bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma
Authors: REN XIAOLIANG , DAA TSUTOMU , YADA NAOMI , KASHIMA KENJI , FUJITOMI YUTAKA , YOKOYAMA SHIGEO 
Published: November 2011

Ren XL, Daa T, Yada N, Kashima K, Fujitomi Y, Yokoyama S. Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma. APMIS 2012; 120: 358–67.Recepteur d’origine nantais (RON) is a receptor tyrosine kinase closely related to MET and involved in tumorigenesis. We investigated the roles of aberrations in RON and its ligand, macrophage‐stimulating protein (MSP), in invasive ductal carcinoma (IDC, n = 81), ductal carcinoma in situ (DCIS, n = 26), and in benign lesions (n = 20) of mammary gland. Expression of RON and MSP was evaluated by immunohistochemistry and the mutational status of a region containing the proteolytic cleavage site in exon 1 and each exon of the kinase domain (exon 14–20) of RON was screened by polymerase chain reaction‐single strand conformational polymorphism (PCR‐SSCP) analysis. The proportion of cases positive for RON expression was significantly different between malignant [86% (92/107)] and benign [40% (8/20)] lesions. RON expression was positive in both IDC and DCIS [90% (73/81) and 73% (19/26), respectively], whereas MSP expression was present in 54% (44/81) of IDC and absent in DCIS. RON expression correlated significantly with the histological grade of DCIS. No mutations were detected in the examined regions of RON in breast cancer samples as confirmed by PCR‐SSCP. The findings suggest the involvement of RON expression in the development of breast cancer, and that an autocrine/paracrine loop of RON seems to affect tumor invasiveness.
Biochemical Disclosure of the Mycolate Outer Membrane of Corynebacterium glutamicum
Authors: Marchand Christophe H. , Salmeron Christophe , Bou Raad Roland , Méniche Xavier , Chami Mohamed , Masi Muriel , Blanot Didier , Daffé Mamadou , Tropis Marielle , Huc Emilie , Le Maréchal Pierre , Decottignies Paulette , Bayan Nicolas 
Published: November 2011

ABSTRACT

Corynebacterineae
is a specific suborder of Gram-positive bacteria that includes
Mycobacterium tuberculosis
and
Corynebacterium glutamicum
. The cell wall of these bacteria is composed of a heteropolymer of peptidoglycan (PG) linked to arabinogalactan (AG), which in turn is covalently associated with an atypical outer membrane, here called mycomembrane (M). The latter structure has been visualized by cryo-electron microscopy of vitreous sections, but its biochemical composition is still poorly defined, thereby hampering the elucidation of its physiological function. In this report, we show for the first time that the mycomembrane-linked heteropolymer of PG and AG (M-AG-PG) of
C. glutamicum
can be physically separated from the inner membrane on a flotation density gradient. Analysis of purified M-AG-PG showed that the lipids that composed the mycomembrane consisted almost exclusively of mycolic acid derivatives, with only a tiny amount, if any, of phospholipids and lipomannans, which were found with the characteristic lipoarabinomannans in the plasma membrane. Proteins associated with or inserted in the mycomembrane were extracted from M-AG-PG with lauryl-dimethylamine-oxide (LDAO), loaded on an SDS-PAGE gel, and analyzed by tandem mass spectrometry or by Western blotting. Sixty-eight different proteins were identified, 19 of which were also found in mycomembrane fragments released by the terminal-arabinosyl-transferase-defective Δ
AftB
strain. Almost all of them are predicted to contain a signal sequence and to adopt the characteristic β-barrel structure of Gram-negative outer membrane proteins. These presumed mycomembrane proteins include the already-known pore-forming proteins (PorA and PorB), 5 mycoloyltransferases (cMytA, cMytB, cMytC, cMytD, and cMytF), several lipoproteins, and unknown proteins typified by a putative C-terminal hydrophobic anchor.
HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network–associated Lck signaling
Authors: Pan Xiaoyu , Rudolph Jochen M. , Abraham Libin , Habermann Anja , Haller Claudia , Krijnse-Locker Jacomine , Fackler Oliver T. 
Published: November 2011

Abstract
The Nef protein of HIV-1 facilitates viral replication and disease progression in vivo. Nef disturbs the organization of immunological synapses between infected CD4+ T lymphocytes and antigen-presenting B-lymphocytes to interfere with TCR proximal signaling. Paradoxically, Nef enhances distal TCR signaling in infected CD4+ T lymphocytes, an effect thought to be involved in its role in AIDS pathogenesis. Using quantitative confocal microscopy and cell fractionation of Nef-expressing cells and HIV-1–infected primary human T lymphocytes, we found that Nef induces intracellular compartmentalization of TCR signaling to adjust TCR responses to antigenic stimulation. Nef reroutes kinase-active pools of the TCR signaling master switch Lck away from the plasma membrane (PM) to the trans-Golgi network (TGN), thereby preventing the recruitment of active Lck to the immunological synapse after TCR engagement and limiting signal initiation at the PM. Instead, Nef triggers Lck-dependent activation of TGN-associated Ras-Erk signaling to promote the production of the T lymphocyte survival factor IL-2 and to enhance virus spread. Overexpression of the Lck PM transporter Unc119 restores Nef-induced subversions of Lck trafficking and TCR signaling. Nef therefore hijacks Lck sorting to selectively activate TGN-associated arms of compartmentalized TCR signaling. By tailoring T-lymphocyte responses to antigenic stimulation, Nef optimizes the environment for HIV-1 replication.
Development of a Risk-Stratification Tool for Medical Child Abuse in Failure to Thrive
Authors: Mash Constance , Frazier Thomas , Nowacki Amy , Worley Sarah , Goldfarb Johanna 
Published: November 2011

OBJECTIVE:
To develop a risk-stratification tool to help identify medical child abuse (MCA) in children evaluated for failure to thrive (FTT).

PATIENTS AND METHODS:
In this case-control study, the control group consisted of children who were seen in the pediatric gastroenterology department and diagnosed with FTT before the age of 5 years between 2000 and 2010. Cases were distinguished by having also been referred to the Child Advocacy Committee at the Cleveland Clinic Foundation (CCF) and/or reported to the Department of Child and Family Services by the CCF as a possible case of MCA. We used retrospective chart review to compare 17 cases of MCA with 68 controls. Classification-tree analysis was used to generate the risk-stratification tool.

RESULTS:
A risk-stratification tool, in the form of a classification tree, was developed and incorporated the following individual risk indicators: (1) ≥5 organ systems involved; (2) absence of serious congenital anomaly or confirmed genetic disorder; (3) ≥5 reported allergies; and (4) refusal of services from a multidisciplinary feeding team. Overall, the classification tree had a sensitivity of 100% and a specificity of 96%.

CONCLUSIONS:
The results of this study suggest that a diagnosis of MCA may be suspected in children with FTT on the basis of features in the initial presentation and clinical course. Using the proposed risk-stratification tool that incorporates these features might assist in earlier identification of medically abused children and reduce morbidity and mortality.
Direct Electrochemistry of Hemoglobin Based on Fe3O4@SiO2 Nanoparticles Modified Electrode
Authors: Cui Rongjing , Yin Fan , Zhou Lijuan , Pan Hongcheng 
Published: November 2011

AbstractA biosensor based on hemoglobin‐Fe3O4@SiO2 nanoparticle bioconjunctions modified indium‐tin‐oxide (Hb/Fe3O4@SiO2/ITO) electrode was fabricated to determine the concentration of H2O2. UV‐vis absorption spectra, fourier transform infrared (FT‐IR) spectroscopy, cyclic voltammetry (CV) and high‐resolution transmission electron microscopy (HRTEM) were used to characterize the bioconjunction of Fe3O4@SiO2 with Hb. Experimental results demonstrate that the immobilized Hb on the Fe3O4@SiO2 matrix retained its native structure well. In addition, Fe3O4@SiO2 nanoparticles (NPs) are very effective in facilitating electron transfer of the immobilized enzyme, which can be attributed to the unique nanostructure and larger surface area of the Fe3O4@SiO2 NPs. The biosensor displayed good performance for the detection of H2O2 with a wide linear range from 2.03×10−6 to 4.05×10−3 mol/L and a detection limit of 0.32 µmol/L. The resulting biosensor exhibited fast amperometric response, good stability, reproducibility, and selectivity to H2O2.
Maternal use of antibiotics and the risk of orofacial clefts: a nationwide cohort study
Authors: Mølgaard‐Nielsen Ditte , Hviid Anders 
Published: November 2011

ABSTRACTPurposeTo study the association between antibiotic use in early pregnancy and the risk of isolated orofacial clefts.MethodsWe conducted a cohort study of 806 011 live births in Denmark from 1996 through September 2008. Individual‐level information on prescribed antibiotics during pregnancy, orofacial cleft diagnosis, and possible confounders were ascertained from nationwide health registries. The main outcome measure was prevalence odds ratios (PORs) of orofacial clefts by exposure to antibiotics.ResultsMaternal use of any antibiotics in early pregnancy was not associated with an increased risk of cleft lip with or without cleft palate (CL/P) (POR, 1.08; 95%CI, 0.89–1.30) or cleft palate alone (CP) (POR, 1.14; 95%CI, 0.86–1.51). Further analyses of specific classes showed an increased risk of CL/P associated with 2nd month use of doxycycline/tetracycline (2 exposed cases; POR, 7.30; 95%CI, 1.81–29.46) and sulfamethizole (18 exposed cases; POR, 1.76; 95%CI, 1.10–2.81). An increased risk of CP was seen for first trimester use of trimethoprim (2 exposed cases; POR, 14.29; 95%CI, 3.46–59.05) and 3rd month use of pivmecillinam (9 exposed cases; POR, 2.34; 95%CI, 1.20–4.54).ConclusionAntibiotic use in early pregnancy was not a major risk factor for isolated orofacial clefts in our study. Some classes of antibiotics used in the critical period for development of CL/P and CP may increase the risk; however, other factors such as indications for use and chance may explain these findings. Copyright © 2011 John Wiley & Sons, Ltd.
Effects of predator species, vegetation and prey assemblage on prey preferences of predators with emphasis on vulnerability of age‐0 common carp
Authors: WEBER M. J. , BROWN M. L. 
Published: November 2011

Abstract  Predation is an important force structuring aquatic communities, but predator–prey interactions are complex and regulated by multiple factors. Invasive fishes may interact with native fishes to alter predator–prey preferences and community dynamics. For example, common carp, Cyprinus carpio L., is an invasive species that can become abundant and negatively affect aquatic ecosystems. Juvenile common carp are occasionally found in predator diets, but predator preferences for common carp compared with alternative prey remains unknown. Prey selection and feeding behaviour of five piscivores (flathead catfish, Pylodictis olivaris (Rafinesque); largemouth bass, Micropterus salmoides (Lacepède); smallmouth bass, M. dolomieu Lacepède; walleye, Sander vitreus (Mitchill); and northern pike, Esox lucius L.) foraging on juvenile common carp and two alternative prey (fathead minnow, Pimephales promelas Rafinesque, and yellow perch, Perca flavescens Mitchill) at variable densities and habitats were evaluated. Common carp and fathead minnow were generally selected for or neutrally selected across predator species, habitat types and prey assemblages. By contrast, yellow perch was generally selected against. Common carp were easily captured but difficult to manipulate and ingest compared with other prey. These results reveal that common carp are vulnerable to a variety of predators, suggesting control of this detrimental invader may be possible through biomanipulation.
The Impacts of Hg(II) Tightly Binding on the Alzheimer’s Tau Construct R3: Misfolding and Aggregation
Authors: Yang Dan-Jing , Shi Shuo , Yao Tian-Ming , Ji Liang-Nian 
Published: November 2011

Abstract
Mercury, a known neurotoxin, is increasingly believed to be relevant to trigger the pathological positive feedback circle of Alzheimer’s disease (AD). In this study, we originally set out to determine the possible mechanisms for Hg(II)-stimulated fibrillation of R3, which is pivotal to the biochemical properties of full tau protein. In an isothermal titration calorimetry experiment, we demonstrate that R3 shows high affinity to Hg(II), and it yields two types of coordination intermediates in the Hg(II)–R3 binding process. The exceptionally large magnitude of heat release suggests that the most possible coordinating site is the thiol group of cysteine residue (Cys322). By circular dichroism spectrum, we reveal that the coordination of Hg(II) significantly alters the conformation of natively unstructured R3, specifically from random coil to β-turn structure. Furthermore, we find that the tight binding of Hg(II) exerts a pronounced acceleration of the heparin-induced aggregation of R3, giving relatively more R3 filaments, by ThS fluorescence assay and electron microscopy. This investigation could help us to understand the detailed mechanism of misfolding development and self-aggregation of the tau protein from a toxicological perspective of metal ion to AD.
Theoretical Study of the Intramolecular Proton Transfer in the Tautomers of Cytosine Assisted by Water
Authors: Zheng Haitao , Zhao Dongxia , Yang Zhongzhi 
Published: November 2011

AbstractAb initio MP2 and DFT studies on the tautomers of cytosine and the related hydrated tautomers have been carried out. The ground‐state structures of four tautomers of cytosine and related transition states were fully optimized. The vibrational frequency analysis was performed on all the optimized structures. Detailed intrinsic reaction coordinate (IRC) calculations were carried out to guarantee the optimized transition‐state structures being connected to the related tautomers. We obtained the relative stability order for the tautomers of cytosine and the related hydrated tautomers. In the isolated and hydrated condition, the bond types of C(2)O(7) and C(4)N(8) greatly affect the stability of the cytosine tautomers. Moreover, we have explored the influence of the water molecules on the intramolecular proton transfer between the keto and enol forms of the cytosine tautomers. The first water molecule obviously decreases the isomerization activation energy for the monohydrated cytosine tautomers. It is shown that the isomerization energy barrier changes only a little when the second and third water molecules are added in the reaction loop. The solvent effects have an obvious influence on the proton‐transfer barrier of the isolated cytosine. However, the solvent effects seem to be insignificant for the isomerization energy barriers of the monohydrated, dihydrated and trihydrated cytosine. The water molecule in these complexes can be looked on as the explicit water. Therefore, the explicit water model may be more credible to explore the intramolecular proton transfer, in comparison with the PCM which is the implicit water model.
Molecular lesions in childhood and adult acute megakaryoblastic leukaemia
Authors: Hama Asahito , Muramatsu Hideki , Makishima Hideki , Sugimoto Yuka , Szpurka Hadrian , Jasek Monika , O’Keefe Christine , Takahashi Yoshiyuki , Sakaguchi Hirotoshi , Doisaki Sayoko , Shimada Akira , Watanabe Nobuhiro , Kato Koji , Kiyoi Hitoshi , Naoe Tomoki , Kojima Seiji , Maciejewski Jaroslaw P. 
Published: November 2011

SummaryWhile acute megakaryoblastic leukaemia (AMKL) occurs in children with (DS‐AMKL) and without (paediatric non‐DS‐AMKL) Down syndrome, it can also affect adults without DS (adult non‐DS‐AMKL). We have analysed these subgroups of patients (11 children with DS‐AMKL, 12 children and four adults with non‐DS‐AMKL) for the presence of molecular lesions, including mutations and chromosomal abnormalities studied by sequencing and single nucleotide polymorphism array‐based karyotyping, respectively. In children, AMKL was associated with trisomy 21 (somatic in non‐DS‐AMKL), while numerical aberrations of chromosome 21 were only rarely associated with adult AMKL. DS‐AMKL was also associated with recurrent somatic gains of 1q (4/11 DS‐AMKL patients). In contrast to trisomy 21 and gains of 1q, other additional chromosomal lesions were evenly distributed between children and adults with AMKL. A mutational screen found GATA1 mutations in 11/12 DS‐AMKL, but mutations were rare in paediatric non‐DS‐AMKL (1/12) and adult AMKL (0/4). JAK3 (1/11), JAK2 (1/11), and TP53 mutations (1/11) were found only in patients with DS‐AMKL. ASXL1, IDH1/2, DNMT3A, RUNX1 and CBL mutations were not found in any of the patient group studied, while NRAS mutation was identified in two patients with paediatric non‐DS‐AMKL.
HopX1 in Erwinia amylovora Functions as an Avirulence Protein in Apple and Is Regulated by HrpL
Authors: Bocsanczy A. M. , Schneider D. J. , DeClerck G. A. , Cartinhour S. , Beer S. V. 
Published: November 2011

ABSTRACT

Fire blight is a devastating disease of rosaceous plants caused by the Gram-negative bacterium
Erwinia amylovora
. This pathogen delivers virulence proteins into host cells utilizing the type III secretion system (T3SS). Expression of the T3SS and of translocated and secreted substrates is activated by the alternative sigma factor HrpL, which recognizes
hrp
box promoters upstream of regulated genes. A collection of hidden Markov model (HMM) profiles was used to identify putative
hrp
boxes in the genome sequence of Ea273, a highly virulent strain of
E. amylovora
. Among potential virulence factors preceded by putative
hrp
boxes, two genes previously known as Eop3 and Eop2 were characterized. The presence of functionally active
hrp
boxes upstream of these two genes was confirmed by β-glucuronidase (GUS) assays. Deletion mutants of the latter candidate genes, renamed

hopX1
Ea

and

hopAK1
Ea

, respectively, did not differ in virulence from the wild-type strain when assayed in pear fruit and apple shoots. The

hopX1
Ea

deletion mutant of Ea273, complemented with a plasmid overexpressing

hopX1
E

a
, suppressed the development of the hypersensitivity response (HR) when inoculated into
Nicotiana benthamiana
; however, it contributed to HR in
Nicotiana tabacum
and significantly reduced the progress of disease in apple shoots, suggesting that HopX1
Ea
may act as an avirulence protein in apple shoots.
Effects of Cortex Peptidoglycan Structure and Cortex Hydrolysis on the Kinetics of Ca
2+
-Dipicolinic Acid Release during Bacillus subtilis Spore Germination
Authors: Zhang Pengfei , Thomas Stacy , Li Yong-qing , Setlow Peter 
Published: November 2011

ABSTRACT

The kinetic parameters of the release of Ca
2+
-dipicolinic acid (CaDPA) during germination of spore populations and multiple individual spores of
Bacillus subtilis
strains with major alterations in the structure of the spore peptidoglycan (PG) cortex or lacking one or both of the two redundant enzymes involved in cortex hydrolysis (cortex-lytic enzymes [CLEs]) were determined. The lack of the CLE CwlJ greatly slowed CaDPA release with a germinant receptor (GR)-dependent germinant,
l
-valine, or a non-GR-dependent germinant, dodecylamine. The absence of the cortex-specific PG modification muramic acid–δ-lactam also increased the time needed for full CaDPA release during germination with both types of germinants. In contrast, increased cortex PG cross-linking was associated with faster times for initiation of CaDPA release with both
l
-valine and dodecylamine but not with faster CaDPA release once this release had been initiated. These data suggest that the precise structure of the spore cortex plays a significant role in determining the timing and the rate of CaDPA release during
B. subtilis
spore germination and, further, that this effect is independent of effects of GRs.
Biomarkers and Cardiovascular Risk Assessment for Primary Prevention: An Update
Authors: Gilstrap Lauren G , Wang Thomas J 
Published: November 2011

Abstract

BACKGROUND
Interest in cardiovascular biomarkers in primary prevention has increased dramatically in the past decade. This increase has been fueled by an improved understanding of cardiovascular pathophysiology, as well as novel technologies for biomarker identification.

CONTENT
In this review we provide a brief overview of recent concepts in the evaluation of screening biomarkers, because biomarkers may behave differently when used for screening as opposed to diagnosis or disease staging. The following specific biomarker examples are then discussed, with a focus on data from primary prevention studies: high-sensitivity C-reactive protein, B-type natriuretic peptide, lipoprotein-associated phospholipase A2, and high-sensitivity troponin T. The article concludes by addressing novel platforms for biomarker discovery, reviewing recent examples from the field of metabolomics.

SUMMARY
An ongoing challenge is to develop screening strategies that can identify individuals at risk for cardiovascular events well before symptoms appear. For this purpose, the measurement of soluble biomarkers could be an important adjunct to traditional cardiovascular risk assessment. Recent studies highlight both the strengths and limitations of “novel” circulating biomarkers, and suggest that substantial work is still needed to identify biomarkers that are sufficiently accurate and cost-effective for routine use in primary prevention.
QTc Values Among Children and Adolescents Presenting to the Emergency Department
Authors: Van Dorn Charlotte S. , Johnson Jonathan N. , Taggart Nathaniel W. , Thorkelson Lois , Ackerman Michael J. 
Published: November 2011

OBJECTIVE:
Long-QT syndrome (LQTS) is both underdiagnosed and overdiagnosed. Many patients are incorrectly diagnosed as having LQTS after presenting to an emergency department (ED) with presyncope/syncope and demonstrating “borderline” QT-interval prolongation (QTc ≥ 440 milliseconds) in a sentinel ED-obtained electrocardiogram (ECG). We sought to evaluate the distribution and clinical significance of QT intervals in the ED.

METHODS:
We retrospectively reviewed data for all patients 22 years of age or younger (N = 626; 369 females; age, mean ± SD: 17 ± 5 years) who had ECGs obtained in our ED between July 1, 2007, and June 30, 2008. A total of 223 patients were excluded because of known structural heart disease, arrhythmias, electrolyte abnormalities, or exposure to QT-interval–prolonging medications.

RESULTS:
The average QTc was 428 ± 28 milliseconds (range: 344–566 milliseconds), and approximately one-third of patients had QTc values of ≥440 milliseconds (females: 41%; males: 21%). Overall, 104 patients presented with presyncope/syncope, of whom 14 (13%) had follow-up ECGs. On follow-up, these patients demonstrated significant decreases in QTc values of 33 ± 43 milliseconds (P &lt; .04). Only 8 (31%) of 26 patients with presyncope/syncope with borderline QT values had follow-up ECGs performed, in 5 of which the QTc values were decreased significantly. No patients ultimately received LQTS diagnoses.

CONCLUSIONS:
In the ED setting, approximately one-third of pediatric patients exhibited QTc values of ≥440 milliseconds and had significant normalization of QTc values in follow-up evaluations. First-time ECGs obtained after a syncopal episode must be interpreted with caution, particularly in the context of so-called borderline QT intervals.