bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes
Authors: Kvam Augusta I. , Mavenyengwa Rooyen T. , Radtke Andreas , Maeland Johan A. 
Published: June 2011

ABSTRACTMost isolates of group B streptococci (GBS) express an alpha-like protein (Alp), Cα (encoded bybca), Alp1 (also called epsilon;alp1), Alp2 (alp2), Alp3 (alp3), Alp4 (alp4), or R4/Rib (rib). These proteins are chimeras with a mosaic structure and with antigenic determinants with variable immunological cross-reactivities between the Alps, including Alp1 and Cα cross-reactivity. This study focused on antigenic domains of Alp1, studied by using rabbit antisera in immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA)-based tests and whole cells of GBS or trypsin-extracted and partially purified antigens from the strains A909 (serotype Ia/Cα, Cβ) and 335 (Ia/Alp1). Alp1 and Cα shared an antigenic determinant, Alp1/Cα common, not harbored by other Alps, probably located in the Alp1 and Cα repeat units, as these units are nearly identical in genomic sequence. An antigenic Alp1 determinant was Alp1 specific and was most likely located in the N-terminal unit of Alp1 in which an Alp1-specific primer site for PCR is also located. In addition, Alp1 possessed a domain with low immunogenicity which cross-reacted immunologically with Alp2 and Alp3, with unknown location in Alp1. Alp1 was partially degraded by trypsin during antigen extraction but with the antigenic domains preserved. The results indicate that Cα and Alp1 are immunologically related in the same manner that R4 (Rib) and Alp3 are related. The domain called Alp1 specific should be important in GBS serotyping as a surface-anchored serosubtype marker. The Alp1/Cα common determinant may be of prime interest as an immunogenic domain in a GBS vaccine.
Detection of AmpC Beta-Lactamase in Escherichia coli: Comparison of Three Phenotypic Confirmation Assays and Genetic Analysis
Authors: Peter-Getzlaff S. , Polsfuss S. , Poledica M. , Hombach M. , Giger J. , Böttger E. C. , Zbinden R. , Bloemberg G. V. 
Published: June 2011

ABSTRACT

Two mechanisms account for AmpC activity in
Escherichia coli
, namely, mutations in the
ampC
promoter and attenuator regions resulting in
ampC
overexpression and acquisition of plasmid-carried
ampC
genes. In this study, we analyzed 51 clinical
E. coli
isolates with reduced susceptibility to amoxicillin-clavulanic acid, piperacillin-tazobactam, or extended-spectrum cephalosporins for the presence of AmpC production. Three phenotypic AmpC confirmation assays (cefoxitin-cloxacillin disk diffusion test, cefoxitin-EDTA disk diffusion test, and AmpC Etest) were compared for the detection of AmpC activity. All 51 isolates were characterized genetically by mutational analysis of the chromosomal
ampC
promoter/attenuator region and by PCR detection of plasmid-carried
ampC
genes. Altogether, 21/51 (41%)
E. coli
isolates were considered true AmpC producers. AmpC activity due to chromosomal
ampC
promoter/attenuator mutations was found in 12/21 strains, and plasmid-carried
ampC
genes were detected in 8/21 isolates. One strain contained both
ampC
promoter mutations and a plasmid-carried
ampC
gene. All three phenotypic tests were able to detect the majority (>90%) of AmpC-positive strains correctly. Cefoxitin resistance was found to be a discriminative parameter, detecting 20/21 AmpC-producing strains. Susceptibility to extended-spectrum cephalosporins, e.g., ceftriaxone, ceftazidime, and cefotaxime, was found in 9 of the 21 AmpC-positive strains. Considering the elevated zone diameter breakpoints of the 2010 CLSI guidelines, 2/21 AmpC-positive strains were categorized as susceptible to extended-spectrum cephalosporins.
Colletotrichum truncatum: an Unusual Pathogen Causing Mycotic Keratitis and Endophthalmitis
Authors: Shivaprakash M. R. , Appannanavar Suma B. , Dhaliwal Manpreet , Gupta Amit , Gupta Sunita , Gupta Amod , Chakrabarti Arunaloke 
Published: June 2011

ABSTRACT

In recent years, the well-known plant pathogens of the
Colletotrichum
genus were increasingly reported to cause ophthalmic infections in humans. Among 66 species in the
Colletotrichum
genus, only a few are known to be pathogenic for humans. We report here five cases of ophthalmic infections due to
Colletotrichum truncatum
, a species never reported earlier to cause human infection. The isolates were identified by morphological characteristics and the sequencing of internal spacer regions of ribosomal DNA. The progress of lesions in those patients was slow compared to that of lesions caused by
Aspergillus
or
Fusarium
infections. The surgical management included total penetrating keratoplasty in patients with keratitis and pars plana vitrectomy in endophthalmitis. Two patients were treated additionally with intravitreal amphotericin B deoxycholate, one patient with oral itraconazole, and another patient with oral and topical fluconazole therapy. The present series therefore highlights the expanding spectrum of agents causing eye infections and the inclusion of
C. truncatum
as a human pathogen.
Influenza A Virus N5 Neuraminidase Has an Extended 150-Cavity
Authors: Wang Mingyang , Qi Jianxun , Liu Yue , Vavricka Christopher J. , Wu Yan , Li Qing , Gao George F. 
Published: June 2011

ABSTRACT
There are 9 serotypes of neuraminidase (NA) from influenza A virus (N1 to N9), which are classified into two groups based on primary sequences (groups 1 and 2). The structural hallmark of the two groups is the presence or absence of an extra 150-cavity (formed by the 150-loop) in the active site. Thus far, structures of NAs from 6 out of the 9 serotypes have been solved. Here, we solved the N5 structure, the last unknown structure group 1 serotype with a unique Asn147 residue in its 150-loop, demonstrating that it has an extended 150-cavity that closes upon inhibitor binding.
Active Depletion of Host Cell Inhibitor-of-Apoptosis Proteins Triggers Apoptosis upon Baculovirus DNA Replication
Authors: Vandergaast Rianna , Schultz Kimberly L. W. , Cerio Rebecca J. , Friesen Paul D. 
Published: June 2011

ABSTRACT

Apoptosis is an important antivirus defense by virtue of its impact on virus multiplication and pathogenesis. To define molecular mechanisms by which viruses are detected and the apoptotic response is initiated, we examined the antiviral role of host inhibitor-of-apoptosis (IAP) proteins in insect cells. We report here that the principal IAPs, DIAP1 and SfIAP, of the model insects
Drosophila melanogaster
and
Spodoptera frugiperda
, respectively, are rapidly depleted and thereby inactivated upon infection with the apoptosis-inducing baculovirus
Autographa californica
multicapsid nucleopolyhedrovirus (AcMNPV). Virus-induced loss of these host IAPs triggered caspase activation and apoptotic death. Elevation of IAP levels by ectopic expression repressed caspase activation. Loss of host IAP in both species was triggered by AcMNPV DNA replication. By using selected inhibitors, we found that virus-induced IAP depletion was mediated in part by the proteasome but not by caspase cleavage. Consistent with this conclusion, mutagenic disruption of the SfIAP RING motif, which acts as an E3 ubiquitin ligase, stabilized SfIAP during infection. Importantly, SfIAP was also stabilized upon the removal of its 99-residue N-terminal leader, which serves as a critical determinant of IAP turnover. These data indicated that a host pathway initiated by virus DNA replication and acting through instability motifs embedded within IAP triggers IAP depletion and thereby causes apoptosis. Taken together, the results of our study suggest that host modulation of cellular IAP levels is a conserved mechanism by which insects mount an apoptotic antiviral response. Thus, host IAPs may function as critical sentinels of virus invasion in insects.
Retinoic Acid as a Vaccine Adjuvant Enhances CD8+T Cell Response and Mucosal Protection from Viral Challenge
Authors: Tan Xuefang , Sande Jamie L. , Pufnock Jeffrey S. , Blattman Joseph N. , Greenberg Philip D. 
Published: June 2011

ABSTRACTVaccine-induced memory T cells localized at mucosal sites can provide rapid protection from viral infection. All-trans-retinoic acid (ATRA) has been shown to act physiologically to induce the expression of gut-homing receptors on lymphocytes. We tested whether the administration of exogenous ATRA during a systemic vaccination of mice could enhance the generation of mucosal CD8+T cell immunity, which might represent a strategy for establishing better protection from viral infection via mucosal routes. ATRA induced the expression of CCR9 and α4β7 on both mouse and human CD8+T cells activatedin vitro. The administration of ATRA to mice duringin vivopriming with a replication-defective recombinant adenovirus vector expressing the lymphocytic choriomeningitis virus glycoprotein (LCMVgp) (Ad5gp) increased numbers of both effector and memory T cells in intestinal mucosal tissues and showed higher frequencies of systemic central memory-like T cells that exhibited enhanced proliferation during boosting immunization with recombinant modified vaccinia virus Ankara expressing LCMVgp (MVAgp). Mice that received ATRA during Ad5gp vaccination were more resistant to intravaginal challenge by recombinant vaccinia virus expressing LCMVgp (VVgp), reflecting in part stronger T cell recall responsesin situ. Thus, ATRA appears to be useful as an adjuvant during vaccination to increase memory T cell responses and protection from viral infection at mucosal sites and may facilitate the development of more effective vaccines against mucosally transmitted pathogens such as HIV.
Evolution of Human Immunodeficiency Virus Type 1 in a Patient with Cross-Reactive Neutralizing Activity in Serum
Authors: van Gils Marit J. , Edo-Matas Diana , Bowles Emma J. , Burger Judith A. , Stewart-Jones Guillaume B. , Schuitemaker Hanneke 
Published: June 2011

ABSTRACT

Analysis of longitudinally obtained HIV-1
env
sequences from an individual with reported cross-reactive neutralizing activity revealed that the majority of viral variants obtained from serum between 4 and 7 years after seroconversion were unable to persist in peripheral blood. Here we show that these viral variants were more sensitive to autologous serum neutralization, had shorter envelopes with fewer potential N-linked glycosylation sites, and showed lower replication kinetics than successfully evolving HIV-1 variants. These data reflect the host selection pressures on phenotypic characteristics of HIV-1 and illustrate in detail the dynamic interaction between HIV-1 and its host's humoral immune responses.
The Bicyclists' Injuries and the Cycling Environment study: a protocol to tackle methodological issues facing studies of bicycling safety
Authors: Harris M Anne , Reynolds Conor C O , Winters Meghan , Chipman Mary , Cripton Peter A , Cusimano Michael D , Teschke Kay 
Published: June 2011

Background and aimsBicycling may be less appealing in parts of the world where cycling is less safe. Differences between jurisdictions suggest route design is key to improving safety and increasing ridership. Previous studies faced difficulties in effectively assessing denominators for risk calculations and controlling confounding. This paper describes the advantages of the case-crossover design of the Bicyclists' Injuries and the Cycling Environment study to address these challenges to observational studies of cycling safety.MethodsInjured cyclists were recruited from the emergency departments of five hospitals in Vancouver and Toronto, Canada. In 18 months, 690 participants were successfully recruited and interviewed. Each participant was interviewed to map the route of their injury trip, identify the injury site and select two control sites at random from the same route. Infrastructural characteristics at each study site were scored by site observers who were blinded as to whether sites were crash or comparison sites. Analyses will compare infrastructural variables between case and control sites with conditional logistic regression.DiscussionThis study presents a novel application of the case-crossover design to the evaluation of relationships between infrastructure and cycling safety while controlling confounders and exposure to risk. It is hoped that the value of this method and the efficiency of the recruitment process will encourage replication in other locations, to expand the range of cycling infrastructure compared and to facilitate evidence-based cycling infrastructure choices that can make cycling safer and more appealing.
Biomechanical attributes of microcatheters used in liquid embolization of intracranial aneurysms
Authors: Simon Scott D , Reig Adam S , Archer Kellie J , Mericle Robert A 
Published: June 2011

ObjectiveA steel-reinforced and a nitanol-reinforced microcatheter are both approved for use with Onyx HD-500 embolization of intracranial aneurysms. The biomechanical behavior of these catheters when used with high viscosity embolic liquids is poorly understood. We performed biomechanical laboratory testing and examined our clinical experience to identify situations where one catheter might have an advantage over the other.MethodsThe catheters were tested for detachment force from aneurysm cast, burst pressure, burst location, and pressure under dynamic delivery pressure. The results were compared using ANOVA.ResultsThe average detachment forces for the Echelon 10, 14, and Rebar 14 catheters were 97.6, 76.825, and 62.6 g, respectively (p=0.023). The average burst pressures for the Echelon 10, 14, and Rebar 14 were 1108, 1213, and 1365 psi, respectively (p=0.003). The average burst location was 26.0, 20.0, and 4.5 mm, respectively, from the tip (p=0.035). There was no significant difference regarding burst location (p=0.39). The delivery pressures of the catheters were not significant (p=0.98). Two cases are presented that illustrate the importance of these findings and how they can be incorporated into practice.ConclusionThe lower detachment force of the Rebar 14 makes it ideal for liquid embolization, but its stiffness makes it less desirable for accessing smaller aneurysms or navigating tortuous anatomy. The Echelon 10 should be avoided unless it is the only catheter that can access an aneurysm because of small size or tortuous anatomy. In such cases, the higher detachment force suggests a stent should be in place to prevent the cast from being destabilized.
Selection ofMycoplasma genitaliumstrains harbouring macrolide resistance-associated 23S rRNA mutations by treatment with a single 1 g dose of azithromycin: Table 1
Authors: Ito Shin , Shimada Yasushi , Yamaguchi Yuko , Yasuda Mitsuru , Yokoi Shigeaki , Ito Shin-ichi , Nakano Masahiro , Ishiko Hiroaki , Deguchi Takashi 
Published: June 2011

ObjectiveA single 1 g dose regimen of azithromycin has been recommended for the treatment ofMycoplasma genitaliuminfections. The authors evaluated whether this regimen could selectM genitaliumstrains with macrolide resistance after treatment forM genitalium-positive non-gonococcal urethritis.MethodsIn seven men with non-gonococcal urethritis, who were infected withM genitaliumwithout macrolide resistance-associated mutations but experienced microbiological azithromycin treatment failure,M genitaliumDNAs in their post-treatment urine specimens were examined for mutations in the 23S rRNA gene and the ribosomal protein genes of L4 and L22. To assess the relatedness ofM genitaliumstrains before and after treatment, their DNAs in pretreatment and post-treatment urine were genotyped by analysing short tandem repeats of an AGT/AAT unit in the MG309 gene and single nucleotide polymorphisms in the MG191 gene.ResultsIn four of seven patients,M genitaliumin post-treatment urine had an A-to-G transition at nucleotide position 2071 or 2072, corresponding to 2058 or 2059 in the 23S rRNA gene ofEscherichia coli. In one of the four strains, Pro81Ser in the ribosomal protein L4 accompanied the mutation in the 23S rRNA gene. The genotyping ofM genitaliumDNAs suggested that these four post-treatment strains were selected from the respective closely related or identical pretreatment strains without macrolide resistance-associated mutations by the treatment.ConclusionsThe single 1 g dose treatment of azithromycin could selectM genitaliumstrains harbouring macrolide resistance-associated mutations. ForM genitalium, this regimen might increase the risk of macrolide resistance selection after treatment.
EGFR Signals Downregulate Tumor Suppressors miR-143 and miR-145 in Western Diet–Promoted Murine Colon Cancer: Role of G1 Regulators
Authors: Zhu Hongyan , Dougherty Urszula , Robinson Victoria , Mustafi Reba , Pekow Joel , Kupfer Sonia , Li Yan-Chun , Hart John , Goss Kathleen , Fichera Alessandro , Joseph Loren , Bissonnette Marc 
Published: June 2011

Abstract
Epidermal growth factor receptors (EGFR) contribute to colonic tumorigenesis in experimental models of colon cancer. We previously showed that EGFR was also required for colonic tumor promotion by Western diet. The goal of this study was to identify EGFR-regulated microRNAs that contribute to diet-promoted colonic tumorigenesis. Murine colonic tumors from Egfrwt and hypomorphic Egfrwa2 mice were screened using micro RNA (miRNA) arrays and miR-143 and miR-145 changes confirmed by Northern, real-time PCR, and in situ analysis. Rodent and human sporadic and ulcerative colitis (UC)-associated colon cancers were examined for miR-143 and miR-145. Effects of EGFR on miR-143 and miR-145 expression were assessed in murine and human colonic cells and their putative targets examined in vitro and in vivo. miR-143 and miR-145 were readily detected in normal colonocytes and comparable in Egfrwt and Egfrwa2 mice. These miRNAs were downregulated in azoxymethane and inflammation-associated colonic tumors from Egfrwt mice but upregulated in Egfrwa2 tumors. They were also reduced in human sporadic and UC colon cancers. EGFR signals suppressed miR-143 and miR-145 in human and murine colonic cells. Transfected miR-143 and miR-145 inhibited HCT116 cell growth in vitro and in vivo and downregulated G1 regulators, K-Ras, MYC, CCND2, cdk6, and E2F3, putative or established targets of these miRNAs. miRNA targets Ras and MYC were increased in colonic tumors from Egfrwt but not Egfrwa2 mice fed a Western diet. EGFR suppresses miR-143 and miR-145 in murine models of colon cancer. Furthermore, Western diet unmasks the tumor suppressor roles of these EGFR-regulated miRNAs. Mol Cancer Res; 9(7); 960–75. ©2011 AACR.
Haemostatic profiles assessed by thromboelastography in patients with end-stage renal disease
Authors: Darlington Andrew , Luis Ferreiro Josè , Ueno Masafumi , Suzuki Yoshi , Desai Bhaloo , Capranzano Piera , Capodanno Davide , Tello-Montoliu Antonio , Bass Theodore A. , Nahman Norris S , Angiolillo Dominick J. 
Published: June 2011

SummaryPatients with end-stage renal disease (ESRD) have abnormalities in the cellular and plasmatic systems regulating blood homeostasis, which may contribute to their risk for thrombotic and bleeding complications. However, their relative contributions in this population are poorly understood. The aim of this study was to evaluate the distribution of enzymatic and cellular abnormalities in ESRD patients on haemodialysis as assessed by thromboelastography (TEG®). Whole blood samples were analysed by TEG in ESRD patients (n=70) and in a control group (n=70) of subjects with coronary artery disease. Profiles were constructed considering the maximum amplitude (MA), a marker of platelet function, and reaction time (R), a marker of thrombin generation, values. R values were higher in ESRD patients compared with the control group (8.2 ± 2.8 vs. 5.7 ± 1.9 minutes [min], p <0.0001), while there were no differences in MA (66.7 ± 8.1 vs. 66.2 ± 6.6 mm, p=0.562). Nor mal manufacturer defined coagulation (2–8 min) and aggregation (51–69 mm) parameters were present in 31% of ESRD patients compared with 56% of controls (p=0.006). A hypocoagulable status was observed in 42.9% of ESRD patients compared with 8.9% in the control group (p<0.0001). There were no differences in platelet function, which showed a hyperaggregable status in 41.4% versus 35.7% of cases (p=0.603). Abnormalities in both parameters were observed in 15.7% of ESRD patients versus 1.4% in the control group (p = 0.004), which were more common among older patients (p= 0.005). In conclusion, patients with ESRD have an elevated prevalence of abnormal haemostatic profiles, which may contribute to their elevated risk of bleeding and thrombotic complications.
Hyperhomocysteinemia impairs endothelium-derived hyperpolarizing factor–mediated vasorelaxation in transgenic cystathionine beta synthase–deficient mice
Authors: Cheng Zhongjian , Jiang Xiaohua , Kruger Warren D. , Praticò Domenico , Gupta Sapna , Mallilankaraman Karthik , Madesh Muniswamy , Schafer Andrew I. , Durante William , Yang Xiaofeng , Wang Hong 
Published: June 2011

Abstract
Hyperhomocysteinemia (HHcy) is associated with endothelial dysfunction (ED), but the mechanism is largely unknown. In this study, we investigated the role and mechanism of HHcy-induced ED in microvasculature in our newly established mouse model of severe HHcy (plasma total homocysteine, 169.5μM). We found that severe HHcy impaired nitric oxide (NO)– and endothelium-derived hyperpolarizing factor (EDHF)–mediated, endothelium-dependent relaxations of small mesenteric arteries (SMAs). Endothelium-independent and prostacyclin-mediated endothelium-dependent relaxations were not changed. A nonselective Ca2+-activated potassium channel (KCa) inhibitor completely blocked EDHF-mediated relaxation. Selective blockers for small-conductance KCa (SK) or intermediate-conductance KCa (IK) failed to inhibit EDHF-mediated relaxation in HHcy mice. HHcy increased the levels of SK3 and IK1 protein, superoxide (O2−), and 3-nitrotyrosine in the endothelium of SMAs. Preincubation with antioxidants and peroxynitrite (ONOO−) inhibitors improved endothelium-dependent and EDHF-mediated relaxations and decreased O2− production in SMAs from HHcy mice. Further, EDHF-mediated relaxation was inhibited by ONOO− and prevented by catalase in the control mice. Finally, L-homocysteine stimulated O2− production, which was reversed by antioxidants, and increased SK/IK protein levels and tyrosine nitration in cultured human cardiac microvascular endothelial cells. Our results suggest that HHcy impairs EDHF relaxation in SMAs by inhibiting SK/IK activities via oxidation- and tyrosine nitration–related mechanisms.
New mutations and pathogenesis of myeloproliferative neoplasms
Authors: Vainchenker William , Delhommeau François , Constantinescu Stefan N. , Bernard Olivier A. 
Published: June 2011

AbstractMyeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature blood cells. In the majority of classic MPN—polycythemia vera, essential thrombocythemia, and primitive myelofibrosis—driver oncogenic mutations affecting Janus kinase 2 (JAK2) or MPL lead to constitutive activation of cytokine-regulated intracellular signaling pathways. LNK, c-CBL, or SOCSs (all negative regulators of signaling pathways), although infrequently targeted, may either drive the disease or synergize with JAK2 and MPL mutations. IZF1 deletions or TP53 mutations are mainly found at transformation phases and are present at greater frequency than in de novo acute myeloid leukemias. Loss-of-function mutations in 3 genes involved in epigenetic regulation, TET2, ASXL1, and EZH2, may be early events preceding JAK2V617F but may also occur late during disease progression. They are more frequently observed in PMF than PV and ET and are also present in other types of malignant myeloid diseases. A likely hypothesis is that they facilitate clonal selection, allowing the dominance of the JAK2V617F subclone during the chronic phase and, together with cooperating mutations, promote blast crisis. Their precise roles in hematopoiesis and in the pathogenesis of MPN, as well as their prognostic impact and potential as a therapeutic target, are currently under investigation.