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy
Authors: Takaku Tomoiku , Malide Daniela , Chen Jichun , Calado Rodrigo T. , Kajigaya Sachiko , Young Neal S. 
Published: July 2010

AbstractIn many animals, blood cell production occurs in the bone marrow. Hematopoiesis is complex, requiring self-renewing and pluripotent stem cells, differentiated progenitor and precursor cells, and supportive stroma, adipose tissue, vascular structures, and extracellular matrix. Although imaging is a vital tool in hematology research, the 3-dimensional architecture of the bone marrow tissue in situ remains largely uncharacterized. The major hindrance to imaging the intact marrow is the surrounding bone structures are almost impossible to cut/image through. We have overcome these obstacles and describe a method whereby whole-mounts of bone marrow tissue were immunostained and imaged in 3 dimensions by confocal fluorescence and reflection microscopy. We have successfully mapped by multicolor immunofluorescence the localization pattern of as many as 4 cell features simultaneously over large tiled views and to depths of approximately 150 μm. Three-dimensional images can be assessed qualitatively and quantitatively to appreciate the distribution of cell types and their interrelationships, with minimal perturbations of the tissue. We demonstrate its application to normal mouse and human marrow, to murine models of marrow failure, and to patients with aplastic anemia, myeloid, and lymphoid cell malignancies. The technique should be generally adaptable for basic laboratory investigation and for clinical diagnosis of hematologic diseases.
GeneBrowser 2: an application to explore and identify common biological traits in a set of genes
Authors: Arrais Joel P , Fernandes João , Pereira João , Oliveira José Luís 
Published: July 2010

Abstract

Background
The development of high-throughput laboratory techniques created a demand for computer-assisted result analysis tools. Many of these techniques return lists of genes whose interpretation requires finding relevant biological roles for the problem at hand. The required information is typically available in public databases, and usually, this information must be manually retrieved to complement the analysis. This process is a very time-consuming task that should be automated as much as possible.

Results
GeneBrowser is a web-based tool that, for a given list of genes, combines data from several public databases with visualisation and analysis methods to help identify the most relevant and common biological characteristics. The functionalities provided include the following: a central point with the most relevant biological information for each inserted gene; a list of the most related papers in PubMed and gene expression studies in ArrayExpress; and an extended approach to functional analysis applied to Gene Ontology, homologies, gene chromosomal localisation and pathways.

Conclusions
GeneBrowser provides a unique entry point to several visualisation and analysis methods, providing fast and easy analysis of a set of genes. GeneBrowser fills the gap between Web portals that analyse one gene at a time and functional analysis tools that are limited in scope and usually desktop-based.
Paralysis and delayed Z-disc formation in the Xenopus tropicalis unc45b mutant dicky ticker
Authors: Geach Timothy J , Zimmerman Lyle B 
Published: July 2010

Abstract
Background
The protein components of mature skeletal muscle have largely been characterized, but the mechanics and sequence of their assembly during normal development remain an active field of study. Chaperone proteins specific to sarcomeric myosins have been shown to be necessary in zebrafish and invertebrates for proper muscle assembly and function.

Results
The Xenopus tropicalis mutation dicky ticker results in disrupted skeletal muscle myofibrillogenesis, paralysis, and lack of heartbeat, and maps to a missense mutation in the muscle-specific chaperone unc45b. Unc45b is known to be required for folding the head domains of myosin heavy chains, and mutant embryos fail to incorporate muscle myosin into sarcomeres. Mutants also show delayed polymerization of α-actinin-rich Z-bodies into the Z-disks that flank the myosin-containing A-band.

Conclusions
The dicky ticker phenotype confirms that a requirement for myosin-specific chaperones is conserved in tetrapod sarcomerogenesis, and also suggests a novel role for myosin chaperone function in Z-body maturation.
High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors
Authors: Neske Florian , Prifert Christiane , Scheiner Barbara , Ewald Moritz , Schubert Jörg , Opitz Andreas , Weissbrich Benedikt 
Published: July 2010

Abstract

Background
DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population.

Methods
The capsid proteins VP1 of WUPyV and KIPyV and VP2 of HBoV were cloned into baculovirus vectors and expressed in Sf9 insect cells. IgG antibodies against WUPyV VP1, KIPyV VP1, and HBoV VP2 were determined by immunofluorescence assays in 100 plasma samples of blood donors.

Results
The median age of the blood donors was 31 years (range 20 - 66 yrs), 52% were male. 89% of the samples were positive for WUPyV IgG (median age 31 yrs, 49.4% male), 67% were positive for KIPyV IgG (median age 32 yrs, 46.3% male), and 76% were positive for HBoV IgG (median age 32 yrs, 51.3% male). For WUPyV and HBoV, there were no significant differences of the seropositivity rates with respect to age groups or gender. For KIPyV, the seropositivity rate increased significantly from 59% in the age group 20 - 29 years to 100% in the age group > 50 years.

Conclusions
High prevalences of antibodies against WUPyV, KIPyV, and HBoV were found in plasma samples of healthy adults. The results indicate that primary infection with these viruses occurs during childhood or youth. For KIPyV, the seropositivity appears to increase further during adulthood.
Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins
Authors: Teutschbein Janka , Haydn Johannes M , Samans Birgit , Krause Michael , Eilers Martin , Schartl Manfred , Meierjohann Svenja 
Published: July 2010

Abstract

Background
Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.

Methods
Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.

Results
Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration.

Conclusion
Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.