bluuebunny/crossref_metadata_2025_split huggingface dataset:
High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women
Authors: Andersson Helena M. , Siegerink Bob , Luken Brenda M. , Crawley James T. B. , Algra Ale , Lane David A. , Rosendaal Frits R. 
Published: November 2011

Abstract
VWF and ADAMTS13 are major determinants of platelet adhesion after vessel injury. In the present study, we aimed to determine whether VWF or ADAMTS13 plasma antigen levels influence the risks of ischemic stroke (IS) or myocardial infarction (MI) in young women and how these risks are affected by oral contraceptive (OC) use. VWF and ADAMTS13 plasma antigen levels were measured in a frequency-matched case-control study of 1018 young (18-49 years) women including 175 IS patients and 205 MI patients. Increasing levels of VWF and decreasing levels of ADAMTS13 were associated with the risk of IS and MI in a dose-dependent manner. Having both high VWF and low ADAMTS13 resulted in an odds ratio (OR) of 6.9 (95% confidence interval [95% CI], 2.0-23.0) for IS and 11.3 (95% CI, 3.6-35.2) for MI. Use of OCs increased the risk of IS and MI associated with high VWF (OR = 12; 95% CI, 5.5-26.2 and OR = 7.5, 95% CI, 3.6-15.7, respectively) and the risk of IS associated with low ADAMTS13 (OR = 5.8, 95% CI, 2.7-12.4). We conclude that high VWF and low ADAMTS13 plasma levels both increase the risk of IS and MI. The risks associated with high VWF or low ADAMTS13 levels are further increased by the use of OCs.
Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives
Authors: de Souza Martins Sheila C , Agbulut Onnik , Diguet Nicolas , Larcher Jean-Christophe , Paulsen Bruna S , Rehen Stevens K , Moura-Neto Vivaldo , Paulin Denise , Li Zhenlin , Xue Zhigang 
Published: November 2011

Abstract

Background
Intermediate filaments (IFs) are major components of the mammalian cytoskeleton and expressed in cell-type-specific patterns. Morphological changes during cell differentiation are linked to IF network remodeling. However, little is known concerning the presence and the role of IFs in embryonic stem (ES) cells and during their differentiation.

Results
We have examined the expression profile of synemin isoforms in mouse pluripotent ES cells and during their neural differentiation induced by retinoic acid. Using RT-PCR, Western blotting and immunostaining, we show that synemin M is present at both mRNA and protein levels in undifferentiated ES cells as early as pluripotency factor Oct-3/4 and IF keratin 8. Synemin H was produced only in neural precursors when neural differentiation started, concurrently with synemin M, nestin and glial fibrillary acidic protein. However, both synemin H and M were restricted to the progenitor line during the neural differentiation program. Our in vivo analysis also confirmed the expression of synemins H/M in multipotent neural stem cells in the subventricular zone of the adult brain, a neurogenic germinal niche of the mice. Knocking down synemin in ES cells by shRNA lentiviral particles transduction has no influence on expression of Oct4, Nanog and SOX2, but decreased keratin 8 expression.

Conclusions
Our study shows a developmental stage specific regulation of synemin isoforms in ES cells and its neural derivatives. These findings represent the first evidence that synemins could potentially be useful markers for distinguishing multipotent ES cells from undifferentiated neural stem cells and more committed progenitor cells.
The mitogen-activated protein kinome from Anopheles gambiae: identification, phylogeny and functional characterization of the ERK, JNK and p38 MAP kinases
Authors: Horton Ashley A , Wang Bo , Camp Lauren , Price Mark S , Arshi Arora , Nagy Mate , Nadler Steven A , Faeder James R , Luckhart Shirley 
Published: November 2011

Abstract

Background

Anopheles gambiae is the primary mosquito vector of human malaria parasites in sub-Saharan Africa. To date, three innate immune signaling pathways, including the nuclear factor (NF)-kappaB-dependent Toll and immune deficient (IMD) pathways and the Janus kinase/signal transducers and activators of transcription (Jak-STAT) pathway, have been extensively characterized in An. gambiae. However, in addition to NF-kappaB-dependent signaling, three mitogen-activated protein kinase (MAPK) pathways regulated by JNK, ERK and p38 MAPK are critical mediators of innate immunity in other invertebrates and in mammals. Our understanding of the roles of the MAPK signaling cascades in anopheline innate immunity is limited, so identification of the encoded complement of these proteins, their upstream activators, and phosphorylation profiles in response to relevant immune signals was warranted.

Results
In this study, we present the orthologs and phylogeny of 17 An. gambiae MAPKs, two of which were previously unknown and two others that were incompletely annotated. We also provide detailed temporal activation profiles for ERK, JNK, and p38 MAPK in An. gambiae cells in vitro to immune signals that are relevant to malaria parasite infection (human insulin, human transforming growth factor-beta1, hydrogen peroxide) and to bacterial lipopolysaccharide. These activation profiles and possible upstream regulatory pathways are interpreted in light of known MAPK signaling cascades.

Conclusions
The establishment of a MAPK "road map" based on the most advanced mosquito genome annotation can accelerate our understanding of host-pathogen interactions and broader physiology of An. gambiae and other mosquito species. Further, future efforts to develop predictive models of anopheline cell signaling responses, based on iterative construction and refinement of data-based and literature-based knowledge of the MAP kinase cascades and other networked pathways will facilitate identification of the "master signaling regulators" in biomedically important mosquito species.
Francisella RNA polymerase contains a heterodimer of non-identical α subunits
Authors: Mukhamedyarov Damir , Makarova Kira S , Severinov Konstantin , Kuznedelov Konstantin 
Published: November 2011

Abstract

Background
All sequenced genomes of representatives of the Francisella genus contain two rpoA genes, which encode non-identical RNA polymerase (RNAP) subunits, α1 and α2. In all other bacteria studied to date, a dimer of identical α subunits initiates the assembly of the catalytically proficient RNAP core (subunit composition α2ββ'). Based on an observation that both α1 and α2 are incorporated into Francisella RNAP, Charity et al. (2007) previously suggested that up to four different species of RNAP core enzyme might form in the same Francisella cell.

Results
By in vitro assembly from fully denatured state, we determined that both Francisella α subunits are required for efficient dimerization; no homodimer formation was detected. Bacterial two-hybrid system analysis likewise indicated strong interactions between the α1 and α2 N-terminal domains (NTDs, responsible for dimerization). NTDs of α2 did not interact detectably, while weak interaction between α1 NTDs was observed. This weak homotypic interaction may explain low-level transcription activity observed in in vitro RNAP reconstitution reactions containing Francisella large subunits (β', β) and α1. No activity was observed with RNAP reconstitution reactions containing α2, while robust transcription activity was detected in reactions containing α1 and α2. Phylogenetic analysis based on RpoA resulted in a tree compatible with standard bacterial taxonomy with both Francisella RpoA branches positioned within γ-proteobacteria. The observed phylogeny and analysis of constrained trees are compatible with Francisella lineage-specific rpoA duplication followed by acceleration of evolutionary rate and subfunctionalization.

Conclusions
The results strongly suggest that most Francisella RNAP contains α heterodimer with a minor subfraction possibly containing α1 homodimer. Comparative sequence analysis suggests that this heterodimer is oriented, in a sense that only one monomer, α1, interacts with the β subunit during the α2β RNAP subassembly formation. Most likely the two rpoA copies in Francisella have emerged through a lineage-specific duplication followed by subfunctionalization of interacting paralogs.
Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies
Authors: Chen Chien-Yuan , Sheng Wang-Huei , Cheng Aristine , Tsay Woei , Huang Shang-Yi , Tang Jih-Luh , Chen Yee-Chun , Wang Jaun-Yuan , Tien Hwei-Fang , Chang Shan-Chwen 
Published: November 2011

Abstract

Background
Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated.

Methods
Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes.

Results
Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs.

Conclusions
TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity.
Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells
Authors: Taylor David J , Parsons Christine E , Han Haiyong , Jayaraman Arul , Rege Kaushal 
Published: November 2011

Abstract

Background

Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis.

Methods
FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis.

Results
Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells.

Conclusions
The identification of a number of FDA-approved drugs as TRAIL sensitizers can expand chemotherapeutic options for combination treatments in prostate and pancreatic cancer diseases.
Isolation of a nanomolar scFv inhibiting the endopeptidase activity of botulinum toxin A, by single-round panning of an immune phage-displayed library of macaque origin
Authors: Chahboun Siham , Hust Michael , Liu Yvonne , Pelat Thibaut , Miethe Sebastian , Helmsing Saskia , Jones Russell GA , Sesardic Dorothea , Thullier Philippe 
Published: November 2011

Abstract

Background
Botulinum neurotoxin A (BoNT/A), mainly represented by subtype A1, is the most toxic substance known. It causes naturally-occurring food poisoning, and is among the biological agents at the highest risk of being weaponized. Several antibodies neutralizing BoNT/A by targeting its heavy chain (BoNT/A-H) have been isolated in the past. For the first time however, an IgG (4LCA) recently isolated by hybridoma technology and targeting the BoNT/A light chain (BoNT/A-L), was shown to inhibit BoNT/A endopeptidase activity and protect in vivo against BoNT/A. In the present study, a phage-displayed library was constructed from a macaque (Macaca fascicularis) hyper-immunized with BoNTA/L in order to isolate scFvs inhibiting BoNT/A endopeptidase activity for clinical use.

Results
Diversity of the scFvs constituting the library was limited due to the frequent presence, within the genes intended to be part of the library, of restriction sites utilized for its construction. After screening with several rounds of increasing stringency, as is usual with phage technology, the library got overwhelmed by phagemids encoding incomplete scFvs. The screening was successfully re-performed with a single round of high stringency. In particular, one of the isolated scFvs, 2H8, bound BoNT/A1 with a 3.3 nM affinity and effectively inhibited BoNT/A1 endopeptidase activity. The sequence encoding 2H8 was 88% identical to human germline genes and its average G-score was -0.72, quantifying the high human-like quality of 2H8.

Conclusions
The presence of restrictions sites within many of the sequences that were to be part of the library did not prevent the isolation of an scFv, 2H8, by an adapted panning strategy. ScFv 2H8 inhibited toxin endopeptidase activity in vitro and possessed human-like quality required for clinical development. More generally, the construction and screening of phage-displayed libraries built from hyper-immunized non-human primates is an efficient solution to isolate antibody fragments with therapeutic potential.
Anti-tumor effects of fibroblast growth factor-binding protein (FGF-BP) knockdown in colon carcinoma
Authors: Schulze Daniel , Plohmann Philipp , Höbel Sabrina , Aigner Achim 
Published: November 2011

AbstractBackgroundFibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM). One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP) which, upon reversible binding to FGF-1 or -2, leads to their release from the ECM. FGF-BP increases tumorigenicity and is highly expressed in tumors like colon carcinoma. In this paper, we analyse cellular and molecular consequences of RNAi-mediated FGF-BP knockdown in colon carcinoma, and explore the therapeutic effects of the nanoparticle-mediated delivery of small interfering RNAs (siRNAs) for FGF-BP targeting.ResultsEmploying stable RNAi cells, we establish a dose-dependence of cell proliferation on FGF-BP expression levels. Decreased proliferation is mirrored by alterations in cell cycle distribution and upregulation of p21, which is relevant for mediating FGF-BP effects. While inhibition of proliferation is mainly associated with reduced Akt and increased GSK3β activation, antibody array-based analyses also reveal other alterations in MAPK signalling. Additionally, we demonstrate induction of apoptosis, mediated through caspase-3/7 activation, and alterations in redox status upon FGF-BP knockdown. These effects are based on the upregulation of Bad, Bax and HIF-1α, and the downregulation of catalase. In a therapeutic FGF-BP knockdown approach based on RNAi, we employ polymer-based nanoparticles for the in vivo delivery of siRNAs into established wildtype colon carcinoma xenografts. We show that the systemic treatment of mice leads to the inhibition of tumor growth based on FGF-BP knockdown.ConclusionsFGF-BP is integrated in a complex network of cytoprotective effects, and represents a promising therapeutic target for RNAi-based knockdown approaches.
Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review
Authors: Watkins Casey E , Litchfield John , Song Eunkyung , Jaishankar Gayatri B , Misra Niva , Holla Nikhil , Duffourc Michelle , Krishnaswamy Guha 
Published: November 2011

Abstract
Chronic Granulomatous Disease (CGD), a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans). Deletions and missense, frameshift, or nonsense mutations in the gp91phox gene (also termed CYBB), located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.
A one-dimensional extremely covalent material: monatomic carbon linear chain
Authors: Zhang Yaozhong , Su Yanjie , Wang Liang , Kong Eric Siu-Wai , Chen XiaoShuang , Zhang Yafei 
Published: November 2011

AbstractPolyyne and cumulene of infinite length as the typical covalent one-dimensional (1D) monatomic linear chains of carbon have been demonstrated to be metallic and semiconductor (Eg = 1.859 eV), respectively, by first-principles calculations. Comparing with single-walled carbon nanotubes, the densities are evidently low and the thermodynamic properties are similar below room temperature but much different at the high temperature range. Polyyne possesses a Young's modulus as high as 1.304 TPa, which means it is even much stiffer than carbon nanotubes and to be the superlative strong 1D material along the axial direction. The Young's modulus of cumulene is estimated to be 760.78 GPa. In addition, polyyne is predicted to be as a one-dimensional electronic material with very high mobility.
Characterization of ultrathin InSb nanocrystals film deposited on SiO2/Si substrate
Authors: Li Dengyue , Li Hongtao , Sun Hehui , Zhao Liancheng 
Published: November 2011

AbstractRecently, solid-phase recrystallization of ultrathin indium antimonide nanocrystals (InSb NCs (films grown on SiO2/Si substrate is very attractive, because of the rapid development of thermal annealing technique. In this study, the recrystallization behavior of 35 nm indium antimonide film was studied. Through X-ray diffraction (XRD) analysis, it is demonstrated that the InSb film is composed of nanocrystals after high temperature rapid thermal annealing. Scanning electron microscopy shows that the film has a smooth surface and is composed of tightly packed spherical grains, the average grain size is about 12.3 nm according to XRD results. The optical bandgap of the InSb NCs film analyzed by Fourier Transform infrared spectroscopy measurement is around 0.26 eV. According to the current-voltage characteristics of the InSb NCs/SiO2/p-Si heterojunction, the film has the rectifying behavior and the turn-on voltage value is near 1 V.
The existence of fixed points for new nonlinear multivalued maps and their applications
Authors: He Zhenhua , Du Wei-Shih , Lin Ing-Jer 
Published: November 2011

AbstractIn this paper, we first establish some new fixed point theorems for
M
T
-functions. By using these results, we can obtain some generalizations of Kannan's fixed point theorem and Chatterjea's fixed point theorem for nonlinear multivalued contractive maps in complete metric spaces. Our results generalize and improve some main results in the literature and references therein.Mathematics Subject Classifications47H10; 54H25
A generalised fixed point theorem of presic type in cone metric spaces and application to markov process
Authors: George Reny , Reshma KP , Rajagopalan R 
Published: November 2011

AbstractA generalised common fixed point theorem of Presic type for two mappings f: X → X and T: X
k
→ X in a cone metric space is proved. Our result generalises many well-known results.2000 Mathematics Subject Classification47H10
Children with disorders of sex development: A qualitative study of early parental experience
Authors: Crissman Halley P , Warner Lauren , Gardner Melissa , Carr Meagan , Schast Aileen , Quittner Alexandra L , Kogan Barry , Sandberg David E 
Published: November 2011

AbstractBackgroundClinical research on psychological aspects of disorders of sex development (DSD) has focused on psychosexual differentiation with relatively little attention directed toward parents' experiences of early clinical management and their influence on patient and family psychosocial adaptation.ObjectivesTo characterize parental experiences in the early clinical care of children born with DSD.Study DesignContent analysis of interviews with parents (n = 41) of 28 children, newborn to 6 years, with DSD.ResultsFour major domains emerged as salient to parents: (1) the gender assignment process, (2) decisions regarding genital surgery, (3) disclosing information about their child's DSD, and (4) interacting with healthcare providers. Findings suggested discordance between scientific and parental understandings of the determinants of "sex" and "gender." Parents' expectations regarding the benefits of genital surgery appear largely met; however, parents still had concerns about their child's future physical, social and sexual development. Two areas experienced by many parents as particularly stressful were: (1) uncertainties regarding diagnosis and optimal management, and (2) conflicts between maintaining privacy versus disclosing the condition to access social support.ConclusionsParents' experiences and gaps in understanding can be used to inform the clinical care of patients with DSD and their families. Improving communication between parents and providers (and between parents and their support providers) throughout the early clinical management process may be important in decreasing stress and improving outcomes for families of children with DSD.