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Sample records for coxiella type iv

  1. Refining the plasmid-encoded type IV secretion system substrate repertoire of Coxiella burnetii.

    Science.gov (United States)

    Maturana, Pauline; Graham, Joseph G; Sharma, Uma M; Voth, Daniel E

    2013-07-01

    The intracellular bacterial agent of Q fever, Coxiella burnetii, translocates effector proteins into its host cell cytosol via a Dot/Icm type IV secretion system (T4SS). The T4SS is essential for parasitophorous vacuole formation, intracellular replication, and inhibition of host cell death, but the effectors mediating these events remain largely undefined. Six Dot/Icm substrate-encoding genes were recently discovered on the C. burnetii cryptic QpH1 plasmid, three of which are conserved among all C. burnetii isolates, suggesting that they are critical for conserved pathogen functions. However, the remaining hypothetical proteins encoded by plasmid genes have not been assessed for their potential as T4SS substrates. In the current study, we further defined the T4SS effector repertoire encoded by the C. burnetii QpH1, QpRS, and QpDG plasmids that were originally isolated from acute-disease, chronic-disease, and severely attenuated isolates, respectively. Hypothetical proteins, including those specific to QpRS or QpDG, were screened for translocation using the well-established Legionella pneumophila T4SS secretion model. In total, six novel plasmid-encoded proteins were translocated into macrophage-like cells by the Dot/Icm T4SS. Four newly identified effectors are encoded by genes present only on the QpDG plasmid from severely attenuated Dugway isolates, suggesting that the presence of specific effectors correlates with decreased virulence. These results further support the idea of a critical role for extrachromosomal elements in C. burnetii pathogenesis.

  2. Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole.

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    Hayley J Newton

    Full Text Available The human pathogen Coxiella burnetii encodes a type IV secretion system called Dot/Icm that is essential for intracellular replication. The Dot/Icm system delivers bacterial effector proteins into the host cytosol during infection. The effector proteins delivered by C. burnetii are predicted to have important functions during infection, but when these proteins are needed during infection has not been clearly defined. Here, we use a reporter system consisting of fusion proteins that have a β-lactamase enzyme (BlaM fused to C. burnetii effector proteins to study protein translocation by the Dot/Icm system. Translocation of BlaM fused to the effector proteins CBU0077, CBU1823 and CBU1524 was not detected until 8-hours after infection of HeLa cells, which are permissive for C. burnetii replication. Translocation of these effector fusion proteins by the Dot/Icm system required acidification of the Coxiella-containing vacuole. Silencing of the host genes encoding the membrane transport regulators Rab5 or Rab7 interfered with effector translocation, which indicates that effectors are not translocated until bacteria traffic to a late endocytic compartment in the host cell. Similar requirements for effector translocation were discerned in bone marrow macrophages derived from C57BL/6 mice, which are primary cells that restrict the intracellular replication of C. burnetii. In addition to requiring endocytic maturation of the vacuole for Dot/Icm-mediated translocation of effectors, bacterial transcription was required for this process. Thus, translocation of effector proteins by the C. burnetii Dot/Icm system occurs after acidification of the CCV and maturation of this specialized organelle to a late endocytic compartment. This indicates that creation of the specialized vacuole in which C. burnetii replicates represents a two-stage process mediated initially by host factors that regulate endocytic maturation and then by bacterial effectors delivered into

  3. Rapid typing of Coxiella burnetii.

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    Heidie M Hornstra

    Full Text Available Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels among multispacer sequence typing (MST loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies.

  4. Mucopolysaccharidosis type IV

    Science.gov (United States)

    MPS IV; Morquio syndrome; Mucopolysaccharidosis type IVA; MPS IVA; Galactosamine-6-sulfatase deficiency; Mucopolysaccharidosis type IVB; MPS IVB; Beta galactosidase deficiency; Lysosomal storage disease - mucopolysaccharidosis type IV

  5. DNA gyrase and topoisomerase IV mutations in an in vitro fluoroquinolone-resistant Coxiella burnetii strain.

    Science.gov (United States)

    Vranakis, Iosif; Sandalakis, Vassilios; Chochlakis, Dimosthenis; Tselentis, Yannis; Psaroulaki, Anna

    2010-06-01

    The etiological agent of Q fever, Coxiella burnetii, is an obligate intracellular bacterium that multiplies within a vacuole with lysosomal characteristics. Quinolones have been used as an alternative therapy for Q fever. In this study, quinolone-resistance-determining regions of the genes coding for DNA gyrase and topoisomerase IV were analyzed by DNA sequencing from an in vitro fluoroquinolone-resistant C. burnetii strain (Q212). Sequencing and aligning of DNA gyrase encoding genes (gyrA and gyrB) and topoisomerase IV genes (parC and parE) revealed one gyrA mutation leading to the amino acid substitution Asp87Gly (Escherichia coli numbering), two gyrB mutations leading to the amino acid substitutions Ser431Pro and Met518Ile, and three parC mutations leading to the amino acid substitutions Asp69Asn, Thr80Ile, and Gly104Ser. The corresponding alignment of the C. burnetii Q212 reference strain, the in vitro developed fluoroquinolone-resistant C. burnetii Q212 strain, and E. coli resulted in the identification of several other naturally occurring mutations within and outside the quinolone-resistance-determining regions of C. burnetii providing indications of possible natural resistance to fluoroquinolones. The present study adds additional potential mutations in the DNA topoisomerases that may be involved in fluoroquinolone resistance in C. burnetii due to their previous characterization in other bacterial species.

  6. Localization and visualization of a coxiella-type symbiont within the lone star tick, Amblyomma americanum.

    Science.gov (United States)

    Klyachko, Olga; Stein, Barry D; Grindle, Nathan; Clay, Keith; Fuqua, Clay

    2007-10-01

    A Coxiella-type microbe occurs at 100% frequency in all Amblyomma americanum ticks thus far tested. Using laboratory-reared ticks free of other microbes, we identified the Amblyomma-associated Coxiella microbe in several types of tissue and at various stages of the life cycle of A. americanum by 16S rRNA gene sequencing and diagnostic PCR. We visualized Amblyomma-associated Coxiella through the use of a diagnostic fluorescence in situ hybridization (FISH) assay supplemented with PCR-based detection, nucleic acid fluorescent staining, wide-field epifluorescence and confocal microscopy, and transmission electron microscopy (TEM). Specific fluorescent foci were observed in several tick tissues, including the midgut and the Malpighian tubules, but particularly bright signals were observed in the granular acini of salivary gland clusters and in both small and large oocytes. TEM confirmed intracellular bacterial structures in the same tissues. The presence of Amblyomma-associated Coxiella within oocytes is consistent with the vertical transmission of these endosymbionts. Further, the presence of the Amblyomma-associated Coxiella symbiont in other tissues such as salivary glands could potentially lead to interactions with horizontally acquired pathogens.

  7. COXIELLA BURNETII PATHOGENICITY MOLECULAR BASIS

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    Yu. A. Panferova

    2016-01-01

    Full Text Available Coxiella burnetii is an obligate intracellular gram-negative bacterial pathogen, an ethiological agent of Q-fever, a zoonotic disease, elapsing as an acute (mostly atypical pneumonia or a chronic (mostly endocarditis form. The host range is represented by wide range of mammal, avian and arthropod species, but the main source of human infection are farm animals. The main route of infection is aerosolic. In case of contact with organism pathogen binds with phagocytal monocytic-macrophagal cell line. C. burnetii promotes maturation of specific phagolysosome-like compartment in host cell, called coxiella-containing vacuole, within this vacuole pathogen becames metabolically activated and actively replicates. Coxiella persists as metabolically inactive spore-like form in environment. Internalisation of C. burnetii occurs using actin-mediated phagocytosis and zipper mechanism. After internalization of bacteria maturation of phagolysosome-like compartment and large coxiella-containing vacuole formation occure, and vacuole can occupy nearly the whole cytoplasm of the host cell. Survivance of infected cells is important for chronic infection with C. burnetii. C. burnetii elongate the viability of host cell by two ways: it actively inhibits apoptotic signal cascades and induce pro-survival factors. Exceptthat C. burnetii involves autophagic pathway during coxiella-containing vacuole formation, and induction of autophagy promotes pathogen replication. During infection C. burnetii translocates effector substrates from bacterial cytosole to euca ryotic host cell cytosole using type IV secretion system, where effectors modulate host cell proteins. Overall approximately 130 secreted effectors of type IV transport system, but function of most of them remains unknown to date. Specific sec reted proteins for variety of strains and isolates were identified, confirmed that certain pathotypes of C. burnetii can exist. Identification and

  8. Glycogen Storage Disease Type IV

    DEFF Research Database (Denmark)

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B

    2016-01-01

    molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made......A 30-yr-old woman presented with 2 consecutive miscarriages within 7 mo. Histopathologic examination of the placental tissue showed intracytoplasmic inclusion vacuoles with a strong reaction in Periodic acid-Schiff staining and a slightly pallor reaction in alcian blue staining. Additional...... on histopathologic examination. Genetic analysis is required to confirm the diagnosis and to offer prenatal genetic testing in future pregnancies....

  9. Genetics Home Reference: glycogen storage disease type IV

    Science.gov (United States)

    ... Home Health Conditions Glycogen storage disease type IV Glycogen storage disease type IV Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type IV (GSD IV) is an inherited disorder ...

  10. Mirizzi Syndrome Type IV: A challenging diagnosis

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    Daniel Navarini

    2016-05-01

    Full Text Available Mirizzi Syndrome type IV is an extremely rare condition, which is confused with the diagnosis of cholangiocarcinoma in many cases. This report describes a case of a forty-three-year old patient, who was forwarded to our department of general surgery with a high suspicion of a choledochal neoplasic lesion. During the hospitalization he was diagnosed with Mirizzi Syndrome type IV. We concisely describe the case and the literature review about this pathology.

  11. Type IV Wind Turbine Model

    DEFF Research Database (Denmark)

    Hansen, Anca Daniela; Margaris, Ioannis D.

    (WPP) will be considered. The aggregate WPP model, which will be based on the upscaling of the individual wind turbine model on the electrical part, will make use of an equivalent wind speed. The implemented model follows the basic structure of the generic standard Type 4 wind turbine model proposed...... by the International Electrotechnical Commission (IEC), in the IEC61400-27-1 Committee Draft for electrical simulation models for wind power generation, which is currently under review, [1]. The Type 4 wind turbine model described in this report includes a set of adjustments of the standard Type 4 wind turbine model...... project to be incorporated in the wind power plant level. This document describes the Type 4 wind turbine simulation model, implemented in the EaseWind project. The implemented wind turbine model is one of the initial necessary steps toward integrating new control services in the wind power plant level...

  12. Muscle Function in Osteogenesis Imperfecta Type IV.

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    Veilleux, Louis-Nicolas; Darsaklis, Vasiliki B; Montpetit, Kathleen; Glorieux, Francis H; Rauch, Frank

    2017-10-01

    Results of previous studies suggest that children and adolescents with osteogenesis imperfecta (OI) type IV have muscle force deficits. However, muscle function remains to be objectively quantified in this population. This study aimed to assess upper and lower extremity muscle function in patients with OI type IV. It was carried out in the outpatient department of a pediatric orthopedic hospital; 27 individuals with OI type IV (7-21 years; 13 males), 27 age- and sex-matched individuals with OI type I, and 27 age- and sex-matched controls. Upper extremity muscle force was assessed with hydraulic hand dynamometry, and lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by mechanography through five tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Upper-limb grip force was normal for patients with OI type IV when compared to height and sex reference data (average z-score = 0.17 ± 1.30; P = 0.88). Compared to age- and sex-matched controls, patients with OI type IV had approximately 30% lower-limb peak force and 50% peak power deficits (P values <0.05). At the lower-limb level, they had a 50% lower peak power than age- and sex-matched patients with OI type I (P < 0.05). Patients with OI type IV have normal upper-limb muscle force but a muscle function deficit at the lower-limb level. These results suggest that lower-limb muscle weakness may contribute to functional deficits in these individuals.

  13. Ehlers-Danlos syndrome type IV

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    Germain, Dominique P

    2007-01-01

    Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering

  14. Ehlers-Danlos syndrome type IV

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    Germain Dominique P

    2007-07-01

    Full Text Available Abstract Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS, is an inherited connective tissue disorder defined by characteristic facial features (acrogeria in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular

  15. Type IV secretion and Brucella virulence.

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    Boschiroli, Maria Laura; Ouahrani-Bettache, Safia; Foulongne, Vincent; Michaux-Charachon, Sylvie; Bourg, Gisele; Allardet-Servent, Annick; Cazevieille, Chantal; Lavigne, Jean-Phillipe; Liautard, Jean Pierre; Ramuz, Michel; O'Callaghan, David

    2002-12-20

    The type IV secretion system, encoded by the virB region, is a key virulence factor for Brucella. The 12 genes of the region form an operon that is specifically induced by phagosome acidification in cells after phagocytosis. We speculate that the system serves to secrete unknown effector molecules, which allow Brucella to pervert the host cell endosomal pathways and to create a novel intracellular compartment in which it can replicate. Copyright 2002 Elsevier Science B.V.

  16. Delayed-type hypersensitivity (type IV) reactions in dental anesthesia.

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    Melamed, Julian; Beaucher, Wilfred N

    2007-01-01

    The recommended methodology of evaluating patients who have presented with reactions to local anesthetics consists of epicutaneous skin testing and serial subcutaneous challenge. However, the role of type IV reactions in this group has been poorly documented. Epicutaneous routine testing and subcutaneous challenge to local anesthetic was performed, as well as patch testing and subcutaneous rechallenge of both at 24 and 48 hours with evaluation up to 72 hours was performed. Three patients presented with a history of localized edema after dental anesthesia. All had negative lidocaine and mepivacaine testing as well as negative lidocaine challenge on evaluation at 1 hour. The first patient, who had previously reacted to EMLA, reacted to both lidocaine and mepivacaine patch testing and challenge, with delayed swelling at 24 and 48 hours after challenge. This patient subsequently tolerated the ester anesthetic chloroprocaine. Two other patients had strong histories of contact dermatitis. Patch testing and challenge with lidocaine was negative, but strong reactions were found to benzocaine on patch testing. Patients undergoing local anesthetic testing should be screened historically for features and risk factors associated with type IV reactions. This should be considered in patients who react to multiple amide anesthetics, who have delayed swelling, or who have a history of severe contact dermatitis. We confirm previous data showing that patients reacting to benzocaine can tolerate lidocaine and that lidocaine-allergic individuals can tolerate ester anesthetics.

  17. Genetics Home Reference: mucopolysaccharidosis type IV

    Science.gov (United States)

    ... build up inside the lysosomes are called lysosomal storage disorders. In MPS IV, GAGs accumulate to toxic levels ... clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007 ... and Morquio B patients. J Lipid Res. 2007 Oct;48(10):2275-82. Epub ...

  18. Hepatocellular carcinoma in glycogen storage disease type IV

    OpenAIRE

    de Moor, R A; Schweizer, J; van Hoek, B; Wasser, M; Vink, R; Maaswinkel-Mooy, P

    2000-01-01

    A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.



  19. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

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    Dolores L. Guzmán-Herrador

    2017-08-01

    Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  20. [Mucolipidoses type IV in a patient with mapuche ancestry].

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    Hernández Ch, Marta; Méndez C, José Ignacio; Concha G, María José; Huete L, Isidro; González B, Sergio; Durán S, Gloria P

    2008-07-01

    We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at 3 years of age. At 5 years of age, a slow neurological deterioration started, associated to visual impairment. Optic atrophy was added to the typical neurological exam of ataxic cerebral palsy and the diagnosis was re-considered. Neuroimaging showed a slow and progressive atrophy of intracerebral structures and ultramicroscopy revealed intracytoplasmatic inclusions in conjunctiva and skin, compatible with mucolipidoses type IV (ML-IV). ML-IV must be included in the differential diagnosis of cerebral palsy associated with loss of acquired skills and progressive visual impairment. Electron microscopy of skin or conjunctiva is a useful diagnostic test. Suspicion of ML-IV must not be restricted to Ashkenazi Jewish population.

  1. Evolutionary origin of type IV classical cadherins in arthropods.

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    Sasaki, Mizuki; Akiyama-Oda, Yasuko; Oda, Hiroki

    2017-06-17

    Classical cadherins are a metazoan-specific family of homophilic cell-cell adhesion molecules that regulate morphogenesis. Type I and type IV cadherins in this family function at adherens junctions in the major epithelial tissues of vertebrates and insects, respectively, but they have distinct, relatively simple domain organizations that are thought to have evolved by independent reductive changes from an ancestral type III cadherin, which is larger than derived paralogs and has a complicated domain organization. Although both type III and type IV cadherins have been identified in hexapods and branchiopods, the process by which the type IV cadherin evolved is still largely unclear. Through an analysis of arthropod genome sequences, we found that the only classical cadherin encoded in chelicerate genomes was the type III cadherin and that the two type III cadherin genes found in the spider Parasteatoda tepidariorum genome exhibited a complex yet ancestral exon-intron organization in arthropods. Genomic and transcriptomic data from branchiopod, copepod, isopod, amphipod, and decapod crustaceans led us to redefine the type IV cadherin category, which we separated into type IVa and type IVb, which displayed a similar domain organization, except type IVb cadherins have a larger number of extracellular cadherin (EC) domains than do type IVa cadherins (nine versus seven). We also showed that type IVa cadherin genes occurred in the hexapod, branchiopod, and copepod genomes whereas only type IVb cadherin genes were present in malacostracans. Furthermore, comparative characterization of the type IVb cadherins suggested that the presence of two extra EC domains in their N-terminal regions represented primitive characteristics. In addition, we identified an evolutionary loss of two highly conserved cysteine residues among the type IVa cadherins of insects. We provide a genomic perspective of the evolution of classical cadherins among bilaterians, with a focus on the Arthropoda

  2. Sequence Domain Harmonic Modeling of Type-IV Wind Turbines

    DEFF Research Database (Denmark)

    Guest, Emerson; Jensen, Kim Høj; Rasmussen, Tonny Wederberg

    2017-01-01

    -sampled pulsewidth modulation and an analysis of converter generated voltage harmonics due to compensated dead-time. The decoupling capabilities of the proposed the SD harmonic model are verified through a power quality (PQ) assessment of a 3MW Type-IV wind turbine. The assessment shows that the magnitude and phase...... of low-order odd converter generated voltage harmonics are dependent on the converter operating point and the phase of the fundamental component of converter current respectively. The SD harmonic model can be used to make PQ assessments of Type-IV wind turbines or incorporated into harmonic load flows...... for computation of PQ in wind power plants....

  3. Prevalence and molecular typing of Coxiella burnetii in bulk tank milk in Belgian dairy goats, 2009-2013.

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    Boarbi, Samira; Mori, Marcella; Rousset, Elodie; Sidi-Boumedine, Karim; Van Esbroeck, Marjan; Fretin, David

    2014-05-14

    Q fever, a worldwide zoonosis, is an arousing public health concern in many countries since the recent Dutch outbreak. An emerging C. burnetii clone, genotype CbNL01, was identified as responsible for the Dutch human Q fever cluster cases. Since 2009, Q fever surveillance in the goat industry was implemented by the Belgian authorities. The herd prevalence (December 2009-March 2013) ranged between 6.3 and 12.1%. Genotypic analysis highlighted the molecular diversity of the Belgian strains from goats and identified an emerging CbNL01-like genotype. This follow-up allowed the description of shedding profiles in positive farms which was either continuous (type I) and associated to the CbNL01-like genotype; or intermittent (type II) and linked to other genotypes. Despite the circulation of a CbNL01-like strain, the number of notified Belgian human cases was very low. The mandatory vaccination (in June 2011) on positive dairy goat farms in Belgium, contributed to a decrease in shedding. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Osteogenesis imperfecta Type IV: a newly identified variant at ...

    African Journals Online (AJOL)

    Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis ...

  5. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants

    DEFF Research Database (Denmark)

    Klausen, M.; Heydorn, Arne; Ragas, Paula Cornelia

    2003-01-01

    Biofilm formation by Gfp-tagged Pseudomonas aeruginosa PAO1 wild type, flagella and type IV pili mutants in flow chambers irrigated with citrate minimal medium was characterized by the use of confocal laser scanning microscopy and comstat image analysis. Flagella and type IV pili were not necessary...... for P. aeruginosa initial attachment or biofilm formation, but the cell appendages had roles in biofilm development, as wild type, flagella and type IV pili mutants formed biofilms with different structures. Dynamics and selection during biofilm formation were investigated by tagging the wild type...... and flagella/type IV mutants with Yfp and Cfp and performing time-lapse confocal laser scanning microscopy in mixed colour biofilms. The initial microcolony formation occurred by clonal growth, after which wild-type P. aeruginosa bacteria spread over the substratum by means of twitching motility. The wild-type...

  6. Coxiella burnetii in pregnant goats

    NARCIS (Netherlands)

    Roest, H.I.J.

    2013-01-01

    Coxiella burnetii is the causative agent of Q fever. Since it was first recognised as a disease in the 1930s, knowledge about the agent and the disease itself has increased, although knowledge gaps are still present. Therefore the name Q(uery) fever still holds true.

  7. Coxiella burnetii in pregnant goats

    NARCIS (Netherlands)

    Roest, H.I.J.

    2013-01-01

    Coxiella burnetii is an intracellular bacterium and the causative agent of Q fever. The zoonotic impact of Q fever was recently underlined by the Dutch Q fever outbreak, which emerged from an endemic state. In this outbreak dairy goats and dairy sheep were deemed responsible for the human cases,

  8. Significance of combinative determination of urinary type IV collagen and trace albumin in type 2 diabetics

    International Nuclear Information System (INIS)

    Yang Libin

    2004-01-01

    In order to evaluate the diagnostic value of combinative determination of urinary trace albumin(Alb) and urinary type IV collagen (C-IV) for early damage of renal function in type 2 diabetics, 24-hr urine was collected each from 30 normal subjects and 165 type 2 diabetics, and RIA was carried out to determine simultaneously Alb and C-IV (concentration method). The results showed: (1) the content of Alb in 24-hr urine of normal subjects was 6.45±2.04 mg/24 hrs, and that of C-IV was 86.68 ± 11.98 μg/L; (2) The type 2 diabetics were divided into A and B groups according to their Alb content in 24-hr urine. In group A(n=130) the Alb content was ≥30 mg/24 hrs and their C-IV was 120.03 ± 34.02 μg/L, whereas in group B(n=35) the corresponding values were < 30 mg/24 hrs and 97.14 ± 24.93 μg/L, respectively. Conclusion: When the Alb content of type 2 diabetics is still within the normal upper limit, the level of C-IV has already been elevated in part of them, indicating C-IV level can be more able to reflect early damage of renal function in type 2 diabetics than Alb content does. (authors)

  9. Audiological findings in children with mucopolysaccharidoses type i-iv.

    Science.gov (United States)

    Vargas-Gamarra, María F; de Paula-Vernetta, Carlos; Vitoria Miñana, Isidro; Ibañez-Alcañiz, Isabel; Cavallé-Garrido, Laura; Alamar-Velazquez, Agustín

    The aim of our study is to reflect hearing impairment of 23children diagnosed with mucopolysaccharidosis (MPS) typeI, II, III and IV. Retrospective study of the clinical, audiological and treatment (medical vs surgical) findings of 23children diagnosed with MPS typeI, II, III or IV followed at a Tertiary Referral Hospital between 1997 and 2015. Six cases of MPSI, 8 of MPSII, 4 of MPSIII and 5 of MPSIV were reviewed. 71.2% of patients had secretory otitis media (SOM) and 54% of patients had some type of hearing loss (HL). The behaviour of hearing loss was variable in each of the subgroups of MPS, finding greater involvement and variability in typesI and II. Children with MPS have a high risk of hearing loss. A significant percentage of transmissive HL progressing to mixed or sensorineural HL was observed. This was more common in typesI and II. Periodic follow up of these patients is mandatory because of hearing impairment and consequences for their development and quality of life. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  10. Symptomatic Type IV Dual Left Anterior Descending Coronary Artery

    Directory of Open Access Journals (Sweden)

    Kyriacos Papadopoulos MD

    2016-12-01

    Full Text Available Dual left anterior descending coronary artery is a rare congenital anomaly with 4 subtypes. Double left anterior descending coronary artery originating from the left main stem and the right coronary artery (type IV dual left anterior descending artery has been reported to occur in 0.01% to 0.7% of patients undergoing cardiac catheterization. We report a case of a 49-year-old woman who was found to have this anomaly during coronary angiography. The patient had been complaining of chest pain that mimics angina pectoris and exercise tolerance test was positive for myocardial ischemia.

  11. Conservation of the Type IV secretion system throughout Wolbachia evolution

    DEFF Research Database (Denmark)

    Pichon, Samuel; Bouchon, Didier; Cordaux, Richard

    2009-01-01

    The Type IV Secretion System (T4SS) is an efficient pathway with which bacteria can mediate the transfer of DNA and/or proteins to eukaryotic cells. In Wolbachia pipientis, a maternally inherited obligate endosymbiont of arthropods and nematodes, two operons of vir genes, virB3-B6 and virB8-D4......, encoding a T4SS were previously identified and characterized at two separate genomic loci. Using the largest data set of Wolbachia strains studied so far, we show that vir gene sequence and organization are strictly conserved among 37 Wolbachia strains inducing various phenotypes such as cytoplasmic...

  12. Prophylaxis after Exposure to Coxiella burnetii

    Centers for Disease Control (CDC) Podcasts

    2008-10-02

    In this podcast, Dr. David Swerdlow discusses prophylaxis after exposure to Coxiella burnetii. It is important to know who should be treated and how they should be treated after an intentional release with possible bioterrorism agents, including Coxiella burnetii.  Created: 10/2/2008 by Emerging Infectious Diseases.   Date Released: 10/2/2008.

  13. Hoge resolutie typering van Coxiella burnetii

    NARCIS (Netherlands)

    Janse, I.; Bossers, A.; Roest, H.I.J.; Rotterdam, van B.

    2011-01-01

    Dit rapport beschrijft het onderzoek wat uitgevoerd is in het kader van het project ‘Hoge Resolutie Typering Coxiella burnetii’’. Het doel van dit project was om de genoomsequenties van een aantal Nederlandse isolaten van de bacterie Coxiella burnetii, de veroorzaker van Q-koorts, in kaart te

  14. Identification of mutations in Type IV glycogen storage disease

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Y.; Kishnani, P.; Chen, Y.T. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1994-09-01

    Type IV glycogen storage disease (GSD IV, Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE) activity, which results in the accumulation of glycogen with unbranched, long, outer chains in the tissues. The molecular basis of the disease is not known. We studied four patients with the disease; three with typical presentation of progressive liver cirrhosis and failure, and one with severe and fatal neonatal hypotonia and cardiomyopathy. Southern blot analysis with EcoRI or MspI did not detect gross DNA rearrangement, deletion or duplication in patients` glycogen branching enzyme genes. Northern analysis with total cellular RNAs isolated from skin fibroblast MI strains of three patients with typical clinical presentation showed a normal level and size (2.95 kb) of GBE mRNA hybridization band in two and absent mRNA hybridization band in the remaining one. The patient with atypical severe neonatal hypotonia demonstrated a less intense and smaller size (2.75 kb) of mRNA hybridization band. A 210 hp deletion from nucleotide sequence 873 to 1082 which causes 70 amino acids missing from amino acid sequence 262 to 331 was detected in all 17 clones sequenced from the fatal hypotonia patient. This deletion is located in the region which is highly conserved between prokaryotic, yeast and human GBE polypeptide sequences, and also includes the first of the four regions which constitute the catalytic active sites of most of amylolytic enzymes. A point mutation C-T (1633) which changes the amino acid from Arginine to Cystine was found in 19 of 20 cDNA clones from a patient with classical clinical presentation. This point mutation was unique to this patient and was not observed in three other patients or normal controls. This is the first report on the molecular basis of GSD IV and our data indicated the presence of extensive genetic heterogeneity in the disease.

  15. Role of type IV pili in predation by Bdellovibrio bacteriovorus.

    Directory of Open Access Journals (Sweden)

    Ryan M Chanyi

    Full Text Available Bdellovibrio bacteriovorus, as an obligate predator of Gram-negative bacteria, requires contact with the surface of a prey cell in order to initiate the life cycle. After attachment, the predator penetrates the prey cell outer membrane and enters the periplasmic space. Attack phase cells of B. bacteriovorus have polar Type IV pili that are required for predation. In other bacteria, these pili have the ability to extend and retract via the PilT protein. B. bacteriovorus has two pilT genes, pilT1 and pilT2, that have been implicated in the invasion process. Markerless in-frame deletion mutants were constructed in a prey-independent mutant to assess the role of PilT1 and PilT2 in the life cycle. When predation was assessed using liquid cocultures, all mutants produced bdelloplasts of Escherichia coli. These results demonstrated that PilT1 and PilT2 are not required for invasion of prey cells. Predation of the mutants on biofilms of E. coli was also assessed. Wild type B. bacteriovorus 109JA and the pilT1 mutant decreased the mass of the biofilm to 35.4% and 27.9% respectively. The pilT1pilT2 mutant was able to prey on the biofilm, albeit less efficiently with 50.2% of the biofilm remaining. The pilT2 mutant was unable to disrupt the biofilm, leaving 92.5% of the original biofilm after predation. The lack of PilT2 function may impede the ability of B. bacteriovorus to move in the extracellular polymeric matrix and find a prey cell. The role of Type IV pili in the life cycle of B. bacteriovorus is thus for initial recognition of and attachment to a prey cell in liquid cocultures, and possibly for movement within the matrix of a biofilm.

  16. Liver transplantation for type I and type IV glycogen storage disease

    OpenAIRE

    Selby, R.; Starzl, T.E.; Yunis, E.; Todo, S.; Tzakis, A.G.; Brown, B.I.; Kendall, R.S.

    1993-01-01

    Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression...

  17. Borrmann type IV adenocarcinoma versus gastric lymphoma : spiral CT evaluation

    International Nuclear Information System (INIS)

    Seo, Bo Kyoung; Kim, Yun Hwan; Shin, Kue Hee; Hong, Suk Joo; Kim, Hong Weon; Park, Cheol Min; Chung, Kyoo Byung; Cho, Hyun Deuk

    1999-01-01

    To distinguish the spiral CT findings of Borrmann type IV adenocarcinoma from those of gastric lymphoma with diffuse gastric wall thickening. We retrospectively reviewed the spiral CT scans of 30 patients with Borrmann type IV adenocarcinoma and nine with gastric lymphoma with diffuse gastric wall thickening. In all patients the respective condition was pathologically confirmed by gastrectomy. CT scanning was performed after peroral administration of 500-700ml of water. A total of 120-140 ml bolus of nonionic contrast material was administered intravenously at a flow rate of 3 ml/sec and two-phase images were obtained at 35-45 sec(early phase) and 180 sec(delayed phase) after the start of bolus injection. Spiral CT was performed with 10mm collimation, 10mm/sec table feed and 10mm reconstruction. We evaluated the degree and homogeneity of enhancement of thickened entire gastric wall, and the enhancement pattern of gastric inner layer, as seen on early-phase CT scans. On early and delayed views, the thickness of gastric wall and the presence of perigastric fat infiltration were determined. The enhancement patterns of gastric inner layer were classified as either continuous or discontinuous thick enhancement, thin enhancement, or nonenhancement. The thickness of gastric wall was 1.2-3.5cm(mean 2.2cm) in cases of adenocarcinoma and 1.2-7.6cm(mean 4cm) in lymphoma. Perigastric fat infiltration was seen in 24 patients with adenocarcinoma(80%) and four with lymphoma(44%). In those with adenocarcinoma, the degree of enhancement of entire gastric wall was hyperdense in fifteen patients(50%) and isointense in eleven (37%). Seven patients with lymphoma(78%)showed hypodensity. In those with adenocarcinoma, continuous thick enhancement of gastric inner layer was seen in 18 patients(60%) and discontinuous thick enhancement in nine(30%). In lymphoma cases, no thick enhancement was observed. Thin enhancement of gastric inner layer was demonstrated in three patients with

  18. Syndactyly type IV/hexadactyly of feet associated with unilateral absence of the tibia.

    Science.gov (United States)

    Rambaud-Cousson, A; Dudin, A A; Zuaiter, A S; Thalji, A

    1991-08-01

    We report on a newborn girl with syndactyly type IV, hexadactyly of feet, and right tibial hemimelia. She has 5 other relatives with identical anomalies of the hands and feet transmitted as an autosomal dominant trait. Syndactyly type IV is rare as is absence of the tibia. We suggest the possibility that syndactyly type IV may be a more complex entity, including lower limb malformations, and transmitted as autosomal dominant with variable expressivity.

  19. Evolution of conjugation and type IV secretion systems.

    Science.gov (United States)

    Guglielmini, Julien; de la Cruz, Fernando; Rocha, Eduardo P C

    2013-02-01

    Genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. Recent works unraveled the functioning of the underlying type IV secretion systems (T4SS) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and T4SS. We show that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in diderm bacteria, possibly Proteobacteria, and then spread to other bacterial phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within the eight monophyletic groups, determined by both taxonomy and structure of the cell envelope. Transfer to monoderms might have occurred only once, but followed diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation system based on an atypical relaxase and an ATPase derived from a dsDNA translocase. The observed evolutionary rates and patterns of presence/absence of specific T4SS proteins show that conjugation systems are often and independently exapted for other functions. This work brings a natural basis for the classification of all kinds of conjugative systems, thus tackling a problem that is growing as fast as genomic databases. Our analysis provides the first global picture of the evolution of conjugation and shows how a self-transferrable complex multiprotein system has adapted to different taxa and often been recruited by the host. As conjugation systems became specific to certain clades and cell envelopes, they may have biased the rate and direction of gene transfer by conjugation within prokaryotes.

  20. Liver transplantation for type I and type IV glycogen storage disease.

    Science.gov (United States)

    Selby, R; Starzl, T E; Yunis, E; Todo, S; Tzakis, A G; Brown, B I; Kendall, R S

    1993-01-01

    Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1-5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types I and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting.

  1. Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer.

    Science.gov (United States)

    Ohlund, D; Lundin, C; Ardnor, B; Oman, M; Naredi, P; Sund, M

    2009-07-07

    Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

  2. Effect of collagen type IV, MMPs and TIMPs on remodeling of radiation pulmonary injury

    International Nuclear Information System (INIS)

    Diao Ruiying; Song Liangwen; Wang Shaoxia; Yin Jiye

    2007-01-01

    Objective: To explore the effect of collagen type IV, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs(TIMPs) on early remodeling after radiation pulmonary injury. Methods: Right lungs of rats were irradiated by 60 Co γ-rays at a dose of 20 Gy to induce radiation pulmonary injury, and the lung specimens were taken at weeks 1, 2, 4 after irradiation. Quantitative analysis was performed on pulmonary collagen type IV, MMP-2, MMP-9, TIMP-2, TIMP-1 at the level of gene expression and protein synthesis using real-time PCR or immunohistochemistry. Results: Gene detection using real-time PCR: gene expression of collagen type IV increased at week 1 and decreased at week 2 after irradiation; MMP-2 reached peak at week 2 in which an opposed alteration trend was displayed; MMP-9 appeared a significant trend of elevation, then decrease and elevation again which was similar to those of collagen type IV; expression of TIMP-1 was lower, and there was no marked difference among all time points; TIMP-2 displayed a trend of slight elevation, then decrease and elevation again, which was opposed to MMP-2. Immunohistochemistry-image analysis: Pulmonary collagen type IV obviously increased at week 1, and began to decrease at week 2; MMP-2 decreased at week 2 and then increased; an opposed alteration trend to that of collagen type IV was displayed; alteration trend of MMP-9 was similar to that of collagen type IV but the extent was higher; gene expression of TIMP-1 slightly increased at 2 week and an opposed trend to of MMP-9 was displayed. Conclusions: Collagen type IV, MMP-2, MMP-9 and their tissue inhibitors were involved in ineffective remodeling in the early radiation pulmonary injury; MMP-2 and MMP-9 play an important role in degradation of collagen type IV; Disturbance of collagen type IV degradation might have relationship with the initiation of pulmonary fibrosis. (authors)

  3. The intervening sequence of Coxiella burnetii: characterization and evolution

    Directory of Open Access Journals (Sweden)

    Indu Warrier

    2016-08-01

    Full Text Available The intervening sequence (IVS of Coxiella burnetii, the agent of Q fever, is a 428-nt selfish genetic element located in helix 45 of the precursor 23S rRNA. The IVS element, in turn, contains an ORF that encodes a hypothetical ribosomal S23 protein (S23p. Although S23p can be synthesized in vitro in the presence of an engineered E. coli promoter and ribosome binding site, results suggest that the protein is not synthesized in vivo. In spite of a high degree of IVS conservation among different strains of C. burnetii, the region immediately upstream of the S23p start codon is prone to change, and the S23p-encoding ORF is evidently undergoing reductive evolution. We determined that IVS excision from 23S rRNA was mediated by RNase III, and IVS RNA was rapidly degraded, thereafter. Levels of the resulting 23S rRNA fragments that flank the IVS, F1 (~1.2 kb and F2 (~1.7 kb, were quantified over C. burnetii’s logarithmic growth phase (1-5d. Results showed that 23S F1 quantities were consistently higher than those of F2 and 16S rRNA. The disparity between levels of the two 23S rRNA fragments following excision of IVS is an interesting phenomenon of unknown significance. Based upon phylogenetic analyses, IVS was acquired through horizontal transfer after C. burnetii’s divergence from an ancestral bacterium and has been subsequently maintained by vertical transfer. The widespread occurrence, maintenance and conservation of the IVS in C. burnetii imply that it plays an adaptive role or has a neutral effect on fitness.

  4. Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV

    International Nuclear Information System (INIS)

    Hagspiel, Klaus D.; Bonatti, Hugo; Sabri, Saher; Arslan, Bulent; Harthun, Nancy L.

    2011-01-01

    Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.

  5. Influence of shelf life on the setting time of type IV gypsum

    Science.gov (United States)

    Hapsari, M. L.; Irawan, B.; Damiyanti, M.

    2017-08-01

    Although expired materials can exhibit a deterioration in their properties, expired type IV gypsum can still be found on the market. In order to evaluate the influence of the shelf life on its setting time, two groups of type IV gypsum (GC Fuji rock EP) with different expiration dates were used in this research. The setting time tests were done in a mold using a Vicat Needle apparatus. The results of the statistical analysis showed a significant difference (pshelf life did influence the setting time of the type IV gypsum.

  6. Coxiella burnetii infections in sheep or goats

    NARCIS (Netherlands)

    Brom, Van den R.; Engelen, van E.; Roest, H.I.J.; Hoek, van der W.; Vellema, P.

    2015-01-01

    Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii, which is able to infect several animal species, as well as humans. Cattle, sheep and goats are the primary animal reservoirs. In small ruminants, infections are mostly without clinical symptoms, however, abortions and

  7. Coxiella burnetii chronic pericarditis: a case report.

    Science.gov (United States)

    Ivić, I; Božić, I; Ledina, D

    2016-10-01

    Coxiella burnetii is capable of causing a variety of acute and chronic infections. We present a case of pericarditis with serologically confirmed chronic C. burnetii infection. This case report emphasises the justification of serological testing for chronic C. burnetii infection in patients with prolonged or recurrent pericarditis, particularly in countries endemic for C. burnetii infection.

  8. Structural Characterization of Outer Membrane Components of the Type IV Pili System in Pathogenic Neisseria

    NARCIS (Netherlands)

    Jain, Samta; Moscicka, Katarzyna B.; Bos, Martine P.; Pachulec, Emilia; Stuart, Marc C. A.; Keegstra, Wilko; Boekema, Egbert J.; van der Does, Chris; B. Mościcka, K.; Ahmed, Niyaz

    2011-01-01

    Structures of the type IV pili secretin complexes from Neisseria gonorrhoeae and Neisseria meningitidis, embedded in outer membranes were investigated by transmission electron microscopy. Single particle averaging revealed additional domains not observed previously. Secretin complexes of N.

  9. Struggling with a Gastric Volvulus Secondary to a Type IV Hiatal Hernia

    Directory of Open Access Journals (Sweden)

    Dafnomilis George

    2010-01-01

    Full Text Available Type IV hiatal hernias are characterized by herniation of the stomach along with associated viscera such as the spleen, colon, small bowel, and pancreas through the esophageal hiatus. They are relatively rare, representing only about 5%–7% of all hernias, and can be associated with severe complications. We report a 71-year-old veteran wrestler who presented to our department with a type IV paraesophageal hernia containing a gastric volvulus and treated successfully with emergency operation.

  10. An evaluation of the mechanical properties of Type III and Type IV gypsum mixed with two disinfectant solutions

    Directory of Open Access Journals (Sweden)

    Roy Sunitha

    2010-01-01

    Full Text Available Background and Objectives: This in-vitro study was conducted to evaluate the strength and properties of Type III and Type IV gypsum mixed with disinfectant solutions. Materials and Methods: Type III and Type IV gypsum were used for the study. Three different mixing solutions namely waterqueous solutions of 0.525% sodium hypochlorite and 2% glutaraldehyde were used. Gypsum materials were subjected to further modification by adding a mixture of 1.0% gum arabic and 0.132% calcium hydroxide before mixing with the disinfectant solutions, at two different liquid/powder (L/P ratios for each. Both, the unmodified and the modified gypsum were tested for compressive and tensile strength after one hour and one week from the start of the mix. The crystalline configuration of the fracture fragments of the unmodified and modified set gypsum were studied under the scanning electron microscope. Results: The disinfectant solutions reduced the strength of both Type III and Type IV gypsum. Water showed higher-strength, which was followed by 0.525% sodium hypochlorite and 2% glutaraldehyde. The modified Type III and Type IV gypsum with reduced L/P ratio also showed strength values less than that of the control groups. Interpretation and Conclusion: Chemical disinfectants reduced the strength of gypsum when used as water substitutes. Gum Arabic and calcium hydroxide additives permitted lower L/P ratio, however, there was still excess water retained in the set gypsum that lowered the strength values of Type III and Type IV gypsum. Hence, further reduction of L/P ratio may increase the properties of the modified Type III and Type IV gypsum.

  11. Cloning, expression, and activity of type IV antifreeze protein from cultured subtropical olive flounder (Paralichthys olivaceus

    Directory of Open Access Journals (Sweden)

    Jong Kyu Lee

    2016-10-01

    Full Text Available Abstract Antifreeze proteins (AFPs lower the freezing point but not the melting point of aqueous solutions by inhibiting the growth of ice crystals via an adsorption-inhibition mechanism. However, the function of type IV AFP (AFP IV is questionable, as its antifreeze activity is on the verge of detectable limits, its physiological concentration in adult fish blood is too low to function as a biological antifreeze, and its homologues are present even in fish from tropic oceans as well as freshwater. Therefore, we speculated that AFP IV may have gained antifreeze activity not by selective pressure but by chance. To test this hypothesis, we cloned, expressed, and assayed AFP IV from cultured subtropical olive flounder (Paralichthys olivaceus, which do not require antifreeze protein for survival. Among the identified expressed sequence tags of the flounder liver sample, a 5′-deleted complementary DNA (cDNA sequence similar to the afp4 gene of the longhorn sculpin was identified, and its full-length cDNA and genome structure were examined. The deduced amino acid sequence of flounder AFP IV shared 55, 53, 52, and 49 % identity with those of Pleuragramma antarcticum, Myoxocephalus octodecemspinosus, Myoxocephalus scorpius, and Notothenia coriiceps, respectively. Furthermore, the genomic structure of this gene was conserved with those of other known AFP IVs. Notably, the recombinant AFP IV showed a weak but distinct thermal hysteresis of 0.07 ± 0.01 °C at the concentration of 0.5 mg/mL, and ice crystals in an AFP IV solution grew star-shaped, which are very similar to those obtained from other polar AFP IVs. Taken together, our results do not support the hypothesis of evolution of AFP IV by selective pressure, suggesting that the antifreeze activity of AFP IV may have been gained by chance.

  12. Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage

    Science.gov (United States)

    Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M

    2011-01-01

    Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332

  13. Dual (type IV) left anterior descending artery | Baskan | SA Journal of ...

    African Journals Online (AJOL)

    Congenital coronary artery anomalies are uncommon. Dual left anterior descending coronary artery (LAD) is defined as the presence of two LADs within the anterior interventricular sulcus (AIVS), and is classified into four types. Type IV is a rarely reported subtype and differs from the others, with a long LAD originating from ...

  14. The Role of Type IV Collagen in Developing Lens in Mouse Fetuses

    Directory of Open Access Journals (Sweden)

    Mehdi Jalali

    2009-09-01

    Full Text Available Objective(sExtracellular matrix (ECM and basement membrane (BM play important roles in many developmental processes during development and after birth. Among the components of the BM, collagen fibers specially type IV are the most important parts. The aim of this study was to determine the time when collagen type IV appears in the BM of lens structure during mouse embryonic development.Materials and MethodsIn this experimental study, 22 female Balb/C mice were randomly selected and were kept under normal condition, finding vaginal plug was assumed as day zero of pregnancy. From embryonic day 10 to 20, all specimens were sacrificed by cervical dislocation and their heads were fixed, serially sectioned and immunohistochemistry study for tracing collagen type IV in lens were carried out.ResultsOur data revealed that collagen type IV appeared at the early stage of gestation day 12 in BM of anterior epithelial lens cells and the amount of this protein gradually increased until days 15-17 in ECM and posterior capsule epithelium. After this period, severe reaction was not observed in any part of the lens.ConclusionThese findings establish the important role of collagen IV in developing optic cup and any changes during critical period of pregnancy may be result in severe visual system defect

  15. Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

    Science.gov (United States)

    Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

    2015-04-02

    Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

  16. Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

    Science.gov (United States)

    Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

    2009-06-01

    Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

  17. Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

    Science.gov (United States)

    Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun

    2014-01-01

    Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803

  18. The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Ib Jarle; Vainer, Ben

    2016-01-01

    PURPOSE: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer. EXPERIMENTAL DESIGN: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation...... and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving...... set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries...

  19. A Solar Stationary Type IV Radio Burst and Its Radiation Mechanism

    Science.gov (United States)

    Liu, Hongyu; Chen, Yao; Cho, Kyungsuk; Feng, Shiwei; Vasanth, Veluchamy; Koval, Artem; Du, Guohui; Wu, Zhao; Li, Chuanyang

    2018-04-01

    A stationary Type IV (IVs) radio burst was observed on September 24, 2011. Observations from the Nançay RadioHeliograph (NRH) show that the brightness temperature (TB) of this burst is extremely high, over 10^{11} K at 150 MHz and over 108 K in general. The degree of circular polarization (q) is between -60% ˜ -100%, which means that it is highly left-handed circularly polarized. The flux-frequency spectrum follows a power-law distribution, and the spectral index is considered to be roughly -3 ˜ -4 throughout the IVs. Radio sources of this event are located in the wake of the coronal mass ejection and are spatially dispersed. They line up to present a formation in which lower-frequency sources are higher. Based on these observations, it is suggested that the IVs was generated through electron cyclotron maser emission.

  20. Clinical significance of determination of serum collagen type IV (IV-C) and transforming growth factor beta1(TGF-β1) levels in patients with diabetic nephropathy

    International Nuclear Information System (INIS)

    Xie Hongfang; Peng Liang

    2006-01-01

    Objective: To investigate the clinical significance of determination of serum collagen type IV (IV-C) and transforming growth factor beta 1 (TGF-β 1 ) levels in patients with diabetic nephropathy. Methods: Serum IV-C levels ( with RIA) and TGF-β 1 levels (with ELISA) were determined in 30 controls and 105 patients with type II diabetis mellitus (45 with diabetic nephropathy and 60 without nephropathy). Results: The serum levels of IV-C and TGF-β 1 in diabetic patients with nephropathy were significantly higher than those in controls (P 0.05). Conclusion: Serum IV-C and TGF-β 1 , levels increased gradually as the diabetic nephropathy got more severe, they could be used as sensitive markers for early diagnosis of development of diabetic nephropathy. (authors)

  1. Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV

    Directory of Open Access Journals (Sweden)

    Ergül Yakup

    2011-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

  2. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes

    DEFF Research Database (Denmark)

    Deacon, Carolyn F; Holst, Jens J

    2005-01-01

    of appetite. Glucagon-like peptide-1 is, however, extremely rapidly inactivated by the serine peptidase, dipeptidyl peptidase IV, so that the native peptide is not useful clinically. A new approach to utilise the beneficial effects of glucagon-like peptide-1 in the treatment of type 2 diabetes has been...... the development of orally active dipeptidyl peptidase IV inhibitors. Preclinical studies have demonstrated that this approach is effective in enhancing endogenous levels of glucagon-like peptide-1, resulting in improved glucose tolerance in glucose-intolerant and diabetic animal models. In recent studies of 3......-12 months duration in patients with type 2 diabetes, dipeptidyl peptidase IV inhibitors have proved efficacious, both as monotherapy and when given in combination with metformin. Fasting and postprandial glucose concentrations were reduced, leading to reductions in glycosylated haemoglobin levels, while...

  3. Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction

    Directory of Open Access Journals (Sweden)

    NM Coelho

    2010-06-01

    Full Text Available Considering the structural role of type IV collagen (Col IV in the assembly of the basement membrane (BM and the perspective of mimicking its organization for vascular tissue engineering purposes, we studied the adsorption pattern of this protein on model hydrophilic (clean glass and hydrophobic trichloro(octadecylsilane (ODS surfaces known to strongly affect the behavior of other matrix proteins. The amount of fluorescently labeled Col IV was quantified showing saturation of the surface for concentration of the adsorbing solution of about 50μg/ml, but with approximately twice more adsorbed protein on ODS. AFM studies revealed a fine – nearly single molecular size – network arrangement of Col IV on hydrophilic glass, which turns into a prominent and growing polygonal network consisting of molecular aggregates on hydrophobic ODS. The protein layer forms within minutes in a concentration-dependent manner. We further found that human umbilical vein endothelial cells (HUVEC attach less efficiently to the aggregated Col IV (on ODS, as judged by the significantly altered cell spreading, focal adhesions formation and the development of actin cytoskeleton. Conversely, the immunofluorescence studies for integrins revealed that the fine Col IV network formed on hydrophilic substrata is better recognized by the cells via both α1 and α2 heterodimers which support cellular interaction, apart from these on hydrophobic ODS where almost no clustering of integrins was observed.

  4. Tibial lengthening for unilateral Crowe type-IV developmental dysplasia of the hip

    Directory of Open Access Journals (Sweden)

    Jun Wan

    2014-01-01

    Conclusions: Tibial lengthening may effectively correct gait and satisfactorily improve body image in young patients with unilateral Crowe type-IV DDH. Mono-lateral external fixator allows for accelerated postoperative rehabilitation and optimal preservation of ankle movements. Lengthening along with intramedullary nails may significantly reduce the external fixation time and the risk of fixator-related complications.

  5. Delayed lysosomal metabolism of lipids in mucolipidosis type IV fibroblasts after LDL-receptor-mediated endocytosis

    NARCIS (Netherlands)

    Jansen, S. M.; Groener, J. E.; Bax, W.; Poorthuis, B. J.

    2001-01-01

    We specifically probed the low-density lipoprotein-receptor-dependent endosomal/lysosomal pathway of lipid degradation in control and mucolipidosis type IV fibroblasts using either [choline-methyl-14C]sphingomyelin in complex with apolipoprotein E, or cholesteryl [14C]oleate-labelled low-density

  6. Archaeal homolog of bacterial type IV prepilin signal peptidases with broad substrate specificity

    NARCIS (Netherlands)

    Albers, Sonja-Verena; Szabó, Zalán; Driessen, Arnold J.M.

    A large number of secretory proteins in the thermoacidophile Sulfolobus solfataricus are synthesized as a precursor with an unusual leader peptide that resembles bacterial type IV prepilin signal sequences. This set of proteins includes the flagellin subunit but also various solute binding proteins.

  7. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT

    1999-01-01

    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy

  8. UV-inducible DNA exchange in hyperthermophilic archaea mediated by type IV pili

    NARCIS (Netherlands)

    Ajon, Malgorzata; Froels, Sabrina; van Wolferen, Marleen; Stoecker, Kilian; Teichmann, Daniela; Driessen, Arnold J. M.; Grogan, Dennis W.; Albers, Sonja-Verena; Schleper, Christa; Ajon, Małgorzata

    2011-01-01

    Archaea, like bacteria and eukaryotes, contain proteins involved in various mechanisms of DNA repair, highlighting the importance of these processes for all forms of life. Species of the order Sulfolobales of hyperthermophilic crenarchaeota are equipped with a strongly UV-inducible type IV pilus

  9. Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response

    NARCIS (Netherlands)

    de Jong, Maarten F.; Starr, Tregei; Winter, Maria G.; den Hartigh, Andreas B.; Child, Robert; Knodler, Leigh A.; van Dijl, Jan Maarten; Celli, Jean; Tsolis, Renee M.

    2013-01-01

    Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces

  10. Energy–momentum localization for Bianchi type-IV Universe in ...

    Indian Academy of Sciences (India)

    In this study we have investigated the energy–momentum distributions for homogeneous and anisotropic Bianchi type-IV in B class Universe. ... Department of Physics, Art and Science Faculty, Çanakkale Onsekiz Mart University, 17020 Çanakkale, Turkey; Çanakkale Onsekiz Mart University, Astrophysics Research Center, ...

  11. Elective reconstruction of thoracoabdominal aortic aneurysm type IV by transabdominal approach

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2012-01-01

    Full Text Available Introduction. Thoracoabdominal aortic aneurysm (TAAA type IV represents an aortic dilatation from the level of the diaphragmatic hiatus to the iliac arteries branches, including visceral branches of the aorta. In the traditional procedure of TAAA type IV repair, the body is opened using thoractomy and laparotomy in order to provide adequate exposure of the descending thoracic and abdominal aorta for safe aortic reconstruction. Case report. We reported a 71-yearold man with elective reconstruction of the TAAA type IV performed by transabdominal approach. Computed tomography scans angiography revealed a TAAA type IV with diameter of 62 mm in the region of celiac trunk and superior mesenteric artery branching, and the largest diameter of 75 mm in the infrarenal aortic level. The patient comorbidity included a chronic obstructive pulmonary disease and hypertension, therefore he was treated for a prolonged period. In preparation for the planned aortic reconstruction asymptomatic carotid disease (occlusion of the left internal carotid artery and subtotal stenosis of the right internal carotid artery was diagnosed. Within the same intervention percutaneous transluminal angioplasty with stent placement in right internal carotid artery was made. In general, under endotracheal anesthesia and epidural analgesia, with transabdominal approach performed aortic reconstruction with tubular dakron graft 24 mm were, and reimplantation of visceral aortic branches into the graft performed. Postoperative course was uneventful, and the patient was discharged on the postoperative day 17. Control computed tomography scan angiography performed three months after the operation showed vascular state of the patient to be in order. Conclusion. Complete transabdominal approach to TAAA type IV represents an appropriate substitute for thoracoabdominal approach, without compromising safety of the patient. This approach is less traumatic, especially in patients with impaired

  12. Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation.

    Science.gov (United States)

    Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion; Longoni, Mauro; Gould, Douglas B; Sun, Yunwei; Maalouf, Faouzi I; Nagy, Nandor; Donahoe, Patricia K

    2016-07-13

    Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum.

  13. Salter-Harris Type III and Type IV Combined Fracture of the Distal Femoral Epiphysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Ali Aydin

    2012-01-01

    Full Text Available Distal femoral physeal fractures are not common but have a high rate of complications. They generally follow one of the patterns described in the Salter-Harris classification. We present a case of combination of Salter-Harris type III and type IV injury. Our case was a 15-year-old boy who had a motor vehicle accident. There was swelling, ecchymosis, severe pain, and valgus deformity, because of medial proximal fracture fragment, on the left knee. We deemed that Salter-Harris type III and type IV combination fracture in our case has not been previously reported. We prepared this paper in consideration of its contribution to the literature.

  14. Coxiella burnetii Lipopolysaccharide: What Do We Know?

    Directory of Open Access Journals (Sweden)

    Prasad Abnave

    2017-11-01

    Full Text Available A small gram-negative bacterium, Coxiella burnetii (C. burnetii, is responsible for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can survive inside microbicidal cells like monocytes and macrophages by hijacking several functions of the immune system. Among several virulence factors, the lipopolysaccharide (LPS of C. burnetii is one of the major factors involved in this immune hijacking because of its atypical composition and structure. Thus, the aim of this mini-review is to summarize the repressive effects of C. burnetii LPS on the antibacterial immunity of cells.

  15. Searching algorithm for type IV secretion system effectors 1.0: a tool for predicting type IV effectors and exploring their genomic context.

    Science.gov (United States)

    Meyer, Damien F; Noroy, Christophe; Moumène, Amal; Raffaele, Sylvain; Albina, Emmanuel; Vachiéry, Nathalie

    2013-11-01

    Type IV effectors (T4Es) are proteins produced by pathogenic bacteria to manipulate host cell gene expression and processes, divert the cell machinery for their own profit and circumvent the immune responses. T4Es have been characterized for some bacteria but many remain to be discovered. To help biologists identify putative T4Es from the complete genome of α- and γ-proteobacteria, we developed a Perl-based command line bioinformatics tool called S4TE (searching algorithm for type-IV secretion system effectors). The tool predicts and ranks T4E candidates by using a combination of 13 sequence characteristics, including homology to known effectors, homology to eukaryotic domains, presence of subcellular localization signals or secretion signals, etc. S4TE software is modular, and specific motif searches are run independently before ultimate combination of the outputs to generate a score and sort the strongest T4Es candidates. The user keeps the possibility to adjust various searching parameters such as the weight of each module, the selection threshold or the input databases. The algorithm also provides a GC% and local gene density analysis, which strengthen the selection of T4E candidates. S4TE is a unique predicting tool for T4Es, finding its utility upstream from experimental biology.

  16. The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the Emergence of the Q Fever Pathogen, Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Olivier Duron

    2015-05-01

    Full Text Available Q fever is a highly infectious disease with a worldwide distribution. Its causative agent, the intracellular bacterium Coxiella burnetii, infects a variety of vertebrate species, including humans. Its evolutionary origin remains almost entirely unknown and uncertainty persists regarding the identity and lifestyle of its ancestors. A few tick species were recently found to harbor maternally-inherited Coxiella-like organisms engaged in symbiotic interactions, but their relationships to the Q fever pathogen remain unclear. Here, we extensively sampled ticks, identifying new and atypical Coxiella strains from 40 of 58 examined species, and used this data to infer the evolutionary processes leading to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and whole-genome sequencing data revealed that Coxiella-like organisms represent an ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii strains originate within this group and are the descendants of a Coxiella-like progenitor hosted by ticks. Using both colony-reared and field-collected gravid females, we further establish the presence of highly efficient maternal transmission of these Coxiella-like organisms in four examined tick species, a pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays also showed that these Coxiella-like organisms were not amenable to culture in the vertebrate cell environment, suggesting different metabolic requirements compared to C. burnetii. Altogether, this corpus of data demonstrates that C. burnetii recently evolved from an inherited symbiont of ticks which succeeded in infecting vertebrate cells, likely by the acquisition of novel virulence factors.

  17. Polyglucosan Bodies in Placental Extravillious Trophoblast for the Diagnosis of Fatal Perinatal Neuromuscular Type Glycogen Storage Disease Type IV.

    Science.gov (United States)

    Yu, Weiming; Brundler, Marie-Anne; Wright, James R

    2017-01-01

    The fatal infantile neuromuscular type is the most severe form of glycogen storage disease type IV. We report a case of a 22-day-old female neonate born at 34 weeks gestation with polyhyramnios, fetal hydrops, and severe hypotonia. Placental examination revealed numerous periodic acid schiff (PAS)-positive diastase-resistant polyglucosan bodies in the cytoplasm of extravillous trophoblast predominantly in the placental basal plate. Muscle biopsy and autopsy findings supported a diagnosis of neuromuscular-type glycogen storage disease IV with extensive involvement of skeletal muscle, heart, and liver. The diagnosis was confirmed by molecular genetic testing. We could only find one prior report in the English literature that describes placental pathological changes. Our findings suggest that placental examination can be a useful adjunct for early diagnosis, as placentas are often received for pathological examination shortly after birth and usually before a diagnostic muscle biopsy can be performed. Pathologists need to be aware of characteristic placental features.

  18. Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Punsiri M Colonne

    2016-10-01

    Full Text Available Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV. C. burnetii manipulates host cAMP-dependent protein kinase (PKA signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E mutant protein prevented optimal PV formation, whereas VASP (S157E mutant expression had no effect. VASP (S239E expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA

  19. Hoge resolutie typering van Coxiella burnetii : Definitieve versie

    NARCIS (Netherlands)

    Janse I; Bossers A; Roest HJ; van Rotterdam B; LZO; cib

    2011-01-01

    Coxiella burnetii is een intracellulaire bacterie die Q-koorts veroorzaakt. De genoomsequenties van een aantal isolaten die verkregen werden tijdens de Nederlandse Q-koorts uitbraak werden opgehelderd. Deze genoomsequenties dienen als basis voor verbeterde typeringsmethodes die nauwkeurigere

  20. Placental histopathology after Coxiella burnetii infection during pregnancy

    NARCIS (Netherlands)

    Munster, J. M.; Leenders, A. C. A. P.; Hamilton, C. J. C. M.; Hak, E.; Aarnoudse, J. G.; Timmer, A.

    Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C burnetii infection during pregnancy and compared these cases with four symptomatic

  1. Effect of shelf life on compressive strength of type iv gypsum

    Science.gov (United States)

    Kusumastuti, K. S.; Irawan, B.; Damiyanti, M.

    2017-08-01

    Type IV gypsum, as a dental material for an indirect restoration’s working model, should have strength and abrasive-resistant properties. These properties depend on the product’s shelf life and its proper storage, which sometimes are easily missed by sellers. The aim of this research was to observe the effect of shelf life on the compressive strength of type IV gypsum with different production dates. Twenty cylindrical specimens were separated into two groups with different production dates and tested with a universal testing with the crosshead speed of 1 mm per minute and a load of 2,500 kgf. The data were analyzed with independent t-tests. There was a significant difference (p<0.05) in the compressive strength between the two groups with an increase in compressive strength seen in the gypsum that was stored longer.

  2. Type IV Sacrococcygeal Teratoma Displacing the Urinary Bladder: Unique Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Sahar Eftekharzadeh

    2016-01-01

    Full Text Available Type IV sacrococcygeal teratoma is a rare pediatric tumor that is confined to the presacral area with no external component. The signs and symptoms often arise due to mass effect and compression of adjacent organs. Urinary retention is an uncommon presenting symptom in these patients. A wide spectrum of imaging findings may be encountered in cases with sacrococcygeal teratoma because of variability of tumor size and components. We hereby present a unique magnetic resonance urography finding in a type IV sacrococcygeal teratoma which caused bladder displacement. A meticulous and complete resection of tumor with special attention to the pelvic plexus led to preservation of normal voiding function and normal bowel function in this patient.

  3. Glycogen Storage Disease Type IV: A Case With Histopathologic Findings in First-Trimester Placental Tissue.

    Science.gov (United States)

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B; Lund, Allan M

    2016-01-01

    A 30-yr-old woman presented with 2 consecutive miscarriages within 7 mo. Histopathologic examination of the placental tissue showed intracytoplasmic inclusion vacuoles with a strong reaction in Periodic acid-Schiff staining and a slightly pallor reaction in alcian blue staining. Additional molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made on histopathologic examination. Genetic analysis is required to confirm the diagnosis and to offer prenatal genetic testing in future pregnancies.

  4. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: ywlee@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  5. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    International Nuclear Information System (INIS)

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-01-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy γ-rays or a fractionated dose of 40 Gy γ-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  6. Energy–momentum localization for Bianchi type-IV Universe in ...

    Indian Academy of Sciences (India)

    physics pp. 531–548. Energy–momentum localization for Bianchi type-IV. Universe in general relativity and teleparallel gravity. SEZG˙IN AYGÜN1,2,∗ and ˙ISMA˙IL TARHAN1,2. 1Department of Physics, Art and Science Faculty, Çanakkale Onsekiz Mart University,. 17020 Çanakkale, Turkey. 2Çanakkale Onsekiz Mart ...

  7. Greater trochanter osteotomy with cementless THA for Crowe type IV DDH.

    Science.gov (United States)

    Lei, Pengfei; Hu, Yihe; Cai, PengDe; Xie, Jie; Yang, XuCheng; Wang, Long

    2013-05-01

    This study explored the surgical method and short-term clinical effect of a greater trochanter osteotomy along with cementless artificial total hip arthroplasty in the treatment of Crowe type IV developmental dysplasia of the hip. The authors conducted a retrospective analysis of 18 patients (22 hips) with Crowe type IV dysplasia who were seen between June 2008 and August 2010. After undergoing cementless artificial total hip arthroplasty using a posterolateral approach, a greater trochanter osteotomy was used to adjust the tension of the gluteal muscle, and an acetabular cup was placed. Average preoperative length shortening of the affected limb was 4.5 cm (range, 3.4-6 cm), and average postoperative length increase was 4.0 cm (range, 3.2-4.8 cm). Average postoperative Harris Hip Score was 87 (range, 79-91), which was higher than the average preoperative score of 38 (range, 32-51). Intraoperatively, 3 hips (3 patients) sustained a proximal femur fracture. Due to the stability of the femoral prosthesis, either no treatment or wire fixation only was given; by 2 months postoperatively, radiographs indicated that all fractures had healed. One patient had symptoms of sciatic nerve paralysis that resolved 3 months postoperatively. Performing a greater trochanter osteotomy after cementless artificial total hip arthroplasty is effective for the treatment of Crowe type IV dysplasia and can rebuild the complex biology and biomechanics of hip dysplasia without increasing the complication risk. Copyright 2013, SLACK Incorporated.

  8. Craniodentofacial Manifestations in a Rare Syndrome: Orofaciodigital Type IV (Mohr-Majewski Syndrome

    Directory of Open Access Journals (Sweden)

    Meltem Ozdemir-Karatas

    2014-01-01

    Full Text Available Background. The orofaciodigital syndromes (OFDS are a heterogeneous group of syndromes that affect the face, oral cavity, and the digits. OFDS type IV (OMIM %258860 is rare and characterized by broad nasal root and tip, orbital hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set ears. Oral symptoms may include cleft lip, cleft or highly arched palate, bifid uvula, cleft or hypoplastic maxillary and mandibular alveolar ridge, oral frenula, lingual hamartoma, and absent or hypoplastic epiglottis. Dental anomalies are common and generally include disturbances in the number of teeth. Case Report. This report presents a six-year-old girl, referred with the chief complaint of missing teeth. She was diagnosed as having OFDS type IV based on clinical findings. Her parents reported three deceased children and two fetuses that had the same phenotype. She was the seventh child of consanguineous parents who were first cousins. Conclusion. This is a very rare syndrome. Many reported OFDS type IV cases have consanguineous parents, consistent with an autosomal recessive trait. Manifestation of cleft palate in the healthy sibling may be mild expression of the disorder or an unrelated isolated cleft.

  9. Alogliptin, a potent and selective dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Deacon, Carolyn F

    2008-01-01

    Takeda San Diego Inc is developing alogliptin, a small-molecule, orally available dipeptidyl peptidase IV (DPP IV) inhibitor, for the potential treatment of type 2 diabetes. In January 2008, Takeda announced that an NDA for alogliptin had been submitted to the FDA.......Takeda San Diego Inc is developing alogliptin, a small-molecule, orally available dipeptidyl peptidase IV (DPP IV) inhibitor, for the potential treatment of type 2 diabetes. In January 2008, Takeda announced that an NDA for alogliptin had been submitted to the FDA....

  10. Validation study for using lab-on-chip technology for Coxiella burnetii multi-locus-VNTR-analysis (MLVA) typing: application for studying genotypic diversity of strains from domestic ruminants in France.

    Science.gov (United States)

    Prigent, Myriam; Rousset, Elodie; Yang, Elise; Thiéry, Richard; Sidi-Boumedine, Karim

    2015-01-01

    Coxiella burnetii, the etiologic bacterium of Q fever zoonosis, is still difficult to control. Ruminants are often carriers and involved in human epidemics. MLVA is a promising genotyping method for molecular epidemiology. Different techniques are used to resolve the MLVA band profiles such as electrophoresis on agarose gels, capillary electrophoresis or using the microfluidic Lab-on-Chip system. In this study, system based on microfluidics electrophoresis with Lab-on-Chip technology was assessed and applied on DNA field samples to investigate the genotypic diversity of C. burnetii strains circulating in France. The Lab-on-Chip technology was first compared to agarose gel electrophoresis. Subsequently, the set-up Lab-on-Chip technology was applied on 97 samples collected from ruminants in France using the 17 markers previously described. A discordance rate of 27% was observed between Lab-on-Chip and agarose gel electrophoresis. These discrepancies were checked and resolved by sequencing. The cluster analysis revealed classification based on host species and/or geographic origin criteria. Moreover, the circulation of different genotypic strains within the same farm was also observed. In this study, MLVA with Lab-on-Chip technology was shown to be more accurate, reproducible, user friendly and safer than gel electrophoresis. It also provides an extended data set from French ruminant C. burnetii circulating strains useful for epidemiological investigations. Finally, it raises some questions regarding the standardization and harmonization of C. burnetii MLVA genotyping. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV

    Science.gov (United States)

    Akman, H. Orhan; Sheiko, Tatiana; Tay, Stacey K.H.; Finegold, Milton J.; DiMauro, Salvatore; Craigen, William J.

    2011-01-01

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic feature of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of disease onset. Absence of enzyme activity is lethal in utero or in infancy affecting primarily muscle and liver. However, residual enzyme activity (5–20%) leads to juvenile or adult onset of a disorder that primarily affects muscle as well as central and peripheral nervous system. Here, we describe two mouse models of GSD IV that reflect this spectrum of disease. Homologous recombination was used to insert flippase recognition target recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase-Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice bearing this mutation (Gbe1neo/neo) exhibit a phenotype similar to juvenile onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1−/−), leading to a phenotype of lethal early onset GSD IV, with significant in utero accumulation of PG. Adult mice with residual GBE exhibit progressive neuromuscular dysfunction and die prematurely. Differently from muscle, PG in liver is a degradable source of glucose and readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. PMID:21856731

  12. Molecular methods routinely used to detect Coxiella burnetii in ticks cross-react with Coxiella-like bacteria

    Directory of Open Access Journals (Sweden)

    Jourdain Elsa

    2015-11-01

    Full Text Available Background: Q fever is a widespread zoonotic disease caused by Coxiella burnetii. Ticks may act as vectors, and many epidemiological studies aim to assess C. burnetii prevalence in ticks. Because ticks may also be infected with Coxiella-like bacteria, screening tools that differentiate between C. burnetii and Coxiella-like bacteria are essential. Methods: In this study, we screened tick specimens from 10 species (Ornithodoros rostratus, O. peruvianus, O. capensis, Ixodes ricinus, Rhipicephalus annulatus, R. decoloratus, R. geigy, O. sonrai, O. occidentalis, and Amblyomma cajennense known to harbor specific Coxiella-like bacteria, by using quantitative PCR primers usually considered to be specific for C. burnetii and targeting, respectively, the IS1111, icd, scvA, p1, and GroEL/htpB genes. Results: We found that some Coxiella-like bacteria, belonging to clades A and C, yield positive PCR results when screened with primers initially believed to be C. burnetii-specific. Conclusions: These results suggest that PCR-based surveys that aim to detect C. burnetii in ticks by using currently available methods must be interpreted with caution if the amplified products cannot be sequenced. Future molecular methods that aim at detecting C. burnetii need to take into account the possibility that cross-reactions may exist with Coxiella-like bacteria.

  13. Inactivation of Coxiella burnetii by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Scott, G.H.; McCaul, T.F. (Army Medical Research Inst. of Infectious Diseases, Fort Detrick, Frederick, MD (USA)); Williams, J.C. (National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA))

    1989-12-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79{sup 0}C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0.64 to 1.2 kGy depending on the phase of the micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing 10{sup 11} C. burnetii ml{sup -1} was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes. (author).

  14. Inactivation of Coxiella burnetti by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Scott, G.H.; McCaul, T.F.; Williams, J.C.

    1989-01-01

    The gamma radiation inactivation kinetics for Coxiella burnetii at - 79 C were exponential. The radiation dose needed to reduce the number of infective C. burnetii by 90% varied from 0-64 to 1.2 kGy depending on the phase of hte micro-organism, purity of the culture and composition of suspending menstruum. The viability of preparations containing C. burnetti was completely abolished by 10 kGy without diminishing antigenicity or ability to elicit a protective immune response in vaccinated mice. Immunocytochemical examinations using monoclonal antibodies and electron microscopy demonstrated that radiation doses of 20 kGy did not alter cell-wall morphology or cell-surface antigenic epitopes.

  15. The gonococcal genetic island and type IV secretion in the pathogenic Neisseria

    Directory of Open Access Journals (Sweden)

    Meghan E Ramsey

    2011-04-01

    Full Text Available Eighty percent of Neisseria gonorrhoeae strains and some Neisseria meningitidis strains encode a 57 kb gonococcal genetic island (GGI. The GGI was horizontally acquired and is inserted in the chromosome at the replication terminus. The GGI is flanked by direct repeats, and site-specific recombination at these sites results in excision of the GGI and may be responsible for its original acquisition. Although the role of the GGI in N. meningitidis is unclear, the GGI in N. gonorrhoeae encodes a type IV secretion system (T4SS. Type IV secretion systems are versatile multi-protein complexes and include both conjugation systems as well as effector systems that translocate either proteins or DNA-protein complexes. In N. gonorrhoeae, the T4SS secretes single-stranded chromosomal DNA into the extracellular milieu in a contact-independent manner. Importantly, the DNA secreted through the T4SS is effective in natural transformation and therefore contributes to the spread of genetic information through Neisseria populations. Mutagenesis experiments have identified genes for DNA secretion including those encoding putative structural components of the apparatus, peptidoglycanases which may act in assembly, and relaxosome components for processing the DNA and delivering it to the apparatus. The T4SS may also play a role in infection by N. gonorrhoeae. During intracellular infection, N. gonorrhoeae requires the Ton complex for iron acquisition and survival. However, N. gonorrhoeae strains that do not express the Ton complex can survive intracellularly if they express structural components of the T4SS. These data provide evidence that the T4SS is expressed during intracellular infection and suggest that the T4SS may provide an advantage for intracellular survival. Here we review our current understanding of how the GGI and type IV secretion affect natural transformation and pathogenesis in N. gonorrhoeae and N. meningitidis.

  16. Identification of capsule, biofilm, lateral flagellum, and type IV pili in Vibrio mimicus strains.

    Science.gov (United States)

    Tercero-Alburo, J J; González-Márquez, H; Bonilla-González, E; Quiñones-Ramírez, E I; Vázquez-Salinas, C

    2014-11-01

    Vibrio mimicus is a bacterium that causes gastroenteritis; it is closely related to Vibrio cholerae, and can cause acute diarrhea like cholera- or dysentery-type diarrhea. It is distributed worldwide. Factors associated with virulence (such as hemolysins, enterotoxins, proteases, phospholipases, aerobactin, and hemagglutinin) have been identified; however, its pathogenicity mechanism is still unknown. In pathogenic Vibrio species such as V. cholerae, Vibrio. parahaemolyticus and Vibrio vulnificus, capsule, biofilms, lateral flagellum, and type IV pili are structures described as essential for pathogenicity. These structures had not been described in V. mimicus until this work. We used 20 V. mimicus strains isolated from water (6), oyster (9), and fish (5) samples and we were able to identify the capsule, biofilm, lateral flagellum, and type IV pili through phenotypic tests, electron microscopy, PCR, and sequencing. In all tested strains, we observed and identified the presence of capsular exopolysaccharide, biofilm formation in an in vitro model, as well as swarming, multiple flagellation, and pili. In addition, we identified homologous genes to those described in other bacteria of the genus in which these structures have been found. Identification of these structures in V. mimicus is a contribution to the biology of this organism and can help to reveal its pathogenic behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    Science.gov (United States)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  18. Ten tips for treating acne vulgaris in Fitzpatrick skin types IV-VI.

    Science.gov (United States)

    Spann, Candace Thornton

    2011-06-01

    During the 21st century, people with skin of color will account for a large portion of the US population. According to race projections from the US Census Bureau, persons of African American, Hispanic, Asian and Native American descent will make up nearly half of the total US population by the year 2050. Because of our changing demographics, it is important that all dermatologists become comfortable in treating skin of color. This article provides 10 practical pearls for management of acne vulgaris in patients with Fitzpatrick skin types IV-VI.

  19. Chaos in periodically forced Holling type IV predator-prey system with impulsive perturbations

    International Nuclear Information System (INIS)

    Zhang Shuwen; Tan Dejun; Chen Lansun

    2006-01-01

    The effect of periodic forcing and impulsive perturbations on predator-prey model with Holling type IV functional response is investigated. The periodic forcing is affected by assuming a periodic variation in the intrinsic growth rate of the prey. The impulsive perturbations are affected by introducing periodic constant impulsive immigration of predator. The dynamical behavior of the system is simulated and bifurcation diagrams are obtained for different parameters. The results show that periodic forcing and impulsive perturbation can easily give rise to complex dynamics, including (1) quasi-periodic oscillating, (2) period doubling cascade, (3) chaos, (4) period halfing cascade

  20. Atlas of fine structures of dynamic spectra of solar type IV-dm and some type II radio bursts

    International Nuclear Information System (INIS)

    Slottje, C.

    1982-01-01

    The author presents an atlas of spectral fine structures of solar radio bursts of types IV and II around 1 m wavelength, as obtained with a multichannel spectrograph at Dwingeloo. The structures form largely a collection of observations of these events during late 1968 through 1974, thus covering almost entirely the declining branch of solar cycle 20. The spectrograph has an extra enhanced contrast output with properties quite different from those of the commonly used swept frequency spectrographs. The corresponding instrumental characteristics and effects are discussed. A classification of fine structures and an analysis of their statistical properties and of those of the pertinent radio events are also given. (Auth.)

  1. Diagnosis of Coxiella burnetii infection: comparison of a whole blood interferon-gamma production assay and a Coxiella ELISPOT.

    Directory of Open Access Journals (Sweden)

    Teske Schoffelen

    Full Text Available Diagnosis of ongoing or past infection with Coxiella burnetii, the causative agent of Q fever, relies heavily on serology: the measurement of C. burnetii-specific antibodies, reflecting the host's humoral immune response. However, cell-mediated immune responses play an important, probably even more relevant, role in infections caused by the intracellular C. burnetii bacterium. Recent studies have investigated interferon-gamma (IFN-γ based assays, including a whole-blood IFN-γ production assay and a Coxiella enzyme-linked immunospot (Coxiella ELISPOT, as potential diagnostic tools for Q fever diagnosis. Both are in-house developed assays using stimulating antigens of different origin. The main objective of this study was to compare the test performance of the IFN-γ production assay and the Coxiella ELISPOT for detecting a cellular immune response to C. burnetii in Q fever patients, and to assess the correlation between both assays. To that end, both tests were performed in a well-defined patient group of chronic Q fever patients (n = 16 and a group of healthy seronegative individuals (n = 17. Among patients, both the Coxiella ELISPOT and the IFN-γ production assay detected positive response in 14/16. Among controls, none were positive in the Coxiella ELISPOT, whereas the IFN-γ production assay detected positive results in 1/17 and 3/17, when using Henzerling and Nine Mile as stimulating antigens, respectively. These results suggest the Coxiella ELISPOT has a somewhat higher specificity than the IFN-γ production assay when Nine Mile is used as antigen stimulus. The assays showed moderate correlation: the Spearman correlation coefficient r ranged between 0.37-0.60, depending on the antigens used. Further investigation of the diagnostic potential for C. burnetii infection of both assays is warranted.

  2. Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

    Science.gov (United States)

    Yi, Haiqing; Zhang, Quan; Brooks, Elizabeth D; Yang, Chunyu; Thurberg, Beth L; Kishnani, Priya S; Sun, Baodong

    2017-03-01

    Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1 ys/ys ). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1 ys/ys mice at a dose of 5 × 10 11 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1 ys/ys mice.

  3. Internal carotid artery dissection in a patient with Ehlers-Danlos syndrome type IV: diagnosis and management

    Directory of Open Access Journals (Sweden)

    Michel Nasser

    2013-06-01

    Full Text Available Ehlers-Danlos syndrome (EDS type IV, also known as vascular EDS, is an inherited connective tissue disorder with an estimated prevalence of 1/100,000 to 1/250,000. In EDS type IV, vascular complications may affect all anatomical areas, with a preference for large- and medium-sized arteries. Dissections of the vertebral and carotid arteries in their extra- and intra-cranial segments are typical. The authors report the case of a patient with EDS type IV for whom the diagnosis was established based on clinical signs and who developed internal carotid artery dissection at the age of 44 years. In the absence of a specific treatment for EDS type IV, medical interventions should focus on symptomatic relief, prophylactic measures, and genetic counseling. Invasive imaging techniques are contraindicated, and a conservative approach to vascular complications is usually recommended.

  4. CHANGES IN THE IMMUNOLOGIC MARKERS OF COLLAGEN TYPE IV DEGRADATION IN SUBJECTS WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Edward Mekenyan

    2012-12-01

    Full Text Available Background: Collagen is the major protein component of the vessels. Collagen type IV is found exclusively in the basal membrane and doesn’t form individual fibers, but instead is presented as a polygonal amorphous matrix that is associated with laminin and other matrix macromolecules to form the unique matrix basal membrane. Under the influence of the risk factors characterizing the metabolic syndrome, a variety of basal memrane degrading enzymes are activated. This leads to an early changes in vascular wall and accelerates the vascular aging The early manifestation of the metabolic syndrome in younger people in the modern society, leads to earlier manifestation of the complications of early vessels aging. Loss of elasticity is a key component in the pathogenesis of cardiovascular complications. Materials and methods: A study is conducted on 62 subjects with metabolic syndrome without vascular complications and 42 controls. The main objective of the study was to compare the imunological markers of Collagen typr IV degradation in both groups and to assess their relationship with the risk factors characterizing the metabolic syndrome. Results: When comparing the levels of Anti Coll IV Ab IgG in the control group and subjects with metabolic syndrome (respectively 0.28 + / - 0.08 and 0.40 + / - 0.11 a statistically significantly higher levels of Anti Coll IV Ab IgG were determined in the group with metabolic syndrome, F = 30.299, p = 0.000, In the whole sample Anti Col IV Ab IgG showed negative correlation with HDL with a correlation Spearman coefficient r = 0,26, and p = 0,02. The antibodies showed positive correlation with the diastolic pressure (DP, blood sugar (Gluc, total cholesterol (Tchol, triglycerides (Tg and LDL. The positive corelations were with Pearson correlation coefficient as follows: DP - r = 0,22, p = 0,04; Gluc – r=0,27, p=0,01; TChol – r=0,30, p=0.005; Tg – r=0,34, p=0,002; LDL – r=0,32, p=0,002. Conclusion: It is

  5. Biomechanical study of modular hemipelvic endoprosthesis for Type I-IV defect of pelvic tumor.

    Science.gov (United States)

    Dong, Yang; Hu, Hai; Zhang, Chang-Qing

    2014-08-01

    The modular hemipelvic prosthesis has been used in patient of Type I-IV pelvic tumor with good outcomes, but how to keep the stability between the prosthesis and the residual sacrum is a problem. An additional screw-rod system seems to solve it, but its biomechanical characters are still not well understood, which need experimental evaluation. Six pelvic specimens were prepared in three conditions (normal intact pelvis, "normal"; the pelvis of left Type I-IV defect and implanted with prosthesis without/with additional screw-rod system, "rod-" and "rod+"). Compressing biomechanical experiments (50-500N) were performed in these three conditions, respectively. The loadings during the experiments are in accordance with the linear elastic control mode. Under the increasing loading, the implanted pelvises displaced asymmetrically, unlike normal intact pelvis. The vertical displacement of "rod+" changed significantly, whereas "rod-" did not. For both implanted pelvis, right side displaced less than left side (P values <0.05). The implanted pelvis showed asymmetric displacement under loading, where healthy side displaced more. The implanted pelvis plus screw-rod system showed less displacement at implanted side but more at contralateral side in comparison with those without screw-rod system.

  6. Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

    Science.gov (United States)

    Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

    2009-07-01

    The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

  7. Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: A rarely reported association

    Directory of Open Access Journals (Sweden)

    Arijit Mitra

    2014-01-01

    Full Text Available A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA of hand movement (HM in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD in right eye. Intraocular pressure (IOP was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA in right eye and cup disc ratio (CDR of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

  8. Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV Bone: An Overview

    Directory of Open Access Journals (Sweden)

    Hamdan S. Alghamdi

    2018-01-01

    Full Text Available Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Brånemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification, in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV bone are described in a general manner in this review.

  9. Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV) Bone: An Overview.

    Science.gov (United States)

    Alghamdi, Hamdan S

    2018-01-13

    Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Brånemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone) conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification), in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV) bone are described in a general manner in this review.

  10. A novel GBE1 gene variant in a child with glycogen storage disease type IV.

    Science.gov (United States)

    Said, Samar M; Murphree, Marine I; Mounajjed, Taofic; El-Youssef, Mounif; Zhang, Lizhi

    2016-08-01

    Glycogen storage disease type IV is an autosomal recessive disorder of carbohydrates caused by deficiency of amylo-1-4-glycanoglycosyltransferase, which leads to accumulation of amylopectin-like polysaccharides in tissues including liver, heart and neuromuscular system. More than 40 different mutations in the glycogen branching enzyme gene (GBE1) have been described. In this study, we report a 2-year-old boy who presented with developmental delay and muscle weakness. He subsequently was diagnosed with glycogen storage disease type IV based on a liver biopsy histology and electron microscopy. Glycogen branching enzyme activity was in the low range. Genetic analysis demonstrated a novel heterozygous variant (c.760A>G; p.Thr254Ala) in exon 6 of the GBE1 gene, which is believed to be pathogenic. This variant was inherited from the patient's mother who was asymptomatic with normal glycogen branching enzyme activity. Whole-exome sequencing failed to reveal additional variations in the GBE1 gene. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Earthworm symbiont Verminephrobacter eiseniae mediates natural transformation within the host egg capsules using type IV pili

    Directory of Open Access Journals (Sweden)

    SEANA Kelyn DAVIDSON

    2014-10-01

    Full Text Available The dense microbial communities commonly associated with plants and animals should offer many opportunities for horizontal gene transfer (HGT through described mechanisms of DNA exchange including natural transformation. However, studies of the significance of natural transformation have focused primarily on pathogens. The study presented here demonstrates highly efficient DNA exchange by natural transformation in a common symbiont of earthworms. The obligate bacterial symbiont Verminephrobacter eiseniae is a member of a microbial consortium of the earthworm Eisenia fetida that is transmitted into the egg capsules to colonize the embryonic worms. In the study presented here, by testing for transformants under different conditions in culture, we demonstrate that V. eiseniae can incorporate free DNA from the environment, that competency is regulated by environmental factors, and that it is sequence specific. Mutations in the type IV pili of V. eiseniae resulted in loss of DNA uptake, implicating the type IV pilus (TFP apparatus in DNA uptake. Furthermore, injection of DNA carrying antibiotic-resistance genes into egg capsules resulted in transformants within the capsule, demonstrating the relevance of DNA uptake within the earthworm system. The ability to take up species-specific DNA from the environment may explain the maintenance of the relatively large, intact genome of this long-associated obligate symbiont, and provides a mechanism for acquisition of foreign genes within the earthworm system.

  12. Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient.

    Science.gov (United States)

    Refaat, Marwan; Hotait, Mostafa; Winston, Brion

    2014-03-16

    Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting.

  13. Genetic analysis of a type IV pili-like locus in the archaeon Methanococcus maripaludis.

    Science.gov (United States)

    Nair, Divya B; Uchida, Kaoru; Aizawa, Shin-Ichi; Jarrell, Ken F

    2014-03-01

    Methanococcus maripaludis is a stringently anaerobic archaeon with two studied surface structures, archaella and type IV pili. Previously, it was shown that three pilin genes (mmp0233 [epdA], mmp0236 [epdB] and mmp0237 [epdC]) located within an 11 gene cluster in the genome were necessary for normal piliation. This study focused on analysis of the remaining genes to determine their potential involvement in piliation. Reverse transcriptase PCR experiments demonstrated the 11 genes formed a single transcriptional unit. Deletions were made in all the non-pilin genes except mmp0231. Electron microscopy revealed that all the genes in the locus except mmp0235 and mmp0238 were essential for piliation. Complementation with a plasmid-borne wild-type copy of the deleted gene restored at least some piliation. We identified genes for an assembly ATPase and two versions of the conserved pilin platform forming protein necessary for pili assembly at a separate genetic locus.

  14. Delusional disorder-jealous type: how inclusive are the DSM-IV diagnostic criteria?

    Science.gov (United States)

    Easton, Judith A; Shackelford, Todd K; Schipper, Lucas D

    2008-03-01

    Delusional disorder-jealous type is a new diagnostic category in the Diagnostic and Statistical Manual for Disorders, Fourth Edition, Text Revision (DSM-IV-TR; American Psychiatric Association, 2000) in which delusions concerning a partner's infidelity must be present. Therefore, patients who experience a jealousy disorder, but do not experience delusions will not fit the diagnostic criteria. Using a database of 398 case histories of jealousy disorders reported in the literature from 1940-2002, we examined the percentage of these cases that met the diagnostic criteria for delusional disorder-jealous type. Only 4% of the cases met all diagnostic criteria. This is the first systematic comparison of the prevalence of these disorders. The results provide evidence that the diagnostic criteria are not inclusive, as most individuals suffering with a jealousy disorder were excluded from the diagnosis.

  15. Amplified QCM biosensor for type IV collagenase based on collagenase-cleavage of gold nanoparticles functionalized peptide.

    Science.gov (United States)

    Dong, Zong-Mu; Jin, Xin; Zhao, Guang-Chao

    2018-05-30

    The present study develops a rapid, simple and efficient method for the determination of type IV collagenase by using a specific peptide-modified quartz crystal microbalance (QCM). A small peptide (P1), contains a specific sequence (Pro-Gly) and a terminal cysteine, was synthetized and immobilized to the surface of QCM electrode via the reaction between Au and thiol of the cysteine. The peptide bond between proline and glycine can be specific hydrolyzed cleavage by type IV collagenase, which enabled the modified electrode with a high selectivity toward type IV collagenase. The cleaving process caused a frequency change of QCM to give a signal related to the concentration of type IV collagenase. The morphologies of the modified electrodes were characterized by scanning electron microscope (SEM) and the specific hydrolyzed cleavage process was monitored by QCM. When P1 was modified with gold nanoparticles (P1-Au NPs), the signal could be amplified to further enhance the sensitivity of the designed sensor due to the high-mass of the modified Au NPs. Compared the direct unamplified assay, the values obtained for the limit of detection for type IV collagenase was 0.96 ng mL -1 , yielding about 6.5 times of magnitude improvement in sensitivity. This signal enhanced peptide based QCM biosensor for type IV collagenase also showed good selectivity and sensitivity in complex matrix. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Draft genome sequence of Coxiella burnetii Dog Utad, a strain isolated from a dog-related outbreak of Q fever

    Directory of Open Access Journals (Sweden)

    F. D’amato

    2014-07-01

    Full Text Available Coxiella burnetii Dog Utad, with a 2 008 938 bp genome is a strain isolated from a parturient dog responsible for a human familial outbreak of acute Q fever in Nova Scotia, Canada. Its genotype, determined by multispacer typing, is 21; the only one found in Canada that includes Q212, which causes endocarditis. Only 107 single nucleotide polymorphisms and 16 INDELs differed from Q212, suggesting a recent clonal radiation.

  17. Complete plasmid sequence carrying type IV-like and type VII secretion systems from an atypical mycobacteria strain

    Directory of Open Access Journals (Sweden)

    Sergio Mascarenhas Morgado

    Full Text Available The genus Mycobacterium is highly diverse and ubiquitous in nature, comprehending fast- and slow-growing species with distinct impact in public health. The plasmid-mediated horizontal gene transfer represents one of the major events in bacteria evolution. Here, we report the complete sequence of a 160,489 bp circular plasmid (pCBMA213_2 from an atypical and fast-growing environmental mycobacteria. This is a unique plasmid, in comparison with the characterised mycobacteria plasmids, harboring a type IV-like and ESX-P2 type VII secretion systems. pCBMA213_2 can be further explored for evolutionary and conjugation studies as well as a tool to manipulate DNA within this bacteria genus.

  18. Motion of the sources for type II and type IV radio bursts and flare-associated interplanetary disturbances

    Science.gov (United States)

    Sakurai, K.; Chao, J. K.

    1974-01-01

    Shock waves are indirectly observed as the source of type II radio bursts, whereas magnetic bottles are identified as the source of moving metric type IV radio bursts. The difference between the expansion speeds of these waves and bottles is examined during their generation and propagation near the flare regions. It is shown that, although generated in the explosive phase of flares, the bottles behave quite differently from the waves and that the bottles are generally much slower than the waves. It has been suggested that the waves are related to flare-associated interplanetary disturbances which produce SSC geomagnetic storms. These disturbances may, therefore, be identified as interplanetary shock waves. The relationship among magnetic bottles, shock waves near the sun, and flare-associated disturbances in interplanetary space is briefly discussed.

  19. Identification of a Novel Conjugative Plasmid in Mycobacteria That Requires Both Type IV and Type VII Secretion

    KAUST Repository

    Ummels, R.

    2014-09-23

    Conjugative plasmids have been identified in a wide variety of different bacteria, ranging from proteobacteria to firmicutes, and conjugation is one of the most efficient routes for horizontal gene transfer. The most widespread mechanism of plasmid conjugation relies on different variants of the type IV secretion pathway. Here, we describe the identification of a novel type of conjugative plasmid that seems to be unique for mycobacteria. Interestingly, while this plasmid is efficiently exchanged between different species of slow-growing mycobacteria, including Mycobacterium tuberculosis, it could not be transferred to any of the fast-growing mycobacteria tested. Genetic analysis of the conjugative plasmid showed the presence of a locus containing homologues of three type IV secretion system components and a relaxase. In addition, a new type VII secretion locus was present. Using transposon insertion mutagenesis, we show that in fact both these secretion systems are essential for conjugation, indicating that this plasmid represents a new class of conjugative plasmids requiring two secretion machineries. This plasmid could form a useful new tool to exchange or introduce DNA in slow-growing mycobacteria. IMPORTANCE: Conjugative plasmids play an important role in horizontal gene transfer between different bacteria and, as such, in their adaptation and evolution. This effect is most obvious in the spread of antibiotic resistance genes. Thus far, conjugation of natural plasmids has been described only rarely for mycobacterial species. In fact, it is generally accepted that M. tuberculosis does not show any recent sign of horizontal gene transfer. In this study, we describe the identification of a new widespread conjugative plasmid that can also be efficiently transferred to M. tuberculosis. This plasmid therefore poses both a threat and an opportunity. The threat is that, through the acquisition of antibiotic resistance markers, this plasmid could start a rapid spread of

  20. A rationalization of the Type IV loading dependence in the Kärger-Pfeifer classification of self-diffusivities

    NARCIS (Netherlands)

    Krishna, R.; van Baten, J.M.

    2011-01-01

    Kärger and Pfeifer (1987) [1] have listed five different types of dependencies of the self-diffusivities, Di,self, on the loading, Θi, of guest molecules in zeolites. Of these five types, the Type IV dependence is particularly intriguing because it displays a maximum in the Di,self − Θi dependence

  1. Systematic analysis and prediction of type IV secreted effector proteins by machine learning approaches.

    Science.gov (United States)

    Wang, Jiawei; Yang, Bingjiao; An, Yi; Marquez-Lago, Tatiana; Leier, André; Wilksch, Jonathan; Hong, Qingyang; Zhang, Yang; Hayashida, Morihiro; Akutsu, Tatsuya; Webb, Geoffrey I; Strugnell, Richard A; Song, Jiangning; Lithgow, Trevor

    2017-11-27

    In the course of infecting their hosts, pathogenic bacteria secrete numerous effectors, namely, bacterial proteins that pervert host cell biology. Many Gram-negative bacteria, including context-dependent human pathogens, use a type IV secretion system (T4SS) to translocate effectors directly into the cytosol of host cells. Various type IV secreted effectors (T4SEs) have been experimentally validated to play crucial roles in virulence by manipulating host cell gene expression and other processes. Consequently, the identification of novel effector proteins is an important step in increasing our understanding of host-pathogen interactions and bacterial pathogenesis. Here, we train and compare six machine learning models, namely, Naïve Bayes (NB), K-nearest neighbor (KNN), logistic regression (LR), random forest (RF), support vector machines (SVMs) and multilayer perceptron (MLP), for the identification of T4SEs using 10 types of selected features and 5-fold cross-validation. Our study shows that: (1) including different but complementary features generally enhance the predictive performance of T4SEs; (2) ensemble models, obtained by integrating individual single-feature models, exhibit a significantly improved predictive performance and (3) the 'majority voting strategy' led to a more stable and accurate classification performance when applied to predicting an ensemble learning model with distinct single features. We further developed a new method to effectively predict T4SEs, Bastion4 (Bacterial secretion effector predictor for T4SS), and we show our ensemble classifier clearly outperforms two recent prediction tools. In summary, we developed a state-of-the-art T4SE predictor by conducting a comprehensive performance evaluation of different machine learning algorithms along with a detailed analysis of single- and multi-feature selections. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Identification of novel Coxiella burnetii genotypes from Ethiopian ticks.

    Directory of Open Access Journals (Sweden)

    Kinga M Sulyok

    Full Text Available BACKGROUND: Coxiella burnetii, the etiologic agent of Q fever, is a highly infectious zoonotic bacterium. Genetic information about the strains of this worldwide distributed agent circulating on the African continent is limited. The aim of the present study was the genetic characterization of C. burnetii DNA samples detected in ticks collected from Ethiopian cattle and their comparison with other genotypes found previously in other parts of the world. METHODOLOGY/PRINCIPAL FINDINGS: A total of 296 tick samples were screened by real-time PCR targeting the IS1111 region of C. burnetii genome and from the 32 positive samples, 8 cases with sufficient C. burnetii DNA load (Amblyomma cohaerens, n = 6; A. variegatum, n = 2 were characterized by multispacer sequence typing (MST and multiple-locus variable-number tandem repeat analysis (MLVA. One novel sequence type (ST, the proposed ST52, was identified by MST. The MLVA-6 discriminated the proposed ST52 into two newly identified MLVA genotypes: type 24 or AH was detected in both Amblyomma species while type 26 or AI was found only in A. cohaerens. CONCLUSIONS/SIGNIFICANCE: Both the MST and MLVA genotypes of the present work are closely related to previously described genotypes found primarily in cattle samples from different parts of the globe. This finding is congruent with the source hosts of the analyzed Ethiopian ticks, as these were also collected from cattle. The present study provides genotype information of C. burnetii from this seldom studied East-African region as well as further evidence for the presumed host-specific adaptation of this agent.

  3. CHIMERISM AFTER LIVER TRANSPLANTATION FOR TYPE IV GLYCOGEN STORAGE DISEASE AND TYPE 1 GAUCHER’S DISEASE

    Science.gov (United States)

    Starzl, Thomas E.; Demetris, Anthony J.; Trucco, Massimo; Ricordi, Camillo; Ildstad, Suzanne; Terasaki, Paul I.; Murase, Noriko; Kendall, Ross S.; Kocova, Mirjana; Rudert, William A.; Zeevi, Adriana; Van Thiel, David

    2010-01-01

    Background Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. Methods We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher’s disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. Results Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher’s disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher’s disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher’s disease. Conclusions Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies. PMID:8437594

  4. A new multiplex PCR for easy screening of methicillin-resistant Staphylococcus aureus SCCmec types I-V

    DEFF Research Database (Denmark)

    Boye, Kit; Bartels, Mette Damkjær; Andersen, Ina S

    2007-01-01

    A multiplex PCR with four primer-pairs was designed to identify the five main known SCCmec types. A clear and easily discriminated band pattern was obtained for all five types. The SCCmec type was identified for 98% of 312 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA......). SCCmec type IV was by far the most common SCCmec type among both hospital- and community-acquired MRSA isolates in Denmark....

  5. A type IV pilus mediates DNA binding during natural transformation in Streptococcus pneumoniae.

    Science.gov (United States)

    Laurenceau, Raphaël; Péhau-Arnaudet, Gérard; Baconnais, Sonia; Gault, Joseph; Malosse, Christian; Dujeancourt, Annick; Campo, Nathalie; Chamot-Rooke, Julia; Le Cam, Eric; Claverys, Jean-Pierre; Fronzes, Rémi

    2013-01-01

    Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material.

  6. A type IV pilus mediates DNA binding during natural transformation in Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Raphaël Laurenceau

    Full Text Available Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material.

  7. Type IV hiatal hernia post laparoscopic Nissen fundoplication: report of a case.

    LENUS (Irish Health Repository)

    Awad, Z T

    2001-01-01

    A postoperative hiatal hernia is a rare but serious complication of fundoplication. We report herein a 62-year-old female who presented with abdominal pain and vomiting 2 years following laparoscopic Nissen fundoplication. At laparotomy, the stomach and the transverse colon were intrathoracic (type IV hiatal hernia); the esophageal hiatus was markedly dilated with no evidence that they had been approximated. At 18 months follow-up, she is doing very well apart from occasional heartburn. A high index of suspicion is needed to diagnose postoperative hiatal hernias. A routine closure of the crura with nonabsorbable suture material and an avoidance of iatrogenic pneumothorax may help to reduce the occurrence of this problem.

  8. Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation.

    Directory of Open Access Journals (Sweden)

    Joseph Gault

    2015-09-01

    Full Text Available The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences.

  9. Evaluation of the Various Drying Methods on Surface Hardness of Type IV Dental Stone

    Science.gov (United States)

    Sudhakar, A; Srivatsa, G; Shetty, Rohit; Rajeswari, C L; Manvi, Supriya

    2015-01-01

    Background: Studies regarding the effect of various methods to increase the surface hardness of Type IV dental stone are not conclusive. Therefore, this study was carried out to evaluate the effect of air drying, micro oven drying and die hardener on surface hardness of Type IV dental stone. Materials and Methods: A standard metal die was fabricated; polyvinyl siloxane impression material was used to make the molds of metal die. A total of 120 specimens were obtained from two different die stones and were grouped as Group A (kalrock) and Group B (pearl stone), and were subjected to air drying for 24 h, micro oven drying and application of die hardener. These models were then subjected to surface hardness testing using the knoop hardness instrument. The obtained data were subjected to statistical analysis. Results: The hardness of Group A specimens was 64 ± 0.54 Knoop hardness number (KHN) after application of die hardener, 60.47 ± 0.41 KHN after 24 h air drying, 58.2 ± 0.88 after microwave oven drying and 24.6 ± 0.4 after 1 h air drying. The hardness of Group B specimens was 45.59 ± 0.63 KHN after application of die hardener, 40.2 ± 0.63 KHN after 24 h air drying, 38.28 ± 0.55 KHN after microwave oven drying and 19.91 ± 0.64 KHN after 1 h air drying. Conclusion: Group A showed better results than Group B at all times. Application of the die hardener showed highest hardness values followed in the order by 24 h air drying, microwave oven drying and 1 h air drying in both groups. The study showed that air drying the dies for 24 h followed by application of a single layer of the die hardener produced the best surface hardness and is recommended to be followed in practice. PMID:26124610

  10. Pelvic reference selection in patients with unilateral Crowe type IV DDH for measuring leg length inequality.

    Science.gov (United States)

    Zhang, Yanbo; Chang, Fei; Wang, Chenyu; Yang, Modi; Wang, Jincheng

    2015-01-01

    We identified the presence of deformities in the affected pelvis of unilateral Crowe type IV DDH patients, and if present, whether the teardrop and ischial lines were parallel with the sacral base line. We also verified whether the sacral base line provided a better pelvic landmark than the teardrop line for determining leg length inequality (LLI). After leveling the pelvis by using a block to lift the short leg, standard anterior-posterior full-length radiography was performed on 10 patients and 10 healthy volunteers as controls. The ratio of pelvic heights on each side of the pelvis, the angles formed by the sacral base line and the other 2 lines between 2 groups were measured. LLI were measured by sacral base line and teardrop line respectively. The ratio between the pelvic heights was lower in the patient group than in the control group (0.95 versus 0.99). The angles between the teardrop and ischial lines and the sacral base line in the patient group were both greater than in the control group (6.08° versus 0.92° and 7.13° versus 0.97°). LLI measured from the sacral base line was larger than from the teardrop line in the patient group (5.55 cm versus 4.36 cm). There was pelvic asymmetry and the sacral base line was not parallel with the other 2 lines in unilateral Crowe type IV DDH. The leveled sacral base line was perpendicular to the longitudinal axis of the body, and may be a better choice for accurate LLI measurement in this situation.

  11. Chronic inflammation of the prostate type IV with respect to risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Antonio B. Porcaro

    2014-09-01

    Full Text Available Background: Chronic inflammatory infiltrate (CII might be involved in prostate cancer (PCA and benign hyperplasia (BPH; however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. Objective: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. Design, setting, and participants: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years and PSA (ug/l; moreover, CII+, glandular atrophy (GA+, glandular hyperplasia (GH+, prostate Intraepithelial neoplasm (PIN+, atypical small acinar cell proliferation (ASAP+ and PCA positive cores (P+ were evaluated as categorical and continuous (proportion of positive cores. Outcome measurements and statistical analysis: Associations of CII+ and PCA risk were assessed by statistical methods. Results and limitations: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8 resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26 and HGPCA (P = 0.0005; OR = 0.05. Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. Conclusions: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in

  12. A novel neuromuscular form of glycogen storage disease type IV with arthrogryposis, spinal stiffness and rare polyglucosan bodies in muscle.

    Science.gov (United States)

    Malfatti, Edoardo; Barnerias, Christine; Hedberg-Oldfors, Carola; Gitiaux, Cyril; Benezit, Audrey; Oldfors, Anders; Carlier, Robert-Yves; Quijano-Roy, Susana; Romero, Norma B

    2016-10-01

    Glycogen storage disease type IV (GSD IV) is an autosomal recessive disorder causing polyglucosan storage in various tissues. Neuromuscular forms present with fetal akinesia deformation sequence, lethal myopathy, or mild hypotonia and weakness. A 3-year-old boy presented with arthrogryposis, motor developmental delay, weakness, and rigid spine. Whole body MRI revealed fibroadipose muscle replacement but sparing of the sartorius, gracilis, adductor longus and vastus intermedialis muscles. Polyglucosan bodies were identified in muscle, and GBE1 gene analysis revealed two pathogenic variants. We describe a novel neuromuscular GSD IV phenotype and confirm the importance of muscle morphological studies in early onset neuromuscular disorders. Copyright © 2016. Published by Elsevier B.V.

  13. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2004-01-01

    in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant...... with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation...

  14. AtlasT4SS: A curated database for type IV secretion systems

    Directory of Open Access Journals (Sweden)

    Souza Rangel C

    2012-08-01

    Full Text Available Abstract Background The type IV secretion system (T4SS can be classified as a large family of macromolecule transporter systems, divided into three recognized sub-families, according to the well-known functions. The major sub-family is the conjugation system, which allows transfer of genetic material, such as a nucleoprotein, via cell contact among bacteria. Also, the conjugation system can transfer genetic material from bacteria to eukaryotic cells; such is the case with the T-DNA transfer of Agrobacterium tumefaciens to host plant cells. The system of effector protein transport constitutes the second sub-family, and the third one corresponds to the DNA uptake/release system. Genome analyses have revealed numerous T4SS in Bacteria and Archaea. The purpose of this work was to organize, classify, and integrate the T4SS data into a single database, called AtlasT4SS - the first public database devoted exclusively to this prokaryotic secretion system. Description The AtlasT4SS is a manual curated database that describes a large number of proteins related to the type IV secretion system reported so far in Gram-negative and Gram-positive bacteria, as well as in Archaea. The database was created using the RDBMS MySQL and the Catalyst Framework based in the Perl programming language and using the Model-View-Controller (MVC design pattern for Web. The current version holds a comprehensive collection of 1,617 T4SS proteins from 58 Bacteria (49 Gram-negative and 9 Gram-Positive, one Archaea and 11 plasmids. By applying the bi-directional best hit (BBH relationship in pairwise genome comparison, it was possible to obtain a core set of 134 clusters of orthologous genes encoding T4SS proteins. Conclusions In our database we present one way of classifying orthologous groups of T4SSs in a hierarchical classification scheme with three levels. The first level comprises four classes that are based on the organization of genetic determinants, shared homologies, and

  15. Type IV Effector Secretion and Subversion of Host Functions by Bartonella and Brucella Species.

    Science.gov (United States)

    Dehio, Christoph; Tsolis, Renée M

    2017-01-01

    Bartonella and Brucella species comprise closely related genera of the order Rhizobiales within the class α-proteobacteria. Both groups of bacteria are mammalian pathogens with a facultative intracellular lifestyle and are capable of causing chronic infections, but members of each genus have evolved broadly different infection and transmission strategies. While Brucella spp. transmit in general via the reproductive tract in their natural hosts, the Bartonella spp. have evolved to transmit via arthropod vectors. However, a shared feature of both groups of pathogens is their reliance on type IV secretion systems (T4SSs) to interact with cells in their mammalian hosts. The genomes of Bartonella spp. encode three types of T4SS, Trw, Vbh/TraG, and VirB/VirD4, whereas those of Brucella spp. uniformly contain a single T4SS of the VirB type. The VirB systems of Bartonella and Brucella are associated with distinct groups of effector proteins that collectively mediate interactions with host cells. This chapter discusses recent findings on the role of T4SS in the biology of Bartonella spp. and Brucella spp. with emphasis on effector repertoires, on recent advances in our understanding of their evolution, how individual effectors function at the molecular level, and on the consequences of these interactions for cellular and immune responses in the host.

  16. Shipment and Disposal of Solidified Organic Waste (Waste Type IV) to the Waste Isolation Pilot Plant (WIPP)

    International Nuclear Information System (INIS)

    D'Amico, E. L; Edmiston, D. R.; O'Leary, G. A.; Rivera, M. A.; Steward, D. M.

    2006-01-01

    In April of 2005, the last shipment of transuranic (TRU) waste from the Rocky Flats Environmental Technology Site to the WIPP was completed. With the completion of this shipment, all transuranic waste generated and stored at Rocky Flats was successfully removed from the site and shipped to and disposed of at the WIPP. Some of the last waste to be shipped and disposed of at the WIPP was waste consisting of solidified organic liquids that is identified as Waste Type IV in the Contact-Handled Transuranic Waste Authorized Methods for Payload Control (CH-TRAMPAC) document. Waste Type IV waste typically has a composition, and associated characteristics, that make it significantly more difficult to ship and dispose of than other Waste Types, especially with respect to gas generation. This paper provides an overview of the experience gained at Rocky Flats for management, transportation and disposal of Type IV waste at WIPP, particularly with respect to gas generation testing. (authors)

  17. Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

    Science.gov (United States)

    de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

    2007-10-01

    The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

  18. Distinctive tomographic abnormalities of the craniocervical region in a patient with osteogenesis imperfecta type IV B

    Energy Technology Data Exchange (ETDEWEB)

    Kaissi, Ali Al; Klaushofer, Klaus, E-mail: ali.alkaissi@osteologie.a [Ludwig Boltzmann Institute of Osteology, Vienna (Austria); Grill, Franz [Orthopaedic Hospital of Speising, Vienna (Austria). Paediatric Dept.

    2010-07-01

    Osteogenesis imperfecta is a clinically and genetically heterogeneous group of heritable disorders of connective tissue characterized by reduced bone mass (osteopenia) with associated bone fragility. The resulting skeletal manifestations are due to a generalized deficiency in the development of both membranous and endochondral bone and include markedly thin calvarium with delayed closure of the fontanelles and the sutures and excessive Wormian bone formation. Sillence et al. developed a classification system of OI subtypes: OI type I, which is characterised by blue sclerae; perinatal lethal OI type II, also known as congenital OI; OI type III, a progressively deforming subtype with normal sclera; and OI type IV, which is characterized by a normal sclera. Levin et al. have suggested that OI subtypes could be further divided into type A and B based on the absence or presence of dentinogenesis imperfecta. Basilar impression involves the upward (vertical) migration of the odontoid process into the foramen magnum with a depression in the cranium. Basilar impression is a developmental defect and refers to the infolding of the occipital condyles, an elevation of the clivus, and the posterior cranial fossa of the skull. The soft bones of the skull base allow for progressive infolding of the dysplastic clivus and translocation of the odontoid into the posterior fossa. The combination of platybasia and basilar impression can lead to severe distortion of the spinal cord and the anterior brain stem. The specific structures that can be involved include the upper cervical cord, medulla, pons, mid-brain, cerebellum, as well as the vertebrobasilar system. (author)

  19. Seroprevalence of Coxiella burnetii in Australian dogs.

    Science.gov (United States)

    Shapiro, A J; Norris, J M; Heller, J; Brown, G; Malik, R; Bosward, K L

    2016-09-01

    The role of dogs in the transmission of Coxiella burnetii to humans is uncertain, and extensive seroprevalence studies of dogs have not been previously conducted in Australia. This study determined C. burnetii exposure in four diverse canine subpopulations by adapting, verifying and comparing an indirect immunofluoresence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) used to detect anti-C. burnetii antibodies in humans. Canine serum samples (n = 1223) were tested with IFA from four subpopulations [breeding establishments; household pets; free-roaming dogs in Aboriginal communities; shelter dogs]. The proportions of seropositive dogs were as follows: breeding (7/309, 2.3%), household pets (10/328, 3%), Aboriginal communities (21/321, 6.5%) and shelters (5/265, 1.9%). Dogs from Aboriginal communities were 2.8 times (CI 1.5-5.1; P dogs from other populations. The ELISA was used on 86 of 1223 sera tested with IFA, and a Cohen's Kappa coefficient of 0.60 (CI 0.43-0.78) indicated good agreement between the two assays. This study has established that Australian dogs within all four subpopulations have been exposed to C. burnetii and that a higher seroprevalence was observed amongst free-roaming dogs associated with Aboriginal communities. As C. burnetii recrudesces during pregnancy and birth products contain the highest concentration of organism, individuals assisting at the time of parturition, those handling pups shortly after birth as well as those residing in the vicinity of whelping dogs are potentially at risk of developing Q fever. However, the identification of active antigen shed in excreta from seropositive dogs is required in order to accurately define and quantify the public health risk. © 2016 Blackwell Verlag GmbH.

  20. Establishment of a genotyping scheme for Coxiella burnetii.

    NARCIS (Netherlands)

    Svraka, Sanela; Toman, Rudolf; Skultety, Ludovit; Slaba, Katarina; Homan, Wieger L

    2006-01-01

    Coxiella burnetii is the causative agent of Q fever. The bacterium is highly infectious and is classified as a category B biological weapon. The tools of molecular biology are of utmost importance in a rapid and unambiguous identification of C. burnetii in naturally occurring Q fever outbreaks, or

  1. A query for Coxiella in veterinary and environmental matrices

    NARCIS (Netherlands)

    de Bruin A; van Rotterdam BJ; LZO

    2011-01-01

    Q fever, caused by Coxiella burnetii, is a zoonosis with a worldwide distribution that affects both humans and animals. In 2007, 2008, and 2009 large community outbreaks of Q fever were observed in the Netherlands. In 2008, several studies were started to investigate potential sources of C. burnetii

  2. Bartonella henselae and Coxiella burnetii Infection and the ...

    African Journals Online (AJOL)

    It was reported that Bartonella henselae, B. quintana and Coxiella burnetii was not strongly associated with coronary artery disease but on the basis of geometric mean titer, C. burnetii infection might have a modest association with coronary artery disease. Serum antibodies to B. henselae from 14 patients with acute phase ...

  3. Coxiella burnetii Seroprevalence in Small Ruminants in The Gambia

    NARCIS (Netherlands)

    Klaasen, M.; Roest, H.J.; van der Hoek, W.; Secka, A.; Stegeman, J.A.|info:eu-repo/dai/nl/137144040

    2014-01-01

    Background: Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia.

  4. Coxiella burnetii Seroprevalence in Small Ruminants in The Gambia

    NARCIS (Netherlands)

    Klaassen, M.; Roest, Hendrik-Jan; Hoek, van der W.; Goossens, B.; Secka, A.; Stegeman, A.

    2014-01-01

    Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia.

  5. Native type IV collagen induces an epithelial to mesenchymal transition-like process in mammary epithelial cells MCF10A.

    Science.gov (United States)

    Espinosa Neira, Roberto; Salazar, Eduardo Perez

    2012-12-01

    Basement membrane (BM) is a complex network of interacting proteins, including type IV collagen (Col IV) that acts as a scaffold that stabilizes the physical structures of tissues and regulates cellular processes. In the mammary gland, BM is a continuous deposit that separates epithelial cells from stroma, and its degradation is related with an increased potential for invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to one mesenchymal state, and is a normal process during embryonic development, tissue remodeling and wound healing, as well as it has been implicated during cancer progression. In breast cancer cells, native Col IV induces migration and gelatinases secretion. However, the role of native Col IV on the EMT process in human mammary epithelial cells remains to be investigated. In the present study, we demonstrate that native Col IV induces down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2 and Sip1 transcripts. Native Col IV also induces an increase in N-cadherin and vimentin expression, an increase of MMP-2 secretion, the activation of FAK and NFκB, cell migration and invasion in MCF10A cells. In summary, these findings demonstrate, for the first time, that native Col IV induces an EMT-like process in MCF10A human mammary non-tumorigenic epithelial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Clinical value of the joint measurement of serum concentrations of type IV collagen and laminin in patients with diabetic nephropathy

    International Nuclear Information System (INIS)

    Wang Lu; Wang Ping; Li Yongpei

    2004-01-01

    Objective: To study clinical value of the joint measurement of serum concentrations of type IV collagen (IV C) and laminin (LN) in patients with diabetic nephropathy (DN) by radioimmunoassay (RIA). Methods: Serum concentrations of IV C, LN were measured by RIA in 35 diabetic patients with normalbuminuria (group A), 28 cases of microalbuminuria (group B), 15 cases of macroalbuminuria (group C) and 30 normal subjects as control . Results: The serum concentrations of IV C, LN in total 78 diabetic patients [(97.6 ± 19.2), (132.4 ± 31.5) μg/L] were higher than that of the controls [(77.4 ± 8.2), (101.5 ± 17.6) μg/L, P<0.05], especially in group B and C, it was remarkably higher compared with the controls (P<0.05, P<0.01). There was significant positive correlation of serum IV C, LN to diabetic duration and the levels of blood urea nitrogen (BUN), creatinine (Cr), urinary albumin excretion rate (UAER). Conclusions: The results suggest that the joint measurement of serum levels of IV C, LN and UAER in DN patients might better evaluate the development process of DN, and be of help for early diagnosis and treatment of DN. Serum levels of IV C, LN and UAER in DN patients may become the reliable clinical markers for assessing the severity and predicting the prognosis of DN

  7. AN ASSESSMENT OF THE SERVICE HISTORY AND CORROSION SUSCEPTIBILITY OF TYPE IV WASTE TANKS

    International Nuclear Information System (INIS)

    Wiersma, B

    2008-01-01

    Type IV waste tanks were designed and built to store waste that does not require auxiliary cooling. Each Type IV tank is a single-shell tank constructed of a steel-lined pre-stressed concrete tank in the form of a vertical cylinder with a concrete domed roof. There are four such tanks in F-area, Tanks 17-20F, and four in H-Area, Tanks 21-24H. Leak sites were discovered in the liners for Tanks 19 and 20F in the 1980's. Although these leaks were visually observed, the investigation to determine the mechanism by which the leaks had occurred was not completed at that time. Therefore, a concern was raised that the same mechanism which caused the leak sites in the Tanks in F-area may also be operable in the H-Area tanks. Data from the construction of the tanks (i.e., certified mill test reports for the steel, no stress-relief), the service history (i.e., waste sample data, temperature data), laboratory tests on actual wastes and simulants (i.e., electrochemical testing), and the results of the visual inspections were reviewed. The following observations and conclusions were made: (1) Comparison of the compositional and microstructural features indicate that the A212 material utilized for construction of the H-Area tanks are far more resistant to SCC than the A285 materials used for construction of the F-Area tanks. (2) A review of the materials of construction, temperature history, service histories concluded that F-Area tanks likely failed by caustic stress corrosion cracking. (3) The environment in the F-Area tanks was more aggressive than that experienced by the H-Area tanks. (4) Based on a review of the service history, the H-Area tanks have not been exposed to an environment that would render the tanks susceptible to either nitrate stress corrosion cracking (i.e., the cause of failures in the Type I and II tanks) or caustic stress corrosion cracking. (5) Due to the very dilute and uninhibited solutions that have been stored in Tank 23H, vapor space corrosion has

  8. AN ASSESSMENT OF THE SERVICE HISTORY AND CORROSION SUSCEPTIBILITY OF TYPE IV WASTE TANKS

    Energy Technology Data Exchange (ETDEWEB)

    Wiersma, B

    2008-09-18

    Type IV waste tanks were designed and built to store waste that does not require auxiliary cooling. Each Type IV tank is a single-shell tank constructed of a steel-lined pre-stressed concrete tank in the form of a vertical cylinder with a concrete domed roof. There are four such tanks in F-area, Tanks 17-20F, and four in H-Area, Tanks 21-24H. Leak sites were discovered in the liners for Tanks 19 and 20F in the 1980's. Although these leaks were visually observed, the investigation to determine the mechanism by which the leaks had occurred was not completed at that time. Therefore, a concern was raised that the same mechanism which caused the leak sites in the Tanks in F-area may also be operable in the H-Area tanks. Data from the construction of the tanks (i.e., certified mill test reports for the steel, no stress-relief), the service history (i.e., waste sample data, temperature data), laboratory tests on actual wastes and simulants (i.e., electrochemical testing), and the results of the visual inspections were reviewed. The following observations and conclusions were made: (1) Comparison of the compositional and microstructural features indicate that the A212 material utilized for construction of the H-Area tanks are far more resistant to SCC than the A285 materials used for construction of the F-Area tanks. (2) A review of the materials of construction, temperature history, service histories concluded that F-Area tanks likely failed by caustic stress corrosion cracking. (3) The environment in the F-Area tanks was more aggressive than that experienced by the H-Area tanks. (4) Based on a review of the service history, the H-Area tanks have not been exposed to an environment that would render the tanks susceptible to either nitrate stress corrosion cracking (i.e., the cause of failures in the Type I and II tanks) or caustic stress corrosion cracking. (5) Due to the very dilute and uninhibited solutions that have been stored in Tank 23H, vapor space corrosion

  9. c-Type cytochrome-dependent formation of U(IV nanoparticles by Shewanella oneidensis.

    Directory of Open Access Journals (Sweden)

    Matthew J Marshall

    2006-09-01

    Full Text Available Modern approaches for bioremediation of radionuclide contaminated environments are based on the ability of microorganisms to effectively catalyze changes in the oxidation states of metals that in turn influence their solubility. Although microbial metal reduction has been identified as an effective means for immobilizing highly-soluble uranium(VI complexes in situ, the biomolecular mechanisms of U(VI reduction are not well understood. Here, we show that c-type cytochromes of a dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1, are essential for the reduction of U(VI and formation of extracellular UO(2 nanoparticles. In particular, the outer membrane (OM decaheme cytochrome MtrC (metal reduction, previously implicated in Mn(IV and Fe(III reduction, directly transferred electrons to U(VI. Additionally, deletions of mtrC and/or omcA significantly affected the in vivo U(VI reduction rate relative to wild-type MR-1. Similar to the wild-type, the mutants accumulated UO(2 nanoparticles extracellularly to high densities in association with an extracellular polymeric substance (EPS. In wild-type cells, this UO(2-EPS matrix exhibited glycocalyx-like properties and contained multiple elements of the OM, polysaccharide, and heme-containing proteins. Using a novel combination of methods including synchrotron-based X-ray fluorescence microscopy and high-resolution immune-electron microscopy, we demonstrate a close association of the extracellular UO(2 nanoparticles with MtrC and OmcA (outer membrane cytochrome. This is the first study to our knowledge to directly localize the OM-associated cytochromes with EPS, which contains biogenic UO(2 nanoparticles. In the environment, such association of UO(2 nanoparticles with biopolymers may exert a strong influence on subsequent behavior including susceptibility to oxidation by O(2 or transport in soils and sediments.

  10. Computational prediction of type III and IV secreted effectors in Gram-negative bacteria

    Energy Technology Data Exchange (ETDEWEB)

    McDermott, Jason E.; Corrigan, Abigail L.; Peterson, Elena S.; Oehmen, Christopher S.; Niemann, George; Cambronne, Eric; Sharp, Danna; Adkins, Joshua N.; Samudrala, Ram; Heffron, Fred

    2011-01-01

    In this review, we provide an overview of the methods employed by four recent papers that described novel methods for computational prediction of secreted effectors from type III and IV secretion systems in Gram-negative bacteria. The results of the studies in terms of performance at accurately predicting secreted effectors and similarities found between secretion signals that may reflect biologically relevant features for recognition. We discuss the web-based tools for secreted effector prediction described in these studies and announce the availability of our tool, the SIEVEserver (http://www.biopilot.org). Finally, we assess the accuracy of the three type III effector prediction methods on a small set of proteins not known prior to the development of these tools that we have recently discovered and validated using both experimental and computational approaches. Our comparison shows that all methods use similar approaches and, in general arrive at similar conclusions. We discuss the possibility of an order-dependent motif in the secretion signal, which was a point of disagreement in the studies. Our results show that there may be classes of effectors in which the signal has a loosely defined motif, and others in which secretion is dependent only on compositional biases. Computational prediction of secreted effectors from protein sequences represents an important step toward better understanding the interaction between pathogens and hosts.

  11. Cardiac Involvement in Glycogen Storage Disease Type IV: Two Cases and the Two Ends of a Spectrum

    Directory of Open Access Journals (Sweden)

    Tolga Aksu

    2012-01-01

    Full Text Available Glycogen storage disease type IV (GSD IV is an autosomal recessive disorder due to the deficiency of α 1,4-glucan branching enzyme, resulting in an accumulation of amylopectin-like polysaccharide in various systems. We describe two cases, a 23-year-old girl with dilated cardiomyopathy who presented with progressive dyspnea and fatigue and a 28-year-old girl with hypertrophic cardiomyopathy who was asymptomatic, secondary to the accumulation of amylopectin-like fibrillar glycogen, in heart. In both patients, the diagnosis was confirmed by enzyme assessment. Our patients showed that GSD IV is not only liver or skeletal muscle disease, but also it can be presented in different form of the spectrum of cardiomyopathy from dilated to hypertrophic and from asymptomatic to decompensated heart failure. Also, to our knowledge, this is the first hypertrophic cardiomyopathy case due to GSD IV in the literature.

  12. Genetic analysis of a Chinese family with members affected with Usher syndrome type II and Waardenburg syndrome type IV.

    Science.gov (United States)

    Wang, Xueling; Lin, Xiao-Jiang; Tang, Xiangrong; Chai, Yong-Chuan; Yu, De-Hong; Chen, Dong-Ye; Wu, Hao

    2017-11-01

    The purpose of this study was to identify the genetic causes of a family presenting with multiple symptoms overlapping Usher syndrome type II (USH2) and Waardenburg syndrome type IV (WS4). Targeted next-generation sequencing including the exon and flanking intron sequences of 79 deafness genes was performed on the proband. Co-segregation of the disease phenotype and the detected variants were confirmed in all family members by PCR amplification and Sanger sequencing. The affected members of this family had two different recessive disorders, USH2 and WS4. By targeted next-generation sequencing, we identified that USH2 was caused by a novel missense mutation, p.V4907D in GPR98; whereas WS4 due to p.V185M in EDNRB. This is the first report of homozygous p.V185M mutation in EDNRB in patient with WS4. This study reported a Chinese family with multiple independent and overlapping phenotypes. In condition, molecular level analysis was efficient to identify the causative variant p.V4907D in GPR98 and p.V185M in EDNRB, also was helpful to confirm the clinical diagnosis of USH2 and WS4. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Structure and assembly of a trans-periplasmic channel for type IV pili in Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Jamie-Lee Berry

    2012-09-01

    Full Text Available Type IV pili are polymeric fibers which protrude from the cell surface and play a critical role in adhesion and invasion by pathogenic bacteria. The secretion of pili across the periplasm and outer membrane is mediated by a specialized secretin protein, PilQ, but the way in which this large channel is formed is unknown. Using NMR, we derived the structures of the periplasmic domains from N. meningitidis PilQ: the N-terminus is shown to consist of two β-domains, which are unique to the type IV pilus-dependent secretins. The structure of the second β-domain revealed an eight-stranded β-sandwich structure which is a novel variant of the HSP20-like fold. The central part of PilQ consists of two α/β fold domains: the structure of the first of these is similar to domains from other secretins, but with an additional α-helix which links it to the second α/β domain. We also determined the structure of the entire PilQ dodecamer by cryoelectron microscopy: it forms a cage-like structure, enclosing a cavity which is approximately 55 Å in internal diameter at its largest extent. Specific regions were identified in the density map which corresponded to the individual PilQ domains: this allowed us to dock them into the cryoelectron microscopy density map, and hence reconstruct the entire PilQ assembly which spans the periplasm. We also show that the C-terminal domain from the lipoprotein PilP, which is essential for pilus assembly, binds specifically to the first α/β domain in PilQ and use NMR chemical shift mapping to generate a model for the PilP:PilQ complex. We conclude that passage of the pilus fiber requires disassembly of both the membrane-spanning and the β-domain regions in PilQ, and that PilP plays an important role in stabilising the PilQ assembly during secretion, through its anchorage in the inner membrane.

  14. [Operative treatment of congenital hip osteoarthritis with high hip luxation (Crowe type IV)].

    Science.gov (United States)

    Kohlhof, H; Ziebarth, K; Gravius, S; Wirtz, D C; Siebenrock, K A

    2013-10-01

    The aim of the therapy is mechanical and functional stabilization of high dislocated hips with dysplasia coxarthrosis using total hip arthroplasty (THA). Developmental dysplasia of the hip (DDH) in adults, symptomatic dysplasia coxarthrosis, high hip dislocation according to Crowe type III/IV, and symptomatic leg length inequality. Cerebrospinal dysfunction, muscular dystrophy, apparent disturbance of bone metabolism, acute or chronic infections, and immunocompromised patients. With the patient in a lateral decubitus position an incision is made between the anterior border of the gluteus maximus muscle and the posterior border of the gluteus medius muscle (Gibson interval). Identification of the sciatic nerve to protect the nerve from traction disorders by visual control. After performing trochanter flip osteotomy, preparation of the true actetabulum if possible. Implantation of the reinforcement ring, preparation of the femur and if necessary for mobilization, resection until the trochanter minor. Test repositioning under control of the sciatic nerve. Finally, refixation of the trochanteric crest. During hospital stay, intensive mobilization of the hip joint using a continuous passive motion machine with maximum flexion of 70°. No active abduction and passive adduction over the body midline. Maximum weight bearing 10-15 kg for 8 weeks, subsequently, first clinical and radiographic follow-up and deep venous thrombosis prophylaxis until full weight bearing. From 1995 to 2012, 28 THAs of a Crow type IV high hip-dislocation were performed in our institute. Until now 14 patients have been analyzed during a follow-up of 8 years in 2012. Mid-term results showed an improvement of the postoperative clinical score (Merle d'Aubigné score) in 86 % of patients. Good to excellent results were obtained in 79 % of cases. Long-term results are not yet available. In one case an iatrogenic neuropraxia of the sciatic nerve was observed and after trauma a redislocation of the

  15. Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex.

    Science.gov (United States)

    Frick-Cheng, Arwen E; Pyburn, Tasia M; Voss, Bradley J; McDonald, W Hayes; Ohi, Melanie D; Cover, Timothy L

    2016-01-12

    Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and can deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization of T4SSs that secrete effector proteins. In this report, we describe the isolation and analysis of a membrane-spanning core complex from the Helicobacter pylori cag T4SS, which has an important role in the pathogenesis of gastric cancer. We show that this complex contains five H. pylori proteins, CagM, CagT, Cag3, CagX, and CagY, each of which is required for cag T4SS activity. CagX and CagY are orthologous to the VirB9 and VirB10 components of T4SSs in other bacterial species, and the other three Cag proteins are unique to H. pylori. Negative stain single-particle electron microscopy revealed complexes 41 nm in diameter, characterized by a 19-nm-diameter central ring linked to an outer ring by spoke-like linkers. Incomplete complexes formed by Δcag3 or ΔcagT mutants retain the 19-nm-diameter ring but lack an organized outer ring. Immunogold labeling studies confirm that Cag3 is a peripheral component of the complex. The cag T4SS core complex has an overall diameter and structural organization that differ considerably from the corresponding features of conjugative T4SSs. These results highlight specialized features of the H. pylori cag T4SS that are optimized for function in the human gastric mucosal environment. Type IV secretion systems (T4SSs) are versatile macromolecular machines that are present in many bacterial species. In this study, we investigated a T4SS found in the bacterium Helicobacter pylori. H. pylori is an important cause of stomach cancer, and the H. pylori T4SS contributes to cancer pathogenesis by mediating entry of CagA (an effector protein regarded as a "bacterial oncoprotein") into gastric epithelial cells. We isolated and analyzed the membrane-spanning core complex of the H. pylori T4SS and showed that it contains unique proteins

  16. Thickness and multi-axial stress creep rupture criteria of the Type IV component of a ferritic steel weld

    OpenAIRE

    Hayhurst, R James; Vakili-Tahami, Farid; Mustata, Radu; Hayhurst, David

    2004-01-01

    The paper summarises previously derived constitutive parameters for the temperatures 575, 590, 600, 620 and 640oC. Values of the multi-axial stress rupture parameter are reviewed and recorded. This constitutive parameter set is used to determine the thickness of the Type IV material zone to be 0.7mm. Next, values of Type IV multi-axial stress rupture parameter are determined for a wide range of butt-welded pipe and crosswelded uni-axial specimens, and an interpolation equation has been derive...

  17. Polarization Characteristics of Zebra Patterns in Type IV Solar Radio Bursts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneda, K.; Misawa, H.; Tsuchiya, F.; Obara, T. [Planetary Plasma and Atmospheric Research Center, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Iwai, K. [National Institute of Information and Communications Technology, 4-2-1, Nukui-Kitamachi, Koganei, Tokyo 184-8795 (Japan); Katoh, Y. [Department of Geophysics, Graduate School of Science, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Masuda, S., E-mail: k.kaneda@pparc.gp.tohoku.ac.jp [Institute for Space—Earth Environmental Research, Nagoya University, Nagoya, Aichi 464-8601 (Japan)

    2017-06-10

    The polarization characteristics of zebra patterns (ZPs) in type IV solar bursts were studied. We analyzed 21 ZP events observed by the Assembly of Metric-band Aperture Telescope and Real-time Analysis System between 2010 and 2015 and identified the following characteristics: a degree of circular polarization (DCP) in the range of 0%–70%, a temporal delay of 0–70 ms between the two circularly polarized components (i.e., the right- and left-handed components), and dominant ordinary-mode emission in about 81% of the events. For most events, the relation between the dominant and delayed components could be interpreted in the framework of fundamental plasma emission and depolarization during propagation, though the values of DCP and delay were distributed across wide ranges. Furthermore, it was found that the DCP and delay were positively correlated (rank correlation coefficient R = 0.62). As a possible interpretation of this relationship, we considered a model based on depolarization due to reflections at sharp density boundaries assuming fundamental plasma emission. The model calculations of depolarization including multiple reflections and group delay during propagation in the inhomogeneous corona showed that the DCP and delay decreased as the number of reflections increased, which is consistent with the observational results. The dispersive polarization characteristics could be explained by the different numbers of reflections causing depolarization.

  18. Type IV pili function upstream of the Dif chemotaxis pathway in Myxococcus xanthus EPS regulation.

    Science.gov (United States)

    Black, Wesley P; Xu, Qian; Yang, Zhaomin

    2006-07-01

    The developmental bacterium Myxococcus xanthus utilizes gliding motility to aggregate during the formation of multicellular fruiting bodies. The social (S) component of M. xanthus gliding motility requires at least two extracellular surface structures, type IV pili (Tfp) and the fibril polysaccharide or exopolysaccharide (EPS). Retraction of Tfp is proposed to power S motility and EPS from neighbouring cells is suggested to provide an anchor and trigger for Tfp retraction. The production of EPS in M. xanthus is regulated in part by the Dif chemosensory pathway; however, the input signal for the Dif pathway in EPS regulation remains to be uncovered. Using a genetic approach combined with quantitative and qualitative analysis, we demonstrate here that Tfp function upstream of the Dif proteins in regulating EPS production. The requirement of Tfp for the production of EPS was verified using various classes of Tfp mutants. Construction and examination of double and triple mutants indicated that mutations in dif are epistatic to those in pil. Furthermore, extracellular complementation between various Tfp and dif mutants suggests that Tfp, instead of being signals, may constitute the sensor or part of the sensor responsible for mediating signal input into the Dif pathway. We propose that S motility involves a regulatory loop in which EPS triggers Tfp retraction and Tfp provide proximity signals to the Dif pathway to modulate EPS production.

  19. Pseudoaneurysm Accompanied by Crowe Type IV Developmental Dysplasia of the Hip: A Case Report

    Directory of Open Access Journals (Sweden)

    Hirotake Yo

    2012-01-01

    Full Text Available We report the case of a 72-year-old woman whose pseudoaneurysm was difficult to diagnose and treat. The patient had a history of congenital dislocated hip and was undergoing anticoagulation therapy with warfarin due to the mitral valve replacement. Her chief complaint was pain and enlargement of the left buttock, and the laboratory tests revealed severe anemia. However, her elderly depression confused her chief complaint, and she was transferred to a psychiatric hospital. Two months after the onset of the symptoms, she was finally diagnosed with a pseudoaneurysm by contrast-enhanced CT and angiography. IDC coils were used for embolization. A plain CT showed hemostasis as well as a reduced hematoma at 2 months after the embolization. The possible contributing factors for the pseudoaneurysm included bleeding due to warfarin combined with an intramuscular hematoma accompanied by Crowe type IV developmental dysplasia of the hip that led to an arterial rupture by impingement between pelvis and femoral head. Since the warfarin treatment could not be halted due to the valve replacement, embolization was chosen for her treatment, and the treatment outcome was favorable.

  20. A Stochastic Proof of the Resonant Scattering Kernel and its Applications for Gen IV Reactors Type

    International Nuclear Information System (INIS)

    Becker, B.; Dagan, R.; Broeders, C.H.M.; Lohnert, G.

    2008-01-01

    Monte Carlo codes such as MCNP are widely accepted as almost-reference for reactor analysis. The Monte Carlo Code should therefore use as few as possible approximations in order to produce 'experimental-level' calculations. In this study we deal with one of the most problematic approximations done in MCNP in which the resonances are ignored for the secondary neutron energy distribution, namely the change of the energy and angular direction of the neutron after interaction with a heavy isotope with pronounced resonances. The endeavour of exploiting the influence of the resonances on the scattering kernel goes back to 1944 where E. Wigner and J. Wilkins developed the first temperature dependent scattering kernel. However only in 1998, the full analytical solution for the double differential resonant dependent scattering kernel was suggested by W. Rothenstein and R. Dagan. An independent stochastic approach is presented for the first time to confirm the above analytical kernel with a complete different methodology. Moreover, by manipulating in a subtle manner the scattering subroutine COLIDN of MCNP, it is proven that this very subroutine is, to some extent, inappropriate as well as the relevant explanation in the MCNP manual. The impact of this improved resonance dependent scattering kernel on diverse types of reactors, in particular for the Generation IV innovative core design HTR, is shown to be significant. (authors)

  1. Minicircle classes heterogeneity within the TcIII and TcIV discrete typing units of Trypanosoma cruzi.

    Science.gov (United States)

    Ortiz, S; Osorio, G; Solari, A

    2017-07-01

    The taxon Trypanosoma cruzi, causative agent of Chagas disease, is composed of several discrete typing units (DTUs) named TcI-TcVI, and Tcbat. The history of the taxon T. cruzi is known, even though several controversial aspects remain as the relationships between TcIII and TcIV. We analyzed cloned T. cruzi stocks pertaining to the seven DTUs by filter hybridization tests of PCR amplicons from minicircle variable regions and kinetoplast DNA probes. Minicircle DNA blots from the cloned stocks and filter hybridization with one TcI, one TcII, one TcV, one TcVI, three TcIII, one TcIV from North America and one TcIV kinetoplast DNA probes from South America revealed minicircle variable region cross-reaction in some T. cruzi DTUs probed. TcIII was heterogeneous in minicircle class composition, even though two TcIII probes revealed that a small fraction of minicircles cross-hybridized with the minicircles from the TcIII, TcV and TcVI DTUs. The minicircles of TcIV from North America cross-reacted only with TcIV from North America but not with TcIV stocks from Brazil and Bolivia. The results on minicircle cross-hybridizations are discussed in the context of RNA editing, mitochondrial function in T. cruzi DTUs. Copyright © 2017. Published by Elsevier B.V.

  2. A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori

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    Silja Wessler

    2017-12-01

    Full Text Available Intercellular junctions are crucial structural elements for the formation and maintenance of epithelial barrier functions to control homeostasis or protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of numerous cancers as well as multiple infectious diseases. Many bacterial pathogens harbor type IV secretion systems (T4SSs, which translocate virulence factors into host cells to hijack cellular processes. The pathology of the gastric pathogen and type-I carcinogen Helicobacter pylori strongly depends on a T4SS encoded by the cag pathogenicity island (cagPAI. This T4SS forms a needle-like pilus and its activity is accomplished by the pilus-associated factors CagL, CagI and CagY which target the host integrin-β1 receptor followed by injection of the CagA oncoprotein into non-polarized AGS gastric epithelial cells. The finding of a T4SS receptor, however, suggested the presence of a sophisticated control mechanism for the injection of CagA. In fact, integrins constitute a group of basolateral receptors, which are normally absent at apical surfaces of the polarized epithelium in vivo. Our new results demonstrate that T4SS-pilus formation during H. pylori infection of polarized epithelial cells occurs preferentially at basolateral sites, and not at apical membranes (Tegtmeyer et al., 2017. We propose a stepwise process how H. pylori interacts with components of intercellular tight junctions (TJs and adherens junctions (AJs, followed by contacting integrin-based focal adhesions to disrupt and transform the epithelial cell layer in the human stomach. The possible impact of this novel signaling cascade on pathogenesis during infection is reviewed.

  3. Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.

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    Aurélie Angot

    2007-01-01

    Full Text Available The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome to destroy earmarked proteins, but depending on the polyubiquitin chain topology, it can also result in new protein properties. Both ubiquitin-orchestrated protein degradation and modification have also been shown to be essential for the host's immune response to pathogens. Many animal and plant pathogenic bacteria utilize type III and/or type IV secretion systems to inject effector proteins into host cells, where they subvert host signaling cascades as part of their infection strategy. Recent progress in the determination of effector function has taught us that playing with the host's ubiquitination system seems a general tactic among bacteria. Here, we discuss how bacteria exploit this system to control the timing of their effectors' action by programming them for degradation, to block specific intermediates in mammalian or plant innate immunity, or to target host proteins for degradation by mimicking specific ubiquitin/proteasome system components. In addition to analyzing the effectors that have been described in the literature, we screened publicly available bacterial genomes for mimicry of ubiquitin proteasome system subunits and detected several new putative effectors. Our understanding of the intimate interplay between pathogens and their host's ubiquitin proteasome system is just beginning. This exciting research field will aid in better understanding this interplay, and may also provide new insights into eukaryotic ubiquitination processes.

  4. [Surgical treatment for talar neck fracture of Hawkins III, IV type with compression hollow screws combined with external fixator].

    Science.gov (United States)

    Wang, Xian-Xun; Wan, Chang-Tao; Yu, Li

    2017-05-25

    To investigate the clinical effects of compression hollow screws combined with external fixator in treating talar neck fracture of Hawkins III, IV type. From March 2010 to August 2014, 15 patients with talar neck fractures of Hawkins III, IV type were treated by open reduction and compression hollow screws fixation complicated with external fixator fixation. Including 9 males and 6 females, aged from 17 to 65 years old with an average of 37.5 years old. There were 9 cases of Hawkins III and 6 cases of Hawkins IV type. Postoperative radiographs and CT of ankle were used to evaluate the fracture healing and talar necrosis. The function of ankle and foot were evaluated by American Society of Ankle and Foot Surgery(AOFAS). All the patients were followed up for 8 to 55 months with an average of 23.5 months and all fractures got bone healing from 13 to 38 weeks with an average of (17.99±6.81) weeks. Traumatic arthritis occurred in 7 cases and talar necrosis in 6 cases (2 cases of type III and 4 cases of type IV) after operation. The average AOFAS score was 61.80±18.75, including excellent in 4 cases, good in 2 cases, fair in 4 cases and poor in 5 cases. Talar neck fracture with Hawkins III, IV type has large possibility to develop avascular necrosis. Hollow compression screw combined with external fixation may late weight-bearing for ankle and can sufficiently guarantee bone healing time, and achieve good results for the treatment of talar neck fracture.

  5. Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.

    Science.gov (United States)

    Deng, Yao; Wei, Shijie; Hu, Shijun; Chen, Jinlan; Tan, Zhiping; Yang, Yifeng

    2015-07-01

    Ehlers-Danlos syndrome type IV is an autosomal dominant connective tissue disease. Mutations in COL3A1 have been identified to underlie this disease; however, to the best of our knowledge, no COL3A1 mutations have been reported in Ehlers-Danlos syndrome type IV patients with an ascending aortic aneurysm. In order to develop further understanding of COL3A1 mutations, an Ehlers-Danlos syndrome type IV patient diagnosed with an ascending aortic aneurysm and a familial history of sudden mortality was analyzed. Genomic DNA was isolated from the peripheral blood of the patient and his family members. All coding exons of eight aneurysm-related genes (FBN1, TGFBR1, TGFBR 2, MYH11, ACTA2, SLC2A10, NOTCH1 and COL3A1) were amplified using polymerase chain reaction (PCR). The PCR products were sequenced with the ABI 3100 Genetic Analyzer, and a mutation was predicted and identified using Polyphen-2, SIFT and Mutation Taster. The novel mutation was identified as c.2950G>A in COL3A1, which results in p.G984R. All three programs predicted this mutation to be deleterous to the protein function. The novel mutation identified in this study is potentially responsible for Ehlers-Danlos syndrome type IV in this patient, and expands the spectrum of COL3A1 mutations.

  6. Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of Type 2 diabetes?

    DEFF Research Database (Denmark)

    Deacon, Carolyn F; Ahrén, Bo; Holst, Jens J

    2004-01-01

    that has warranted the design of inhibitor-based drugs. At the molecular level, DPP IV cleaves two amino acids from the N-terminus of the intact, biologically active forms of both so-called incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (formerly known......, prevent the progressive impairment of glucose metabolism in patients with impaired glucose tolerance and Type 2 diabetes. DPP IV has become a focus of attention for drug design, as it has a pivotal role in the rapid degradation of at least two of the hormones released during food ingestion, a property...

  7. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

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    Carrie L. Shaffer

    2016-04-01

    Full Text Available Bacteria utilize complex type IV secretion systems (T4SSs to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85 that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs.

  8. The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes.

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    Muriel Vayssier-Taussat

    2010-06-01

    Full Text Available Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage

  9. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

    Science.gov (United States)

    Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

    2013-01-01

    The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

  10. Apolipoprotein(a Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

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    Elena Sticchi

    Full Text Available In addition to the established association between high lipoprotein(a [Lp(a] concentrations and coronary artery disease, an association between Lp(a and venous thromboembolism (VTE has also been described. Lp(a is controlled by genetic variants in LPA gene, coding for apolipoprotein(a, including the kringle-IV type 2 (KIV-2 size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs (rs1853021, rs1800769, rs3798220, rs10455872 in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range 11(6-17 vs 15(9-25, p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001. KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9, as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.

  11. Properties of type IV plaster considering variation in the mold/model position during setting stage

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    Tarcisio José de Arruda Paes Junior

    2010-04-01

    Full Text Available Objective: To assess the influence of the position of the mold during the setting stage of type IV stone plaster Durone (Dentsply Ind. Com., Rio de Janeiro, Brazil, on the following properties: surface hardness and roughness. Methods: For the roughness test, two groups (n=6 in the form of pellets were prepared. In the first group, the surface of the base of the device was turned down during the plaster setting stage (N, in the second group this position was inverted, which has been described as an act of capsize it (E. For analysis, a roughness meter with reading precision of 0.01 μm was used. With regard to the hardness analysis, two groups with conical-shaped samples were obtained. The plasters were left to set under the same conditions of the mold/model position described for the previous experiment. Hardness measurement was performed in a durometer with a spherical penetrating tip for Rockwell readout. Three measurements were performed for each test specimen in both tests. Results: The hardness (N - 39.8, standard deviation = 3.3, E - 30.8, standard deviation = 5.6 and roughness data (N - 0.67, standard deviation = 0.17, E - 0.74, standard deviation = 0.13 submitted to the Student’s-t test (5% showed no statistically significant differences for the roughness test (0.489, but showed statistically significant differences for the hardness test (0.014. Conclusion: The variation in the mold/model position influenced the final characteristics of the specimens in terms of hardness, since those obtained with the capsize technique showed lower surface hardness, whereas for roughness these differences were not statistically significant.

  12. Carboxyl terminus heterogeneity of type IV fimbrial subunit protein of Pasteurella multocida isolates.

    Science.gov (United States)

    Shivachandra, Sathish Bhadravati; Kumar, Abhinendra; Yogisharadhya, Revanaiah; Ramakrishnan, M A; Viswas, K N

    2013-12-01

    Pasteurella multocida, a Gram-negative bacterial pathogen, known to affect a wide range of domestic as well as wild animal and avian species throughout the world by causing either systemic or localized infections termed as 'pasteurellosis'. P. multocida isolates are known to possess type IV fimbriae (pili) as one of the major virulence factors based on their role in adhesion to host surfaces and subsequent pathogenesis. In the present study, ptfA gene of Indian P. multocida isolates (n = 8) originated from different animal (buffalo, sheep, goat, pig) and avian host species (chicken, turkey, duck, quail) were amplified, cloned, sequenced and compared with available ptfA/fimbrial protein sequences in GenBank/publications (n = 22) to understand its variability with respect to geography/host/serogroup/disease specific patterns. Multiple sequence alignment revealed highly conserved N-terminus α-1 helix region and heterogeneous C-terminus (68-137 aa) comprised of β-strand regions (β1, β2, β3, β4) with conserved two pairs of cysteine residues. Interestingly, an existence of absolute homogeneity among the P. multocida isolates that caused haemorrhagic septicaemia in bovines and septicaemic pasteurellosis in sheep and goats was noticed. Pig isolates had 99.3% homogeneity. On contrary, more diversity (35.8%) was observed among isolates that caused fowl cholera in avians irrespective of identical capsular/somatic serogroup and similar host species. Phylogenetic analysis based on nucleotide sequences of ptfA gene revealed formation of mixed clusters with isolates representing different disease conditions as well as serogroups irrespective of country of origin which indicated the possible role of cross-species transmission among different animal/avian species. The study indicated highly conserved and host specific fimbriae among animal species than relatively divergent fimbriae among avian species.

  13. Cyclic Mechanical Stretch Induced Smooth Muscle Cell Changes in Cerebral Aneurysm Progress by Reducing Collagen Type IV and Collagen Type VI Levels

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    Peixi Liu

    2018-02-01

    Full Text Available Background/Aims: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. Methods: Saccular cerebral aneurysms (n=10 were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. Results: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05. KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. Conclusion: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic

  14. Colonoscopic perforation leading to a diagnosis of Ehlers Danlos syndrome type IV: a case report and review of the literature

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    Wolfe John

    2011-06-01

    Full Text Available Abstract Introduction Colonoscopic perforation is a rare but serious complication of colonoscopy. Factors known to increase the risk of perforation include colonic strictures, extensive diverticulosis, and friable tissues. We describe the case of a man who was found to have perforation of the sigmoid colon secondary to an undiagnosed connective tissue disorder (Ehlers-Danlos syndrome type IV while undergoing surveillance for hereditary non-polyposis colorectal cancer. Case presentation A 33-year-old Caucasian man presented to our hospital with an acute abdomen following a colonoscopy five days earlier as part of hereditary non-polyposis colorectal cancer screening. His medical history included bilateral clubfoot. His physical examination findings suggested left iliac fossa peritonitis. A computed tomographic scan revealed perforation of the sigmoid colon and incidentally a right common iliac artery aneurysm as well. Hartmann's procedure was performed during laparotomy. The patient recovered well post-operatively and was discharged. Reversal of the Hartmann's procedure was performed six months later. This procedure was challenging because of dense adhesions and friable bowel. The histology of bowel specimens from this surgery revealed thinning and fibrosis of the muscularis externa. The patient was subsequently noted to have transparency of truncal skin with easily visible vessels. An underlying collagen vascular disorder was suspected, and genetic testing revealed a mutation in the collagen type III, α1 (COL3A1 gene, which is consistent with a diagnosis of Ehlers-Danlos syndrome type IV. Conclusions Ehlers-Danlos syndrome type IV, the vascular type, is a rare disorder caused by mutations in the COL3A1 gene on chromosome 2q31. It is characterized by translucent skin, clubfoot, and the potentially fatal complications of spontaneous large vessel rupture, although spontaneous uterine and colonic perforations have also been reported in the

  15. Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis

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    delphine efaugaret

    2014-12-01

    Full Text Available The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type I interferon pathway.

  16. Spine deformities in patients with Ehlers-Danlos syndrome, type IV - late results of surgical treatment

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    Tesiorowski Maciej

    2010-11-01

    Full Text Available Abstract Background Spinal deformities in Ehlers-Danlos syndrome are usually progressive and may require operative treatment. There is limited number of studies describing late results of surgery in this disease. Methods This is a retrospective study of the records of 11 patients with Ehlers-Danlos syndrome type IV, treated surgically between 1990 and 2007. All patients underwent surgical treatment for spinal deformity. Duration of operation, type of instrumentation, intraoperative blood loss, complications and number of additional surgeries were noted. Radiographic measurement was performed on standing AP and lateral radiographs acquired before surgery, just after and at final follow up. Results The mean follow up period was 5.5 ± 2.9 years (range 1-10 years. The mean preoperative thoracic and lumbar curve were 109.5 ± 19.9° (range 83° - 142° and 75.6 ± 26.7° (range 40° - 108° respectively. Posterior spine fusion alone was performed on 6 patients and combined anterior and posterior fusion (one- or two stage on 5 cases. Posterior segmental spinal instrumentation was applied with use of hooks, screws and wires. The mean postoperative thoracic and lumbar curve improved to 79.3 ± 16.1° (range 56° - 105° and 58.5 ± 27.7° (range 10° - 95° respectively, with a slight loss of correction during follow up. The average thoracic and lumbar correction was 26.4 ± 14.9% (range 5.3 - 50.4% and 26.3 ± 21.2% (range 7.9 - 75%. Postoperatively, the mean kyphosis was 79.5 ± 40.3° (range 21° -170°, and lordosis was 50.8 ± 18.6° (range 20° -79°. Hyperkyphosis increased during follow up while lordosis remained stable. Mean Th12-L2 angle was -3.5 ±9.9° (range -19° - 15° postoperatively and did not change significantly during follow up. Conclusions Huge spinal deformities in patients with Ehlers-Danlos syndrome require complex and extensive surgery. There is a big risk of sagittal imbalance in this group.

  17. Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2003-01-01

    GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake i. e. inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satie......, it is as yet uncertain wether DDP-IV inhibitors will affect gastrointestinal motility, appetite and food intake. Even the effects of GLP-1 effects on the pancreatic islets may be partly neurally mediated and therefore uninfluenced by DPP-IV inhibition....

  18. Detection of Coxiella burnetii in Ambient Air after a Large Q Fever Outbreak

    NARCIS (Netherlands)

    de Rooij, Myrna M T; Borlée, Floor; Smit, Lidwien A M; de Bruin, Arnout; Janse, Ingmar; Heederik, Dick J J; Wouters, Inge M

    One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007-2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in

  19. Truncation of type IV pilin induces mucoidy in Pseudomonas aeruginosa strain PAO579.

    Science.gov (United States)

    Ryan Withers, T; Heath Damron, F; Yin, Yeshi; Yu, Hongwei D

    2013-06-01

    Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ(22) ). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP causing the conversion to mucoidy. Pseudomonas aeruginosa strain PAO579, a derivative of the nonmucoid strain PAO1, is mucoid due to an unidentified mutation (muc-23). Using whole genome sequencing, we identified 16 nonsynonymous and 15 synonymous single nucleotide polymorphisms (SNP). We then identified three tandem single point mutations in the pilA gene (PA4525), as the cause of mucoidy in PAO579. These tandem mutations generate a premature stop codon resulting in a truncated version of PilA (PilA(108) ), with a C-terminal motif of phenylalanine-threonine-phenylalanine (FTF). Inactivation of pilA(108) confirmed it was required for mucoidy. Additionally, algW and algU were also required for mucoidy of PAO579. Western blot analysis indicated that MucA was less stable in PAO579 than nonmucoid PAO1 or PAO381. The mucoid phenotype and high PalgU and PalgD promoter activities of PAO579 require pilA(108) , algW, algU, and rpoN encoding the alternative sigma factor σ(54) . We also observed that RpoN regulates expression of algW and pilA in PAO579. Together, these results suggest that truncation in type IV pilin in P. aeruginosa strain PAO579 can induce mucoidy through an AlgW/AlgU-dependent pathway. © 2013 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

  20. An anomalous type IV secretion system in Rickettsia is evolutionarily conserved.

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    Joseph J Gillespie

    Full Text Available Bacterial type IV secretion systems (T4SSs comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir. However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.Superimposition of T4SS structural/functional information over previously identified Rickettsia components implicate a functional Rickettsia T4SS. virB4, virB8 and virB9 are duplicated, yet only one copy of each has the conserved features of similar genes in other T4SSs. An extraordinarily duplicated VirB6 gene encodes five hydrophobic proteins conserved only in a short region known to be involved in DNA transfer in A. tumefaciens. virB1, virB2 and virB7 are newly identified, revealing a Rickettsia T4SS lacking only virB5 relative to the vir archetype. Phylogeny estimation suggests vertical inheritance of all components, despite gene rearrangements into an archipelago of five islets. Similarities of Rickettsia VirB7/VirB9 to ComB7/ComB9 proteins of epsilon-proteobacteria, as well as phylogenetic affinities to the Legionella lvh T4SS, imply the Rickettsiales ancestor acquired a vir-like locus from distantly related bacteria, perhaps while residing in a protozoan host. Modern modifications of these systems likely reflect diversification with various eukaryotic host cells.We present the rvh (Rickettsiales vir homolog T4SS, an evolutionary conserved transporter with an unknown role in rickettsial biology. This work lays the foundation for future laboratory characterization of this system, and also identifies the Legionella lvh T4SS as a suitable genetic model.

  1. The determination of PCBs in Rocky Flats Type IV waste sludge by gas chromatography/electron capture detection. Part 2

    International Nuclear Information System (INIS)

    Parish, K.J.; Applegate, D.V.; Postlethwait, P.D.; Boparai, A.S.; Reedy, G.T.

    1994-12-01

    Before disposal, radioactive sludge (Type IV) from Rocky Flats Plant (RFP) must be evaluated for polychlorinated biphenyl (PCB) content. The Type IV sludge consists of organic solvents, degreasers, cutting oils, and transuranic (TRU) waste mixed with calcium silicate (MicroCel E reg-sign and Oil Dri reg-sign to form a grease or paste-like material. For laboratory testing, a nonradioactive simulated Type 17V RFP sludge was prepared at Argonne National Laboratory-East (ANL-E). This sludge has a composition similar to that expected from field samples. In an earlier effort, a simplified method was developed for extraction, cleanup of extract, and determination of PCBs in samples of simulated sludge spiked with Aroclors 1254 and 1260. The simplified method has now been used to determine the presence and quantities of other Aroclors in the simulated sludge, namely, Aroclors 10 1 6, 1221, 1232, 1242, and 1248. The accuracy and precision of the data for these Aroclors were found to be similar to the data for sludges spiked with Aroclors 1254 and 1260. Since actual sludges may vary in composition, the method was also verified by analyzing another source of Type IV simulated sludge, prepared by Argonne National Laboratory-West (ANL-W)

  2. Expression, purification, crystallization and preliminary crystallographic analysis of PilA from the nontypeable Haemophilus influenzae type IV pilus

    International Nuclear Information System (INIS)

    Kolappan, Subramaniapillai; Tracy, Erin N.; Bakaletz, Lauren O.; Munson, Robert S. Jr; Craig, Lisa

    2012-01-01

    In order to characterize the type IV pili of nontypeable Haemophilus influenzae, an attempt to solve the atomic structure of the major pilin subunit PilA was initiated. A 1.73 Å resolution X-ray diffraction data set was collected from native N-terminally truncated PilA (ΔN-PilA). The type IV pili of nontypeable Haemophilus influenzae (NTHi) are involved in twitching motility, adherence, competence and biofilm formation. They are potential virulence factors for this important human pathogen and are thus considered to be vaccine targets. To characterize these pili, an attempt to solve the atomic structure of the major pilin subunit PilA was initiated. A 1.73 Å resolution X-ray diffraction data set was collected from native N-terminally truncated PilA (ΔN-PilA). Data processing indicated a hexagonal crystal system, which was determined to belong to space group P6 1 or P6 5 based on the systematic absences and near-perfect twinning of the crystal. The unit-cell parameters were a = b = 68.08, c = 197.03 Å with four molecules in the asymmetric unit, giving a solvent content of 50%. Attempts to solve the ΔN-PilA structure by molecular replacement with existing type IV pilin and type II secretion pseudopilin structures are in progress

  3. Genotyping of Coxiella burnetii from domestic ruminants in northern Spain

    Directory of Open Access Journals (Sweden)

    Astobiza Ianire

    2012-12-01

    Full Text Available Abstract Background Information on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA panel and Multispacer Sequence Typing (MST. Results A total of 45 samples from 4 goat herds (placentas, N = 4, 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20 and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21 were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several

  4. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Directory of Open Access Journals (Sweden)

    Joseph L Baker

    2013-04-01

    Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

  5. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Science.gov (United States)

    Baker, Joseph L; Biais, Nicolas; Tama, Florence

    2013-04-01

    Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P) from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD) simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon stretching.

  6. Midterm Outcome of Cementless Total Hip Arthroplasty in Crowe IV-Hartofilakidis Type III Developmental Dysplasia of the Hip.

    Science.gov (United States)

    Mu, Wenbo; Yang, Desheng; Xu, Boyong; Mamtimin, Askar; Guo, Wentao; Cao, Li

    2016-03-01

    Developmental dysplasia of the hip (DDH) is widespread in developing countries, and treating Crowe IV-Hartofilakidis Type III DDH in adults requires the use of a highly demanding technique. We sought to determine the outcome of cementless total hip arthroplasty using Zweymüller components to treat Crowe IV-Hartofilakidis Type III DDH. Fifty-eight patients (71 hips) with a mean age of 35.8 years at time of index operation were included in our study. The average duration of follow-up was 70.5 months. The acetabular component was placed in the true acetabulum in all cases, and subtrochanteric shortening osteotomy was performed in 61 hips. With any component revision for any reason as the end point, Kaplan-Meier survivorship analysis at 98 months revealed a cumulative survival rate for implanted components of 91.40%. The mean Harris Hip Score improved from 35.6 preoperatively to 82.9 postoperatively. There were 20 cases of intraoperative fracture, 1 case of complete nerve palsy, and 7 cases of transient nerve palsy. Revision surgery was performed in 7 patients because of cup loosening in 1, severe polyethylene wear in 4, cup breakage in 1, and dislocation in 1. Midterm results for cementless total hip arthroplasty in patients with Crowe IV-Hartofilakidis Type III DDH was satisfactory; however, intraoperative fracture and polyethylene wear were major complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Selection of optimal dental implant diameter and length in type IV bone: a three-dimensional finite element analysis.

    Science.gov (United States)

    Li, T; Kong, L; Wang, Y; Hu, K; Song, L; Liu, B; Li, D; Shao, J; Ding, Y

    2009-10-01

    This study aimed to create a 3D finite element model for continuous variation of implant diameter and length, thereby identifying their optimal range in type IV bone under biomechanical consideration. Implant diameter ranged from 3.0 to 5.0mm, and implant length ranged from 6.0 to 14.0mm. The results suggest that under axial load, the maximum Von Mises stresses in cortical and cancellous bones decrease by 50% and 27%, respectively; and under buccolingual load, by 52% and 60%, respectively. Under these two loads, the maximum displacements of implant-abutment complex decrease by 39% and 43%, respectively. These results indicate that in type IV bone, implant length is more crucial in reducing bone stress and enhancing the stability of implant-abutment complex than implant diameter. Biomechanically, implant diameter exceeding 4.0mm and implant length exceeding 9.0mm are the combination with optimal properties for a screwed implant in type IV bone.

  8. Immunochemical and autoantigenic properties of the globular domain of basement membrane collagen (type IV).

    Science.gov (United States)

    von der Mark, H; Oberbäumer, I; Timpl, R; Kemler, R; Wick, G

    1985-02-01

    Polyclonal rabbit antibodies raised against the globular domain NC1 of collagen IV from human placenta and a mouse tumor react with conformational antigenic determinants present on the NC1 hexamers and also with the three major subunits obtained after dissociation. The antibodies recognized unique structures within basement membranes and showed a broad tissue reactivity but only limited species cross-reactivity. Using these antibodies, it was possible to detect small amounts of collagen IV antigens from cell cultures and in serum. Monoclonal rat antibodies against mouse NC1 revealed a similar reaction potential. Autoantibodies could be produced in mice against mouse NC1 which react with kidney and lung basement membranes in a pathological manner, mimicking Goodpasture syndrome.

  9. Subtrochanteric femoral shortening osteotomy combined with cementless total hip replacement for Crowe type IV developmental dysplasia: a retrospective study.

    Science.gov (United States)

    Rollo, Giuseppe; Solarino, Giuseppe; Vicenti, Giovanni; Picca, Girolamo; Carrozzo, Massimiliano; Moretti, Biagio

    2017-12-01

    Total hip replacement for high dislocation of the hip presents some difficulties, considering patients' young ages, the abnormal hip anatomy and the high rate of complications. In this study, we present our experience in terms of clinical and radiological results in the treatment of Crowe type IV hips with subtrochanteric femoral shortening osteotomy and cementless total hip replacement. We retrospectively reviewed 15 patients with Crowe type IV hip dysplasia (two bilateral cases for a total of 17 hips) treated with cementless total hip replacement associated with shortening subtrochanteric osteotomies (nine transversal and eight Z-shape osteotomies) between March 2000 to February 2006. The mean follow-up was 88 months (range 63-133). Harris hip score, leg length discrepancy, neurological status, union status of the osteotomy and the component stability were the criteria of the evaluation. All complications were noted. The mean HHS improved from 38.3 (range 32-52) to 85.6 (range 69-90). The mean preoperative leg length discrepancy was of 45 mm (range 38-70) and reduced to a mean of 12 mm (range 9-1.6) postoperatively. All osteotomies resulted healed at an average of 12.3 weeks (range 10-15). No cases of delayed union or nonunion were detected. Two patients (11%) showed early symptoms of sciatic nerve palsy which resolved uneventfully in 6 months. There was no migrations and none of the implants required revision. Cementless THA with shortening subtrochanteric osteotomy is an effective method in the treatment of patients with Crowe type IV development dysplasia of the hip. IV.

  10. A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions.

    Science.gov (United States)

    Wang, Yong-Xin; Xue, Dan-Ting; Liu, Meng; Zhou, Zheng-Min; Shang, Jing

    2016-03-01

    The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions

  11. Laser and Light Treatments for Hair Reduction in Fitzpatrick Skin Types IV-VI: A Comprehensive Review of the Literature.

    Science.gov (United States)

    Fayne, Rachel A; Perper, Marina; Eber, Ariel E; Aldahan, Adam S; Nouri, Keyvan

    2018-04-01

    Unwanted facial and body hair presents as a common finding in many patients, such as females with hirsutism. With advances in laser and light technology, a clinically significant reduction in hair can be achieved in patients with light skin. However, in patients with darker skin, Fitzpatrick skin types (FST) IV-VI, the higher melanin content of the skin interferes with the proposed mechanism of laser-induced selective photothermolysis, which is to target the melanin in the hair follicle to cause permanent destruction of hair bulge stem cells. Many prospective and retrospective studies have been conducted with laser and light hair-removal devices, but most exclude patients with darkly pigmented skin, considering them a high-risk group for unwanted side effects, including pigmentation changes, blisters, and crust formation. We reviewed the published literature to obtain studies that focused on hair reduction for darker skin types. The existing literature for this patient population identifies longer wavelengths as a key element of the treatment protocol and indicates neodymium-doped yttrium aluminum garnet (Nd:YAG), diode, alexandrite, and ruby lasers as well as certain intense pulsed light sources for safe hair reduction with minimal side effects in patients with FST IV-VI, so long as energy settings and wavelengths are appropriate. Based on the findings in this review, safe and effective hair reduction for patients with FST IV-VI is achievable under proper treatment protocols and energy settings.

  12. Identification of branched-chain amino acid aminotransferases active towards (R)-(+)-1-phenylethylamine among PLP fold type IV transaminases.

    Science.gov (United States)

    Bezsudnova, Ekaterina Yu; Dibrova, Daria V; Nikolaeva, Alena Yu; Rakitina, Tatiana V; Popov, Vladimir O

    2018-04-10

    New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity. Earlier, (R)-selective class IV transaminases were found to be active, apart from (R)-PEA, only with some other (R)-primary amines and D-amino acids. Sequences encoding new transaminases with mixed type of activity were found by searching for changes in the conserved motifs of sequences of BCAT by different bioinformatics tools. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Identification of a distinct type IV collagen α chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome

    International Nuclear Information System (INIS)

    Hostikka, S.L.; Hoeyhtyae, M.; Tryggvason, K.; Eddy, R.L.; Byers, M.G.; Shows, T.B.

    1990-01-01

    The authors have identified and extensively characterized a type IV collagen α chain, referred to as α5(IV). Four overlapping cDNA clones isolated contain an open reading frame for 543 amino acid residues of the carboxyl-terminal end of a collagenous domain, a 229-residue carboxyl-terminal noncollagenous domain, and 1201 base pairs coding for a 3' untranslated region. The collagenous Gly-Xaa-Yaa repeat sequence has five imperfections that coincide with those in the corresponding region of the α1(IV) chain. The noncollagenous domain has 12 conserved cysteine residues and 83% and 63% sequence identity with the noncollagenous domains of the α1(IV) and α2(IV) chains, respectively. The α5(IV) chain has less sequence identity with the putative bovine α3(IV) and α4(IV) chains. Antiserum against an α5(IV) synthetic peptide stained a polypeptide chain of about 185 kDa by immunoblot analysis and immunolocalization of the chain in human kidney was almost completely restricted to the glomerulus. The gene was assigned to the Xq22 locus by somatic cell hybrids and in situ hybridization. This may be identical or close to the locus of the X chromosome-linked Alport syndrome that is believed to be a type IV collagen disease

  14. Endovascular treatment for a spontaneous rupture of the posterior tibial artery in a patient with Ehlers-Danlos syndrome Type IV: report of a case.

    Science.gov (United States)

    Matsushima, Kazuhide; Takara, Hiroaki

    2009-01-01

    This report presents the case of a 27-year-old woman with a history of Ehlers-Danlos syndrome Type IV (EDS-IV) who suffered from acute compartment syndrome caused by the spontaneous rupture of the posterior tibial artery. Bleeding control was achieved by endovascular embolization. A fasciotomy was successfully performed without any trouble with hemorrhaging. Endovascular treatment could therefore represent the ideal option for treating infrapopliteal lesions, particularly for EDS-IV patients.

  15. Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2003-01-01

    GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake i. e. inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety...... of the peptide is necessary because of an exceptionally rapid rate of degradation catalyzed the enzyme dipeptidyl peptidase IV. With inhibitors of this enzyme, it is possible to protect the endogenous hormone and thereby elevate both fasting and postprandial levels of the active hormone. This leads to enhanced...

  16. Simulation of a TMI-2 type scenario at the ROSA-IV program's large scale test facility: a first look

    International Nuclear Information System (INIS)

    Schultz, R.R.; Kukita, Yutaka; Tasaka, Kanji

    1984-09-01

    The Three Mile Island-2 (TMI-2) type scenario in a Westinghouse (W) type four loop pressurized water reactor (PWR) was studied in preparation for upcoming tests in the ROSA-IV Program's Large Scale Test Facility (LSTF). The LSTF is a 1/48 scale simulator of a W type four loop PWR with full scale component elevation differences. TMI-2 scenario simulation analyses were conducted to establish a pretest prediction data base for RELAP5 code evaluation purposes and to furnish a means of evaluating the LSTF's capability to simulate the reference PWR. The basis for such RELAP5 calculations and the similarities between the LSTF and reference PWR thermal-hydraulic behaviors during a TMI-2 type scenario are presented. (author)

  17. Detection and differentiation of coxiella burnetii in biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Frazier, Marvin E. (Richland, WA); Mallavia, Louis P. (Moscow, ID); Samuel, James E. (Derwood, MD); Baca, Oswald G. (Albuquerque, NM)

    1993-01-01

    Methods for detecting the presence of Coxiella burnetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA with a DNA probe containing DNA sequences that specifically hybridize with C. burnetii DNA of strains associated with the capacity to cause acute or chronic disease.

  18. Detection and differentiation of coxiella burnetii in biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Frazier, Marvin E. (Richland, WA); Mallavia, Louis P. (Moscow, ID); Samuel, James E. (Pullman, WA); Baca, Oswald G. (Albuquerque, NM)

    1990-01-01

    Methods for detecting the presence of Coxiella burenetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA (specifically rickettsial DNA) with a C. burnetii-specific labeled DNA probe. Radioisotope and biotin labels are preferred, allowing detection through autoradiography and colorimetric assays, respectively.

  19. Detection and differentiation of coxiella burnetii in biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Frazier, Marvin E. (Richland, WA); Mallavia, Louis P. (Moscow, ID); Baca, Oswald G. (Albuquerque, NM); Samuel, James E. (Pullman, WA)

    1989-01-01

    Methods for detecting the presence of Coxiella burnetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA (specifically rickettsial DNA) with a C. burnetii-specific labeled DNA probe. Radioisotope and biotin labels are preferred, allowing detection through autoradiography and colorimetric assays, respectively.

  20. Brucella and Coxiella; if you don't look, you don't find.

    Science.gov (United States)

    Lambourne, Jonathan R; Brooks, Tim

    2015-02-01

    Brucella and Coxiella are similar; both are obligate intracellular, zoonotic pathogens with a broad geographic distribution. Infection in animals is usually asymptomatic, but causes fetal loss and therefore has significant economic impact. Human infection may be asymptomatic or give rise to either organ-specific or multi-system disease. Organism culture is challenging for Coxiella and can lack sensitivity for Brucella. Therefore, infection is most commonly diagnosed by serology, but this may be negative in early infection and serology results may be challenging to interpret. Both Brucella and Coxiella are typically susceptible to a wide range of antimicrobials, but long courses may be needed. © 2015 Royal College of Physicians.

  1. Early venous manifestation of Ehlers-Danlos syndrome Type IV through a novel mutation in COL3A1.

    Science.gov (United States)

    Wendorff, Heiko; Pelisek, Jaroslav; Zimmermann, Alexander; Mayer, Karin; Seidel, Heide; Weirich, Gregor; Hausser, Ingrid; Siegel, Corinna; Zernecke, Alma; Eckstein, Hans-Henning

    2013-01-01

    Ehlers-Danlos syndrome (EDS) leads to abnormalities in the synthesis of collagen and complications involving arterial vessels. We describe here a mutation in the intron 14 of the COL3A1 gene leading to EDS Type IV (EDS IV) associated with venous manifestations only. The patient, an 18-year-old male, suffered from truncal varicosity of the long saphenous vein on both sides. Conventional stripping surgery of the left saphenous vein revealed an extremely vulnerable ectatic superficial femoral vein. An inserted vein graft occluded, and venous thrombectomy was unsuccessful. A conservative anticoagulant and compression therapy finally succeeded. This is the first report describing EDS IV due to a mutation in intron 14 of the COL3A1 gene leading to venous manifestations without affecting arterial vessels at clinical presentation. Our findings imply that molecular genetic analysis should be considered in patients with unusual clinical presentation and that conservative therapy should be applied until a suspected clinical diagnosis has been secured. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. [Clinical value of "Kou mode of hepatic hilar anastomosis" in resection of type III or IV hepatic hilar cholangiocarcinoma].

    Science.gov (United States)

    He, Xiao-dong; Liu, Wei; Tao, Lian-yuan; Zhang, Zhen-huan; Cai, Lei; Zhang, Shuang-min

    2009-08-01

    To evaluate the surgical technique of "Kou mode of hepatic hilar anastomosis" in the treatment for type III or IV hilar cholangiocarcinoma. The clinical data of 89 patients with type III or IV hilar cholangiocarcinoma surgically treated in our department between Jan. 1990 and Jan. 2008 were retrospectively analyzed. Since January 2000, "Kou mode of hepatic hilar anastomosis" was performed for some patients with advanced hilar cholangiocarcinoma. The patients were divided into two groups: group A treated between 1990 and 1999, group B between 2000 and 2008. The rate of resection, therapeutic efficacy and complications in these two groups were compared, respectively. Of the 37 cases with hilar cholangiocarcinoma in group A, 4 were surgically treated (10.8%), with 1 (2.7%) radical resection and 3 (8.1%) palliative resection. Among the 52 cases with hilar cholangiocarcinoma in the group B, 35 (67.3%) received surgical resection, of them 15 (28.8%) underwent radical resection and 20 (38.5%) had palliative resection. Twenty-eight of these 35 cases underwent the "Kou mode of hepatic hilar anastomosis". The resection rate of advanced hilar cholangiocarcinoma in the group B was significantly higher than that in group A (P anastomosis" developed bile leakage to a varying degree and recovered after drainage and symptomatic treatment. The resection rate of type III or IV advanced hilar cholangiocarcinoma can be remarkably improved by using a novel alternative surgical technique called "Kou mode of hepatic hilar anastomosis". However, the long-term outcome still needs to be determined by close follow-up and further observation.

  3. Involvement of a plasmid-encoded type IV secretion system in the plant tissue watersoaking phenotype of Burkholderia cenocepacia.

    Science.gov (United States)

    Engledow, Amanda S; Medrano, Enrique G; Mahenthiralingam, Eshwar; LiPuma, John J; Gonzalez, Carlos F

    2004-09-01

    Burkholderia cenocepacia strain K56-2, a representative of the Burkholderia cepacia complex, is part of the epidemic and clinically problematic ET12 lineage. The strain produced plant tissue watersoaking (ptw) on onion tissue, which is a plant disease-associated trait. Using plasposon mutagenesis, mutants in the ptw phenotype were generated. The translated sequence of a disrupted gene (ptwD4) from a ptw-negative mutant showed homology to VirD4-like proteins. Analysis of the region proximal to the transfer gene homolog identified a gene cluster located on the 92-kb resident plasmid that showed homology to type IV secretion systems. The role of ptwD4, ptwC, ptwB4, and ptwB10 in the expression of ptw activity was determined by conducting site-directed mutagenesis. The ptw phenotype was not expressed by K56-2 derivatives with a disruption in ptwD4, ptwB4, or ptwB10 but was observed in a derivative with a disruption in ptwC. Complementation of ptw-negative K56-2 derivatives in trans resulted in complete restoration of the ptw phenotype. In addition, analysis of culture supernatants revealed that the putative ptw effector(s) was a secreted, heat-stable protein(s) that caused plasmolysis of plant protoplasts. A second chromosomally encoded type IV secretion system with complete homology to the VirB-VirD system was identified in K56-2. Site-directed mutagenesis of key secretory genes in the VirB-VirD system did not affect expression of the ptw phenotype. Our findings indicate that in strain K56-2, the plasmid-encoded Ptw type IV secretion system is responsible for the secretion of a plant cytotoxic protein(s).

  4. T346Hunter: a novel web-based tool for the prediction of type III, type IV and type VI secretion systems in bacterial genomes.

    Directory of Open Access Journals (Sweden)

    Pedro Manuel Martínez-García

    Full Text Available T346Hunter (Type Three, Four and Six secretion system Hunter is a web-based tool for the identification and localisation of type III, type IV and type VI secretion systems (T3SS, T4SS and T6SS, respectively clusters in bacterial genomes. Non-flagellar T3SS (NF-T3SS and T6SS are complex molecular machines that deliver effector proteins from bacterial cells into the environment or into other eukaryotic or prokaryotic cells, with significant implications for pathogenesis of the strains encoding them. Meanwhile, T4SS is a more functionally diverse system, which is involved in not only effector translocation but also conjugation and DNA uptake/release. Development of control strategies against bacterial-mediated diseases requires genomic identification of the virulence arsenal of pathogenic bacteria, with T3SS, T4SS and T6SS being major determinants in this regard. Therefore, computational methods for systematic identification of these specialised machines are of particular interest. With the aim of facilitating this task, T346Hunter provides a user-friendly web-based tool for the prediction of T3SS, T4SS and T6SS clusters in newly sequenced bacterial genomes. After inspection of the available scientific literature, we constructed a database of hidden Markov model (HMM protein profiles and sequences representing the various components of T3SS, T4SS and T6SS. T346Hunter performs searches of such a database against user-supplied bacterial sequences and localises enriched regions in any of these three types of secretion systems. Moreover, through the T346Hunter server, users can visualise the predicted clusters obtained for approximately 1700 bacterial chromosomes and plasmids. T346Hunter offers great help to researchers in advancing their understanding of the biological mechanisms in which these sophisticated molecular machines are involved. T346Hunter is freely available at http://bacterial-virulence-factors.cbgp.upm.es/T346Hunter.

  5. Enhanced Tracking of Nosocomial Transmission of Endemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Type IV Isolates among Patients and Environmental Sites by Use of Whole-Genome Sequencing.

    Science.gov (United States)

    Kinnevey, Peter M; Shore, Anna C; Mac Aogáin, Micheál; Creamer, Eilish; Brennan, Gráinne I; Humphreys, Hilary; Rogers, Thomas R; O'Connell, Brian; Coleman, David C

    2016-02-01

    Whole-genome sequencing (WGS) of 41 patient and environmental sequence type 22 methicillin-resistant Staphylococcus aureus staphylococcal cassette chromosome mec type IV (ST22-MRSA-IV) isolates recovered over 6 weeks in one acute hospital ward in Dublin, Ireland, where ST22-MRSA IV is endemic, revealed 228 pairwise combinations differing by transmission events (CTEs). In contrast, 15 pairwise combinations of isolates representing five CTEs were previously identified by conventional molecular epidemiological typing. WGS enhanced ST22-MRSA-IV tracking and highlighted potential transmission of MRSA via the hospital environment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Hopf and Bautin Bifurcation in a Tritrophic Food Chain Model with Holling Functional Response Types III and IV

    Science.gov (United States)

    Castellanos, Víctor; Castillo-Santos, Francisco Eduardo; Dela-Rosa, Miguel Angel; Loreto-Hernández, Iván

    In this paper, we analyze the Hopf and Bautin bifurcation of a given system of differential equations, corresponding to a tritrophic food chain model with Holling functional response types III and IV for the predator and superpredator, respectively. We distinguish two cases, when the prey has linear or logistic growth. In both cases we guarantee the existence of a limit cycle bifurcating from an equilibrium point in the positive octant of ℝ3. In order to do so, for the Hopf bifurcation we compute explicitly the first Lyapunov coefficient, the transversality Hopf condition, and for the Bautin bifurcation we also compute the second Lyapunov coefficient and verify the regularity conditions.

  7. Does restoration of hip center with subtrochanteric osteotomy provide preferable outcome for Crowe type III–IV irreducible development dysplasia of the hip??

    Directory of Open Access Journals (Sweden)

    Tzu-Cheng Yang

    2017-12-01

    Conclusion: With regard to both clinical outcomes and complication rates, restoration of the hip center using subtrochanteric osteotomy may provide similar benefits to those patients with proximal placement of the acetabular component in treating Crowe type III–IV DDH.

  8. Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne S.; Karsdal, Morten A.; Nawrocki, Arkadiusz

    2011-01-01

    Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens...

  9. First Report of cfr-Carrying Plasmids in the Pandemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Staphylococcal Cassette Chromosome mec Type IV Clone.

    Science.gov (United States)

    Shore, Anna C; Lazaris, Alexandros; Kinnevey, Peter M; Brennan, Orla M; Brennan, Gráinne I; O'Connell, Brian; Feßler, Andrea T; Schwarz, Stefan; Coleman, David C

    2016-05-01

    Linezolid is often the drug of last resort for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins; cfr, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPSA) resistance; its homologue cfr(B); or optrA, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare in S. aureus, and cfr is even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected to cfr PCR, PhLOPSA susceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling, spa typing, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification, cfr plasmid sequence analysis, and optrA and cfr(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosome mec type IV (ST22-MRSA-IV)/spa type t032 isolates, harbored cfr, exhibited the PhLOPSA phenotype, and lacked optrA and cfr(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harbored cfr and fexA on a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harbored cfr and lsa(B) on a novel 27-kb plasmid. This is the first report of cfr in the pandemic ST22-MRSA-IV clone. Different cfr plasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential. Copyright © 2016 Shore et al.

  10. Cementless arthroplasty with a distal femoral shortening for the treatment of Crowe type IV developmental hip dysplasia.

    Science.gov (United States)

    Guo, Chang-Yong; Liang, Bo-Wei; Sha, Mo; Kang, Liang-Qi; Wang, Jiang-Ze; Ding, Zhen-Qi

    2015-01-01

    Severe developmental dysplasia of the hip is a surgical challenge. The purpose of this study is to describe the cementless arthroplasty with a distal femoral shortening osteotomy for Crowe type IV developmental hip dysplasia and to report the results of this technique. 12 patients (2 male and 10 female) of Crowe type IV developmental hip dysplasia operated between January 2005 and December 2010 were included in the study. All had undergone cementless arthroplasty with a distal femoral shortening osteotomy. Acetabular cup was placed at the level of the anatomical position in all the hips. The clinical outcomes were assessed and radiographs were reviewed to evaluate treatment effects. The mean followup for the 12 hips was 52 months (range 36-82 months). The mean Harris hip score improved from 41 points (range 28-54) preoperatively to 85 points (range 79-92) at the final followup. The mean length of bone removed was 30 mm (range 25-40 mm). All the osteotomies healed in a mean time of 13 weeks (range 10-16 weeks). There were no neurovascular injuries, pulmonary embolism or no infections. Our study suggests that cementless arthroplasty with a distal femoral shortening is a safe and effective procedure for severe developmental dysplasia of the hip.

  11. Loss of Col3a1, the gene for Ehlers-Danlos syndrome type IV, results in neocortical dyslamination.

    Directory of Open Access Journals (Sweden)

    Sung-Jin Jeong

    Full Text Available It has recently been discovered that Collagen III, the encoded protein of the type IV Ehlers-Danlos Syndrome (EDS gene, is one of the major constituents of the pial basement membrane (BM and serves as the ligand for GPR56. Mutations in GPR56 cause a severe human brain malformation called bilateral frontoparietal polymicrogyria, in which neurons transmigrate through the BM causing severe mental retardation and frequent seizures. To further characterize the brain phenotype of Col3a1 knockout mice, we performed a detailed histological analysis. We observed a cobblestone-like cortical malformation, with BM breakdown and marginal zone heterotopias in Col3a1⁻/⁻ mouse brains. Surprisingly, the pial BM appeared intact at early stages of development but starting as early as embryonic day (E 11.5, prominent BM defects were observed and accompanied by neuronal overmigration. Although collagen III is expressed in meningeal fibroblasts (MFs, Col3a1⁻/⁻ MFs present no obvious defects. Furthermore, the expression and posttranslational modification of α-dystroglycan was undisturbed in Col3a1⁻/⁻ mice. Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.

  12. Genetic and mass spectrometry analyses of the unusual type IV-like pili of the archaeon Methanococcus maripaludis.

    Science.gov (United States)

    Ng, Sandy Y M; Wu, John; Nair, Divya B; Logan, Susan M; Robotham, Anna; Tessier, Luc; Kelly, John F; Uchida, Kaoru; Aizawa, Shin-Ichi; Jarrell, Ken F

    2011-02-01

    The structure of pili from the archaeon Methanococcus maripaludis is unlike that of any bacterial pili. However, genetic analysis of the genes involved in the formation of these pili has been lacking until this study. Pili were isolated from a nonflagellated (ΔflaK) mutant and shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to consist primarily of subunits with an apparent molecular mass of 17 kDa. In-frame deletions were created in three genes, MMP0233, MMP0236, and MMP0237, which encode proteins with bacterial type IV pilin-like signal peptides previously identified by in silico methodology as likely candidates for pilus structural proteins. Deletion of MMP0236 or MMP0237 resulted in mutant cells completely devoid of pili on the cell surface, while deletion of the third pilin-like gene, MMP0233, resulted in cells greatly reduced in the number of pili on the surface. Complementation with the deleted gene in each case returned the cells to a piliated state. Surprisingly, mass spectrometry analysis of purified pili identified the major structural pilin as another type IV pilin-like protein, MMP1685, whose gene is located outside the first pilus locus. This protein was found to be glycosylated with an N-linked branched pentasaccharide glycan. Deletion and complementation analysis confirmed that MMP1685 is required for piliation.

  13. Two transitional type Ia supernovae located in the Fornax cluster member NGC 1404: SN 2007on and SN 2011iv

    Science.gov (United States)

    Gall, C.; Stritzinger, M. D.; Ashall, C.; Baron, E.; Burns, C. R.; Hoeflich, P.; Hsiao, E. Y.; Mazzali, P. A.; Phillips, M. M.; Filippenko, A. V.; Anderson, J. P.; Benetti, S.; Brown, P. J.; Campillay, A.; Challis, P.; Contreras, C.; Elias de la Rosa, N.; Folatelli, G.; Foley, R. J.; Fraser, M.; Holmbo, S.; Marion, G. H.; Morrell, N.; Pan, Y.-C.; Pignata, G.; Suntzeff, N. B.; Taddia, F.; Robledo, S. Torres; Valenti, S.

    2018-03-01

    We present an analysis of ultraviolet (UV) to near-infrared observations of the fast-declining Type Ia supernovae (SNe Ia) 2007on and 2011iv, hosted by the Fornax cluster member NGC 1404. The B-band light curves of SN 2007on and SN 2011iv are characterised by Δm15 (B) decline-rate values of 1.96 mag and 1.77 mag, respectively. Although they have similar decline rates, their peak B- and H-band magnitudes differ by 0.60 mag and 0.35 mag, respectively. After correcting for the luminosity vs. decline rate and the luminosity vs. colour relations, the peak B-band and H-band light curves provide distances that differ by 14% and 9%, respectively. These findings serve as a cautionary tale for the use of transitional SNe Ia located in early-type hosts in the quest to measure cosmological parameters. Interestingly, even though SN 2011iv is brighter and bluer at early times, by three weeks past maximum and extending over several months, its B - V colour is 0.12 mag redder than that of SN 2007on. To reconcile this unusual behaviour, we turn to guidance from a suite of spherical one-dimensional Chandrasekhar-mass delayed-detonation explosion models. In this context, 56Ni production depends on both the so-called transition density and the central density of the progenitor white dwarf. To first order, the transition density drives the luminosity-width relation, while the central density is an important second-order parameter. Within this context, the differences in the B - V colour evolution along the Lira regime suggest that the progenitor of SN 2011iv had a higher central density than SN 2007on. The photometry tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A58

  14. Detection of Coxiella burnetii in Ambient Air after a Large Q Fever Outbreak.

    Directory of Open Access Journals (Sweden)

    Myrna M T de Rooij

    Full Text Available One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007-2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in ambient air at residential locations in the most affected area in the Netherlands (the South-East, in the year immediately following the outbreak. One-week average ambient particulate matter < 10 μm samples were collected at eight locations from March till September 2011. Presence of Coxiella burnetii DNA was determined by quantitative polymerase chain reaction. Associations with various spatial and temporal characteristics were analyzed by mixed logistic regression. Coxiella burnetii DNA was detected in 56 out of 202 samples (28%. Airborne Coxiella burnetii presence showed a clear seasonal pattern coinciding with goat kidding. The spatial variation was significantly associated with number of goats on the nearest goat farm weighted by the distance to the farm (OR per IQR: 1.89, CI: 1.31-2.76. We conclude that in the year after a large Q fever outbreak, temporal variation of airborne Coxiella burnetii is suggestive to be associated with goat kidding, and spatial variation with distance to and size of goat farms. Aerosol measurements show to have potential for source identification and attribution of an airborne pathogen, which may also be applicable in early stages of an outbreak.

  15. Modulation of Kingella kingae adherence to human epithelial cells by type IV Pili, capsule, and a novel trimeric autotransporter.

    Science.gov (United States)

    Porsch, Eric A; Kehl-Fie, Thomas E; St Geme, Joseph W

    2012-10-23

    Kingella kingae is an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. Colonization of the posterior pharynx is a key step in the pathogenesis of K. kingae disease. Previous work established that type IV pili are necessary for K. kingae adherence to the respiratory epithelium. In this study, we set out to identify additional factors that influence K. kingae interactions with human epithelial cells. We found that genetic disruption of the gene encoding a predicted trimeric autotransporter protein called Knh (Kingella NhhA homolog) resulted in reduced adherence to human epithelial cells. In addition, we established that K. kingae elaborates a surface-associated polysaccharide capsule that requires a predicted ABC-type transporter export operon called ctrABCD for surface presentation. Furthermore, we discovered that the presence of a surface capsule interferes with Knh-mediated adherence to human epithelial cells by nonpiliated organisms and that maximal adherence in the presence of a capsule requires the predicted type IV pilus retraction machinery, PilT/PilU. On the basis of the data presented here, we propose a novel adherence mechanism that allows K. kingae to adhere efficiently to human epithelial cells while remaining encapsulated and more resistant to immune clearance. Kingella kingae is a Gram-negative bacterium that is being recognized increasingly as a cause of joint and bone infections in young children. The pathogenesis of disease due to K. kingae begins with bacterial colonization of the upper respiratory tract, and previous work established that surface hair-like fibers called type IV pili are necessary for K. kingae adherence to respiratory epithelial cells. In this study, we set out to identify additional factors that influence K. kingae interactions with respiratory epithelial cells. We discovered a novel surface protein called

  16. Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex

    International Nuclear Information System (INIS)

    Adachi, Yusuke; Yoshikawa, Yutaka; Yoshida, Jiro; Kodera, Yukihiro; Katoh, Akira; Takada, Jitsuya; Sakurai, Hiromu

    2006-01-01

    Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx) 2 ) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx) 2 was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx) 2 was examined in obesity-linked type 2 diabetic KKA y mice. Treatment of VO(alx) 2 for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA y mice; however, it had no effect on hypoadiponectinemia. VO(alx) 2 also improved hyperleptinemia, following attenuation of obesity in KKA y mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx) 2 is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal

  17. Long-Term Results of Cementless Total Hip Arthroplasty With Subtrochanteric Shortening Osteotomy in Crowe Type IV Developmental Dysplasia.

    Science.gov (United States)

    Wang, Duan; Li, Ling-Li; Wang, Hao-Yang; Pei, Fu-Xing; Zhou, Zong-Ke

    2017-04-01

    When surgeons reconstruct hips with a high dislocation related to severe developmental dysplasia of the hip (DDH) in total hip arthroplasty (THA), archiving long-term stable implant fixation and improving patient function and satisfaction remain challenging. The purpose of this study was to evaluate the 10-year outcomes of transverse subtrochanteric shortening osteotomy in cementless, modular THA in Crowe type IV-Hartofilakidis type III DDH. We reviewed 62 patients (76 hips) who underwent cementless THA with transverse subtrochanteric shortening osteotomy from 2002-2010. There were 49 women and 13 men with a mean age of 38.8 years, all of whom had Crowe type IV DDH. Mean follow-up period was 10 years. The acetabular cup was implanted in placement of the anatomical hip center in all hips. The mean Harris Hip Score significantly improved from 38.8 points to 86.1 points. Similarly, modified Merle d'Aubigne and Postel Hip Score, Hip dysfunction and Osteoarthritis Outcome Score, and SF-12 also significantly improved. The mean limb length discrepancy was reduced from 4.3 cm to 1.0 cm. At mean follow-up of 10 years, there were 3 cases of postoperative dislocation, 2 cases of transient nerve palsy, 1 case of nonunion, and 4 cases of intraoperative fracture. Revision surgery was performed in 2 patients due to isolated loosening of acetabular component and femoral stem, respectively. Our data demonstrated that the cementless, modular THA combined with transverse subtrochanteric shortening osteotomy was an effective and reliable technique with high rates of successful fixation of the implants and satisfactory clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A study of visual double stars with early type primaries. IV. Astrophysical data

    International Nuclear Information System (INIS)

    Lindroos, K.P.

    1985-01-01

    Astrophysical parameters (MK class, colour excess, absolute magnitude, distance, effective temperature mass and age) are derived from calibrations of the uvbyβ indices for the members of 253 double stars with O or B type primaries and faint secondaries. The photometric spectral classification is compared to the MK classes and the agreement is very good. The derived data together with spectroscopic and JHKL data are used for deciding which pairs are likely to be physical and which are optical and it is shown that 98 (34%) of the secondaries are likely to be members of physical systems. For 90% of the physical pairs the projected separations between the components is less than 25000 AU. A majority of the physical secondaries are late type stars and 50% of them are contracting towards the zero-age main-sequence. Also presented are new uvbyβ data for 43 secondaries and a computer programme for determining astrophysical parameters from uvbyβ data

  19. Pelvic reconstruction with different rod-screw systems following Enneking type I/I + IV resection: a clinical study

    Science.gov (United States)

    Lu, Huigen; Zhang, Zhengliang; Lin, Haiqing; Wang, Shengdong; Li, Binghao; Li, Hengyuan; Wang, Zhan; Lin, Nong; Ye, Zhaoming

    2017-01-01

    The mechanical outcomes of patients with pelvic bone tumors involving zone I or zone I + IV who received resection and different reconstructions are not clear. Therefore, the purpose of this study was to compare the outcomes of different rod-screw systems in reconstruction for these patients, and evaluate the relative risk of mechanical failure for them. We reviewed 30 patients for a mean duration of 40.4 months of follow-up (range, 13.1–162.2 months), five patients had mechanical complications. The mechanical survival rate of two-rod and four-screw (TRFS) group was significantly higher than one-rod and two-screw (ORTS) group (p = 0.000). The implant survival rate was correlated with ages (p = 0.010), younger people are more likely to fail. Thus, TRFS fixation for pelvic reconstruction after Enneking type I/I + IV resection can provide better short to long-term mechanical stability compared with ORTS fixation, the strength of ORTS fixation is not enough. In addition, biological reconstruction such as autologous bone graft is recommended for the patients who are younger or suffered from benign tumor. As for the patients who are older, with malignant tumors, underwent adjuvant radiotherapy or chemotherapy, functional reconstruction with bone cement is a good choice. PMID:28465495

  20. Osteogenesis Imperfecta Type I-IV, the Collagenous Disorder of Connective Tissue in Czech Population

    Czech Academy of Sciences Publication Activity Database

    Šormová, L.; Mazura, Ivan

    2011-01-01

    Roč. 7, č. 1 (2011), s. 59-64 ISSN 1801-5603 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : osteogenesis imperfecta * collagen type I * COL1A1 * COL1A2 * MLBR * mutations Subject RIV: IN - Informatics, Computer Science http://www.ejbi.eu/images/2011-1/Sormova_en.pdf

  1. Treatment of Medial Malleolus or Pure Deltoid Ligament Injury in Patients with Supination-External Rotation Type IV Ankle Fractures.

    Science.gov (United States)

    Wang, Xu; Zhang, Chao; Yin, Jian-Wen; Wang, Chen; Huang, Jia-Zhang; Ma, Xin; Wang, Cheng-Wei; Wang, Xue

    2017-02-01

    To investigate the effect of internal fixation on postoperative ankle function in patients with supination-external rotation type IV ankle fractures, including medial malleolus fractures and deltoid ligament injury. Between January 2012 and June 2014, patients with medial structure injuries were enrolled in this study and assigned to the medial malleolus fracture group or the deltoid ligament group. The surgical procedures for the two groups were documented. The follow-up endpoint was the time point when the steel plate or screw was removed from the lateral ankle. The Olerud-Molander ankle scoring system was used to assess ankle function. A total of 84 patients with supination-external rotation type IV ankle fractures had complete medical records and were included in this study. The average age of the patients was 44.16 years (range, 15-75). The patient sample included 39 males and 45 females. Overall, 49 patients (19 males and 30 females) suffered a medial malleolus fracture. The average age of these patients was 40.20 years (range, 15-75). Patients with a posterior malleolar fracture fragment >25% of the articular surface accounted for 81.6% (40 patients) of these patients. Overall, 35 patients (20 males and 15 females) experienced a deltoid ligament injury. The average age of these patients was 44.21 years (range, 17-73). Patients with a posterior malleolar fracture fragment >25% of the articular surface accounted for 11.5% (four patients) of these patients. Open reduction was performed in patients with medial malleolus fractures, and two 4.0-mm cannulated screws were used to fixate the posterior malleolus and the medial malleolus. The suture-anchor technique was used to repair the ligaments in patients with deltoid ligament injuries. The follow-up endpoint was the time point when the steel plate and screws were removed from the lateral ankle in patients. The average follow-up period was 13.4 months (range, 11-17). The Olerud-Molander ankle scoring system was

  2. First molecular evidence of Coxiella burnetii infecting ticks in Cuba.

    Science.gov (United States)

    Noda, Angel A; Rodríguez, Islay; Miranda, Jorge; Contreras, Verónica; Mattar, Salim

    2016-02-01

    Coxiella burnetii is the causative agent of Q fever. In order to explore the occurrence of C. burnetii in ticks, samples were collected from horses, dogs and humans living in a Cuban occidental community. The species most commonly recovered were Amblyomma mixtum (67%), Rhipicephalus sanguineus s.l. (27%) and Dermacentor nitens (6%). Specific IS1111 PCR and amplicon sequencing allowed the identification of C. burnetii DNA in A. mixtum collected from a domestic horse. These findings, for first time in Cuba, indicate the need for an in-depth assessment of the C. burnetii occurrence in hosts and humans at risk of infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. Presence of Coxiella burnetii DNA in inflamed bovine cardiac valves

    DEFF Research Database (Denmark)

    Agerholm, Jørgen S.; Jensen, Tim Kåre; Agger, Jens F.

    2017-01-01

    Bacterial endocarditis is a recognised disease in humans and animals. In humans, infection with Coxiella burnetii can cause endocarditis, but this has not been investigated thoroughly in animals. Endocarditis in cattle is a common post-mortem finding in abattoirs and studies have identified...... Trueperella pyogenes as a major cause. Despite exposure of cattle to C. burnetii, the significance of this particular bacterium for development and progression of endocarditis has not been studied in detail. Cardiac valves of cattle affected with endocarditis (n = 100) were examined by histology, fluorescence......% of endocarditis valve samples as being positive. C. burnetii was not detected by FISH, probably due to the low infection levels. Most cattle had chronic valvular vegetative endocarditis with lesions being characterised by a core of fibrous tissue covered by significant amounts of fibrin, sometimes with areas...

  4. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  5. Intimal aortic sarcoma mimicking ruptured thoracoabdominal type IV aneurysm. a rare case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Dedeilias Panagiotis

    2011-12-01

    Full Text Available Abstract Primary intimal aortic sarcoma represents a very rare and highly lethal medical entity. Diagnosis is made either by embolic events caused by the tumor or by surrounding tissue symptoms such as pain. Herein we report an extremely rare case of a 51-year-old man previously operated for ascending aortic aneurysm, who presented with clinical and radiological findings suggestive of a ruptured thoracoabdominal type IV aneurysm. The patient underwent radical resection of the aorta and surrounding tissue with placement of a composite 4-branched graft. The diagnosis was made by frozen section and regular histopathologic examination of the specimen and the patient received adjuvant chemotherapy. Nine months after surgery the patient is still alive and has no signs of recurrence. We review the literature and discuss the option of postoperative chemotherapy.

  6. Physeal fractures of the distal tibia and fibula (Salter-Harris Type I, II, III, and IV fractures).

    Science.gov (United States)

    Podeszwa, David A; Mubarak, Scott J

    2012-06-01

    Physeal fractures of the distal tibia and fibula are common and can be seen at any age, although most are seen in the adolescent. An understanding of the unique anatomy of the skeletally immature ankle in relation to the mechanism of injury will help one understand the injury patterns seen in this population. A thorough clinical exam is critical to the diagnosis and treatment of these injuries and the avoidance of potentially catastrophic complications. Nondisplaced physeal fractures of the distal tibia and fibula can be safely treated nonoperatively. Displaced fractures should undergo a gentle reduction with appropriate anesthesia while multiple reduction attempts should be avoided. Gapping of the physis >3 mm after reduction should raise the suspicion of entrapped periosteum that will increase the risk of premature physeal closure. Open reduction of displaced Salter-Harris type III and IV fractures is critical to maintain joint congruity and minimize the risk of physeal arrest.

  7. Photon storage in ¿-type optically dense atomic media. IV. Optimal control using gradient ascent

    DEFF Research Database (Denmark)

    Gorshkov, Alexey V.; Calarco, Tomasso; Lukin, Mikhail D.

    2008-01-01

    We use the numerical gradient ascent method from optimal control theory to extend efficient photon storage in -type media to previouslyinaccessible regimes and to provide simple intuitive explanations for our optimization techniques. In particular, by using gradient ascent to shape classical....... We also demonstrate that the often discussed connection between time reversal andoptimality in photon storage follows naturally from gradient ascent. Finally, we discuss the optimization of controlled reversible inhomogeneous broadening....... control pulses used to mediate photon storage, we open up the possibility of high efficiency photon storage in thenonadiabatic limit, in which analytical solutions to the equations of motion do not exist. This control shaping technique enables an order-of-magnitude increase in the bandwidth of the memory...

  8. Surgical pitfalls in patients with Ehlers–Danlos type IV: A case of spontaneous sigmoid perforation in a 17-year-old male

    Directory of Open Access Journals (Sweden)

    Kai Lyn Ng

    2011-07-01

    Full Text Available Ehlers–Danlos syndrome (EDS is a group of well described connective tissue disorders in which collagen production is impaired. The surgical management of affected individuals remains challenging, with no general consensus. We report a case of spontaneous sigmoid perforation in a 17-year-old Eurasian male, in whom we subsequently established the diagnosis of EDS type IV (EDS-IV. We review the literature to discuss the clinical features and diagnosis, and the recommended therapeutic management.

  9. Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove-related skin symptoms.

    Science.gov (United States)

    Nettis, E; Assennato, G; Ferrannini, A; Tursi, A

    2002-03-01

    It has been established that there are type I and type IV allergens in latex gloves. The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.

  10. Classification of bulimic-type eating disorders: from DSM-IV to DSM-5

    Science.gov (United States)

    2013-01-01

    Proposed changes to the classification of bulimic-type eating disorders in the lead up to the publication of DSM-5 are reviewed. Several of the proposed changes, including according formal diagnostic status to binge eating disorder (BED), removing the separation of bulimia nervosa (BN) into purging and non-purging subtypes, and reducing the binge frequency threshold from twice per week to once per week for both BN and (BED), have considerable empirical evidence to support them and will likely have the effect of facilitating clinical practice, improving access to care, improving public and professional awareness and understanding of these disorders and stimulating the additional research needed to address at least some problematic issues. However, the omission of any reference to variants of BN characterized by subjective, but not objective, binge eating episodes, and to the undue influence of weight or shape on self-evaluation or similar cognitive criterion in relation to the diagnosis of BED, is regrettable, given their potential to inform clinical and research practice and given that there is considerable evidence to support specific reference to these distinctions. Other aspects of the proposed criteria, such as retention of behavioral indicators of impaired control associated with binge eating and the presence of marked distress regarding binge eating among the diagnostic for BED, appear anomalous in that there is little or no evidence to support their validity or clinical utility. It is hoped that these issues will be addressed in final phase of the DSM-5 development process. PMID:24999412

  11. SVBR-100 module-type fast reactor of the IV generation for regional power industry

    Science.gov (United States)

    Zrodnikov, A. V.; Toshinsky, G. I.; Komlev, O. G.; Stepanov, V. S.; Klimov, N. N.

    2011-08-01

    In the report the following is presented: basic conceptual provisions of the innovative nuclear power technology (NPT) based on modular fast reactors (FR) SVBR-100, summarized results of calculations of the reactor, analysis of the opportunities of multi-purpose application of such reactor facilities (RF) including export potentials with due account of nonproliferation requirements. The most important features of the proposed NPT analyzed in the report are as follows: (1) integral (monoblock) arrangement of the primary circuit equipment with entire elimination of the primary circuit pipelines and valves that considerably reduces the construction and assembly works period and coupling with high boiling point of lead-bismuth coolant (LBC) deterministically eliminates accidents of the LOCA type, (2) option for 100 MWe power and dimensions of the reactor provide: on the one hand, an opportunity to transport the reactor monoblock in factory-readiness by railway as well as other kinds of transport, on the other hand, core breeding ratio (CBR) exceeds 1 while MOX-fuel is used. The preferable area of application of RF SVBR-100 is regional and small power requiring power-units of electric power in a range of (100-600) MW, which could be used for cogeneration-based district heating while locating them nearby cities as well as for generation of electric power in a mode of load tracking in the regions with low network systems.

  12. Experimental holographic movie IV: the projection-type display system using a retro-directive screen

    Science.gov (United States)

    Higuchi, Kazuhito; Ishii, Ken'ichiro; Ishikawa, Jun; Hiyama, Shigeo

    1995-04-01

    Holographic movies can be seen as a tool to estimate the picture quality of moving holographic images as a step towards holographic television. The authors have previously developed three versions of an experimental holographic movie system, and this paper is a report on an improved version 4 of the system. The new version features a newly-developed projection-type display with a retro-directive beaded-screen, and an automatic film driver unit which moves perforated 35 mm holographic film intermittently with a shutter. A twin diamond-shaped hologram format, which was developed in the earlier version 2, is adopted for the films. The films comprise a series of reconstructed moving holographic images with minimal blurring. The optical arrangement and structure of the version 4 system enable the viewers to watch the film images in an open space, which in turn relieves them of the psychological pressure they felt with the previous three versions, when they had to squint into a narrow window built into a wall on the side of the device.

  13. SVBR-100 module-type fast reactor of the IV generation for regional power industry

    Energy Technology Data Exchange (ETDEWEB)

    Zrodnikov, A.V. [FSUE State Scientific Center of Russian Federation Institute for Physics and Power Engineering 1, Bondarenko sq., Obninsk, Kaluga rg. 249033 (Russian Federation); Toshinsky, G.I., E-mail: toshinsky@ippe.ru [FSUE State Scientific Center of Russian Federation Institute for Physics and Power Engineering 1, Bondarenko sq., Obninsk, Kaluga rg. 249033 (Russian Federation); Komlev, O.G. [FSUE State Scientific Center of Russian Federation Institute for Physics and Power Engineering 1, Bondarenko sq., Obninsk, Kaluga rg. 249033 (Russian Federation); Stepanov, V.S.; Klimov, N.N. [JSC Experimental Design Bureau ' Gidropress' 21, Ordzhonikidze st., Podolsk, Moscow rg. 142103 (Russian Federation)

    2011-08-31

    In the report the following is presented: basic conceptual provisions of the innovative nuclear power technology (NPT) based on modular fast reactors (FR) SVBR-100, summarized results of calculations of the reactor, analysis of the opportunities of multi-purpose application of such reactor facilities (RF) including export potentials with due account of nonproliferation requirements. The most important features of the proposed NPT analyzed in the report are as follows: (1) integral (monoblock) arrangement of the primary circuit equipment with entire elimination of the primary circuit pipelines and valves that considerably reduces the construction and assembly works period and coupling with high boiling point of lead-bismuth coolant (LBC) deterministically eliminates accidents of the LOCA type, (2) option for 100 MWe power and dimensions of the reactor provide: on the one hand, an opportunity to transport the reactor monoblock in factory-readiness by railway as well as other kinds of transport, on the other hand, core breeding ratio (CBR) exceeds 1 while MOX-fuel is used. The preferable area of application of RF SVBR-100 is regional and small power requiring power-units of electric power in a range of (100-600) MW, which could be used for cogeneration-based district heating while locating them nearby cities as well as for generation of electric power in a mode of load tracking in the regions with low network systems.

  14. Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Knop, F K; Vilsbøll, T; Madsbad, S

    2007-01-01

    significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion...... ingestion of glucose, while isoglycaemic i.v. administration of glucose results in normal suppression of glucagon. We suggest that this phenomenon contributes both to the glucose intolerance and to the reduced incretin effect observed in patients with type 2 diabetes.......AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes. MATERIALS AND METHODS: Ten patients (eight men) with type 2 diabetes (age: 64...

  15. Burst pressure investigation of filament wound type IV composite pressure vessel

    Science.gov (United States)

    Farhood, Naseer H.; Karuppanan, Saravanan; Ya, H. H.; Baharom, Mohamad Ariff

    2017-12-01

    Currently, composite pressure vessels (PVs) are employed in many industries such as aerospace, transportations, medical etc. Basically, the use of PVs in automotive application as a compressed natural gas (CNG) storage cylinder has been growing rapidly. Burst failure due to the laminate failure is the most critical failure mechanism for composite pressure vessels. It is predominantly caused by excessive internal pressure due to an overfilling or an overheating. In order to reduce fabrication difficulties and increase the structural efficiency, researches and studies are conducted continuously towards the proper selection of vessel design parameters. Hence, this paper is focused on the prediction of first ply failure pressure for such vessels utilizing finite element simulation based on Tsai-Wu and maximum stress failure criterions. The effects of laminate stacking sequence and orientation angle on the burst pressure were investigated in this work for a constant layered thickness PV. Two types of winding design, A [90°2/∓θ16/90°2] and B [90°2/∓θ]ns with different orientations of helical winding reinforcement were analyzed for carbon/epoxy composite material. It was found that laminate A sustained a maximum burst pressure of 55 MPa for a sequence of [90°2/∓15°16/90°2] while the laminate B returned a maximum burst pressure of 45 MPa corresponding to a stacking sequence of [90°2/±15°/90°2/±15°/90°2/±15° ....] up to 20 layers for a constant vessel thickness. For verification, a comparison was done with the literature under similar conditions of analysis and good agreement was achieved with a maximum difference of 4% and 10% for symmetrical and unsymmetrical layout, respectively.

  16. Evaluation of three analytical techniques used to determine high levels of volatile organic compounds in type IV sludge from Rocky Flats Plant

    International Nuclear Information System (INIS)

    Parish, K.J.; Applegate, D.V.; Tsai, Y.

    1996-01-01

    Before disposal, radioactive sludge (Type IV) from Rocky Flats Plant (RFP) must be evaluated for volatile organic compound (VOC) content. The Type IV sludge consists of organic solvents, degreasers, cutting oils, and transuranic (TRU) waste mixed with calcium silicate (MicroCel E reg-sign) and Oil Dri reg-sign to form a grease or paste-like material. For laboratory testing, a simulated Type IV RFP sludge (nonradioactive) was prepared at Argonne National Laboratory-East. This sludge has a composition similar to that expected from field samples. On the basis of historical information, a typical Type IV sludge is expected to contain approximately 1-10 percent of three target VOCs. The objective of this work is to evaluate three proposed methods for the determination of high levels of these three VOCs in Type IV sludge. The three methods are (1) static headspace gas analysis, (2) methanol extraction, and (3) ethylene glycol extraction. All three methods employ gas chromatography/mass spectrometry (GC/MS). They were evaluated regarding general method performance criteria, ease of operation, and amounts of secondary mixed waste generated

  17. Total hip arthroplasty for patients with Crowe type IV developmental dysplasia of the hip: Ten years results.

    Science.gov (United States)

    Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Zhang, Xin; Fan, Hua-Quan; Chen, Guang-Xing; Guo, Lin; Duan, Xiao-Jun; Zhou, Qiang; Yang, Liu

    2017-06-01

    The aim of this study was to determine the rate of union, functional results and complications in patients with Crowe IV developmental dysplasia of the hip (DDH) who underwent cementless total hip arthroplasty (THA) with S-ROM prostheses and subtrochanteric transverse shortening osteotomy. Forty-five patients (52 hips) operated between January 2005 and May 2008, with a mean age of 40.6 years at surgery were followed. The mean follow-up period was 9.8 years. Clinical outcomes, radiographic outcomes and complications were evaluated. Osteotomy union occurred in 52 of 52 femurs (100%). Mean Harris hip score improved from 33.7 ± 4.7 preoperatively to 81.2 ± 6.3, 90.8 ± 5.3 and 89.8 ± 7.1 at 1, 5 and 10 years postoperatively. Two patients had temporary sciatic nerve paralysis postoperatively, and 2 patients experienced early postoperative dislocation. Two patients complained about mild longer limb length than the non-operated limb at the last follow-up. Three hips showed osteolysis in Gruen zone 1, and 1 hip showed osteolysis in zone 1 and 7. No implants were revised, and no signs of component loosening and migration were observed at the last follow-up visit. S-ROM stem combined with transverse subtrochanteric shortening osteotomy in THA for patients with Crowe type IV DDH has good clinical results with small risk of complications. Copyright © 2017. Published by Elsevier Ltd.

  18. [Double-plate fixation via combined approaches for the treatment of old tibial plateau fractures of Schatzker type IV].

    Science.gov (United States)

    Tan, Hong-Lue; Dai, Peng-Yi; Liu, Wei-Feng; Yuan, Yan-Hao

    2017-10-25

    To explore the clinical efficacy of double-plate fixation for the treatment of old tibial plateau fractures with Schatzker type IV through anterior midline and posteromedial approaches. From July 2013 to July 2015, 15 patients with old tibial plateau fractures were treated with internal fixation using locking reconstructive plate for the posteromedial fragment and anatomical locking plate for anteromedial fragment through antero midline and posteromedial approaches. There were 9 males and 6 females, with an average age of 49.2 years old (ranged, 21 to 61 years old). Eight patients had injured in the left side and 7 in the right side. According to Schatzker classification, all patients were type IV. The mean interval from injury to operation was 26.5 days (ranged, 21 to 65 days). The main clinical symptoms before operation were knee joint swelling, pain, deformity and limitation of motion. The X-ray and CT confirmed the fracture type. The indexes such as tibial plateau tibial shaft angle (TPA), femoral tibial angle (FTA) and posterior slope angle (PSA) were compared between immediate postoperation and final follow-up using postoperative X-ray film. The knee functions were evaluated using the HSS (Hospital for Special Surgery) knee score system. Two patients had incision complications which healed by correct treatment, 1 patient had traumatic arthritis. All patients were followed up for mean 16.6 months (ranged, 13 to 24 months). No infections, deep venous thrombosis, implant loosening and breakage, fragment displacement, plateau surface collapse and bone nonunion found. The bone union time ranged from 3 to 8 months (mean 6.07 months) after operation. The average immediate postoperative value of TPA, FTA and PSA were(86.81±1.67)°, (168.00±3.29)° and(10.20±1.47)° respectively; and(86.47±1.67)°, (168.53±3.03)° and (10.54±1.21)° respectively at the final follow-up evaluation, showing no statistical differences( P >0.05). According to the HSS score system, 26

  19. Type IV Pili are required for virulence, twitching motility, and biofilm formation of acidovorax avenae subsp. Citrulli.

    Science.gov (United States)

    Bahar, Ofir; Goffer, Tal; Burdman, Saul

    2009-08-01

    Acidovorax avenae subsp. citrulli is the causal agent of bacterial fruit blotch (BFB), a threatening disease of watermelon, melon, and other cucurbits. Despite the economic importance of BFB, relatively little is known about basic aspects of the pathogen's biology and the molecular basis of its interaction with host plants. To identify A. avenae subsp. citrulli genes associated with pathogenicity, we generated a transposon (Tn5) mutant library on the background of strain M6, a group I strain of A. avenae subsp. citrulli, and screened it for reduced virulence by seed-transmission assays with melon. Here, we report the identification of a Tn5 mutant with reduced virulence that is impaired in pilM, which encodes a protein involved in assembly of type IV pili (TFP). Further characterization of this mutant revealed that A. avenae subsp. citrulli requires TFP for twitching motility and wild-type levels of biofilm formation. Significant reductions in virulence and biofilm formation as well as abolishment of twitching were also observed in insertional mutants affected in other TFP genes. We also provide the first evidence that group I strains of A. avenae subsp. citrulli can colonize and move through host xylem vessels.

  20. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits type I-IV allergic inflammation and pro-inflammatory enzymes.

    Science.gov (United States)

    Lee, Ji Yun; Kim, Chang Jong

    2010-06-01

    We previously reported that arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan isolated from Forsythia koreana, exhibits anti-inflammatory, antioxidant, and analgesic effects in animal models. In addition, arctigenin inhibited eosinophil peroxidase and activated myeloperoxidase in inflamed tissues. In this study, we tested the effects of arctigenin on type I-IV allergic inflammation and pro-inflammatory enzymes in vitro and in vivo. Arctigenin significantly inhibited the heterologous passive cutaneous anaphylaxis induced by ovalbumin in mice at 15 mg/kg, p.o., and compound 48/80-induced histamine release from rat peritoneal mast cells at 10 microM. Arctigenin (15 mg/kg, p.o.) significantly inhibited reversed cutaneous anaphylaxis. Further, arctigenin (15 mg/kg, p.o.) significantly inhibited the Arthus reaction to sheep's red blood cells, decreasing the hemolysis titer, the hemagglutination titer, and the plaque-forming cell number for SRBCs. In addition, arctigenin significantly inhibited delayed type hypersensitivity at 15 mg/kg, p.o. and the formation of rosette-forming cells at 45 mg/kg, p.o. Contact dermatitis induced by picrylchloride and dinitrofluorobenzene was significantly (p arctigenin (0.3 mg/ear). Furthermore, arctigenin dose-dependently inhibited pro-inflammatory enzymes, such as cyclooxygenase-1 and 2, 5-lipoxygenase, phospholipase A2, and phosphodiesterase. Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes.

  1. Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV.

    Science.gov (United States)

    Wang, Hong-Han; Chen, Hong-Sheng; Li, Hai-Bo; Zhang, Hua; Mei, Ling-Yun; He, Chu-Feng; Wang, Xing-Wei; Men, Mei-Chao; Jiang, Lu; Liao, Xin-Bin; Wu, Hong; Feng, Yong

    2014-03-15

    Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present study, we reported a case of a Chinese patient with clinical features of WS4. In addition, the three genes mentioned above were sequenced in order to identify whether mutations are responsible for the case. We revealed a novel nonsense mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same mutation was not found in three unaffected family members or 100 unrelated controls. Then, the function and mechanism of the mutation were investigated in vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the expected size and their expression levels are equivalent. The mutant protein also localized in the nucleus and retained the DNA-binding activity as WT counterpart; however, it lost its transactivation capability on the MITF promoter and acted as a dominant-negative repressor impairing function of the WT SOX10. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake

    DEFF Research Database (Denmark)

    Ryskjaer, Jakob; Deacon, Carolyn F; Carr, Richard D

    2006-01-01

    hormones are metabolized quickly by the enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired incretin effect. Therefore, the aim of the present study was to investigate plasma DPP-IV activity in the fasting and the postprandial state in type-2 diabetic...... patients and control subjects. DESIGN: The study included two protocols. Protocol one involved 40 fasting type-2 diabetic patients (28 men); age 61 +/- 1.4 (mean +/- s.e.m.) years; body mass index (BMI) 31 +/- 0.6 kg/m(2); HbAlc 7.2 +/- 0.2%; and 20 matched control subjects (14 men) were studied. Protocol...... two involved eight type-2 diabetic patients (six men); age 63 +/- 1.2 years; BMI 33 +/- 0.5 kg/m(2); HbAlc 7.5 +/- 0.4%; eight matched control subjects were included. METHODS: In protocol one, fasting values of DPP-IV activity were evaluated and in protocol two, postprandial DPP-IV activity during...

  3. Immunohistochemical distribution of laminin-332 and collagen type IV in the basement membrane of normal horses and horses with induced laminitis.

    Science.gov (United States)

    Visser, M B; Pollitt, C C

    2011-07-01

    The basement membrane (BM) is a thin layer of extracellular matrix that regulates cell functions as well as providing support to tissues of the body. Primary components of the BM of epithelial tissues are laminin-332 (Ln-332) and collagen type IV. Equine laminitis is a disease characterized by destruction and dislocation of the hoof lamellar BM. Immunohistochemistry was used to characterize the distribution of Ln-332 and collagen type IV in the organs of normal horses and these proteins were found to be widespread. Analysis of a panel of tissue samples from horses with experimentally-induced laminitis revealed that Ln-332 and collagen type IV degradation occurs in the skin and stomach in addition to the hoof lamellae. These findings suggest that BM degradation is common to many epithelial tissues during equine laminitis and suggests a role for systemic trigger factors in this disease. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  4. Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.

    Science.gov (United States)

    Magoulas, Pilar L; El-Hattab, Ayman W; Roy, Angshumoy; Bali, Deeksha S; Finegold, Milton J; Craigen, William J

    2012-06-01

    Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort

    Directory of Open Access Journals (Sweden)

    Karnes Jason H

    2013-01-01

    Full Text Available Abstract Background Recently, the high-mobility group A1 gene (HMGA1 variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American populations. We sought to investigate the HMGA1-diabetes association and to characterize IVS5-13insC allele frequencies and linkage disequilibrium (LD in 3,070 Caucasian, Hispanic, and African American patients from the INternational VErapamil SR-Trandolapril STudy (INVEST. Methods INVEST was a randomized, multicenter trial comparing two antihypertensive treatment strategies in an ethnically diverse cohort of hypertensive, coronary artery disease patients. Controls, who were diabetes-free throughout the study, and type 2 diabetes cases, either prevalent or incident, were genotyped for IVS5-13insC using Taqman®, confirmed with Pyrosequencing and Sanger sequencing. For LD analysis, genotyping for eight additional HMGA1 single nucleotide polymorphisms (SNPs was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the HMGA1 IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry. Results We observed IVS5-13insC minor allele frequencies consistent with previous literature in Caucasians and African Americans (0.03 in cases and 0.04 in controls for both race/ethnic groups, and higher frequencies in Hispanics (0.07 in cases and 0.07 in controls. The IVS5-13insC was not associated with type 2 diabetes overall (odds ratio 0.98 [0.76-1.26], p=0.88 or in any race/ethnic group. Pairwise LD (r2 of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r2=0.47 in Caucasians, r2=0.25 in Hispanics, and r2=0.06 in African Americans. Furthermore, in silico analysis suggested a lack of functional consequences for the IVS5-13insC variant. Conclusions Our results suggest that IVS5-13ins

  6. Matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in paediatric burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors.

    Science.gov (United States)

    Weremijewicz, Artur; Matuszczak, Ewa; Sankiewicz, Anna; Tylicka, Marzena; Komarowska, Marta; Tokarzewicz, Anna; Debek, Wojciech; Gorodkiewicz, Ewa; Hermanowicz, Adam

    2018-01-30

    The purpose of this study was the determination of matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in the blood plasma of burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors. 31 children scalded by hot water who were managed at the Department of Paediatric Surgery between 2014-2015, after primarily presenting with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2,5+1 years). There were 10 girls and 21 boys. Venous blood samples were drawn 2-6h, and 12-16h after the thermal injury, and on the subsequent days 3, 5 and 7. The matrix metalloproteinase-2, collagen type IV and laminin-5 concentrations were assessed using Surface Plasmon Resonance Imaging by the investigators blinded to the other data. The MMP-2, laminin-5 and collagen type IV concentrations in the blood plasma of patients with burns, were highest 12-16h after thermal injury, the difference was statistically significant. The MMP-2, laminin-5 and collagen type IV concentrations measured 3 days, 5 days and 7 days after the thermal injury, slowly decreased over time, and on the 7th day reached the normal range, when compared with the concentration measured in controls. Current work is the first follow-up study regarding MMP-2 in burns. MMP-2, laminin-5 and collagen type IV levels were elevated early after burn injury in the plasma of studied patients, and were highest 12-16h after the injury. MMP-2, laminin-5 and collagen type IV levels were not proportional to the severity of the burn. We believe in the possibility that the gradual decrease of MMP-2, collagen type IV and laminin-5 concentrations could be connected with the process of healing, but to prove it, more investigation is needed in this area. The SPR imaging biosensor is a good diagnostic tool for determination of MMP-2, laminin-5 and collagen type IV in blood plasma of patients with burns. Copyright © 2017 Elsevier Ltd

  7. A selective stepwise heme oxygenase model system: an iron(IV)-oxo porphyrin π-cation radical leads to a verdoheme-type compound via an isoporphyrin intermediate.

    Science.gov (United States)

    Garcia-Bosch, Isaac; Sharma, Savita K; Karlin, Kenneth D

    2013-11-06

    The selective oxidation of the α-position of two heme-Fe(III) tetraarylporphryinate complexes occurs when water(hydroxide) attacks their oxidized Cmpd I-type equivalents, high-valent Fe(IV)═O π-cation radical species ((P(+•))Fe(IV)═O). Stepwise intermediate formation occurs, as detected by UV-vis spectroscopic monitoring or mass spectrometric interrogation, being iron(III) isoporphyrins, iron(III) benzoyl-biliverdins, and the final verdoheme-like products. Heme oxygenase (HO) enzymes could proceed through heterolytic cleavage of an iron(III)-hydroperoxo intermediate to form a transient Cmpd I-type species.

  8. Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii.

    Science.gov (United States)

    Battisti, James M; Watson, Lance A; Naung, Myo T; Drobish, Adam M; Voronina, Ekaterina; Minnick, Michael F

    2017-02-01

    The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(-) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(-) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(-) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.

  9. Enhanced discrimination of highly clonal ST22-methicillin-resistant Staphylococcus aureus IV isolates achieved by combining spa, dru, and pulsed-field gel electrophoresis typing data.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2010-05-01

    ST22-methicillin-resistant Staphylococcus aureus type IV (ST22-MRSA-IV) is endemic in Irish hospitals and is designated antibiogram-resistogram type-pulsed-field group (AR-PFG) 06-01. Isolates of this highly clonal strain exhibit limited numbers of pulsed-field gel electrophoresis (PFGE) patterns and spa types. This study investigated whether combining PFGE and spa typing with DNA sequencing of the staphylococcal cassette chromosome mec element (SCCmec)-associated direct repeat unit (dru typing) would improve isolate discrimination. A total of 173 MRSA isolates recovered in one Irish hospital during periods in 2007 and 2008 were investigated using antibiogram-resistogram (AR), PFGE, spa, dru, and SCCmec typing. Isolates representative of each of the 17 pulsed-field group 01 (PFG-01) spa types identified underwent multilocus sequence typing, and all isolates were ST22. Ninety-seven percent of isolates (168 of 173) exhibited AR-PFG 06-01 or closely related AR patterns, and 163 of these isolates harbored SCCmec type IVh. The combination of PFGE, spa, and dru typing methods significantly improved discrimination of the 168 PFG-01 isolates, yielding 65 type combinations with a Simpson\\'s index of diversity (SID) of 96.53, compared to (i) pairwise combinations of spa and dru typing, spa and PFGE typing, and dru and PFGE typing, which yielded 37, 44, and 43 type combinations with SIDs of 90.84, 91.00, and 93.57, respectively, or (ii) individual spa, dru, and PFGE typing methods, which yielded 17, 17, and 21 types with SIDs of 66.9, 77.83, and 81.34, respectively. Analysis of epidemiological information for a subset of PFG-01 isolates validated the relationships inferred using combined PFGE, spa, and dru typing data. This approach significantly enhances discrimination of ST22-MRSA-IV isolates and could be applied to epidemiological investigations of other highly clonal MRSA strains.

  10. Type-IVC Secretion System: A Novel Subclass of Type IV Secretion System (T4SS) Common Existing in Gram-Positive Genus Streptococcus

    Science.gov (United States)

    Chen, Chen; Gao, George F.

    2012-01-01

    A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. Type IV secretion system (T4SS) is one of versatile secretion systems essential for the virulence and even survival of some bacteria species, and they enable the secretion of protein and DNA substrates across the cell envelope. T4SS was once believed to be present only in Gram-negative bacteria. In this study, we present evidence of a new subclass of T4SS, Type-IVC secretion system and indicate its common existence in the Gram-positive bacterial genus Streptococcus. We further identified that VirB1, VirB4, VirB6 and VirD4 are the minimal key components of this system. Using genome comparisons and evolutionary relationship analysis, we proposed that Type-IVC secretion system is movable via transposon factors and mediates the conjugative transfer of DNA, enhances bacterial pathogenicity, and could cause large-scale outbreaks of infections in humans. PMID:23056296

  11. Phylogenetic inference of Coxiella burnetii by 16S rRNA gene sequencing.

    Directory of Open Access Journals (Sweden)

    Heather P McLaughlin

    Full Text Available Coxiella burnetii is a human pathogen that causes the serious zoonotic disease Q fever. It is ubiquitous in the environment and due to its wide host range, long-range dispersal potential and classification as a bioterrorism agent, this microorganism is considered an HHS Select Agent. In the event of an outbreak or intentional release, laboratory strain typing methods can contribute to epidemiological investigations, law enforcement investigation and the public health response by providing critical information about the relatedness between C. burnetii isolates collected from different sources. Laboratory cultivation of C. burnetii is both time-consuming and challenging. Availability of strain collections is often limited and while several strain typing methods have been described over the years, a true gold-standard method is still elusive. Building upon epidemiological knowledge from limited, historical strain collections and typing data is essential to more accurately infer C. burnetii phylogeny. Harmonization of auspicious high-resolution laboratory typing techniques is critical to support epidemiological and law enforcement investigation. The single nucleotide polymorphism (SNP -based genotyping approach offers simplicity, rapidity and robustness. Herein, we demonstrate SNPs identified within 16S rRNA gene sequences can differentiate C. burnetii strains. Using this method, 55 isolates were assigned to six groups based on six polymorphisms. These 16S rRNA SNP-based genotyping results were largely congruent with those obtained by analyzing restriction-endonuclease (RE-digested DNA separated by SDS-PAGE and by the high-resolution approach based on SNPs within multispacer sequence typing (MST loci. The SNPs identified within the 16S rRNA gene can be used as targets for the development of additional SNP-based genotyping assays for C. burnetii.

  12. The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook.

    Science.gov (United States)

    Stanger, Frédéric V; de Beer, Tjaart A P; Dranow, David M; Schirmer, Tilman; Phan, Isabelle; Dehio, Christoph

    2017-01-03

    The BID (Bep intracellular delivery) domain functions as secretion signal in a subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It mediates transfer of (1) relaxases and the attached DNA during bacterial conjugation, and (2) numerous Bartonella effector proteins (Beps) during protein transfer into host cells infected by pathogenic Bartonella species. Furthermore, BID domains of Beps have often evolved secondary effector functions within host cells. Here, we provide crystal structures for three representative BID domains and describe a novel conserved fold characterized by a compact, antiparallel four-helix bundle topped with a hook. The conserved hydrophobic core provides a rigid scaffold to a surface that, despite a few conserved exposed residues and similarities in charge distribution, displays significant variability. We propose that the genuine function of BID domains as T4S signal may primarily depend on their rigid structure, while the plasticity of their surface may facilitate adaptation to secondary effector functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Vitamin D deficiency and rickets in children and adolescents with ichthyosiform erythroderma in type IV and V skin.

    Science.gov (United States)

    Chouhan, K; Sethuraman, G; Gupta, N; Sharma, V K; Kabra, M; Khaitan, B K; Sreenivas, V; Ramam, M; Kusumakar, S; Thulkar, S; Paller, A S

    2012-03-01

    Ichthyosiform erythroderma due to keratinizing disorders may suppress cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets. To determine the prevalence of vitamin D deficiency and rickets in children and adolescents with congenital ichthyosis and other keratinizing disorders with erythroderma and scaling. In this cross-sectional study, 45 children and adolescents with ichthyosiform erythroderma due to keratinizing disorders, and 66 controls (group 1: age and sex matched, with skin diseases other than keratinizing disorders; group 2: age and sex matched, healthy volunteers) were included. Evidence of rickets was determined clinically (physical examination and radiographs) and biochemically {serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D [25(OH)D] and parathyroid hormone (PTH)}. All patients in the disease group had clinical, radiological or biochemical evidence of rickets [25(OH)D65pgmL(-1) ) was also significantly higher in the disease group than in controls (PChildren and adolescents with various forms of ichthyosiform erythroderma, especially those with pigmented skin (types IV-VI), are at increased risk of developing vitamin D deficiency and clinical rickets. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  14. Correlation Between Intercritical Heat-Affected Zone and Type IV Creep Damage Zone in Grade 91 Steel

    Science.gov (United States)

    Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

    2018-02-01

    A soft zone in Cr-Mo steel weldments has been reported to accompany the infamous Type IV cracking, the highly localized creep damage in the heat-affected zone of creep-resistant steels. However, the microstructural features and formation mechanism of this soft zone are not well understood. In this study, using microhardness profiling and microstructural verification, the initial soft zone in the as-welded condition was identified to be located in the intercritical heat-affected zone of P91 steel weldments. It has a mixed structure, consisting of Cr-rich re-austenitized prior austenite grains and fine Cr-depleted, tempered martensite grains retained from the base metal. The presence of these further-tempered retained grains, originating from the base metal, is directly responsible for the hardness reduction of the identified soft zone in the as-welded condition. The identified soft zone exhibits a high location consistency at three thermal stages. Local chemistry analysis and thermodynamic calculation show that the lower chromium concentrations inside these retained grains thermodynamically decrease their potentials for austenitic transformation during welding. Heterogeneous grain growth is observed in the soft zone during postweld heat treatment. The mismatch of strengths between the weak Cr-depleted grains and strong Cr-rich grains enhances the creep damage. Local deformation of the weaker Cr-depleted grains accelerates the formation of creep cavities.

  15. Twitching motility of bacteria with type-IV pili: Fractal walks, first passage time, and their consequences on microcolonies

    Science.gov (United States)

    Bisht, Konark; Klumpp, Stefan; Banerjee, Varsha; Marathe, Rahul

    2017-11-01

    A human pathogen, Neisseria gonorrhoeae (NG), moves on surfaces by attaching and retracting polymeric structures called Type IV pili. The tug-of-war between the pili results in a two-dimensional stochastic motion called twitching motility. In this paper, with the help of real-time NG trajectories, we develop coarse-grained models for their description. The fractal properties of these trajectories are determined and their influence on first passage time and formation of bacterial microcolonies is studied. Our main observations are as follows: (i) NG performs a fast ballistic walk on small time scales and a slow diffusive walk over long time scales with a long crossover region; (ii) there exists a characteristic persistent length lp*, which yields the fastest growth of bacterial aggregates or biofilms. Our simulations reveal that lp*˜L0.6 , where L ×L is the surface on which the bacteria move; (iii) the morphologies have distinct fractal characteristics as a consequence of the ballistic and diffusive motion of the constituting bacteria.

  16. Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.

    Science.gov (United States)

    Jeanne, Marion; Jorgensen, Jeff; Gould, Douglas B

    2015-05-05

    Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is a lack of effective treatment. Using Col4a1 and Col4a2 mutant mouse models, we investigated the genetic complexity and cellular mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal vascular development, which triggers small-vessel disease, recurrent hemorrhagic strokes, and age-related macroangiopathy. We showed that allelic heterogeneity, genetic context, and environmental factors such as intense exercise or anticoagulant medication modulated disease severity and contributed to phenotypic heterogeneity. We found that intracellular accumulation of mutant collagen in vascular endothelial cells and pericytes was a key triggering factor of ICH. Finally, we showed that treatment of mutant mice with a US Food and Drug Administration-approved chemical chaperone resulted in a decreased collagen intracellular accumulation and a significant reduction in ICH severity. Our data are the first to show therapeutic prevention in vivo of ICH resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting protein folding might also prevent ICH in patients with COL4A1 and COL4A2 mutations. © 2015 American Heart Association, Inc.

  17. Identification of a de novo mutation of SOX10 in a Chinese patient with Waardenburg syndrome type IV.

    Science.gov (United States)

    Liang, Fenghe; Zhao, Min; Fan, Lynn; Zhang, Hongyan; Shi, Yang; Han, Rui; Qu, Chunyan

    2016-12-01

    Waardenburg syndrome is a rare genetic disorder, characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Four subtypes have been classified. The present study aimed to analyze the clinical feature and investigate the genetic cause for a Chinese case of Waardenburg type IV (WS4). The patient and his family members were subjected to mutation detection in the candidate gene SOX10 by Sanger sequencing. The patient has the clinical features of WS4, including sensorineural hearing loss, bright blue irides, premature graying of the hair and Hirschsprung disease. A novel heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5 of SOX10 was detected in the patient, but not found in the unaffected family members and 100 normal controls. This mutation results in a premature stop codon 31 amino acid downstream. The novel mutation c.752_753ins7 (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the proband. This study further characterized the molecular complexity of WS4 and provided a clinical case for genotype-phenotype correlation studies of different phenotypes caused by SOX10 mutations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Cleavage of phosphorothioated DNA and methylated DNA by the type IV restriction endonuclease ScoMcrA.

    Directory of Open Access Journals (Sweden)

    Guang Liu

    2010-12-01

    Full Text Available Many taxonomically diverse prokaryotes enzymatically modify their DNA by replacing a non-bridging oxygen with a sulfur atom at specific sequences. The biological implications of this DNA S-modification (phosphorothioation were unknown. We observed that simultaneous expression of the dndA-E gene cluster from Streptomyces lividans 66, which is responsible for the DNA S-modification, and the putative Streptomyces coelicolor A(32 Type IV methyl-dependent restriction endonuclease ScoA3McrA (Sco4631 leads to cell death in the same host. A His-tagged derivative of ScoA3McrA cleaved S-modified DNA and also Dcm-methylated DNA in vitro near the respective modification sites. Double-strand cleavage occurred 16-28 nucleotides away from the phosphorothioate links. DNase I footprinting demonstrated binding of ScoA3McrA to the Dcm methylation site, but no clear binding could be detected at the S-modified site under cleavage conditions. This is the first report of in vitro endonuclease activity of a McrA homologue and also the first demonstration of an enzyme that specifically cleaves S-modified DNA.

  19. Correlation Between Intercritical Heat-Affected Zone and Type IV Creep Damage Zone in Grade 91 Steel

    Science.gov (United States)

    Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

    2018-04-01

    A soft zone in Cr-Mo steel weldments has been reported to accompany the infamous Type IV cracking, the highly localized creep damage in the heat-affected zone of creep-resistant steels. However, the microstructural features and formation mechanism of this soft zone are not well understood. In this study, using microhardness profiling and microstructural verification, the initial soft zone in the as-welded condition was identified to be located in the intercritical heat-affected zone of P91 steel weldments. It has a mixed structure, consisting of Cr-rich re-austenitized prior austenite grains and fine Cr-depleted, tempered martensite grains retained from the base metal. The presence of these further-tempered retained grains, originating from the base metal, is directly responsible for the hardness reduction of the identified soft zone in the as-welded condition. The identified soft zone exhibits a high location consistency at three thermal stages. Local chemistry analysis and thermodynamic calculation show that the lower chromium concentrations inside these retained grains thermodynamically decrease their potentials for austenitic transformation during welding. Heterogeneous grain growth is observed in the soft zone during postweld heat treatment. The mismatch of strengths between the weak Cr-depleted grains and strong Cr-rich grains enhances the creep damage. Local deformation of the weaker Cr-depleted grains accelerates the formation of creep cavities.

  20. Computational prediction of secretion systems and secretomes of Brucella: identification of novel type IV effectors and their interaction with the host.

    Science.gov (United States)

    Sankarasubramanian, Jagadesan; Vishnu, Udayakumar S; Dinakaran, Vasudevan; Sridhar, Jayavel; Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash

    2016-01-01

    Brucella spp. are facultative intracellular pathogens that cause brucellosis in various mammals including humans. Brucella survive inside the host cells by forming vacuoles and subverting host defence systems. This study was aimed to predict the secretion systems and the secretomes of Brucella spp. from 39 complete genome sequences available in the databases. Furthermore, an attempt was made to identify the type IV secretion effectors and their interactions with host proteins. We predicted the secretion systems of Brucella by the KEGG pathway and SecReT4. Brucella secretomes and type IV effectors (T4SEs) were predicted through genome-wide screening using JVirGel and S4TE, respectively. Protein-protein interactions of Brucella T4SEs with their hosts were analyzed by HPIDB 2.0. Genes coding for Sec and Tat pathways of secretion and type I (T1SS), type IV (T4SS) and type V (T5SS) secretion systems were identified and they are conserved in all the species of Brucella. In addition to the well-known VirB operon coding for the type IV secretion system (T4SS), we have identified the presence of additional genes showing homology with T4SS of other organisms. On the whole, 10.26 to 14.94% of total proteomes were found to be either secreted (secretome) or membrane associated (membrane proteome). Approximately, 1.7 to 3.0% of total proteomes were identified as type IV secretion effectors (T4SEs). Prediction of protein-protein interactions showed 29 and 36 host-pathogen specific interactions between Bos taurus (cattle)-B. abortus and Ovis aries (sheep)-B. melitensis, respectively. Functional characterization of the predicted T4SEs and their interactions with their respective hosts may reveal the secrets of host specificity of Brucella.

  1. Parallel evolution of a type IV secretion system in radiating lineages of the host-restricted bacterial pathogen Bartonella.

    Science.gov (United States)

    Engel, Philipp; Salzburger, Walter; Liesch, Marius; Chang, Chao-Chin; Maruyama, Soichi; Lanz, Christa; Calteau, Alexandra; Lajus, Aurélie; Médigue, Claudine; Schuster, Stephan C; Dehio, Christoph

    2011-02-10

    Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens

  2. Parallel evolution of a type IV secretion system in radiating lineages of the host-restricted bacterial pathogen Bartonella.

    Directory of Open Access Journals (Sweden)

    Philipp Engel

    2011-02-01

    Full Text Available Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS, and thereby translocated Bartonella effector proteins (Beps, evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial

  3. Effective prediction of bacterial type IV secreted effectors by combined features of both C-termini and N-termini

    Science.gov (United States)

    Wang, Yu; Guo, Yanzhi; Pu, Xuemei; Li, Menglong

    2017-11-01

    Various bacterial pathogens can deliver their secreted substrates also called as effectors through type IV secretion systems (T4SSs) into host cells and cause diseases. Since T4SS secreted effectors (T4SEs) play important roles in pathogen-host interactions, identifying them is crucial to our understanding of the pathogenic mechanisms of T4SSs. A few computational methods using machine learning algorithms for T4SEs prediction have been developed by using features of C-terminal residues. However, recent studies have shown that targeting information can also be encoded in the N-terminal region of at least some T4SEs. In this study, we present an effective method for T4SEs prediction by novelly integrating both N-terminal and C-terminal sequence information. First, we collected a comprehensive dataset across multiple bacterial species of known T4SEs and non-T4SEs from literatures. Then, three types of distinctive features, namely amino acid composition, composition, transition and distribution and position-specific scoring matrices were calculated for 50 N-terminal and 100 C-terminal residues. After that, we employed information gain represent to rank the importance score of the 150 different position residues for T4SE secretion signaling. At last, 125 distinctive position residues were singled out for the prediction model to classify T4SEs and non-T4SEs. The support vector machine model yields a high receiver operating curve of 0.916 in the fivefold cross-validation and an accuracy of 85.29% for the independent test set.

  4. Prevalence of Coxiella burnetii in clinically healthy German sheep flocks

    Directory of Open Access Journals (Sweden)

    Hilbert Angela

    2012-03-01

    Full Text Available Abstract Background Current epidemiological data on the situation of Coxiella (C. burnetii infections in sheep are missing, making risk assessment and the implementation of counteractive measures difficult. Using the German state of Thuringia as a model example, the estimated sero-, and antigen prevalence of C. burnetii (10% and 25%, respectively was assessed at flock level in 39/252 randomly selected clinically healthy sheep flocks with more than 100 ewes and unknown abortion rate. Results The CHECKIT™ Q-fever Test Kit identified 11 (28% antibody positive herds, whereas real-time PCR revealed the presence of C. burnetii DNA in 2 (5% of the flocks. Multiple-locus variable number of tandem repeats analysis of 9 isolates obtained from one flock revealed identical profiles. All isolates contained the plasmid QpH1. Conclusions The results demonstrate that C. burnetii is present in clinically inconspicuous sheep flocks and sporadic flare-ups do occur as the notifications to the German animal disease reporting system show. Although C. burnetii infections are not a primary veterinary concern due to the lack of significant clinical impact on animal health (with the exception of goats, the eminent zoonotic risk for humans should not be underestimated. Therefore, strategies combining the interests of public and veterinary public health should include monitoring of flocks, the identification and culling of shedders as well as the administration of protective vaccines.

  5. Prevalence of Coxiella burnetti infection in wild and farmed ungulates.

    Science.gov (United States)

    Ruiz-Fons, Francisco; Rodríguez, Oscar; Torina, Alessandra; Naranjo, Victoria; Gortázar, Christian; de la Fuente, José

    2008-01-01

    The aim of this study was to evaluate by serology and PCR analyses the prevalence of Coxiella burnetti infection in ungulates in Spain. Sera were collected from red deer (Cervus elaphus; n=116), roe deer (Capreolus capreolus; n=39), fallow deer (Dama dama; n=13) and cattle (n=79). Sera were tested for anti-C. burnetii antibody detection by means of an immunofluorescence antibody assay (IFA) and C. burnetii DNA was amplified by PCR in samples from ungulates that had antibodies to phase II antigens. Twenty-nine, 15 and 39 percent of the red deer, roe deer and cattle had antibodies against C. burnetii, respectively. None of the fallow deer sera tested positive. Seroprevalence was statistically higher in farmed than in wild red deer and higher in northern than in southern populations, whereas an inverse pattern was observed for the roe deer. Most of the seropositive animals had only anti-C. burnetii phase II antibodies, thus showing the acute nature of infections in the sampled ungulates. These results show that C. burnetii circulates in wild ungulates in Spain and suggest that they can act as pathogen reservoirs for both domestic animals and humans.

  6. MOLECULAR-GENETIC BASIS OF PHYSIOLOGY AND PATHOGENICITY OF COXIELLA BURNETII

    Directory of Open Access Journals (Sweden)

    Yu. A. Panpherova

    2012-01-01

    Full Text Available Abstract. The agent of Q-fever Coxiella burnetii is unusual intracellular pathogen which is possessed of biggest transporting and metabolic abilities in compare with microorganisms with similar parasitic strategy. It is supposed that different strains of the pathogen exist in various stages of pathological adaption and have different potential of virulence. The structure of C. burnetii genome, characteristics of metabolic routes, mechanisms of interaction with host cells and possible virulence factors are discussed in the review. The special attention is paid to Coxiella genotyping methods and possible correlations between genomic polymorphism of different strains and their virulence potential.

  7. Q fever (Coxiella burnetii) investigations in dairy cattle: challenge of immunity after vaccination.

    Science.gov (United States)

    Behymer, D E; Biberstein, E L; Riemann, H P; Franti, C E; Sawyer, M; Ruppanner, R; Crenshaw, G L

    1976-06-01

    The immunity of Holstein-Friesian dairy cows vaccinated against Coxiella burnetii was challenged with 4 X 10(8) infective guinea pig doses of viable rickettsiae. Cows that were vaccinated had normal full-term calves, whereas 2 nonvaccinated cows aborted late in pregnancy. Intrauterine infection of the fetus was indicated by recovery of the organism from tissues of the fetus. Coxiella burnetii was recovered from milk, colostrum, and placenta of vaccinated and nonvaccinated cows after challenge inoculation, but the rickettsiae recovered were as many as 1,000 times more numerous in nonvacinated cows.

  8. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Mari, A; Sallas, W M; He, Y L

    2005-01-01

    AIMS/HYPOTHESIS: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels...

  9. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Balas, Bogdan; Baig, Muhammad R; Watson, Catherine

    2007-01-01

    AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However...

  10. Ehlers-Danlos syndrome type IV : unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile

    NARCIS (Netherlands)

    Kroes, HY; Pals, G; van Essen, AJ

    A mother and son with Ehlers-Danlos syndrome (EDS) type IV and unusual congenital anomalies are described. The congenital anomalies include, in the mother, amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephaly and, in the son, an

  11. [Selection of low instrumentation vertebrae with CD hybrid technique in king-types III and IV scoliosis].

    Science.gov (United States)

    Zhang, Yonggang; Wang, Yan; Zhang, Xuesong

    2006-04-01

    To review the King-types III and IV patients treated by the CD hybrid technique and evaluate clinical results on the shorter fusion levels. Fifty-eight patients with idiopathic scoliosis were treated by the CD hybrid method from March 2000 to January 2003, among whom 40 were grouped as King-type I and 18 as King-type N; 41 were female and 17 were male. The Cobb angle of the thoracic curve was averaged 64 degrees (range 50-83 degrees), and the curve flexibility was 62%. The compensative lumbar curve was averaged 37 degrees (range 16-48 degrees), and the curve flexibility was 105%. With the neutral rotational vertebrae as a basis to select the low instrumentation vertebrae, the neutral rotational vertebrae or the vertebrae at 1 or 2 levels proximal to the neutral rotational vertebrae were selected as the low instrumentation vertebrae in all the patients. Standing AP and lateral radiographs were taken respectively at the discharge, during the follow-up after discharge, and at the final follow-up. The patients were followed up for an average of 2. 4 years (range 1.8-3.2). The corrected curves lost an average of 3.1 degrees (range--1-5 degrees)and the correction rate of the thoracic curve was 68% at the final follow-up. The plumb line from C7 was parallel to the sacral midline in 56 patients. The lumbar curves were corrected to an average of 8 degrees (2-13 degrees) automatically. The lumbosacral angle was corrected automatically by 53% and the low instrumentation vertebrae in 48 patients turned into stable vertebrae. The low instrumentation vertebrae lost 1.4 segments on average compared with the Harrington principle. No spinal imbalance was clinically observed in all the patients. The choice of the low instrumentation vertebrae as the neutral rotational vertebrae can have a good result in the clinical practice. It can be applied in the CD hybrid technique in treatment of idiopathic thoracic curves.

  12. A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells.

    Science.gov (United States)

    Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph

    2005-01-18

    Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.

  13. Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

    Science.gov (United States)

    Korish, Aida A; Abdel Gader, Abdel Galil; Korashy, Hesham M; Al-Drees, Abdul Majeed; Alhaider, Abdulqader A; Arafah, Maha M

    2015-03-05

    Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Functional mapping of PilF and PilQ in the Pseudomonas aeruginosa type IV pilus system.

    Science.gov (United States)

    Koo, Jason; Tang, Tim; Harvey, Hanjeong; Tammam, Stephanie; Sampaleanu, Liliana; Burrows, Lori L; Howell, P Lynne

    2013-04-30

    Pseudomonas aeruginosa uses type IV pili (T4P) to interact with the environment and as key virulence factors when acting as an opportunistic pathogen. Assembly of the outer membrane PilQ secretin channel through which the pili are extruded is essential for pilus biogenesis. The P. aeruginosa T4P pilotin, PilF, is required for PilQ outer membrane localization and assembly into secretins and contains six tetratricopeptide (TPR) protein-protein interaction motifs, suggesting that the two proteins interact. In this study, we found that the first four TPR motifs of PilF are sufficient for PilQ outer membrane targeting, oligomerization, and function. Guided by our structure of PilF, site-directed mutagenesis of the protein surface revealed that a hydrophobic groove on the first TPR is required for PilF-mediated PilQ assembly. Deletion of individual domains within PilQ suggests that the N0, KH-like, or secretin domain, but not the C-terminus, interacts with PilF. Purified PilQ was found to pull down PilF from Pseudomonas cell lysates. Together, these data allow us to propose a model for PilF function in the T4P system. PilF interacts directly or indirectly with the PilQ monomer after translocation of both proteins through the inner membrane and acts as a co-chaperone with the Lol system to facilitate transit across the periplasm to the outer membrane. The mechanism of PilQ insertion and assembly, which appears to be independent of the Bam system, remains to be determined.

  15. Evidence of transfer by conjugation of type IV secretion system genes between Bartonella species and Rhizobium radiobacter in amoeba.

    Directory of Open Access Journals (Sweden)

    Watcharee Saisongkorh

    Full Text Available BACKGROUND: Bartonella species cospeciate with mammals and live within erythrocytes. Even in these specific niches, it has been recently suggested by bioinformatic analysis of full genome sequences that Lateral Gene Transfer (LGT may occur but this has never been demonstrated biologically. Here we describe the sequence of the B. rattaustraliani (AUST/NH4(T circular plasmid (pNH4 that encodes the tra cluster of the Type IV secretion system (T4SS and we eventually provide evidence that Bartonella species may conjugate and exchange this plasmid inside amoeba. PRINCIPAL FINDINGS: The T4SS of pNH4 is critical for intracellular viability of bacterial pathogens, exhibits bioinformatic evidence of LGT among bacteria living in phagocytic protists. For instance, 3 out of 4 T4SS encoding genes from pNH4 appear to be closely related to Rhizobiales, suggesting that gene exchange occurs between intracellular bacteria from mammals (bartonellae and plants (Rhizobiales. We show that B. rattaustraliani and Rhizobium radiobacter both survived within the amoeba Acanthamoeba polyphaga and can conjugate together. Our findings further support the hypothesis that tra genes might also move into and out of bacterial communities by conjugation, which might be the primary means of genomic evolution for intracellular adaptation by cross-talk of interchangeable genes between Bartonella species and plant pathogens. CONCLUSIONS: Based on this, we speculate that amoeba favor the transfer of genes as phagocytic protists, which allows for intraphagocytic survival and, as a consequence, promotes the creation of potential pathogenic organisms.

  16. Phylogenomics and sequence-structure-function relationships in the GmrSD family of Type IV restriction enzymes.

    Science.gov (United States)

    Machnicka, Magdalena A; Kaminska, Katarzyna H; Dunin-Horkawicz, Stanislaw; Bujnicki, Janusz M

    2015-10-23

    GmrSD is a modification-dependent restriction endonuclease that specifically targets and cleaves glucosylated hydroxymethylcytosine (glc-HMC) modified DNA. It is encoded either as two separate single-domain GmrS and GmrD proteins or as a single protein carrying both domains. Previous studies suggested that GmrS acts as endonuclease and NTPase whereas GmrD binds DNA. In this work we applied homology detection, sequence conservation analysis, fold recognition and homology modeling methods to study sequence-structure-function relationships in the GmrSD restriction endonucleases family. We also analyzed the phylogeny and genomic context of the family members. Results of our comparative genomics study show that GmrS exhibits similarity to proteins from the ParB/Srx fold which can have both NTPase and nuclease activity. In contrast to the previous studies though, we attribute the nuclease activity also to GmrD as we found it to contain the HNH endonuclease motif. We revealed residues potentially important for structure and function in both domains. Moreover, we found that GmrSD systems exist predominantly as a fused, double-domain form rather than as a heterodimer and that their homologs are often encoded in regions enriched in defense and gene mobility-related elements. Finally, phylogenetic reconstructions of GmrS and GmrD domains revealed that they coevolved and only few GmrSD systems appear to be assembled from distantly related GmrS and GmrD components. Our study provides insight into sequence-structure-function relationships in the yet poorly characterized family of Type IV restriction enzymes. Comparative genomics allowed to propose possible role of GmrD domain in the function of the GmrSD enzyme and possible active sites of both GmrS and GmrD domains. Presented results can guide further experimental characterization of these enzymes.

  17. Interaction of Coxiella burnetii Strains of Different Sources and Genotypes with Bovine and Human Monocyte-Derived Macrophages

    Directory of Open Access Journals (Sweden)

    Katharina Sobotta

    2018-01-01

    Full Text Available Most human Q fever infections originate from small ruminants. By contrast, highly prevalent shedding of Coxiella (C. burnetii by bovine milk rarely results in human disease. We hypothesized that primary bovine and human monocyte-derived macrophages (MDM represent a suitable in vitro model for the identification of strain-specific virulence properties at the cellular level. Twelve different C. burnetii strains were selected to represent different host species and multiple loci variable number of tandem repeat analysis (MLVA genotypes. Infection efficiency and replication of C. burnetii were monitored by cell culture re-titration and qPCR. Expression of immunoregulatory factors after MDM infection was measured by qRT-PCR and flow cytometry. Invasion, replication and MDM response differed between C. burnetii strains but not between MDMs of the two hosts. Strains isolated from ruminants were less well internalized than isolates from humans and rodents. Internalization of MLVA group I strains was lower compared to other genogroups. Replication efficacy of C. burnetii in MDM ranged from low (MLVA group III to high (MLVA group IV. Infected human and bovine MDM responded with a principal up-regulation of pro-inflammatory cytokines such as IL-1β, IL-12, and TNF-α. However, MLVA group IV strains induced a pronounced host response whereas infection with group I strains resulted in a milder response. C. burnetii infection marginally affected polarization of MDM. Only one C. burnetii strain of MLVA group IV caused a substantial up-regulation of activation markers (CD40, CD80 on the surface of bovine and human MDM. The study showed that replication of C. burnetii in MDM and the subsequent host cell response is genotype-specific rather than being determined by the host species pointing to a clear distinction in C. burnetii virulence between the genetic groups.

  18. Characterization of type IV antifreeze gene in Nile tilapia (Oreochromis niloticus) and influence of cold and hot weather on its expression and some immune-related genes.

    Science.gov (United States)

    Ammar, Asmma Y; El Nahas, Abeer F; Mahmoud, Shawky; Barakat, Mohamed E; Hassan, Asmaa M

    2018-04-01

    The aim of this work is to study the effect of the thermal stress of ambient temperature during winter and summer on the expression of type IV antifreeze gene (ANF IV) in different tissues of Nile tilapia (Oreochromis niloticus) as well as some immune-related genes. At first, genomic ANF IV gene was characterized from one fish; 124 amino acids were identified with 92.7% similarity with that on the gene bank. Expression of ANF IV and immune-related genes were done twice, once at the end of December (winter sample, temperature 14 °C) and the other at August (summer sample, temperature 36 °C). Assessment of ANF IV gene expression in different organs of fish was done; splenic mRNA was used for assessment of immune-related gene transcripts (CXCl2 chemokine, cc-chemokine, INF-3A, and MHC IIβ). Winter expression analysis of AFP IV in O. niloticus revealed significant upregulation of mRNA transcript levels in the intestine, gills, skin, spleen, liver, and brain with 324.03-, 170.06-, 107.63-, 97.61-, 94.35-, and 27.85-folds, respectively. Furthermore, upregulation in the gene was observed in some organs during summer: in the liver, gills, skin, intestine, and brain with lower levels compared with winter. The level of expression of immune-related genes in winter is significantly higher than summer in all assessed genes. Cc-chemokine gene expression was the most affected in both winter and summer. Variable expression profile of ANF IV in different organs and in different seasons together with its amino acid similarity of N-terminal and C-terminal with apolipoprotein (lipid binder) and form of high-density lipoprotein (HDL) suggests a different role for this protein which may be related to lipid metabolism.

  19. L-arginine mediated renaturation enhances yield of human, α6 Type IV collagen non-collagenous domain from bacterial inclusion bodies.

    Science.gov (United States)

    Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Sudhakar, Yakkanti Akul

    2012-10-01

    The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated.

  20. Spectroscopic Studies of Abiotic and Biological Nanomaterials: Silver Nanoparticles, Rhodamine 6G Adsorbed on Graphene, and c-Type Cytochromes and Type IV Pili in Geobacter sulfurreducens

    Science.gov (United States)

    Thrall, Elizabeth S.

    This thesis describes spectroscopic studies of three different systems: silver nanoparticles, the dye molecule rhodamine 6G adsorbed on graphene, and the type IV pili and c-type cytochromes produced by the dissimilatory metal-reducing bacterium Geobacter sulfurreducens. Although these systems are quite different in some ways, they can all be considered examples of nanomaterials. A nanomaterial is generally defined as having at least one dimension below 100 nm in size. Silver nanoparticles, with sub-100 nm size in all dimensions, are examples of zero-dimensional nanomaterials. Graphene, a single atomic layer of carbon atoms, is the paradigmatic two-dimensional nanomaterial. And although bacterial cells are on the order of 1 μm in size, the type IV pili and multiheme c-type cytochromes produced by G. sulfurreducens can be considered to be one- and zero-dimensional nanomaterials respectively. A further connection between these systems is their strong interaction with visible light, allowing us to study them using similar spectroscopic tools. The first chapter of this thesis describes research on the plasmon-mediated photochemistry of silver nanoparticles. Silver nanoparticles support coherent electron oscillations, known as localized surface plasmons, at resonance frequencies that depend on the particle size and shape and the local dielectric environment. Nanoparticle absorption and scattering cross-sections are maximized at surface plasmon resonance frequencies, and the electromagnetic field is amplified near the particle surface. Plasmonic effects can enhance the photochemistry of silver particles alone or in conjunction with semiconductors according to several mechanisms. We study the photooxidation of citrate by silver nanoparticles in a photoelectrochemical cell, focusing on the wavelength-dependence of the reaction rate and the role of the semiconductor substrate. We find that the citrate photooxidation rate does not track the plasmon resonance of the silver

  1. Urban zoonoses caused by Bartonella, Coxiella, Ehrlichia, and Rickettsia species.

    Science.gov (United States)

    Comer, J A; Paddock, C D; Childs, J E

    2001-01-01

    The last half of the 20th Century witnessed an increase in the occurrence and recognition of urban zoonoses caused by members of the genera Bartonella, Coxiella, Ehrlichia, and Rickettsia, all traditionally considered to be members of the family Rickettsiaceae. In recent years, new human pathogens (Bartonella elizabethae, Bartonella henselae, and Rickettsia felis) have been recognized in urban environments. Other newly recognized pathogens (Ehrlichia chaffeensis and Ehrlichia phagocytophila in the United States) have sylvan zoonotic cycles but are present in urban areas because their vertebrate hosts and associated ectoparasitic arthropod vectors are able to survive in cities. Still other agents, which were primarily of historical importance (Bartonella quintana) or have not traditionally been associated with urban environments (Rickettsia rickettsii), have been recognized as causes of human disease in urban areas. Some diseases that have traditionally been associated with urban environments, such as rickettsialpox (caused by Rickettsia akari) and murine typhus (caused by Rickettsia typhi), still occur in large cities at low or undetermined frequencies and often go undetected, despite the availability of effective measures to diagnose and control them. In addition, alternate transmission cycles have been discovered for Coxiella burnetii, Rickettsia prowazekii, and R. typhi that differ substantially from their established, classic cycles, indicating that the epidemiology of these agents is more complex than originally thought and may be changing. Factors leading to an increase in the incidence of illnesses caused by these bacteria in urban areas include societal changes as well as intrinsic components of the natural history of these organisms that favor their survival in cities. Transovarial and transstadial transmission of many of the agents in their arthropod hosts contributes to the highly focal nature of many of the diseases they cause by allowing the pathogens

  2. Genetic mechanisms of Coxiella burnetii lipopolysaccharide phase variation.

    Science.gov (United States)

    Beare, Paul A; Jeffrey, Brendan M; Long, Carrie M; Martens, Craig M; Heinzen, Robert A

    2018-03-01

    Coxiella burnetii is an intracellular pathogen that causes human Q fever, a disease that normally presents as a severe flu-like illness. Due to high infectivity and disease severity, the pathogen is considered a risk group 3 organism. Full-length lipopolysaccharide (LPS) is required for full virulence and disease by C. burnetii and is the only virulence factor currently defined by infection of an immunocompetent animal. Transition of virulent phase I bacteria with smooth LPS, to avirulent phase II bacteria with rough LPS, occurs during in vitro passage. Semi-rough intermediate forms are also observed. Here, the genetic basis of LPS phase conversion was investigated to obtain a more complete understanding of C. burnetii pathogenesis. Whole genome sequencing of strains producing intermediate and/or phase II LPS identified several common mutations in predicted LPS biosynthesis genes. After passage in broth culture for 30 weeks, phase I strains from different genomic groups exhibited similar phase transition kinetics and elevation of mutations in LPS biosynthesis genes. Targeted mutagenesis and genetic complementation using a new C. burnetii nutritional selection system based on lysine auxotrophy confirmed that six of the mutated genes were necessary for production of phase I LPS. Disruption of two of these genes in a C. burnetii phase I strain resulted in production of phase II LPS, suggesting inhibition of the encoded enzymes could represent a new therapeutic strategy for treatment of Q fever. Additionally, targeted mutagenesis of genes encoding LPS biosynthesis enzymes can now be used to construct new phase II strains from different genomic groups for use in pathogen-host studies at a risk group 2 level.

  3. Coxiella burnetii seroprevalence in small ruminants in The Gambia.

    Directory of Open Access Journals (Sweden)

    Marieke Klaasen

    Full Text Available BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia. METHODOLOGY/PRINCIPAL FINDINGS: This survey was carried out from March to May 2012 at two areas in The Gambia. The first area comprised a cluster of seven rural villages situated 5-15 km west of Farafenni as well as the local abattoir. A second sampling was done at the central abattoir in Abuko (30 km from the capital, Banjul in the Western Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67 milk samples were obtained from lactating dams. Sera were tested with a Q fever ELISA kit. C. burnetii DNA was extracted from milk samples and then detected using a specific quantitative multiplex PCR assay, targeting the IS1111a element. A multivariable mixed logistic regression model was used to examine the relationship between seropositivity and explanatory variables. An overall seroprevalence of 21.6% was found. Goats had a significantly higher seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals were significantly older than seronegative animals. Animals from the villages had a significantly lower seroprevalence than animals from the central abattoir (15.1% versus 29.1%. C. burnetii DNA was detected in 2 out of 67 milk samples, whereas 8 samples gave a doubtful result. CONCLUSION/SIGNIFICANCE: A substantial C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated. People living in close proximity to small ruminants are exposed to C. burnetii. Q fever should be considered as a possible cause of acute febrile illness in humans in The Gambia. Future studies should include a simultaneous assessment of veterinary and human serology, and include aetiology of febrile illness in local clinics.

  4. From Q Fever to Coxiella burnetii Infection: a Paradigm Change

    Science.gov (United States)

    Eldin, Carole; Mélenotte, Cléa; Mediannikov, Oleg; Ghigo, Eric; Million, Matthieu; Edouard, Sophie; Mege, Jean-Louis; Maurin, Max

    2016-01-01

    SUMMARY Coxiella burnetii is the agent of Q fever, or “query fever,” a zoonosis first described in Australia in 1937. Since this first description, knowledge about this pathogen and its associated infections has increased dramatically. We review here all the progress made over the last 20 years on this topic. C. burnetii is classically a strict intracellular, Gram-negative bacterium. However, a major step in the characterization of this pathogen was achieved by the establishment of its axenic culture. C. burnetii infects a wide range of animals, from arthropods to humans. The genetic determinants of virulence are now better known, thanks to the achievement of determining the genome sequences of several strains of this species and comparative genomic analyses. Q fever can be found worldwide, but the epidemiological features of this disease vary according to the geographic area considered, including situations where it is endemic or hyperendemic, and the occurrence of large epidemic outbreaks. In recent years, a major breakthrough in the understanding of the natural history of human infection with C. burnetii was the breaking of the old dichotomy between “acute” and “chronic” Q fever. The clinical presentation of C. burnetii infection depends on both the virulence of the infecting C. burnetii strain and specific risks factors in the infected patient. Moreover, no persistent infection can exist without a focus of infection. This paradigm change should allow better diagnosis and management of primary infection and long-term complications in patients with C. burnetii infection. PMID:27856520

  5. Reduction of Coxiella burnetii prevalence by vaccination of goats and sheep, the Netherlands

    NARCIS (Netherlands)

    Hogerweg, R.; Brom, Van den R.; Roest, H.I.J.; Bouma, A.; Vellema, P.; Pieterse, M.; Dercksen, D.; Nielen, M.

    2011-01-01

    Recently, the number of human Q fever cases in the Netherlands increased dramatically. In response to this increase, dairy goats and dairy sheep were vaccinated against Coxiella burnetii. All pregnant dairy goats and dairy sheep in herds positive for Q fever were culled. We identified the effect of

  6. Draft Genome Sequences of Six Ruminant Coxiella burnetii Isolates of European Origin

    DEFF Research Database (Denmark)

    Sidi-Boumedine, Karim; Ellis, Richard J.; Adam, Gilbert

    2014-01-01

    Coxiella burnetii is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European C. burnetii isolates from ruminants are presented here. The availability of these genomes will help in under...

  7. Risk factors of Coxiella burnetii (Q fever) seropositivity in veterinary medicine students.

    NARCIS (Netherlands)

    de Rooij, M.M.T.; Schimmer, B; Versteeg, B.; Schneeberger, P.; Berends, B.R.; Heederik, D.; van der Hoek, W; Wouters, I.M.

    2012-01-01

    BACKGROUND: Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors. METHODS: A

  8. Cell-Free Propagation of Coxiella burnetii Does Not Affect Its Relative Virulence

    NARCIS (Netherlands)

    Kuley, R.; Smith, H.E.; Frangoulidis, D.; Smits, M.A.; Roest, H.I.J.; Bossers, A.

    2015-01-01

    Q fever is caused by the obligate intracellular bacterium Coxiella burnetii. In vitro growth of the bacterium is usually limited to viable eukaryotic host cells imposing experimental constraints for molecular studies, such as the identification and characterisation of major virulence factors.

  9. Protein composition of the phase I Coxiella burnetii soluble antigen prepared by extraction with trichloroacetic acid

    Czech Academy of Sciences Publication Activity Database

    Flores-Ramírez, G.; Kmeťová, E.; Danchenko, M.; Špitalská, E.; Havlíček, Vladimír; Škultéty, L'udovít

    2017-01-01

    Roč. 61, č. 3 (2017), s. 361-368 ISSN 0001-723X Institutional support: RVO:61388971 Keywords : Chemovaccine * Coxiella burnetii * Outbreaks in Slovakia Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 0.673, year: 2016

  10. Q fever: the answer is blowing in the wind : Detection of Coxiella burnetii in aerosols

    NARCIS (Netherlands)

    de Bruin A; van der Plaats R; Janse I; van Rotterdam B; LZO; cib

    2011-01-01

    Coxiella burnetii is a bacterium that causes Q fever, a zoonosis that affects large numbers of both humans and animals. From 2007 to 2010, large outbreaks of Q fever were observed in a rural area in the Netherlands. In 2009, field studies were started to investigate if C. burnetii DNA can be

  11. Detection of Coxiella burnetii using (q)PCR: a comparison of available assays

    NARCIS (Netherlands)

    de Bruin A; van Rotterdam B; LZO; cib

    2012-01-01

    Q fever, caused by the bacterium Coxiella burnetii, has become an emerging public health problem in the Netherlands since 2007. Diagnosis of Q fever, both in humans and animals, is mainly based on serology. Serological techniques are less suitable for direct transmission and source-finding studies

  12. Prevalence of Coxiella Burnetii in Ticks After a Large Outbreak of Q Fever

    NARCIS (Netherlands)

    Sprong, H.; Tijsse-Klasen, E.; Langelaar, M.; de Bruin, A.; Fonville, M.; Gassner, F.; Takken, W.; van Wieren, S.; Nijhof, A.; Jongejan, F.; Maassen, C. B. M.; Scholte, E.-J.; Hovius, J. W.; Emil Hovius, K.; Spitalská, E.; van Duynhoven, Y. T.

    2012-01-01

    Q fever has emerged as an important human and veterinary public health problem in the Netherlands with major outbreaks in three consecutive years. Goat farms are probably the prime source from which Coxiella burnetii have spread throughout the environment, infecting people living in the vicinity.

  13. Screening of blood donors for chronic Coxiella burnetii infection after large Q fever outbreaks

    NARCIS (Netherlands)

    Slot, Ed; Hogema, Boris M.; Molier, Michel; Zaaijer, Hans L.

    2014-01-01

    The Netherlands experienced major Q fever outbreaks from 2007 through 2009. An increasing number of human chronic Q fever cases has been reported in the affected area. Blood donors unaware of chronic Coxiella burnetii infection might be infectious for transfusion recipients. Local blood donations

  14. Q fever in pregnant Goats: PAthogenesis and excretion of Coxiella burnetii

    NARCIS (Netherlands)

    Roest, H.I.J.; Gelderen, van E.; Dinkla, A.; Frangoulidis, D.; Zijderveld, van F.G.; Rebel, J.M.J.; Keulen, van L.J.M.

    2012-01-01

    Coxiella burnetii is an intracellular bacterial pathogen that causes Q fever. Infected pregnant goats are a major source of human infection. However, the tissue dissemination and excretion pathway of the pathogen in goats are still poorly understood. To better understand Q fever pathogenesis, we

  15. In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella burnetii lipopolysaccharide

    Science.gov (United States)

    Background: Coxiella burnetii is Gram-negative bacterium responsible for the zoonosis Q-fever. While it has an obligate intracellulargrowth habit, it is able to persist for extended periods outside of a host cell and can resist environmental conditions that would be lethal to most prokaryotes. It is...

  16. Coxiella burnetii seroprevalence and risk factors on commercial sheep farms in The Netherlands

    NARCIS (Netherlands)

    Schimmer, B.; Lange, M.M. De; Hautvast, J.L.A.; Vellema, P.; Duynhoven, Y.T.H.P. van

    2014-01-01

    Coxiella burnetii seroprevalence was assessed on Dutch dairy and non-dairy sheep farms using ELISA. Risk factors for seropositivity on non-dairy sheep farms were identified at farm and sheep level by univariate and multivariate multilevel analyses. Based on 953 dairy and 5671 non-dairy serum

  17. On the type Ia supernovae 2007on and 2011iv: Evidence for Chandrasekhar-mass explosions at the faint end of the luminosity-width relationship.

    Science.gov (United States)

    Ashall, C.; Mazzali, P. A.; Stritzinger, M. D.; Hoeflich, P.; Burns, C. R.; Gall, C.; Hsiao, E. Y.; Phillips, M. M.; Morrell, N.; Foley, Ryan J.

    2018-03-01

    Radiative transfer models of two transitional type Ia supernova (SNe Ia) have been produced using the abundance stratification technique. These two objects -designated SN 2007on and SN 2011iv- both exploded in the same galaxy, NGC 1404, which allows for a direct comparison. SN 2007on synthesised 0.25 M⊙ of 56Ni and was less luminous than SN 2011iv, which produced 0.31 M⊙ of 56Ni. SN 2007on had a lower central density (ρc) and higher explosion energy (Ekin ˜1.3 ± 0.3 × 1051erg) than SN 2011iv, and it produced less nuclear statistical equilibrium (NSE) elements (0.06 M⊙). Whereas, SN 2011iv had a larger ρc, which increased the electron capture rate in the lowest velocity regions, and produced 0.35 M⊙ of stable NSE elements. SN 2011iv had an explosion energy of ˜Ekin ˜0.9 ± 0.2 × 1051erg. Both objects had an ejecta mass consistent with the Chandrasekhar mass (Ch-mass), and their observational properties are well described by predictions from delayed-detonation explosion models. Within this framework, comparison to the sub-luminous SN 1986G indicates SN 2011iv and SN 1986G have different transition densities (ρtr) but similar ρc. Whereas, SN 1986G and SN 2007on had a similar ρtr but different ρc. Finally, we examine the colour-stretch parameter sBV vs. Lmax relation and determine that the bulk of SNe Ia (including the sub-luminous ones) are consistent with Ch-mass delayed-detonation explosions, where the main parameter driving the diversity is ρtr. We also find ρc to be driving the second order scatter observed at the faint end of the luminosity-width relationship.

  18. Analysis of I-V characteristics on Au/n-type GaAs Schottky structures in wide temperature range

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, S. [Department of Physics, Faculty of Sciences and Arts, University of Kahramanmaras Suetcue Imam, Kahramanmaras 46100 (Turkey)]. E-mail: skaratas@ksu.edu.tr; Altindal, S. [Department of Physics, Faculty of Sciences and Arts, Gazi University, 06500 Besevler, Ankara (Turkey)

    2005-09-15

    The current-voltage (I-V) characteristics of Au/n-GaAs Schottky barrier diodes (SBD) were determined in the temperature range 80-400K. SBD parameters such as ideality factor n, series resistance R{sub S} and barrier height {phi}{sub b} were extracted from I-V curves using Cheung's method. The barrier height for current transport decreases and the ideality factor increases with the decrease temperatures. Such behavior is attributed to barrier inhomogeneities by assuming a Gaussian distribution of barrier heights at the interface. So that barrier height {phi}{sub I-V} have been corrected by taking into account quality factors (n) and the electron tunneling factor ({alpha}{chi}{sup 1/2}{delta}) in the expression of saturation current (I{sub 0}) of the Au/n-GaAs Schottky diodes. Thus, a modified ln(I{sub 0}/T{sup 2})-q{sup 2}{sigma}{sub 0}{sup 2}/2k{sup 2}T{sup 2} versus 1/T gives {phi}-bar {sub b0}(T=0) and A{sup *} as 0.73eV and 11.08A/(cm{sup 2}K{sup 2}), respectively, without using the temperature coefficient of the barrier heights. Therefore, it has been concluded that the temperature dependent I-V characteristics of the device can be successfully explained with Gaussian distribution of the BHs.

  19. Enzyme-linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S)

    DEFF Research Database (Denmark)

    Leeming, Diana J; Nielsen, Mette J; Dai, Yueqin

    2012-01-01

    Aim:  The present study describes the ability of a newly developed N-terminal pro-peptides of type IV collagen 7S domain (P4NP 7S) competitive enzyme-linked immunosorbent assay (ELISA) for describing liver fibrosis. The assay applies a monoclonal antibody specific for a PIVNP 7S epitope 100...... were significantly elevated in rat with liver fibrosis as seen by histology (CCL4: 283% elevated in the highest quartile of total hepatic collagen compared with controls, P = 0.001; BDL: 183% elevated at week 4 compared with sham, P type IV collagen...... expression in BDL rats (r = 0.49, P serum assay specific for P4NP 7S was highly related to liver fibrosis...

  20. Improvement of hyperglycaemia and metabolic syndromes in type 2 diabetic KKAy mice by oral treatment with [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxovanadium(IV)(4-) complex.

    Science.gov (United States)

    Saha, Tapan Kumar; Yoshikawa, Yutaka; Sakurai, Hiromu

    2007-03-01

    Recently, we reported that [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadium(IV)(4-), VO(tpps), shows in-vitro insulin-mimetic and in-vivo anti-diabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability in type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in-vivo anti-diabetic activity of VO(tpps), compared with that of vanadium(IV) oxide sulfate, VS, as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V/kg body weight to the KKA(y) mice for 28 days. VO(tpps) normalized the hyperglycaemia within 15 days, while VS lowered the blood glucose concentration only by a small degree. In addition, metabolic syndromes characterized by insulin and leptin resistance were significantly improved in VO(tpps)-treated KKA(y) mice compared with those treated with VS. The improvement in diabetes was validated by oral glucose tolerance test and decrease in HbA(1c) concentration. Based on these observations, VO(tpps) is proposed to be an orally active oxovanadium(IV)-porphyrin complex for treating not only type 2 diabetes but also metabolic syndromes in animals.

  1. Endovenous surgery for recurrent varicose veins with a one-year follow up in a patient with Ehlers Danlos syndrome type IV.

    Science.gov (United States)

    Whiteley, Mark S; Holdstock, Judith M

    2015-08-01

    We present a woman with severe symptomatic recurrent varicose veins who was treated with endovenous laser ablation and transluminal occlusion of perforator with attempted phlebectomies for extensive varices. The phlebectomies turned out to be near impossible due to friability of the veins. Her treatment was completed with post-operative ultrasound guided foam sclerotherapy seven months later. She was subsequently diagnosed as Ehlers Danlos syndrome type IV. A duplex ultrasound scan 18 months post-endovenous laser ablation and transluminal occlusion of perforator and 11 months after ultrasound guided foam sclerotherapy confirmed successful closure with virtual atrophy of all treated veins. She was found to be reflux free and only showed a few scattered cosmetic reticular veins. Open varicose vein surgery has been reported as being hazardous in the past in a patient with Ehlers Danlos syndrome type IV. Our experience has shown that endovenous laser ablation, transluminal occlusion of perforator and ultrasound guided foam sclerotherapy appear to be effective in treating this patient with Ehlers Danlos syndrome type IV, although phlebectomies were technically impossible. © The Author(s) 2014.

  2. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2004-01-01

    analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. Clinical studies...... with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation......Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. In agreement with these actions, it has been shown to be highly effective...

  3. Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma

    Science.gov (United States)

    2017-12-20

    ALK Fusion Protein Expression; BRAF wt Allele; Invasive Skin Melanoma; MET Fusion Gene Positive; NRAS wt Allele; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; RET Fusion Positive; ROS1 Fusion Positive; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  4. (IV) phosphates

    Indian Academy of Sciences (India)

    M(IV) phosphates of the class of tetravalent metal acid (TMA) salts where M (IV) = Zr, Ti, Sn has been synthesized by the sol-gel method. These materials have been characterized for elemental analysis (ICP-AES), thermal analysis (TGA, DSC), X-ray analysis and FTIR spectroscopy. Chemical resistivity of these materials ...

  5. Coxiella burnetii Infections in Small Ruminants and Humans in Switzerland.

    Science.gov (United States)

    Magouras, I; Hunninghaus, J; Scherrer, S; Wittenbrink, M M; Hamburger, A; Stärk, K D C; Schüpbach-Regula, G

    2017-02-01

    The recent Q fever epidemic in the Netherlands raised concerns about the potential risk of outbreaks in other European countries. In Switzerland, the prevalence of Q fever in animals and humans has not been studied in recent years. In this study, we describe the current situation with respect to Coxiella (C.) burnetii infections in small ruminants and humans in Switzerland, as a basis for future epidemiological investigations and public health risk assessments. Specific objectives of this cross-sectional study were to (i) estimate the seroprevalence of C. burnetii in sheep and goats, (ii) quantify the amount of bacteria shed during abortion and (iii) analyse temporal trends in human C. burnetii infections. The seroprevalence of C. burnetii in small ruminants was determined by commercial ELISA from a representative sample of 100 sheep flocks and 72 goat herds. Herd-level seroprevalence was 5.0% (95% CI: 1.6-11.3) for sheep and 11.1% (95% CI: 4.9-20.7) for goats. Animal-level seroprevalence was 1.8% (95% CI: 0.8-3.4) for sheep and 3.4% (95% CI: 1.7-6) for goats. The quantification of C. burnetii in 97 ovine and caprine abortion samples by real-time PCR indicated shedding of >10 4 bacteria/g in 13.4% of all samples tested. To our knowledge, this is the first study reporting C. burnetii quantities in a large number of small ruminant abortion samples. Annual human Q fever serology data were provided by five major Swiss laboratories. Overall, seroprevalence in humans ranged between 1.7% and 3.5% from 2007 to 2011, and no temporal trends were observed. Interestingly, the two laboratories with significantly higher seroprevalences are located in the regions with the largest goat populations as well as, for one laboratory, with the highest livestock density in Switzerland. However, a direct link between animal and human infection data could not be established in this study. © 2015 Blackwell Verlag GmbH.

  6. Transmission of endemic ST22-MRSA-IV on four acute hospital wards investigated using a combination of spa, dru and pulsed-field gel electrophoresis typing.

    LENUS (Irish Health Repository)

    Creamer, E

    2012-11-01

    The transmission of meticillin-resistant Staphylococcus aureus (MRSA) between individual patients is difficult to track in institutions where MRSA is endemic. We investigated the transmission of MRSA where ST22-MRSA-IV is endemic on four wards using demographic data, patient and environmental screening, and molecular typing of isolates. A total of 939 patients were screened, 636 within 72 h of admission (on admission) and 303 >72 h after admission, and 1,252 environmental samples were obtained. Isolates were typed by spa, dru and pulsed-field gel electrophoresis (PFGE) typing. A composite dendrogram generated from the three sets of typing data was used to divide isolates into \\'dendrogram groups\\' (DGs). Ten percent of patients (92\\/939) were MRSA-positive; 7 % (44\\/636) on admission and 16 % (48\\/303) >72 h after admission (p = 0.0007). MRSA was recovered from 5 % of environmental specimens (65\\/1,252). Most isolates from patients (97 %, 85\\/88) and the environment (97 %, 63\\/65) exhibited the ST22-MRSA-IV genotype. Four DGs (DG1, DG4, DG16 and DG17) accounted for 58 % of ST22-MRSA-IV isolates from patients. Epidemiological evidence suggested cross-transmission among 44\\/92 patients (48 %) but molecular typing confirmed probable cross-transmission in only 11 instances (13 %, 11\\/88), with the majority of cross-transmission (64 %; 7\\/11) occurring on one ward. In the setting of highly clonal endemic MRSA, the combination of local epidemiology, PFGE, spa and dru typing provided valuable insights into MRSA transmission.

  7. A catalogue of the Coelenterate type specimens of the Zoological Museum of Amsterdam. IV. Gorgonacea, Actiniaria, Scleractinia

    NARCIS (Netherlands)

    Soest, van R.W.M.

    1979-01-01

    This final part of the Coelenterate type catalogue lists 274 nominal types (183 Gorgonacea, 9 Actiniaria and 82 Scleractinia). Six not previously depicted types are represented by photographic illustrations of their habit. Furthermore lists are provided of schizotypes, i.e. fragments of types housed

  8. Prevalence of Coxiella burnetii in western grey kangaroos (Macropus fuliginosus) in Western Australia.

    Science.gov (United States)

    Potter, Abbey S; Banazis, Michael J; Yang, Rongchang; Reid, Simon A; Fenwick, Stan G

    2011-10-01

    We investigated the role of the western grey kangaroo (Macropus fuliginosus) in the maintenance and transmission of Coxiella burnetii in Western Australia. Sera from 1,017 kangaroos were tested using an indirect enzyme-linked immunosorbent assay (ELISA) for the presence of C. burnetii antibodies. The overall antibody prevalence across 12 locations throughout mid- to southwestern Western Australia was 24.1% (95% CI: 21.6-26.8). Feces from 990 of the same animals were tested using PCR to identify active shedding of C. burnetii in excreta. Coxiella burnetii DNA was detected in 4.1% (95% CI: 3.1-5.6) of samples. Our results suggest that kangaroos are reservoirs for C. burnetii in Western Australia and may contribute to transmission of the organism to domestic livestock and humans.

  9. Lipopolysaccharide phase variation determines the complement-mediated serum susceptibility of Coxiella burnetii.

    OpenAIRE

    Vishwanath, S; Hackstadt, T

    1988-01-01

    Phase variation of Coxiella burnetii is due to variation of the lipopolysaccharide (LPS), a phenomenon analogous to smooth-to-rough LPS variation of gram-negative enteric bacteria. Virulent enterobacteria usually have a smooth LPS and resist serum killing, whereas avirulent rough LPS mutants are sensitive to complement-mediated serum killing. Like gram-negative enterobacteria, smooth LPS phase variants of C. burnetii are virulent, whereas the rough LPS variants are avirulent. We therefore stu...

  10. Presence of antibodies against Coxiella burnetii and risk of spontaneous abortion

    DEFF Research Database (Denmark)

    Nielsen, Stine Yde; Hjøllund, Niels Henrik; Andersen, Anne-Marie Nybo

    2012-01-01

    Q fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during...... pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion....

  11. The nebular spectra of the transitional Type Ia Supernovae 2007on and 2011iv: broad, multiple components indicate aspherical explosion cores

    Science.gov (United States)

    Mazzali, P. A.; Ashall, C.; Pian, E.; Stritzinger, M. D.; Gall, C.; Phillips, M. M.; Höflich, P.; Hsiao, E.

    2018-02-01

    The nebular-epoch spectrum of the rapidly declining, "transitional" type Ia supernova (SN) 2007on showed double emission peaks, which have been interpreted as indicating that the SN was the result of the direct collision of two white dwarfs. The spectrum can be reproduced using two distinct emission components, one red-shifted and one blue-shifted. These components are similar in mass but have slightly different degrees of ionization. They recede from one another at a line-of-sight speed larger than the sum of the combined expansion velocities of their emitting cores, thereby acting as two independent nebulae. While this configuration appears to be consistent with the scenario of two white dwarfs colliding, it may also indicate an off-centre delayed detonation explosion of a near Chandrasekhar-mass white dwarf. In either case, broad emission line widths and a rapidly evolving light curve can be expected for the bolometric luminosity of the SN. This is the case for both SNe 2007on and 2011iv, also a transitional SN Ia which exploded in the same elliptical galaxy, NGC 1404. Although SN 2011iv does not show double-peaked emission line profiles, the width of its emission lines is such that a two-component model yields somewhat better results than a single-component model. Most of the mass ejected is in one component, however, which suggests that SN 2011iv was the result of the off-centre ignition of a Chandrasekhar-mass white dwarf.

  12. The nebular spectra of the transitional Type Ia Supernovae 2007on and 2011iv: broad, multiple components indicate aspherical explosion cores

    Science.gov (United States)

    Mazzali, P. A.; Ashall, C.; Pian, E.; Stritzinger, M. D.; Gall, C.; Phillips, M. M.; Höflich, P.; Hsiao, E.

    2018-05-01

    The nebular-epoch spectrum of the rapidly declining, `transitional' Type Ia supernova (SN) 2007on showed double emission peaks, which have been interpreted as indicating that the SN was the result of the direct collision of two white dwarfs. The spectrum can be reproduced using two distinct emission components, one redshifted and one blueshifted. These components are similar in mass but have slightly different degrees of ionization. They recede from one another at a line-of-sight speed larger than the sum of the combined expansion velocities of their emitting cores, thereby acting as two independent nebulae. While this configuration appears to be consistent with the scenario of two white dwarfs colliding, it may also indicate an off-centre delayed detonation explosion of a near-Chandrasekhar-mass white dwarf. In either case, broad emission line widths and a rapidly evolving light curve can be expected for the bolometric luminosity of the SN. This is the case for both SNe 2007on and 2011iv, also a transitional SN Ia that exploded in the same elliptical galaxy, NGC 1404. Although SN 2011iv does not show double-peaked emission line profiles, the width of its emission lines is such that a two-component model yields somewhat better results than a single-component model. Most of the mass ejected is in one component, however, which suggests that SN 2011iv was the result of the off-centre ignition of a Chandrasekhar-mass white dwarf.

  13. A new multiplex PCR for easy screening of methicillin-resistant Staphylococcus aureus SCCmec types I-V

    DEFF Research Database (Denmark)

    Boye, Kit; Bartels, Mette Damkjær; Andersen, Ina S

    2007-01-01

    A multiplex PCR with four primer-pairs was designed to identify the five main known SCCmec types. A clear and easily discriminated band pattern was obtained for all five types. The SCCmec type was identified for 98% of 312 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA...

  14. The effects of pulsed and sinusoidal electromagnetic fields on E-cadherin and type IV collagen in gingiva: a histopathological and immunohistochemical study.

    Science.gov (United States)

    Dogru, Arzum G; Tunik, Selcuk; Akpolat, Veysi; Dogru, Mehmet; Saribas, Ebru E; Kaya, Filiz A; Nergiz, Yusuf

    2013-01-01

    The potential beneficial effects of extremely low frequency pulsed and sinusoidal electromagnetic fields have been shown on many tissues. Gingival epithelium plays an important role in immunosurveillance of the periodontal tissues. The epithelium acts as a mechanical barrier through cell junctions such as E-cadherin. Investigation of the effects of extremely low frequency magnetic fields on gingiva. Twenty-seven male Wistar albino rats were used. The rats were divided into three groups: control group (n = 9), SEMF group (n = 9), PEMF group (n = 9). The SEMF and PEMF (pulse time: 25 µsn, pulse frequency: 50 Hz) groups were subjected to 1.5 mT, 50 Hz, exposure 6 h a day, 5 days a week for 28 days in methacrylate boxes. The gingival tissue pieces processed for routine histological and immunohistochemical examination and tissue sections were stained with H-E and Masson trichrome. In addition, E-cadherin and type IV collagen expressions were examined immunohistochemically. Intraepithelial lymphocytes and proliferation of epithelial cells increased in both electromagnetic field groups. The over-expressions of E-cadherin on gingival epithelium was detected in the PEMF and SEMF groups. The expression level of type IV collagen was not significant between the control and electromagnetic field treated groups, except for a significant increase in the basal cell layer of the PEMF group, as compared to the control and SEMF groups. PEMF and SEMF have a local pro-inflammatory effect on gingiva, leading to an increase in E-cadherin level but not type IV collagen. Both PEMF and SEMF can be used as a supportive device in the treatment of gingival diseases, especially those which lead to defects in the epithelial barrier.

  15. Ehlers-Danlos syndrome type IV and recurrent carotid-cavernous fistula: review of the literature, endovascular approach, technique and difficulties

    Energy Technology Data Exchange (ETDEWEB)

    Desal, H.A.; Toulgoat, F.; Raoul, S.; Guillon, B.; Bommard, S.; Naudou-Giron, E.; Auffary-Calvier, E.; Kersaint-Gilly, A. de [Department of Neuroradiology, Laennec Hospital, University of Nantes (France); 1

    2005-04-01

    We report the follow-up of a previously published case (Forlodou et al. Neuroradiology 38:595-597, 1996) of carotido-cavernous fistulas (CCFs) in a patient presenting with type IV Ehlers-Danlos syndrome (EDS 4) that were successfully treated twice by an endovascular approach. Initial treatment with a detachable balloon was in 1994 for a right CCF, and, 8 years later, a left CCF was treated by selective transarterial occlusion of the cavernous sinus with coils. Unfortunately, the patient suffered from a spontaneous post-operative intracranial haemorrhage in the left hemisphere and died. Review of the literature, technical considerations for bilateral CCF and complication are discussed.

  16. Enterococcus faecalis PcfC, a Spatially Localized Substrate Receptor for Type IV Secretion of the pCF10 Transfer Intermediate▿

    OpenAIRE

    Chen, Yuqing; Zhang, Xiaolin; Manias, Dawn; Yeo, Hye-Jeong; Dunny, Gary M.; Christie, Peter J.

    2008-01-01

    Upon sensing of peptide pheromone, Enterococcus faecalis efficiently transfers plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand-specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we present evidence that PcfF and PcfG spatially coordinate docking of the pCF10 transfer intermediate with PcfC, a membrane-bound putative ATPase related to the coupling proteins of gram-...

  17. Incidence and specificity of antibodies to types I, II, III, IV, and V collagen in rheumatoid arthritis and other rheumatic diseases as measured by 125I-radioimmunoassay

    International Nuclear Information System (INIS)

    Stuart, J.M.; Huffstutter, E.H.; Townes, A.S.; Kang, A.H.

    1983-01-01

    Antibodies to human native and denatured types I, II, III, IV, and V collagens were measured using 125I-radioimmunoassay. Mean levels of binding by sera from 30 rheumatoid arthritis patients were significantly higher than those from 20 normal subjects against all of the collagens tested. The relative antibody concentration was higher in synovial fluid than in simultaneously obtained serum. Many patients with gout or various other rheumatic diseases also had detectable anticollagen antibodies. With a few notable exceptions, the majority of the reactivity detected in all patient groups was directed against covalent structural determinants present on all of the denatured collagens, suggesting a secondary reaction to tissue injury

  18. Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

    Science.gov (United States)

    Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

    2013-01-01

    Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (pFabry disease, as well as for those with the classic type. PMID:23864212

  19. Multiple Substrate Usage of Coxiella burnetii to Feed a Bipartite Metabolic Network

    Directory of Open Access Journals (Sweden)

    Ina Häuslein

    2017-06-01

    Full Text Available The human pathogen Coxiella burnetii causes Q-fever and is classified as a category B bio-weapon. Exploiting the development of the axenic growth medium ACCM-2, we have now used 13C-labeling experiments and isotopolog profiling to investigate the highly diverse metabolic network of C. burnetii. To this aim, C. burnetii RSA 439 NMII was cultured in ACCM-2 containing 5 mM of either [U-13C3]serine, [U-13C6]glucose, or [U-13C3]glycerol until the late-logarithmic phase. GC/MS-based isotopolog profiling of protein-derived amino acids, methanol-soluble polar metabolites, fatty acids, and cell wall components (e.g., diaminopimelate and sugars from the labeled bacteria revealed differential incorporation rates and isotopolog profiles. These data served to decipher the diverse usages of the labeled substrates and the relative carbon fluxes into the core metabolism of the pathogen. Whereas, de novo biosynthesis from any of these substrates could not be found for histidine, isoleucine, leucine, lysine, phenylalanine, proline and valine, the other amino acids and metabolites under study acquired 13C-label at specific rates depending on the nature of the tracer compound. Glucose was directly used for cell wall biosynthesis, but was also converted into pyruvate (and its downstream metabolites through the glycolytic pathway or into erythrose 4-phosphate (e.g., for the biosynthesis of tyrosine via the non-oxidative pentose phosphate pathway. Glycerol efficiently served as a gluconeogenetic substrate and could also be used via phosphoenolpyruvate and diaminopimelate as a major carbon source for cell wall biosynthesis. In contrast, exogenous serine was mainly utilized in downstream metabolic processes, e.g., via acetyl-CoA in a complete citrate cycle with fluxes in the oxidative direction and as a carbon feed for fatty acid biosynthesis. In summary, the data reflect multiple and differential substrate usages by C. burnetii in a bipartite-type metabolic network

  20. Comparative evaluation of few physical properties of epoxy resin, resin-modified gypsum and conventional type IV gypsum die materials: an in vitro study.

    Science.gov (United States)

    Gujjarlapudi, Manmohan Choudary; Reddy, S Varalakshmi; Madineni, Praveen Kumar; Ealla, Kranti Kiran Reddy; Nunna, Venkata Narayana; Manne, Sanjay Dutt

    2012-01-01

    To compare and evaluate few physical properties of epoxy resin, resin-modified gypsum and conventional type-IV gypsum die material. In the present study, dimensional accuracy, surface detail reproduction and transverse strength of three die materials like epoxy resin (Diemet-E), resin-modified gypsum (Synarock) and conventional type-IV gypsum (Ultrarock) are analyzed. For dimensional accuracy, master die (Bailey's die) is used and calibrations were made with digital microscope. For surface detail reproduction and transverse strength, rectangular stainless steel master die (Duke's die) was used and calibrations were made with Toolmaker's microscope and Instron universal testing machine respectively. One-way analysis of variance (ANOVA) was performed on the means and standard deviation for groups of each test. The results of the study showed statistically significant difference among these materials in dimensional accuracy, surface detail reproduction and transverse strength. Epoxy resin exhibited superiority in dimensional accuracy, surface detail reproduction and transverse strength and is nearest to the standards of accurate die material.

  1. 4-Hydroxy-2-nonenal Alkylated and Peroxynitrite Nitrated Proteins Localize to the Fused Mitochondria in Malpighian Epithelial Cells of Type IV Collagen Drosophila Mutants

    Directory of Open Access Journals (Sweden)

    András A. Kiss

    2018-01-01

    Full Text Available Background. Human type IV collagenopathy is associated with mutations within the COL4A1 and to a less extent the COL4A2 genes. The proteins encoded by these genes form heterotrimers and are the highest molar ratio components of the ubiquitous basement membrane. The clinical manifestations of the COL4A1/A2 mutations are systemic affecting many tissues and organs among these kidneys. In order to uncover the cellular and biochemical alterations associated with aberrant type IV collagen, we have explored the phenotype of the Malpighian tubules, the secretory organ and insect kidney model, in col4a1 collagen gene mutants of the fruit fly Drosophila melanogaster. In Malpighian epithelial cells of col4a1 mutants, robust mitochondrial fusion indicated mutation-induced stress. Immunohistochemistry detected proteins nitrated by peroxynitrite that localized to the enlarged mitochondria and increased level of membrane peroxidation, assessed by the amount of proteins alkylated by 4-hydroxy-2-nonenal that similarly localized to the fused mitochondria. Nuclei within the Malpighian epithelium showed TUNEL-positivity suggesting cell degradation. The results demonstrated that col4a1 mutations affect the epithelia and, consequently, secretory function of the Malpighian tubules and provide mechanistic insight into col4a1 mutation-associated functional impairments not yet reported in human patients and in mouse models with mutant COL4A1.

  2. Surfactant Protein D Binds to Coxiella burnetii and Results in a Decrease in Interactions with Murine Alveolar Macrophages.

    Directory of Open Access Journals (Sweden)

    Kelly A Soltysiak

    Full Text Available Coxiella burnetii is a Gram-negative, obligate intracellular bacterium and the causative agent of Q fever. Infections are usually acquired after inhalation of contaminated particles, where C. burnetii infects its cellular target cells, alveolar macrophages. Respiratory pathogens encounter the C-type lectin surfactant protein D (SP-D during the course of natural infection. SP-D is a component of the innate immune response in the lungs and other mucosal surfaces. Many Gram-negative pulmonary pathogens interact with SP-D, which can cause aggregation, bactericidal effects and aid in bacterial clearance. Here we show that SP-D binds to C. burnetii in a calcium-dependent manner with no detectable bacterial aggregation or bactericidal effects. Since SP-D interactions with bacteria often alter macrophage interactions, it was determined that SP-D treatment resulted in a significant decrease in C. burnetii interactions to a mouse alveolar macrophage model cell line MH-S indicating SP-D causes a significant decrease in phagocytosis. The ability of SP-D to modulate macrophage activation by C. burnetii was tested and it was determined that SP-D does not alter the correlates measured for macrophage activation. Taken together these studies support those demonstrating limited activation of alveolar macrophages with C. burnetii and demonstrate interactions with SP-D participate in reduction of phagocyte attachment and phagocytosis.

  3. Characterization of type I, II, III, IV, and V collagens by time-resolved laser-induced fluorescence spectroscopy

    Science.gov (United States)

    Marcu, Laura; Cohen, David; Maarek, Jean-Michel I.; Grundfest, Warren S.

    2000-04-01

    The relative proportions of genetically distinct collagen types in connective tissues vary with tissue type and change during disease progression, development, wound healing, aging. This study aims to 1) characterize the spectro- temporal fluorescence emission of fiber different types of collagen and 2) assess the ability of time-resolved laser- induced fluorescence spectroscopy to distinguish between collagen types. Fluorescence emission of commercially available purified samples was induced with nitrogen laser excitation pulses and detected with a MCP-PMT connected to a digital storage oscilloscope. The recorded time-resolved emission spectra displayed distinct fluorescence emission characteristics for each collagen type. The time domain information complemented the spectral domain intensity data for improved discrimination between different collagen types. Our results reveal that analysis of the fluorescence emission can be used to characterize different species of collagen. Also, the results suggest that time-resolved spectroscopy can be used for monitoring of connective tissue matrix composition changes due to various pathological and non-pathological conditions.

  4. Class of diatomic ferroelectrics with multifunctional properties: IV-VI compounds in the distorted NiAs-type structure

    Science.gov (United States)

    Zhang, Hu; Deng, Bei; Wang, Wei-Chao; Shi, Xing-Qiang

    2017-12-01

    Ferroelectrics have attracted a great deal of attention, but diatomic ferroelectrics are less common. Here we establish a class of diatomic ferroelectrics in the distorted NiAs-type structure based on state-of-the-art first-principles calculations. These compounds, with giant Rashba effect, possess rich phases, ranging from ferroelectric semiconductors to ferroelectric semimetals. Topological surface states and type-II bulk Dirac fermions are found in the undistorted phases. This class of multifunctional materials has potential applications in spin-orbitronics.

  5. Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Deacon, Carolyn F

    2004-01-01

    Proof-of-concept for the efficacy of a glucagon-like peptide 1 (GLP-1)-based therapy of patients with type 2 diabetes was provided in 2002 by means of prolonged continuous subcutaneous infusion of native GLP-1. Since then, several long-acting analogues of GLP-1, as well as inhibitors of dipeptidyl...

  6. Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

    Science.gov (United States)

    Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Muniandy, Sekaran

    2015-01-01

    Background A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy. Methods We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome). Results Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels. Conclusion Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin

  7. Graf Type-IV Hips Have a Higher Risk of Residual Acetabular Dysplasia at 1 Year of Age Following Successful Pavlik Harness Treatment for Developmental Hip Dysplasia.

    Science.gov (United States)

    Novais, Eduardo N; Sanders, Julia; Kestel, Lauryn A; Carry, Patrick M; Meyers, Mariana L

    2016-09-22

    We asked whether patient-specific factors and ultrasound (US) measurements of hip dysplasia severity at initial examination influence short-term residual acetabular dysplasia in patients successfully treated with Pavlik harness for developmental hip dysplasia. After IRB approval, 134 hips (84 patients) successfully treated by the Pavlik method between August 2011 and October 2014 with follow-up at 12 months of age were identified. Early successful treatment was defined as normal examination and US after approximately 12 weeks of Pavlik treatment. Multivariate linear and logistic regression models were used to identify factors associated with acetabular index (AI) measurements at 12 months as well as factors associated with an increase in AI between the 6- and 12-month timepoints (dysplastic progression). The study consisted of 134 hips (84 patients). The distribution of dysplastic, Barlow, and Ortolani hips was 44.8% (N=60), 30.6% (N=41), and 24.6% (N=33), respectively. The crude incidence of residual dysplasia at the 6-month visit (AI>30 degrees) was 11.7% (12/102). The incidence of residual dysplasia at the 12-month visit (AI>28 degrees) was 11.8% (13/111). Graf type was the only variable associated with AI values at the 12-month visit (mean difference: Graf type-IV-Other, 2.6; 95% confidence interval, 0.3-4.9; P=0.026). The risk of residual acetabular dysplasia after normal hip US following Pavlik treatment is not negligible. Radiographic surveillance is warranted to monitor and screen for dysplasia progression. Patients with dislocated Graf type-IV hips at diagnosis are at increased risk of residual acetabular dysplasia at 1 year after successful treatment with the Pavlik method. Level III-therapeutic study.

  8. Long pulsed Nd: YAG laser with inbuilt cool sapphire tip for long term hair reduction on type- IV and V skin: A prospective analysis of 200 patients

    Directory of Open Access Journals (Sweden)

    Nanda Soni

    2010-01-01

    Full Text Available Background: Laser hair reduction has become a very popular means to get rid of unwanted hair. Aims: We conducted the current study to evaluate the safety and efficacy of Nd: YAG laser on dark skin. We also evaluated the effect of increasing the gap between sessions on the long term efficacy of hair reduction achieved with long pulsed Nd: YAG laser. Methods: A prospective study was conducted on 200 consecutive female patients who underwent laser hair reduction for unwanted hair over the face, at Kaya skin clinic Delhi, with long pulsed Nd: YAG laser, from May 2006 to May 2009. The gap between sessions was increased from 2 nd session itself. Results were evaluated 6 months after 6 sessions. Also a note was made of worsening of hair growth or any side effects experienced the patient during any of the sessions. Results: A total of 200 female patients (160 skin type IV and 40 skin type V were followed up. Of these, 64 enrolled for lower face, 88 for chin or upper neck and 48 for upper lip. 6 months after 6 sessions, more than 50% improvement was seen in 68.7% of lower face, 89.69% cases of chin and 59% of upper lip cases. None of the patients had any worsening. Conclusions: The current study shows that long pulsed Nd: YAG is a very safe and effective means of hair reduction in skin types IV and V. Adequate fluences and increasing the gap between sessions from the 2 nd session could be the key to achieving long term hair reduction with Nd: YAG laser. Adequate cooling and proper shaving are the key factors determining the safety.

  9. SDSS-IV MaNGA: Spatially resolved star formation histories in galaxies as a function of galaxy mass and type

    Science.gov (United States)

    Goddard, D.; Thomas, D.; Maraston, C.; Westfall, K.; Etherington, J.; Riffel, R.; Mallmann, N. D.; Zheng, Z.; Argudo-Fernández, M.; Lian, J.; Bershady, M.; Bundy, K.; Drory, N.; Law, D.; Yan, R.; Wake, D.; Weijmans, A.; Bizyaev, D.; Brownstein, J.; Lane, R. R.; Maiolino, R.; Masters, K.; Merrifield, M.; Nitschelm, C.; Pan, K.; Roman-Lopes, A.; Storchi-Bergmann, T.; Schneider, D. P.

    2017-04-01

    We study the internal gradients of stellar population properties within 1.5 Re for a representative sample of 721 galaxies, with stellar masses ranging between 109 M⊙ and 1011.5 M⊙ from the SDSS-IV MaNGA Integral-Field-Unit survey. Through the use of our full spectral fitting code firefly, we derive light- and mass-weighted stellar population properties and their radial gradients, as well as full star formation and metal enrichment histories. We also quantify the impact that different stellar population models and full spectral fitting routines have on the derived stellar population properties and the radial gradient measurements. In our analysis, we find that age gradients tend to be shallow for both early-type and late-type galaxies. Mass-weighted age gradients of early-types arepositive (˜0.09 dex/Re) pointing to 'outside-in' progression of star formation, while late-type galaxies have negative light-weighted age gradients (˜-0.11 dex/Re), suggesting an 'inside-out' formation of discs. We detect negative metallicity gradients in both early- and late-type galaxies, but these are significantly steeper in late-types, suggesting that the radial dependence of chemical enrichment processes and the effect of gas inflow and metal transport are far more pronounced in discs. Metallicity gradients of both morphological classes correlate with galaxy mass, with negative metallicity gradients becoming steeper with increasing galaxy mass. The correlation with mass is stronger for late-type galaxies, with a slope of d(∇[Z/H])/d(log M) ˜ -0.2 ± 0.05 , compared to d(∇[Z/H])/d(log M) ˜ -0.05 ± 0.05 for early-types. This result suggests that the merger history plays a relatively small role in shaping metallicity gradients of galaxies.

  10. Impregnated-electrode-type liquid metal ion source (IV): Extraction of Si, Ge, Sb by using eutectic alloy

    International Nuclear Information System (INIS)

    Chen, G.; Gotoh, Y.; Tsuji, H.; Ishikawa, J.; Takagi, T.

    1985-01-01

    An impregnated-electrode-type liquid metal ion source has been developed in which a sintered porous tungsten tip is used. There has been an increasing interest in liquid metal ion source to obtain focused ion beams. The focused ion beam can perform three useful process steps: direct-write ion implantation to semiconductor, ion sputtering to make thin films and ion exposure to define resist. It is necessary to extract various ions for this purpose. It is possible to extract ions of Ga, Au, and Ag with impregnated-electrode-type liquid metal ion source. For micro-electronic application, ions of Si, Ge and Sb are desirable for doping, but their high melting points or high vapour pressures prohibit their use in elemental form. The purpose of the present investigation is to fabricate eutectic alloys which can be used in impregnated-electrode-type liquid metal ion source. The authors have been successful to obtain ions of Si, Ge and Sb, and revealed relevant basic ion source parameters such as current-voltage characteristics, mass spectra and life time

  11. SDSS-IV MaNGA: A Distinct Mass Distribution Explored in Slow-Rotating Early-type Galaxies

    Science.gov (United States)

    Rong, Yu; Li, Hongyu; Wang, Jie; Gao, Liang; Li, Ran; Ge, Junqiang; Jing, Yingjie; Pan, Jun; Fernández-Trincado, J. G.; Valenzuela, Octavio; Ortíz, Erik Aquino

    2018-03-01

    We study the radial acceleration relation (RAR) for early-type galaxies (ETGs) in the SDSS MaNGA MPL5 dataset. The complete ETG sample show a slightly offset RAR from the relation reported by McGaugh et al. (2016) at the low-acceleration end; we find that the deviation is due to the fact that the slow rotators show a systematically higher acceleration relation than the McGaugh's RAR, while the fast rotators show a consistent acceleration relation to McGaugh's RAR. There is a 1σ significant difference between the acceleration relations of the fast and slow rotators, suggesting that the acceleration relation correlates with the galactic spins, and that the slow rotators may have a different mass distribution compared with fast rotators and late-type galaxies. We suspect that the acceleration relation deviation of slow rotators may be attributed to more galaxy merger events, which would disrupt the original spins and correlated distributions of baryons and dark matter orbits in galaxies.

  12. Osteogenesis imperfecta Type IV: a newly identified variant at position c.560 (G > T; p.Gly187Val) in the COL1A2 gene.

    Science.gov (United States)

    Usta, Akin; Karademir, Dilay; Sen, Eylem; Yazici, Selcuk; Adali, Ertan; Erdem, Erkan; Karacan, Meric

    2017-01-01

    Osteogenesis imperfecta is a clinically heterogenous disease caused by defective collagen syntesis associated with a mutation in the COL1A1 or COL1A2 genes. In this report, we present a case of osteogenesis imperfecta (OI) type IV, seen in a female fetus with incurved femurs at 18 weeks of gestation. Molecular analysis of the newborn revealed a novel mutation at position c.560 (c.560 G > T) of the exon 12 in the COL1A2 gene; which lead to the glycine modification with valine (p.Gly187Val) at codon 187. The pregnancy follow-up was uneventful. After delivery, the newborn underwent biphosponat therapy and no fracture was detected until 1 year old.

  13. Immuno-localization of type-IV collagen in the blood-gas barrier and the epithelial-epithelial cell connections of the avian lung.

    Science.gov (United States)

    Jimoh, S A; Maina, J N

    2013-02-23

    The terminal respiratory units of the gas exchange tissue of the avian lung, the air capillaries (ACs) and the blood capillaries (BCs), are small and rigid: the basis of this mechanical feature has been highly contentious. Because the strength of the blood-gas barrier (BGB) of the mammalian lung has been attributed to the presence of type-IV collagen (T-IVc), localization of T-IVc in the basement membranes (BM) of the BGB and the epithelial-epithelial cell connections (E-ECCs) of the exchange tissue of the lung of the avian (chicken) lung was performed in order to determine whether it may likewise contribute to the strength of the BGB. T-IVc was localized in both the BM and the E-ECCs. As part of an integrated fibroskeletal scaffold on the lung, T-IVc may directly contribute to the strengths of the ACs and the BCs.

  14. Immuno-localization of type-IV collagen in the blood-gas barrier and the epithelial–epithelial cell connections of the avian lung

    Science.gov (United States)

    Jimoh, S. A.; Maina, J. N.

    2013-01-01

    The terminal respiratory units of the gas exchange tissue of the avian lung, the air capillaries (ACs) and the blood capillaries (BCs), are small and rigid: the basis of this mechanical feature has been highly contentious. Because the strength of the blood-gas barrier (BGB) of the mammalian lung has been attributed to the presence of type-IV collagen (T-IVc), localization of T-IVc in the basement membranes (BM) of the BGB and the epithelial–epithelial cell connections (E-ECCs) of the exchange tissue of the lung of the avian (chicken) lung was performed in order to determine whether it may likewise contribute to the strength of the BGB. T-IVc was localized in both the BM and the E-ECCs. As part of an integrated fibroskeletal scaffold on the lung, T-IVc may directly contribute to the strengths of the ACs and the BCs. PMID:23193049

  15. Steered molecular dynamics simulations of a bacterial type IV pilus reveal characteristics of an experimentally-observed, force-induced conformational transition

    Science.gov (United States)

    Baker, Joseph; Biais, Nicolas; Tama, Florence

    2011-10-01

    Type IV pili (T4P) are long, filamentous structures that emanate from the cellular surface of many infectious bacteria. They are built from a 158 amino acid long subunit called pilin. T4P can grow to many micrometers in length, and can withstand large tension forces. During the infection process, pili attach themselves to host cells, and therefore naturally find themselves under tension. We investigated the response of a T4 pilus to a pulling force using the method of steered molecular dynamics (SMD) simulation. Our simulations expose to the external environment an amino acid sequence initially hidden in the native filament, in agreement with experimental data. Therefore, our simulations might be probing the initial stage of the transition to a force-induced conformation of the T4 pilus. Additional exposed amino acid sequences that might be useful targets for drugs designed to mitigate bacterial infection were also predicted.

  16. Sensitivitas dan Spesifisitas Nested Polymerase Chain Reaction untuk Mendeteksi DNA Coxiella burnetii (SENSITIVITY AND SPECIFICITY OF NESTED POLYMERASE CHAIN REACTION FOR DETECTION OF COXIELLA BURNETII DNA

    Directory of Open Access Journals (Sweden)

    Trioso Purnawarman

    2014-04-01

    Full Text Available Sensitivity and specificity of nested polymerase chain reaction (nested PCR to detect Coxiella burnetii(C. burnetii DNA were studied. The primer system which consists of external primers (OMP1 and OMP2and internal primers (OMP3 and OMP4, was designed from the nucleotide sequence of the com I geneencoding for 27 kDa outer membrane protein and used to specifically amplify a 501 bp and 438 bp fragment.This nested PCR assay was 50 fold more sensitive than that of using PCR external primer only. TheNested PCR has a detection limit as low as 300 pg/?l. Specificity studies showed that nested PCR onlydetected C. burnetii DNA and did not happened Brucella abortus, Escherichia coli, Pseudomonas aeruginosaand Campylobacter Jejuni DNA. Nested PCR has high senstively and specificaly diagnostic method of C.burnetii as agent of Q fever disease.

  17. Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes.

    Science.gov (United States)

    Moens, F; De Vuyst, L

    2017-05-30

    Four selected butyrate-producing colon bacterial strains belonging to Clostridium cluster IV (Butyricicoccus pullicaecorum DSM 23266 T and Faecalibacterium prausnitzii DSM 17677 T ) and XIVa (Eubacterium hallii DSM 17630 and Eubacterium rectale CIP 105953 T ) were studied as to their capacity to degrade inulin-type fructans and concomitant metabolite production. Cultivation of these strains was performed in bottles and fermentors containing a modified medium for colon bacteria, including acetate, supplemented with either fructose, oligofructose, or inulin as the sole energy source. Inulin-type fructan degradation was not a general characteristic among these strains. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 could only ferment fructose and did not degrade oligofructose or inulin. E. rectale CIP 105953 T and F. prausnitzii DSM 17677 T fermented fructose and could degrade both oligofructose and inulin. All chain length fractions of oligofructose were degraded simultaneously (both strains) and both long and short chain length fractions of inulin were degraded either simultaneously (E. rectale CIP 105953 T ) or consecutively (F. prausnitzii DSM 17677 T ), indicating an extracellular polymer degradation mechanism. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 produced high concentrations of butyrate, CO 2 , and H 2 from fructose. E. rectale CIP 105953 T produced lactate, butyrate, CO 2 , and H 2 , from fructose, oligofructose, and inulin, whereas F. prausnitzii DSM 17677 T produced butyrate, formate, CO 2 , and traces of lactate from fructose, oligofructose, and inulin. Based on carbon recovery and theoretical metabolite production calculations, an adapted stoichiometrically balanced metabolic pathway for butyrate, formate, lactate, CO 2 , and H 2 production by members of both Clostridium cluster IV and XIVa butyrate-producing bacteria was constructed.

  18. Postreplication Roles of the Brucella VirB Type IV Secretion System Uncovered via Conditional Expression of the VirB11 ATPase

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    Erin P. Smith

    2016-11-01

    Full Text Available Brucella abortus, the bacterial agent of the worldwide zoonosis brucellosis, primarily infects host phagocytes, where it undergoes an intracellular cycle within a dedicated membrane-bound vacuole, the Brucella-containing vacuole (BCV. Initially of endosomal origin (eBCV, BCVs are remodeled into replication-permissive organelles (rBCV derived from the host endoplasmic reticulum, a process that requires modulation of host secretory functions via delivery of effector proteins by the Brucella VirB type IV secretion system (T4SS. Following replication, rBCVs are converted into autophagic vacuoles (aBCVs that facilitate bacterial egress and subsequent infections, arguing that the bacterium sequentially manipulates multiple cellular pathways to complete its cycle. The VirB T4SS is essential for rBCV biogenesis, as VirB-deficient mutants are stalled in eBCVs and cannot mediate rBCV biogenesis. This has precluded analysis of whether the VirB apparatus also drives subsequent stages of the Brucella intracellular cycle. To address this issue, we have generated a B. abortus strain in which VirB T4SS function is conditionally controlled via anhydrotetracycline (ATc-dependent complementation of a deletion of the virB11 gene encoding the VirB11 ATPase. We show in murine bone marrow-derived macrophages (BMMs that early VirB production is essential for optimal rBCV biogenesis and bacterial replication. Transient expression of virB11 prior to infection was sufficient to mediate normal rBCV biogenesis and bacterial replication but led to T4SS inactivation and decreased aBCV formation and bacterial release, indicating that these postreplication stages are also T4SS dependent. Hence, our findings support the hypothesis of additional, postreplication roles of type IV secretion in the Brucella intracellular cycle.

  19. A Coxiella-Like Endosymbiont Is a Potential Vitamin Source for the Lone Star Tick

    Science.gov (United States)

    Smith, Todd A; Driscoll, Timothy; Gillespie, Joseph J; Raghavan, Rahul

    2015-01-01

    Amblyomma americanum (Lone star tick) is an important disease vector in the United States. It transmits several human pathogens, including the agents of human monocytic ehrlichiosis, tularemia, and southern tick-associated rash illness. Blood-feeding insects (Class Insecta) depend on bacterial endosymbionts to provide vitamins and cofactors that are scarce in blood. It is unclear how this deficiency is compensated in ticks (Class Arachnida) that feed exclusively on mammalian blood. A bacterium related to Coxiella burnetii, the agent of human Q fever, has been observed previously within cells of A. americanum. Eliminating this bacterium (CLEAA, Coxiella-like endosymbiont of A. americanum) with antibiotics reduced tick fecundity, indicating that it is an essential endosymbiont. In an effort to determine its role within this symbiosis, we sequenced the CLEAA genome. While highly reduced (656,901 bp) compared with C. burnetii (1,995,281 bp), the CLEAA genome encodes most major vitamin and cofactor biosynthesis pathways, implicating CLEAA as a vitamin provisioning endosymbiont. In contrast, CLEAA lacks any recognizable virulence genes, indicating that it is not a pathogen despite its presence in tick salivary glands. As both C. burnetii and numerous “Coxiella-like bacteria” have been reported from several species of ticks, we determined the evolutionary relationship between the two bacteria. Phylogeny estimation revealed that CLEAA is a close relative of C. burnetii, but was not derived from it. Our results are important for strategies geared toward controlling A. americanum and the pathogens it vectors, and also contribute novel information regarding the metabolic interdependencies of ticks and their nutrient-provisioning endosymbionts. PMID:25618142

  20. SDSS-IV MaNGA: Variation of the Stellar Initial Mass Function in Spiral and Early-type Galaxies

    Science.gov (United States)

    Li, Hongyu; Ge, Junqiang; Mao, Shude; Cappellari, Michele; Long, R. J.; Li, Ran; Emsellem, Eric; Dutton, Aaron A.; Li, Cheng; Bundy, Kevin; Thomas, Daniel; Drory, Niv; Lopes, Alexandre Roman

    2017-04-01

    We perform Jeans anisotropic modeling (JAM) on elliptical and spiral galaxies from the MaNGA DR13 sample. By comparing the stellar mass-to-light ratios estimated from stellar population synthesis and from JAM, we find a systematic variation of the initial mass function (IMF) similar to that in the earlier {{ATLAS}}3{{D}} results. Early-type galaxies (elliptical and lenticular) with lower velocity dispersions within one effective radius are consistent with a Chabrier-like IMF, while galaxies with higher velocity dispersions are consistent with a more bottom-heavy IMF such as the Salpeter IMF. Spiral galaxies have similar systematic IMF variations, but with slightly different slopes and larger scatters, due to the uncertainties caused by the higher gas fractions and extinctions for these galaxies. Furthermore, we examine the effects of stellar mass-to-light ratio gradients on our JAM modeling, and we find that the trends become stronger after considering the gradients.

  1. SDSS-IV MaNGA: The Spatially Resolved Stellar Initial Mass Function in ˜400 Early-Type Galaxies

    Science.gov (United States)

    Parikh, Taniya; Thomas, Daniel; Maraston, Claudia; Westfall, Kyle B.; Goddard, Daniel; Lian, Jianhui; Meneses-Goytia, Sofia; Jones, Amy; Vaughan, Sam; Andrews, Brett H.; Bershady, Matthew; Bizyaev, Dmitry; Brinkmann, Jonathan; Brownstein, Joel R.; Bundy, Kevin; Drory, Niv; Emsellem, Eric; Law, David R.; Newman, Jeffrey A.; Roman-Lopes, Alexandre; Wake, David; Yan, Renbin; Zheng, Zheng

    2018-03-01

    MaNGA provides the opportunity to make precise spatially resolved measurements of the IMF slope in galaxies owing to its unique combination of spatial resolution, wavelength coverage and sample size. We derive radial gradients in age, element abundances and IMF slope analysing optical and near-infrared absorption features from stacked spectra out to the half-light radius of 366 early-type galaxies with masses 9.9 - 10.8 log M/M⊙. We find flat gradients in age and [α/Fe] ratio, as well as negative gradients in metallicity, consistent with the literature. We further derive significant negative gradients in the [Na/Fe] ratio with galaxy centres being well enhanced in Na abundance by up to 0.5 dex. Finally, we find a gradient in IMF slope with a bottom-heavy IMF in the centre (typical mass excess factor of 1.5) and a Milky Way-type IMF at the half-light radius. This pattern is mass-dependent with the lowest mass galaxies in our sample featuring only a shallow gradient around a Milky Way IMF. Our results imply the local IMF-σ relation within galaxies to be even steeper than the global relation and hint towards the local metallicity being the dominating factor behind the IMF variations. We also employ different stellar population models in our analysis and show that a radial IMF gradient is found independently of the stellar population model used. A similar analysis of the Wing-Ford band provides inconsistent results and further evidence of the difficulty in measuring and modelling this particular feature.

  2. Coxiella burnetii, the agent of Q fever, in domestic sheep flocks from Wyoming, United States.

    Science.gov (United States)

    Loftis, Amanda D; Reeves, Will K; Miller, Myrna M; Massung, Robert F

    2012-03-01

    Coxiella burnetii, the agent of Q fever, is an intracellular bacterial pathogen. It has a nearly cosmopolitan distribution. We conducted a serological survey of domestic sheep herds for infections with C. burnetii in Wyoming following reports of abortion and open ewes. Based on the serologic evidence, there was no link between reproductive problems and exposure to C. burnetii. However, the overall prevalence of C. burnetii in WY sheep was 7%, which indicates that the agent is present in the environment and could pose a threat to public health.

  3. Identification of novel small RNAs and characterization of the 6S RNA of Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Indu Warrier

    Full Text Available Coxiella burnetii, an obligate intracellular bacterial pathogen that causes Q fever, undergoes a biphasic developmental cycle that alternates between a metabolically-active large cell variant (LCV and a dormant small cell variant (SCV. As such, the bacterium undoubtedly employs complex modes of regulating its lifecycle, metabolism and pathogenesis. Small RNAs (sRNAs have been shown to play important regulatory roles in controlling metabolism and virulence in several pathogenic bacteria. We hypothesize that sRNAs are involved in regulating growth and development of C. burnetii and its infection of host cells. To address the hypothesis and identify potential sRNAs, we subjected total RNA isolated from Coxiella cultured axenically and in Vero host cells to deep-sequencing. Using this approach, we identified fifteen novel C. burnetii sRNAs (CbSRs. Fourteen CbSRs were validated by Northern blotting. Most CbSRs showed differential expression, with increased levels in LCVs. Eight CbSRs were upregulated (≥2-fold during intracellular growth as compared to growth in axenic medium. Along with the fifteen sRNAs, we also identified three sRNAs that have been previously described from other bacteria, including RNase P RNA, tmRNA and 6S RNA. The 6S regulatory sRNA of C. burnetii was found to accumulate over log phase-growth with a maximum level attained in the SCV stage. The 6S RNA-encoding gene (ssrS was mapped to the 5' UTR of ygfA; a highly conserved linkage in eubacteria. The predicted secondary structure of the 6S RNA possesses three highly conserved domains found in 6S RNAs of other eubacteria. We also demonstrate that Coxiella's 6S RNA interacts with RNA polymerase (RNAP in a specific manner. Finally, transcript levels of 6S RNA were found to be at much higher levels when Coxiella was grown in host cells relative to axenic culture, indicating a potential role in regulating the bacterium's intracellular stress response by interacting with RNAP during

  4. PRELIMINARY STUDY ON THE PREVALENCE OF COXIELLA BURNETII IN CHEESES PRODUCED IN SOUTHERN ITALY

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    Y.T.R. Proroga

    2011-08-01

    Full Text Available In this study the presence of Coxiella burnetii in cow, buffalo and small ruminants (sheep and goat cheeses produced in southern Italy has been evaluated with the aim to analyze the risk of infection for consumers. The survey was performed using molecular assays (Real-Time PCR to detect the presence of C. burnetii DNA. The samples have been furthermore tested with specific methods for species identification in milk and dairy products. C. burnetii has been detected in 75% of cow cheese samples, while in small ruminants and buffaloes diary products have been assessed at 45,9% and 23,9% respectively.

  5. Community-acquired methicillin-resistant Staphylococcus aureus carrying SCCmec type IV and V isolated from healthy children attending public daycares in northeastern Brazil

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    Suzi P. de Carvalho

    2017-07-01

    Full Text Available Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA have increasingly been reported in healthy communities. This study aimed to assess the rate of S. aureus in general and MRSA in particular from nasal secretion of children in daycare centers in Vitória da Conquista, Brazil. The isolates were identified based on morphology, biochemical tests and by PCR. Detection of virulence genes, biofilm production, and susceptibility test by disk diffusion agar were performed. MRSA isolates were characterized by spa, SCCmec, and multilocus sequence typing (MLST. S. aureus were recovered from 70 (47.3% of 148 children. Among the 11 MRSA strains (15.7%, two SCCmec types (IV and V were detected. MLST identified four STs related to three clonal complexes (CC: 5, 45, and 398. Four spa types were found circulating in this setting. Resistance of S. aureus isolates to ampicillin, erythromycin, ciprofloxacin, clindamycin, and tetracycline was 80%, 32.8%, 7.1%, 7.1% and 4.3%, respectively. One isolate presented intermediate resistance to vancomycin detected by Etest methodology. All strains were biofilm producers. The virulence genes seb, sec, spa, and pvl were detected in some isolates. This study revealed a high rate of children carrying MRSA among healthy attendees in daycare centers in Vitória da Conquista, Brazil.

  6. SDSS-IV MaNGA: Uncovering the Angular Momentum Content of Central and Satellite Early-type Galaxies

    Science.gov (United States)

    Greene, J. E.; Leauthaud, A.; Emsellem, E.; Ge, J.; Aragón-Salamanca, A.; Greco, J.; Lin, Y.-T.; Mao, S.; Masters, K.; Merrifield, M.; More, S.; Okabe, N.; Schneider, D. P.; Thomas, D.; Wake, D. A.; Pan, K.; Bizyaev, D.; Oravetz, D.; Simmons, A.; Yan, R.; van den Bosch, F.

    2018-01-01

    We study 379 central and 159 satellite early-type galaxies with two-dimensional kinematics from the integral-field survey Mapping Nearby Galaxies at APO (MaNGA) to determine how their angular momentum content depends on stellar and halo mass. Using the Yang et al. group catalog, we identify central and satellite galaxies in groups with halo masses in the range {10}12.5 {h}-1 {M}ȯ {10}11 {h}-2 {M}ȯ tend to have very little rotation, while nearly all galaxies at lower mass show some net rotation. The ∼30% of high-mass galaxies that have significant rotation do not stand out in other galaxy properties, except for a higher incidence of ionized gas emission. Our data are consistent with recent simulation results suggesting that major merging and gas accretion have more impact on the rotational support of lower-mass galaxies. When carefully matching the stellar mass distributions, we find no residual differences in angular momentum content between satellite and central galaxies at the 20% level. Similarly, at fixed mass, galaxies have consistent rotation properties across a wide range of halo mass. However, we find that errors in classification of central and satellite galaxies with group finders systematically lower differences between satellite and central galaxies at a level that is comparable to current measurement uncertainties. To improve constraints, the impact of group-finding methods will have to be forward-modeled via mock catalogs.

  7. The lanthanoid(III) chloride oxoselenates(IV) MCl[SeO3] (M = Sm - Lu) with HoCl[TeO3]- or B-type structure

    International Nuclear Information System (INIS)

    Lipp, C.; Schleid, T.

    2008-01-01

    The B-type lanthanoid(III) chloride oxoselenates(IV) MCl[SeO 3 ] (M = Sm - Lu) crystallize in the orthorhombic space group Pnma (no. 62) with Z = 4 in the structure type of HoCl[TeO 3 ]. Their lattice constants are decreasing following the lanthanoid contraction from a = 730.01(7), b = 707.90(7), c 895.64(9) pm for SmCl[SeO 3 ] to a = 714.63(7), b = 681.76(7), c = 864.05(9) pm for LuCl[SeO 3 ]. In contrast to NdCl[SeO 3 ], the only representative of the A-type structure, where the coordination numbers of the Nd 3+ cations are 7+2 and 8, the B-type structure is dominated by pentagonal bipyramids [MO 5 Cl 2 ] 9- (CN(M 3+ ) = 7), which are connected via trans-oriented O..O edges to ∞ 1 {[MO 4/2 e O 1/1 t Cl 2/1 t ] 5- } chains (e = edge-sharing, t = terminal) running parallel to the [010] direction. Their inclination relative to each other allows for an alternating interconnection of these chains via Cl - and ψ 1 -tetrahedral [SeO 3 ] 2- anions to form a three-dimensional structure. The distances within the [SeO 3 ] 2- groups are in the normal range (d(Se-O) = 165 - 172 pm), while those of the O 2- and Cl - anions to the central M 3+ cation diminish in dependence of the increasing atomic number (d(M-O) = 226 - 244 pm / 216 - 232 pm, d(M-Cl) 277 - 278 pm / 266 - 270 pm, M = Sm / Lu). For the synthesis of the chloride oxoselenates(IV) MCl[SeO 3 ] the respective lanthanoid sesquioxide (M 2 O 3 ) and selenium dioxide (SeO 2 ) were reacted with either an eutectic mixture of RbCl and LiCl or with the corresponding lanthanoid trichloride (MCl 3 ) in evacuated silica ampoules for either five weeks at 500 C or one week at 850 C. (orig.)

  8. Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3Al) allele produces ehlers-danlos syndrome type IV in the heterozygous offspring

    Energy Technology Data Exchange (ETDEWEB)

    McGookey Milewicz, D.; Witz, A.M.; Byers, P.H. (Univ of Washington, Seattle (United States)); Smith, A.C.M.; Manchester, D.K.; Waldstein, G. (Children' s Hospital, Denver, CO (United States))

    1993-07-01

    Ehlers-Danlos syndrome (EDS) type IV is a dominantly inherited disorder that results from mutation in the type III collagen gene (COL3A1). The authors studied the structure of the COL3A1 gene of an individual with EDS type IV and that of her phenotypically normal parents. The proband was heterozygous for a 2-kb deletion in COL3A1, while her father was mosaic for the same deletion in somatic and germ cells. In fibroblasts from the father, approximately two-fifths of the COL3A1 alleles carried the deletion, but only 10% of the COL3A1 alleles in white blood cells were of the mutant species. The deletion in the mutant allele extended from intron 7 into intron 11. There was a 12-bp direct repeat in intron 7 and intron 11, the latter about 60 bp 5' to the junction. At the breakpoint there was a duplication of 10 bp from intron 11 separated by an insertion of 4 bp contained within the duplicated sequence. The father was mosaic for the deletion so that the gene rearrangement occurred during his early embryonic development prior to lineage allocation. These findings suggest that at least some of the deletions seen in human genes may occur during replication, rather than as a consequence of meiotic crossing-over, and that they thus have a risk for recurrence when observed de novo. 71 refs., 4 figs., 2 tabs.

  9. Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation

    Directory of Open Access Journals (Sweden)

    Edmund H. Jooste

    2017-08-01

    dropped by 10% in two patients, but resolved without need for manual ventilation. All other reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78 patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine was well-tolerated in pediatric patients undergoing procedure-type sedation.

  10. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

  11. A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen.

    Science.gov (United States)

    Gale, Daniel P; Oygar, D Deren; Lin, Fujun; Oygar, P Derin; Khan, Nadia; Connor, Thomas M F; Lapsley, Marta; Maxwell, Patrick H; Neild, Guy H

    2016-11-01

    Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

  12. Prevalence and risk factors for Coxiella burnetii (Q fever) in Dutch dairy cattle herds based on bulk tank milk testing

    NARCIS (Netherlands)

    Engelen, E. van; Schotten, N.; Schimmer, B.; Hautvast, J.L.; Schaik, G. van; Duijnhoven, Y.T. van

    2014-01-01

    Despite cattle herds can harbor Coxiella burnetii, risk factors for C. burnetii presence in dairy cattle herds are largely unknown. Therefore, C. burnetii herd prevalence and risk factors for bulk tank milk (BTM) positivity were investigated. In this cross-sectional study, a questionnaire was filled

  13. Molecular evidence of Coxiella-like microorganism harbored by Haemaphysalis concinnae ticks in the Russian Far East.

    Science.gov (United States)

    Mediannikov, Oleg; Ivanov, Leonid; Nishikawa, Makoto; Saito, Reiko; Sidelnikov, Yury N; Zdanovskaya, Nina I; Tarasevich, Irina V; Suzuki, Hiroshi

    2003-06-01

    Twenty female imago of Haemaphysalis concinnae ticks collected from wild vegetation in May of 2001 in the Obor region near Khabarovsk in the Russian Far East were studied. DNA was extracted with commercially available kits following manufacturer's instructions. We used broad range primers SFG3 and SFG6 proposed for amplification of 16S ribosomal RNA gene's portion of spotted fever group Rickettsia. Initial amplification resulted in positive results in all 20 ticks. Direct sequencing of five randomly chosen amplicons showed that obtained sequences belong to a new species. Closest homology was found in Coxiella burnetii 16S rDNA. Using the obtained sequence as a basis, we designed internal primers highly specific for that sequence. Then we confirmed our results by nested PCR amplification with newly designed primers Cox1 and Cox2-all 20 samples also were positive. Having combined these primers with universal eubacterial primers fD1 and rP2 we retrieved a 1,043 bp portion of the 16S rRNA gene. Consecutive homology search demonstrated that the closest sequence similarity belongs to new Coxiella sp. recently found in Rhipicephalus sanguineus ticks (95.2% of homology) and Coxiella burnetii (94% of homology). So, our results suggest that a novel Coxiella-like microorganism, provisionally called here "Cenerentola," is harbored by Haemaphysalis concinnae ticks in the Russian Far East.

  14. Interlaboratory evaluation of different extraction and real-time PCR methods for detection of Coxiella burnetii DNA in serum

    NARCIS (Netherlands)

    Tilburg, Jeroen J. H. C.; Melchers, Willem J. G.; Pettersson, Annika M.; Rossen, John W. A.; Hermans, Mirjam H. A.; van Hannen, Erik J.; Nabuurs-Franssen, Marrigje H.; de Vries, Maaike C.; Horrevorts, Alphons M.; Klaassen, Corne H. W.

    2010-01-01

    In the Netherlands, there is an ongoing and unparalleled outbreak of Q fever. Rapid and reliable methods to identify patients infected with Coxiella burnetii, the causative agent of Q fever, are urgently needed. We evaluated the performance of different DNA extraction methods and real-time PCR

  15. Screening for Coxiella burnetii infection during pregnancy : pros and cons according to the Wilson and Jungner criteria

    NARCIS (Netherlands)

    Munster, Janna; Steggerda, L.; Leenders, A.; Aarnoudse, J.; Hak, E.

    2012-01-01

    In Europe the incidence of human Q fever has dramatically increased over the previous years. Untreated infections with Coxiella burnetii, the causal agent of Q fever, have been associated with both obstetric and maternal complications. The majority of pregnant women with a C. burnetii infection

  16. Airborne Transmission of Coxiella burnetii : Spatial dispersion modelling and the effects of meteorological and environmental conditions on Q fever incidence

    NARCIS (Netherlands)

    van Leuken, J.P.G.

    2015-01-01

    The Netherlands experienced the largest human and veterinary Q fever epidemic ever described. From 2007 through 2010, over 4,000 human cases were notified and approximately a twelve-fold higher number was probably infected by Coxiella burnetii, the causative agent of Q fever. Dairy goat farms, and

  17. Screening of post-mortem tissue donors for Coxiella burnetii infection after large outbreaks of Q fever in The Netherlands

    NARCIS (Netherlands)

    van Wijk, Marja J.; Maas, D. Willemijn; Renders, Nicole H. M.; Hermans, Mirjam H. A.; Zaaijer, Hans L.; Hogema, Boris M.

    2014-01-01

    After the largest outbreaks of Q fever ever recorded in history occurred in the Netherlands, concern arose that Coxiella may be transmitted via donated tissues of latent or chronically infected donors. The Dutch Health Council recently advised to screen tissue donors, donating high risk tissues, for

  18. Genotypic diversity of Coxiella burnetii in the 2007-2010 Q fever outbreak episodes in The Netherlands

    NARCIS (Netherlands)

    Tilburg, Jeroen J. H. C.; Rossen, John W. A.; van Hannen, Erik J.; Melchers, Willem J. G.; Hermans, Mirjam H. A.; van de Bovenkamp, Jeroen; Roest, Hendrik Jan I. J.; de Bruin, Arnout; Nabuurs-Franssen, Marrigje H.; Horrevorts, Alphons M.; Klaassen, Corne H. W.

    The genotypic diversity of Coxiella burnetii in clinical samples obtained from the Dutch Q fever outbreak episodes of 2007-2010 was determined by using a 6-locus variable-number tandem repeat analysis panel. The results are consistent with the introduction of one founder genotype that is gradually

  19. Clinical microbiology of Coxiella burnetii and relevant aspects for the diagnosis and control of the zoonotic disease Q fever

    NARCIS (Netherlands)

    Roest, H.I.J.; Bossers, A.; Zijderveld, van F.G.; Rebel, J.M.J.

    2013-01-01

    Coxiella burnetii is the causative agent of the zoonotic disease Q fever. Since its first recognition as a disease in the 1930s, the knowledge about the agent and the disease itself has increased. This review summarizes the current knowledge on C. burnetii and Q fever, its pathogenesis, diagnosis

  20. Detection of phase I IgG antibodies to Coxiella burnetii with EIA as a screening test for blood donations

    NARCIS (Netherlands)

    van der Hoek, W.; Wielders, C. C. H.; Schimmer, B.; Wegdam-Blans, M. C. A.; Meekelenkamp, J.; Zaaijer, H. L.; Schneeberger, P. M.

    2012-01-01

    The presence of a high phase I IgG antibody titre may indicate chronic infection and a risk for the transmission of Coxiella burnetii through blood transfusion. The outbreak of Q fever in the Netherlands allowed for the comparison of an enzyme immunoassay (EIA) with the reference immunofluorescence

  1. Borrelia, Coxiella, and Rickettsia in Carios capensis (Acari: Argasidae) from a brown pelican (Pelecanus occidentalis) rookery in South Carolina, USA.

    Science.gov (United States)

    Reeves, Will K; Loftis, Amanda D; Sanders, Felicia; Spinks, Mark D; Wills, William; Denison, Amy M; Dasch, Gregory A

    2006-01-01

    Argasid ticks are vectors of viral and bacterial agents of humans and animals. Carios capensis, a tick of seabirds, infests the nests of brown pelicans, Pelecanus occidentalis, and other ground nesting birds along the coast of South Carolina. This tick is associated with pelican nest abandonment and could pose a threat to humans visiting pelican rookeries if visitors are exposed to ticks harboring infectious agents. We collected ticks from a pelican rookery on Deveaux Bank, South Carolina and screened 64 individual ticks, six pools of larvae, and an egg mass for DNA from Bartonella, Borrelia, Coxiella, and Rickettsia by polymerase chain reaction amplification and sequencing. Ticks harbored DNA from "Borrelia lonestari", a novel Coxiella sp., and three species of Rickettsia, including Rickettsia felis and two undescribed Rickettsia spp. DNA from the Coxiella and two undescribed Rickettsia were detected in unfed larvae that emerged in the laboratory, which implies these agents are transmitted vertically by female ticks. We partially characterize the novel Coxiella by molecular means.

  2. Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate.

    Science.gov (United States)

    Lindahl, K; Kindmark, A; Rubin, C-J; Malmgren, B; Grigelioniene, G; Söderhäll, S; Ljunggren, Ö; Åström, E

    2016-06-01

    Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe OI; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated. COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n=33, type III n=25 and type IV n=21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non-vertebral and vertebral fractures were collected prior to, and at several time points during treatment. An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to Δ LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p4yrs Pamidronate. Twice as many boys as girls with OI type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p=0.0236). Greater Δ LS BMD, but smaller Δ fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11years of age at treatment initiation (p<0.0001). Pamidronate treatment in children with all types of OI increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Looking for new hybrid polymer fillers: synthesis of nanosized α-type Zr(IV) organophosphonates through an unconventional topotactic anion exchange reaction.

    Science.gov (United States)

    Pica, Monica; Donnadio, Anna; Troni, Elisabetta; Capitani, Donatella; Casciola, Mario

    2013-07-01

    Gels of α-type zirconium(IV) phosphate alkylphosphonates, ZP(Cn)x, were prepared by reacting, at room temperature, propanol intercalated nanosized α-zirconium phosphate (α-ZrP) with propanol solutions of alkylphosphonic acids (H2Cn, n = number of carbon atoms in the alkyl chain = 4, 5, 6), with (H2Cn/Zr) molar ratios in the range 0.4-4.0. (31)P MAS NMR showed the presence of resonances due to the phosphate and phosphonate groups bonded to the Zr atoms mainly by three oxygen atoms, as in the α-type layer. The composition of the ZP(Cn)x materials, obtained by thermogravimetric analysis, ranges from x ≈ 0.2 to x ≈ 1.1. On the basis of the NMR data and of the analysis of the X-ray patterns of gels and powders, it is inferred that the ZP(Cn)x compounds have an α-type layered structure and that the reaction between α-ZrP and H2Cn is a topotactic anion exchange process. The evolution of the X-ray patterns during propanol deintercalation is consistent with a random distribution of the alkylphosphonate groups on the α-type layers which gives rise to porous pathways in the interlayer region. To test the possibility of using ZP(Cn)x as mechanical reinforcement of a polymer matrix, a starch membrane filled with 5 wt % ZP(C6)0.54 was prepared and characterized by stress-strain mechanical tests. Besides an excellent flexibility, this membrane exhibited a proportional increase of the Young's modulus by 230% in comparison with neat starch.

  4. Coxiella burnetii as a possible cause of autoimmune liver disease: a case report

    Directory of Open Access Journals (Sweden)

    Kaech Chloe

    2009-08-01

    Full Text Available Abstract Introduction Q fever is a zoonotic infection that may cause severe hepatitis. Q-fever hepatitis has not yet been associated with autoimmune hepatitis and/or primary biliary cirrhosis. Case presentation We describe a 39-year-old man of Sri Lankan origin with chronic Q-fever hepatitis who developed autoantibodies compatible with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Ursodeoxycholic acid in addition to antibiotic therapy markedly improved hepatic enzyme levels suggesting that autoimmunity, potentially triggered by the underlying infection, was involved in the pathogenesis of liver damage. Conclusion We suggest that Coxiella burnetii might trigger autoimmune liver disease. Patients with Q-fever hepatitis who respond poorly to antibiotics should be investigated for serological evidence of autoimmune hepatitis, primary biliary cirrhosis or overlap syndrome, as these patients could benefit from adjunctive therapy with ursodeoxycholic acid. Conversely, C. burnetii serology might be necessary in patients with autoimmune liver disease in order to exclude underlying Coxiella infection.

  5. Serosurvey of Coxiella burnetii (Q fever) in Dromedary Camels (Camelus dromedarius) in Laikipia County, Kenya.

    Science.gov (United States)

    Browne, A S; Fèvre, E M; Kinnaird, M; Muloi, D M; Wang, C A; Larsen, P S; O'Brien, T; Deem, S L

    2017-11-01

    Dromedary camels (Camelus dromedarius) are an important protein source for people in semi-arid and arid regions of Africa. In Kenya, camel populations have grown dramatically in the past few decades resulting in the potential for increased disease transmission between humans and camels. An estimated four million Kenyans drink unpasteurized camel milk, which poses a disease risk. We evaluated the seroprevalence of a significant zoonotic pathogen, Coxiella burnetii (Q fever), among 334 camels from nine herds in Laikipia County, Kenya. Serum testing revealed 18.6% positive seroprevalence of Coxiella burnetii (n = 344). Increasing camel age was positively associated with C. burnetii seroprevalence (OR = 5.36). Our study confirmed that camels living in Laikipia County, Kenya, have been exposed to the zoonotic pathogen, C. burnetii. Further research to evaluate the role of camels in disease transmission to other livestock, wildlife and humans in Kenya should be conducted. © 2017 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

  6. Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

    Directory of Open Access Journals (Sweden)

    Matthew Calverley

    Full Text Available Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM. However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

  7. Effect of endocytosis inhibitors on Coxiella burnetii interaction with host cells

    International Nuclear Information System (INIS)

    Tujulin, E.; Macellaro, A.; Norlander, L.; Liliehoeoek, B.

    1998-01-01

    The obligate intracellular rickettsia Coxiella burnetii has previously been reported to reach the intra-vacuolar compartment of host cells by phagocytosis. With the aim to further examine the mechanisms of C. burnetii internalisation, macrophage monolayers were treated with well characterised inhibitors of endocytosis. The treatment with two general inhibitors, colchicine and methylamine, resulted in a pronounced dose-dependent decrease of radiolabelled phase II rickettsiae retained from the intracellular fraction. A third inhibitor used, amiloride, has been reported to reduce effectively clathrin-independent pinocytic pathways. The internalisation of C. burnetii was shown to be substantially reduced also by amiloride and the effect was dependent on its concentration. The passive role of C. burnetii in the internalisation was verified by using heat-killed C. burnetii. Host cells treated with either of the three inhibitors (amiloride, colchicine and methylamine) showed a similar reduction of intracellular C. burnetii after exposure to killed as weal as live organisms. The data presented indicate that different endocytic mechanisms, pinocytosis as well as phagocytosis, may mediate the uptake of C. burnetii by a host cell. Key words: Coxiella burnetii; internalisation; endocytosis (authors)

  8. Transient Silencing of a Type IV P-Type ATPase, Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    S. E. Hurst

    2012-01-01

    Full Text Available Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs, p38, and p44/42. Additionally, glucose transporter-1 (GLUT1 was significantly upregulated; no changes in glucose transporter-4 (GLUT4 expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate that Atp10c regulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

  9. A 48 kDa collagen-binding phosphoprotein isolated from bovine aortic endothelial cells interacts with the collagenous domain, but not the globular domain, of collagen type IV.

    Science.gov (United States)

    Yannariello-Brown, J; Madri, J A

    1990-01-15

    We have identified collagen-binding proteins in detergent extracts of metabolically labelled bovine aortic endothelial cells (BAEC) by collagen type IV-Sepharose affinity chromatography. The major collagen type IV-binding protein identified by SDS/PAGE had a molecular mass of 48 kDa, which we term the 'collagen-binding 48 kDa protein' (CB48). The pI of CB48 was 8.0-8.3 in a two-dimensional gel system, running non-equilibrium pH gel electrophoresis in the first dimension and SDS/PAGE in the second dimension. Under these conditions CB48 separated into two major (a and b) and one minor isoform (c); a was the most basic of the three isoforms. Two-dimensional chymotryptic peptide maps derived from each individual isoform were virtually identical. The charge differences between the isoforms were due in part to differential H3(32)PO4 incorporation by the protein. CB48 bound to intact collagen type IV and the collagenous region of collagen type IV, but not to the globular NC1 domain. Cell-surface labelling and indirect immunofluorescence experiments localized the bulk of CB48 intracellularly in the endoplasmic reticulum Golgi region, with a minor population of molecules on the cell surface. A specific rabbit polyclonal anti-CB48 serum did not inhibit the attachment or spreading of BAEC to collagen type IV in an 'in vitro' adhesion assay, suggesting that the cell-surface population of CB48 is not involved in BAEC adhesion. We conclude that CB48 is a collagen-binding phosphoprotein that interacts with the collagenous domain of collagen type IV and may be involved in intracellular transport of collagen molecules.

  10. Ehlers-Danlos Syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen

    Energy Technology Data Exchange (ETDEWEB)

    Superti-Furga, A.; Gugler, E.; Gitzelmann, R.; Steinmann, B.

    1988-05-05

    The authors have studied a patient with severe, dominantly inherited Ehlers-Danlos syndrome type IV. The results indicate that this patient carries a deletion of 3.3 kilobase pairs in the triple helical coding domain of one of the two alleles for the pro-..cap alpha..-chains of type III collagen (COL3A1). His cultured skin fibroblasts contain equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesize both normal and shortened pro-..cap alpha..1(III)-chains. In procollagen molecules containing one or more shortened chains, a triple helix is formed with a length of only about 780 amino acids. The mutant procollagen molecules have decreased thermal stability, are less efficiently secreted, and are not processed as their normal counterpart. The deletion in this family is the first mutation to be described in COL3A1.

  11. Membrane and core periplasmic Agrobacterium tumefaciens virulence Type IV secretion system components localize to multiple sites around the bacterial perimeter during lateral attachment to plant cells.

    Science.gov (United States)

    Aguilar, Julieta; Cameron, Todd A; Zupan, John; Zambryski, Patricia

    2011-01-01

    Type IV secretion systems (T4SS) transfer DNA and/or proteins into recipient cells. Here we performed immunofluorescence deconvolution microscopy to localize the assembled T4SS by detection of its native components VirB1, VirB2, VirB4, VirB5, VirB7, VirB8, VirB9, VirB10, and VirB11 in the C58 nopaline strain of Agrobacterium tumefaciens, following induction of virulence (vir) gene expression. These different proteins represent T4SS components spanning the inner membrane, periplasm, or outer membrane. Native VirB2, VirB5, VirB7, and VirB8 were also localized in the A. tumefaciens octopine strain A348. Quantitative analyses of the localization of all the above Vir proteins in nopaline and octopine strains revealed multiple foci in single optical sections in over 80% and 70% of the bacterial cells, respectively. Green fluorescent protein (GFP)-VirB8 expression following vir induction was used to monitor bacterial binding to live host plant cells; bacteria bind predominantly along their lengths, with few bacteria binding via their poles or subpoles. vir-induced attachment-defective bacteria or bacteria without the Ti plasmid do not bind to plant cells. These data support a model where multiple vir-T4SS around the perimeter of the bacterium maximize effective contact with the host to facilitate efficient transfer of DNA and protein substrates. Transfer of DNA and/or proteins to host cells through multiprotein type IV secretion system (T4SS) complexes that span the bacterial cell envelope is critical to bacterial pathogenesis. Early reports suggested that T4SS components localized at the cell poles. Now, higher-resolution deconvolution fluorescence microscopy reveals that all structural components of the Agrobacterium tumefaciens vir-T4SS, as well as its transported protein substrates, localize to multiple foci around the cell perimeter. These results lead to a new model of A. tumefaciens attachment to a plant cell, where A. tumefaciens takes advantage of the multiple

  12. A 48 kDa collagen-binding phosphoprotein isolated from bovine aortic endothelial cells interacts with the collagenous domain, but not the globular domain, of collagen type IV.

    OpenAIRE

    Yannariello-Brown, J; Madri, J A

    1990-01-01

    We have identified collagen-binding proteins in detergent extracts of metabolically labelled bovine aortic endothelial cells (BAEC) by collagen type IV-Sepharose affinity chromatography. The major collagen type IV-binding protein identified by SDS/PAGE had a molecular mass of 48 kDa, which we term the 'collagen-binding 48 kDa protein' (CB48). The pI of CB48 was 8.0-8.3 in a two-dimensional gel system, running non-equilibrium pH gel electrophoresis in the first dimension and SDS/PAGE in the se...

  13. Coxiella burnetii Circulation in a Naturally Infected Flock of Sheep: Individual Follow-Up of Antibodies in Serum and Milk.

    Science.gov (United States)

    Joulié, A; Rousset, E; Gasqui, P; Lepetitcolin, E; Leblond, A; Sidi-Boumedine, K; Jourdain, E

    2017-07-01

    The control of Q fever, a zoonotic disease caused by the Coxiella burnetii bacterium, remains a scientific challenge. Domestic ruminants are considered the main reservoir, shedding C. burnetii essentially through parturition products during abortion or birth. Sheep are particularly frequently associated with human outbreaks, but there are insufficient field data to fully understand disease dynamics and to instigate efficient control measures. A longitudinal follow-up study of a naturally infected sheep flock was performed (i) to investigate relationships between seropositivity and bacterial shedding in the vaginal mucus, (ii) to describe the kinetics of antibodies, including responses to vaccination, (iii) to monitor maternal antibodies in ewe lambs, and (iv) to compare serological results for milk and serum samples. For 8 months, we collected blood samples every 3 weeks from 11 aborting and 26 nonaborting dairy ewes, 20 nonaborting suckler ewes, and 9 ewe lambs. Individual milk samples were also obtained from lactating females. All serum and milk samples were tested by enzyme-linked immunosorbent assay (ELISA), whereas vaginal swabs were tested by quantitative PCR. We found that some dairy females did not seroconvert despite shedding C. burnetii in their vaginal mucus. Overall, antibody levels in adult females were found to remain stable over time, with exceptions during the mating and lambing periods. Maternal antibodies decreased during the first month after birth. Interestingly, antibody levels in milk were correlated with those in serum. This study provides valuable field data that will help improve Q fever surveillance and within-flock management measures. IMPORTANCE Field data are necessary to improve the surveillance, diagnosis, and sanitary management of Q fever in livestock. Here, we provide extensive serological data obtained from serum and milk samples from infected and vaccinated ewes belonging to a naturally infected flock of sheep. We show that

  14. Asteroids IV

    Science.gov (United States)

    Michel, Patrick; DeMeo, Francesca E.; Bottke, William F.

    . Asteroids, like planets, are driven by a great variety of both dynamical and physical mechanisms. In fact, images sent back by space missions show a collection of small worlds whose characteristics seem designed to overthrow our preconceived notions. Given their wide range of sizes and surface compositions, it is clear that many formed in very different places and at different times within the solar nebula. These characteristics make them an exciting challenge for researchers who crave complex problems. The return of samples from these bodies may ultimately be needed to provide us with solutions. In the book Asteroids IV, the editors and authors have taken major strides in the long journey toward a much deeper understanding of our fascinating planetary ancestors. This book reviews major advances in 43 chapters that have been written and reviewed by a team of more than 200 international authorities in asteroids. It is aimed to be as comprehensive as possible while also remaining accessible to students and researchers who are interested in learning about these small but nonetheless important worlds. We hope this volume will serve as a leading reference on the topic of asteroids for the decade to come. We are deeply indebted to the many authors and referees for their tremendous efforts in helping us create Asteroids IV. We also thank the members of the Asteroids IV scientific organizing committee for helping us shape the structure and content of the book. The conference associated with the book, "Asteroids Comets Meteors 2014" held June 30-July 4, 2014, in Helsinki, Finland, did an outstanding job of demonstrating how much progress we have made in the field over the last decade. We are extremely grateful to our host Karri Muinonnen and his team. The editors are also grateful to the Asteroids IV production staff, namely Renée Dotson and her colleagues at the Lunar and Planetary Institute, for their efforts, their invaluable assistance, and their enthusiasm; they made life as

  15. Delineation of polar localization domains of Agrobacterium tumefaciens type IV secretion apparatus proteins VirB4 and VirB11.

    Science.gov (United States)

    Das, Aditi; Das, Anath

    2014-10-01

    Agrobacterium tumefaciens transfers DNA and proteins to a plant cell through a type IV secretion apparatus assembled by the VirB proteins. All VirB proteins localized to a cell pole, although these conclusions are in dispute. To study subcellular location of the VirB proteins and to identify determinants of their subcellular location, we tagged two proteins, VirB4 and VirB11, with the visual marker green fluorescent protein (GFP) and studied localization of the fusion proteins by epifluorescence microscopy. Both GFP-VirB4 and GFP-VirB11 fusions localized to a single cell pole. GFP-VirB11 was also functional in DNA transfer. To identify the polar localization domains (PLDs) of VirB4 and VirB11, we analyzed fusions of GFP with smaller segments of the two proteins. Two noncontiguous regions in VirB4, residues 236-470 and 592-789, contain PLDs. The VirB11 PLD mapped to a 69 amino acid segment, residues 149-217, in the central region of the protein. These domains are probably involved in interactions that target the two proteins to a cell pole. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Optimization of Extrusion Process of Directly Expanded Snacks Based on Potato Starch in a Single Step for the Formation of Type IV Resistant Starch.

    Science.gov (United States)

    Calvo-López, Amira Daniela; Martínez-Bustos, Fernando

    2017-09-01

    Resistant starch type IV (RSIV) can be produced by chemical modifications (etherized or esterified) such as conversion, substitution, or cross-linking, which can prevent its digestion by blocking enzyme access and forming atypical linkages. In this research, the effects of barrel temperature (145.86-174.14 °C), the screw speed (42.93-57.07 Hz) and derivatization (esterification) in the formation of RSIV content of directly expanded snacks (second generation snacks) were studied. Potato starch was chemically modified by phosphorylation and succinylation, and expanded by using the extrusion cooking process. Snacks with phosphorylated starch showed expansion index from 2.57 to 3.23, bulk density from 306.19 to 479.00 kg/m 3 and RSIV from 43.27 to 55.81%. Snacks with succinylated starch had expansion index from 3.52 to 3.82, bulk density from 99.85 to 134.51 kg/m 3 and RSIV from 23.17 to 35.01%. The results found in this work showed that it is possible to manufacture extruded directly expanded snacks (second-generation snacks) such as a ready-to-eat (RTE) with good physicochemical properties and without substantial loss of extrusion functionality, which could bring a healthy benefit due to the presence of RSIV.

  17. Two novel splicing mutations in the SLC45A2 gene cause Oculocutaneous Albinism Type IV by unmasking cryptic splice sites.

    Science.gov (United States)

    Straniero, Letizia; Rimoldi, Valeria; Soldà, Giulia; Mauri, Lucia; Manfredini, Emanuela; Andreucci, Elena; Bargiacchi, Sara; Penco, Silvana; Gesu, Giovanni P; Del Longo, Alessandra; Piozzi, Elena; Asselta, Rosanna; Primignani, Paola

    2015-09-01

    Oculocutaneous albinism (OCA) is characterized by hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities caused by a deficiency in melanin biosynthesis. OCA type IV (OCA4) is one of the four commonly recognized forms of albinism, and is determined by mutation in the SLC45A2 gene. Here, we investigated the genetic basis of OCA4 in an Italian child. The mutational screening of the SLC45A2 gene identified two novel potentially pathogenic splicing mutations: a synonymous transition (c.888G>A) involving the last nucleotide of exon 3 and a single-nucleotide insertion (c.1156+2dupT) within the consensus sequence of the donor splice site of intron 5. As computer-assisted analysis for mutant splice-site prediction was not conclusive, we investigated the effects on pre-mRNA splicing of these two variants by using an in vitro minigene approach. Production of mutant transcripts in HeLa cells demonstrated that both mutations cause the almost complete abolishment of the physiologic donor splice site, with the concomitant unmasking of cryptic donor splice sites. To our knowledge, this work represents the first in-depth molecular characterization of splicing defects in a OCA4 patient.

  18. Treatment of a direct carotid-cavernous fistula in a patient with type IV Ehlers-Danlos syndrome: a novel approach

    Energy Technology Data Exchange (ETDEWEB)

    Hollands, J.K.; Santarius, T.; Kirkpatrick, P.J. [Addenbrooke' s Hospital, Department of Neurosurgery, Cambridge (United Kingdom); Higgins, J.N. [Addenbrooke' s Hospital, Department of Neuroradiology, Cambridge (United Kingdom)

    2006-07-15

    We report a case of a 34-year-old female with type IV Ehlers-Danlos syndrome diagnosed with a carotid cavernous fistula presenting with progressive proptosis. Endovascular embolization using balloons or coils carries a high risk of complications in this group of patients, owing to the extreme fragility of the blood vessels. Initial treatment was conservative until an intracerebral haemorrhage occurred. To avoid transfemoral angiography, the ipsilateral carotid arteries and the internal jugular vein were surgically exposed for insertion of two endovascular sheaths. The patient was transferred from theatre to the angiography suite and the sheaths were used for embolization access. The fistula was closed, with preservation of the carotid artery, using Guglielmi detachable coils deployed in the cavernous sinus from the arterial and venous sides. Rapid resolution of symptoms and signs followed, which was sustained at 6-month follow-up. This technique offers alternative access for endovascular treatment, which may reduce the high incidence of mortality associated with catheter angiography in this condition. (orig.)

  19. The predicted ABC transporter AbcEDCBA is required for type IV secretion system expression and lysosomal evasion by Brucella ovis.

    Directory of Open Access Journals (Sweden)

    Teane M A Silva

    Full Text Available Brucella ovis is a major cause of reproductive failure in rams and it is one of the few well-described Brucella species that is not zoonotic. Previous work showed that a B. ovis mutant lacking a species-specific ABC transporter (ΔabcBA was attenuated in mice and was unable to survive in macrophages. The aim of this study was to evaluate the role of this ABC transporter during intracellular survival of B. ovis. In HeLa cells, B. ovis WT was able to survive and replicate at later time point (48 hpi, whereas an ΔabcBA mutant was attenuated at 24 hpi. The reduced survival of the ΔabcBA mutant was associated with a decreased ability to exclude the lysosomal marker LAMP1 from its vacuolar membrane, suggesting a failure to establish a replicative niche. The ΔabcBA mutant showed a reduced abundance of the Type IV secretion system (T4SS proteins VirB8 and VirB11 in both rich and acid media, when compared to WT B. ovis. However, mRNA levels of virB1, virB8, hutC, and vjbR were similar in both strains. These results support the notion that the ABC transporter encoded by abcEDCBA or its transported substrate acts at a post-transcriptional level to promote the optimal expression of the B. ovis T4SS within infected host cells.

  20. Factors associated with the support of pricking (female genital cutting type IV) among Somali immigrants - a cross-sectional study in Sweden.

    Science.gov (United States)

    Wahlberg, Anna; Johnsdotter, Sara; Ekholm Selling, Katarina; Källestål, Carina; Essén, Birgitta

    2017-08-08

    Pricking, classified as female genital cutting (FGC) type IV by the World Health Organization, is an under-researched area gaining momentum among diaspora communities. Our aim was to explore factors associated with being supportive of pricking among Somalis in Sweden. In a cross-sectional design, attitudes and knowledge regarding FGC, and measures of socioeconomic status, acculturation, and social capital, were assessed by a 49-item questionnaire in four municipalities in Sweden. Data were collected in 2015 from 648 Somali men and women, ≥ 18 years old, of which 113 supported the continuation of pricking. Logistic regression was used for the analysis. Those more likely to support the continuation of pricking were older, originally from rural areas, and newly arrived in Sweden. Further, those who reported that they thought pricking was: acceptable, according to their religion (aOR: 10.59, 95% CI: 5.44-20.62); not a violation of children's rights (aOR: 2.86, 95% CI: 1.46-5.61); and did not cause long-term health complications (aOR: 5.52, 95% CI: 2.25-13.52) had higher odds of supporting pricking. Religion was strongly associated with the support of pricking among both genders. However, for men, children's rights and the definition of pricking as FGC or not were important aspects in how they viewed pricking, while, for women, health complications and respectability were important. Values known to be associated with FGC in general are also related to pricking. Hence, there seems to be a change in what types of FGC are supported rather than in their perceived values.

  1. Single-catheter approach for ablation of the slow pathway in a patient with type IV Ehlers-Danlos syndrome and AV nodal reentrant tachycardia using a magnetic navigation system

    NARCIS (Netherlands)

    T. Szili-Torok (Tamas); E. Jessurun; L.J.L.M. Jordaens (Luc)

    2008-01-01

    textabstractPatients with Ehlers-Danlos syndrome type IV have thin-walled, friable arteries and veins. Invasive procedures carry a significantly increased risk for perforation of blood vessels. The aim of this case report is to demonstrate the feasibility and potential benefits of using a

  2. Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella type IV secretion system

    NARCIS (Netherlands)

    de Jong, Maarten F.; Sun, Yao-Hui; den Hartigh, Andreas B.; van Dijl, Jan Maarten; Tsolis, Renee M.

    2008-01-01

    Survival and replication inside host cells by Brucella spp. requires a type IV secretion system (T4SS), encoded by the virB locus. However, the identity of the molecules secreted by the T4SS has remained elusive. We hypothesized that proteins translocated by the T4SS would be co-regulated with the

  3. IS1111 insertion sequences of Coxiella burnetii: characterization and use for repetitive element PCR-based differentiation of Coxiella burnetii isolates

    Directory of Open Access Journals (Sweden)

    Massung Robert F

    2007-10-01

    Full Text Available Abstract Background Coxiella burnetii contains the IS1111 transposase which is present 20 times in the Nine Mile phase I (9Mi/I genome. A single PCR primer that binds to each IS element, and primers specific to a region ~500-bp upstream of each of the 20 IS1111 elements were designed. The amplified products were characterized and used to develop a repetitive element PCR genotyping method. Results Isolates Nine Mile phase II, Nine Mile RSA 514, Nine Mile Baca, Scottish, Ohio, Australian QD, Henzerling phase I, Henzerling phase II, M44, KAV, PAV, Q238, Q195 and WAV were tested by PCR and compared to 9Mi/I. Sequencing was used to determine the exact differences in isolates which lacked specific IS elements or produced PCR products of differing size. From this data, an algorithm was created utilizing four primer pairs that allows for differentiation of unknown isolates into five genomic groups. Additional isolates (Priscilla Q177, Idaho Q, Qiyi, Poker Cat, Q229 and Q172 and nine veterinary samples were characterized using the algorithm which resulted in their placement into three distinct genomic groups. Conclusion Through this study significant differences, including missing elements and sequence alterations within and near IS element coding regions, were found between the isolates tested. Further, a method for differentiation of C. burnetii isolates into one of five genomic groups was created. This algorithm may ultimately help to determine the relatedness between known and unknown isolates of C. burnetii.

  4. Association of DSM-IV Posttraumatic Stress Disorder With Traumatic Experience Type and History in the World Health Organization World Mental Health Surveys.

    Science.gov (United States)

    Liu, Howard; Petukhova, Maria V; Sampson, Nancy A; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Andrade, Laura Helena; Bromet, Evelyn J; de Girolamo, Giovanni; Haro, Josep Maria; Hinkov, Hristo; Kawakami, Norito; Koenen, Karestan C; Kovess-Masfety, Viviane; Lee, Sing; Medina-Mora, Maria Elena; Navarro-Mateu, Fernando; O'Neill, Siobhan; Piazza, Marina; Posada-Villa, José; Scott, Kate M; Shahly, Victoria; Stein, Dan J; Ten Have, Margreet; Torres, Yolanda; Gureje, Oye; Zaslavsky, Alan M; Kessler, Ronald C

    2017-03-01

    Previous research has documented significant variation in the prevalence of posttraumatic stress disorder (PTSD) depending on the type of traumatic experience (TE) and history of TE exposure, but the relatively small sample sizes in these studies resulted in a number of unresolved basic questions. To examine disaggregated associations of type of TE history with PTSD in a large cross-national community epidemiologic data set. The World Health Organization World Mental Health surveys assessed 29 TE types (lifetime exposure, age at first exposure) with DSM-IV PTSD that was associated with 1 randomly selected TE exposure (the random TE) for each respondent. Surveys were administered in 20 countries (n = 34 676 respondents) from 2001 to 2012. Data were analyzed from October 1, 2015, to September 1, 2016. Prevalence of PTSD assessed with the Composite International Diagnostic Interview. Among the 34 676 respondents (55.4% [SE, 0.6%] men and 44.6% [SE, 0.6%] women; mean [SE] age, 43.7 [0.2] years), lifetime TE exposure was reported by a weighted 70.3% of respondents (mean [SE] number of exposures, 4.5 [0.04] among respondents with any TE). Weighted (by TE frequency) prevalence of PTSD associated with random TEs was 4.0%. Odds ratios (ORs) of PTSD were elevated for TEs involving sexual violence (2.7; 95% CI, 2.0-3.8) and witnessing atrocities (4.2; 95% CI, 1.0-17.8). Prior exposure to some, but not all, same-type TEs was associated with increased vulnerability (eg, physical assault; OR, 3.2; 95% CI, 1.3-7.9) or resilience (eg, participation in sectarian violence; OR, 0.3; 95% CI, 0.1-0.9) to PTSD after the random TE. The finding of earlier studies that more general history of TE exposure was associated with increased vulnerability to PTSD across the full range of random TE types was replicated, but this generalized vulnerability was limited to prior TEs involving violence, including participation in organized violence (OR, 1.3; 95% CI, 1.0-1.6), experience of

  5. Coxiella burnetii associated placental lesions and infection level in parturient cows

    DEFF Research Database (Denmark)

    Hansen, Mette Sif; Rodolakis, Annie; Cochonneau, Denis

    2011-01-01

    Cotyledons (n=170) from dairy cattle were analysed for Coxiella burnetii by real-time (rt) PCR targeting the IS1111a and icd genes. Positive cases (n=90) and a random selection of negative cases (n=20) were examined by histology, immunohistochemistry and, if infection level was high...... in herds with low antibody levels. Histological examination revealed a range of mostly mild cotyledonary changes; C. burnetii infection was only rarely associated with inflammation. This may explain why bovine Q fever is usually not clinically apparent. Nevertheless, infected cattle will shed C. burnetii......, by fluorescence in situ hybridisation. PCR results were compared to bulk tank milk (BTM) antibody levels.Placental infection was detected in cows from herds at all BTM antibody levels. However the likelihood of placental infection was generally higher in herds with intermediate or high BMT antibody levels than...

  6. Factors associated with Coxiella burnetii antibody positivity in Danish dairy cows

    DEFF Research Database (Denmark)

    Paul, Suman; Agger, Jens Frederik Gramstrup; Markussen, Bo

    2012-01-01

    The aim of the study was to identify associations between the level of Coxiella burnetii (C. burnetii) antibodies in individual milk samples and cow and herd level factors in Danish dairy cows. The study, designed as a prospective cross sectional study with follow up, included 24 herds identified...... testing, and cows were considered test positive for S/P values ≥40, and otherwise negative. Individual cow information was extracted from the Danish Cattle Database and herd information was obtained from a telephone interview with each farmer. From multivariable logistic regression analysis accounting...... by a stratified random sampling procedure according to the level of C. burnetii antibodies in one bulk tank milk (BTM) sample at the beginning of the study. Ten herds were BTM positive, ten herds were BTM negative and four herds had an intermediate level. The samples were tested with an ELISA and results...

  7. Application of fluorescent in situ hybridisation for demonstration of Coxiella burnetti in placentas from ruminant abortions

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Montgomery, Donald L.; Jaeger, Paula T.

    2007-01-01

    A fluorescent in situ hybridisation (FISH) assay targeting 16S ribosomal RNA was developed for detection of the zoonotic bacterium Coxiella burnetii in formalin-fixed, paraffin-embedded tissue, and applied on placentas from ruminant abortions. The applicability of the FISH assay was compared...... to immunohistochemistry (IHC) using human positive control serum in 12 cases of C burnetii-associated placentitis as well as 7 negative control tissue samples. In all 12 cases the bacterium was detected within trophoblasts as well as free in the placental debris by both FISH and IHC. Extensive and significant infection...... by C. burnetii was revealed in 10 of the cases, whereas a slighter and focal distribution of the bacterium was observed in two cases. 90 aborted placentas from Danish ruminants were investigated by FISH. C burnetii was detected in one bovine case only, representing the first confirmation of C burnetii...

  8. Risk factors for Coxiella burnetii antibodies in bulk tank milk from Danish dairy herds

    DEFF Research Database (Denmark)

    Agger, Jens Frederik; Paul, Suman; Christoffersen, Anna-Bodil

    2013-01-01

    The aim was to identify risk factors associated with Coxiella burnetii antibody positivity in bulk tank milk (BTM) samples from 100 randomly selected Danish dairy cattle herds. Antibody levels were measured by an enzyme-linked immuno-sorbent assay. Before testing the herds, the farm managers were...... interviewed about hired labour, biosecurity, housing and herd health during the 12 months prior to the study. Variables considered important for C. burnetii antibody positivity in multivariable logistic regression analysis included the sharing of machines between farms (OR = 3.6), human contacts (OR = 4...... of calving and disease pens also showed significant association in univariable analysis. This study demonstrates that strict biosecurity is important for the prevention of infections with C. burnetii....

  9. Prevalence of Coxiella burnetii in women exposed to livestock animals, Denmark, 1996 to 2002

    DEFF Research Database (Denmark)

    Nielsen, Stine Yde; Molbak, K; Andersen, Anne-Marie Nybo

    2013-01-01

    Q fever is a zoonotic infection which can pose a danger to pregnant women. To our knowledge, Denmark has never experienced a clinically verified Q fever outbreak. We aimed to quantify risk of infection in pregnant women occupationally and environmentally exposed to Coxiella burnetii. The Danish....... Samples were screened for antibodies against C. burnetii by commercial enzyme-linked immunosorbent assay. Positive samples were confirmed by immunofluorescence (cut-off titre ≥1:128). The proportion of seropositive women was higher in the occupationally exposed (47.2% seropositive; relative risk (RR): 9.......8; 95% confidence interval (CI): 6.4–15.2) and the domestically exposed population (32.2% seropositive; RR: 6.7; 95% CI: 4.3–10.6) than in unexposed women (4.8% seropositive). We found a high prevalence of antibodies to C. burnetii among pregnant women with occupational or domestic exposure to cattle...

  10. Seroprevalence of Coxiella burnetii in domestic ruminants in Gran Canaria Island, Spain.

    Science.gov (United States)

    Rodríguez, N F; Carranza, C; Bolaños, M; Pérez-Arellano, J L; Gutierrez, C

    2010-04-01

    Coxiella burnetii is the causative agent of Q fever, a zoonosis with worldwide occurrence. In the Canary Islands, the overall seroprevalence in humans has been estimated to be 21.5%. Gran Canaria island concentrates the highest ruminant population in the archipelago and the prevalence of the human infection is 23.5%. To evaluate the seroprevalence in livestock and the affected areas in Gran Canaria island, a total of 1249 ruminants were randomly selected for this study (733 goats, 369 sheep and 147 cattle). The samples were evaluated using an indirect ELISA Kit. The results showed seroprevalences of 60.4%, 31.7% and 12.2% in goats, sheep and cattle, respectively. Based on these results, Q fever could be considered as endemic in Gran Canaria island. Sanitary measures should be taken at the farm level to minimize the risk of exposure of C. burnetii to humans.

  11. Q fever: prevalence of antibodies to Coxiella burnetii in the Basque country.

    Science.gov (United States)

    Sanzo, J M; Garcia-Calabuig, M A; Audicana, A; Dehesa, V

    1993-12-01

    The aim of this study was to ascertain the prevalence of Coxiella burnetii infection in the Basque population. To this end a stratified sampling was carried out taking as a criterion the size of the population in a given area of residence. Residents in sparsely populated areas were found to have a prevalence of 38.5%, significantly greater than in highly populated areas (odds ratio [OR] = 1.56; 95% confidence interval [CI]: 1.08-2.27 and OR = 1.58; 95% CI: 1.09-2.30). The prevalence was significantly higher in males (36.3%) than in females (29%), and was found to increase significantly with age. Current or previous participation in activities relating to agriculture and/or livestock farming or even having contact with cattle, goats or sheep were also found to be risk factors for the infection. A fuller study of the determinants of chronic Q fever should be initiated.

  12. Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens.

    Science.gov (United States)

    Hendrick, William A; Orr, Mona W; Murray, Samantha R; Lee, Vincent T; Melville, Stephen B

    2017-05-15

    The Gram-positive pathogen Clostridium perfringens possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens , called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected in vivo or in vitro even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from C. perfringens (CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels in vivo but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from in vivo studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium. IMPORTANCE Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species Clostridium perfringens was used to study proteins involved in

  13. Evolutionary Dynamics of Pathoadaptation Revealed by Three Independent Acquisitions of the VirB/D4 Type IV Secretion System in Bartonella.

    Science.gov (United States)

    Harms, Alexander; Segers, Francisca H I D; Quebatte, Maxime; Mistl, Claudia; Manfredi, Pablo; Körner, Jonas; Chomel, Bruno B; Kosoy, Michael; Maruyama, Soichi; Engel, Philipp; Dehio, Christoph

    2017-03-01

    The α-proteobacterial genus Bartonella comprises a group of ubiquitous mammalian pathogens that are studied as a model for the evolution of bacterial pathogenesis. Vast abundance of two particular phylogenetic lineages of Bartonella had been linked to enhanced host adaptability enabled by lineage-specific acquisition of a VirB/D4 type IV secretion system (T4SS) and parallel evolution of complex effector repertoires. However, the limited availability of genome sequences from one of those lineages as well as other, remote branches of Bartonella has so far hampered comprehensive understanding of how the VirB/D4 T4SS and its effectors called Beps have shaped Bartonella evolution. Here, we report the discovery of a third repertoire of Beps associated with the VirB/D4 T4SS of B. ancashensis, a novel human pathogen that lacks any signs of host adaptability and is only distantly related to the two species-rich lineages encoding a VirB/D4 T4SS. Furthermore, sequencing of ten new Bartonella isolates from under-sampled lineages enabled combined in silico analyses and wet lab experiments that suggest several parallel layers of functional diversification during evolution of the three Bep repertoires from a single ancestral effector. Our analyses show that the Beps of B. ancashensis share many features with the two other repertoires, but may represent a more ancestral state that has not yet unleashed the adaptive potential of such an effector set. We anticipate that the effectors of B. ancashensis will enable future studies to dissect the evolutionary history of Bartonella effectors and help unraveling the evolutionary forces underlying bacterial host adaptation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. The 2.5 Å structure of the enterococcus conjugation protein TraM resembles VirB8 type IV secretion proteins.

    Science.gov (United States)

    Goessweiner-Mohr, Nikolaus; Grumet, Lukas; Arends, Karsten; Pavkov-Keller, Tea; Gruber, Christian C; Gruber, Karl; Birner-Gruenberger, Ruth; Kropec-Huebner, Andrea; Huebner, Johannes; Grohmann, Elisabeth; Keller, Walter

    2013-01-18

    Conjugative plasmid transfer is the most important means of spreading antibiotic resistance and virulence genes among bacteria and therefore presents a serious threat to human health. The process requires direct cell-cell contact made possible by a multiprotein complex that spans cellular membranes and serves as a channel for macromolecular secretion. Thus far, well studied conjugative type IV secretion systems (T4SS) are of Gram-negative (G-) origin. Although many medically relevant pathogens (e.g., enterococci, staphylococci, and streptococci) are Gram-positive (G+), their conjugation systems have received little attention. This study provides structural information for the transfer protein TraM of the G+ broad host range Enterococcus conjugative plasmid pIP501. Immunolocalization demonstrated that the protein localizes to the cell wall. We then used opsonophagocytosis as a novel tool to verify that TraM was exposed on the cell surface. In these assays, antibodies generated to TraM recruited macrophages and enabled killing of pIP501 harboring Enteroccocus faecalis cells. The crystal structure of the C-terminal, surface-exposed domain of TraM was determined to 2.5 Å resolution. The structure, molecular dynamics, and cross-linking studies indicated that a TraM trimer acts as the biological unit. Despite the absence of sequence-based similarity, TraM unexpectedly displayed a fold similar to the T4SS VirB8 proteins from Agrobacterium tumefaciens and Brucella suis (G-) and to the transfer protein TcpC from Clostridium perfringens plasmid pCW3 (G+). Based on the alignments of secondary structure elements of VirB8-like proteins from mobile genetic elements and chromosomally encoded T4SS from G+ and G- bacteria, we propose a new classification scheme of VirB8-like proteins.

  15. The conjugation protein TcpC from Clostridium perfringens is structurally related to the type IV secretion system protein VirB8 from Gram-negative bacteria.

    Science.gov (United States)

    Porter, Corrine J; Bantwal, Radhika; Bannam, Trudi L; Rosado, Carlos J; Pearce, Mary C; Adams, Vicki; Lyras, Dena; Whisstock, James C; Rood, Julian I

    2012-01-01

    Bacterial conjugation is important for the acquisition of virulence and antibiotic resistance genes. We investigated the mechanism of conjugation in Gram-positive pathogens using a model plasmid pCW3 from Clostridium perfringens. pCW3 encodes tetracycline resistance and contains the tcp locus, which is essential for conjugation. We showed that the unique TcpC protein (359 amino acids, 41 kDa) was required for efficient conjugative transfer, localized to the cell membrane independently of other conjugation proteins, and that membrane localization was important for its function, oligomerization and interaction with the conjugation proteins TcpA, TcpH and TcpG. The crystal structure of the C-terminal component of TcpC (TcpC(99-359)) was determined to 1.8-Å resolution. TcpC(99-359) contained two NTF2-like domains separated by a short linker. Unexpectedly, comparative structural analysis showed that each of these domains was structurally homologous to the periplasmic region of VirB8, a component of the type IV secretion system from Agrobacterium tumefaciens. Bacterial two-hybrid studies revealed that the C-terminal domain was critical for interactions with other conjugation proteins. The N-terminal region of TcpC was required for efficient conjugation, oligomerization and protein-protein interactions. We conclude that by forming oligomeric complexes, TcpC contributes to the stability and integrity of the conjugation apparatus, facilitating efficient pCW3 transfer. © 2011 Blackwell Publishing Ltd.

  16. Iron Starvation Conditions Upregulate Ehrlichia ruminantium Type IV Secretion System, tr1 Transcription Factor and map1 Genes Family through the Master Regulatory Protein ErxR

    Directory of Open Access Journals (Sweden)

    Amal Moumène

    2018-01-01

    Full Text Available Ehrlichia ruminantium is an obligatory intracellular bacterium that causes heartwater, a fatal disease in ruminants. Due to its intracellular nature, E. ruminantium requires a set of specific virulence factors, such as the type IV secretion system (T4SS, and outer membrane proteins (Map proteins in order to avoid and subvert the host's immune response. Several studies have been conducted to understand the regulation of the T4SS or outer membrane proteins, in Ehrlichia, but no integrated approach has been used to understand the regulation of Ehrlichia pathogenicity determinants in response to environmental cues. Iron is known to be a key nutrient for bacterial growth both in the environment and within hosts. In this study, we experimentally demonstrated the regulation of virB, map1, and tr1 genes by the newly identified master regulator ErxR (for Ehrlichia ruminantium expression regulator. We also analyzed the effect of iron depletion on the expression of erxR gene, tr1 transcription factor, T4SS and map1 genes clusters in E. ruminantium. We show that exposure of E. ruminantium to iron starvation induces erxR and subsequently tr1, virB, and map1 genes. Our results reveal tight co-regulation of T4SS and map1 genes via the ErxR regulatory protein at the transcriptional level, and, for the first time link map genes to the virulence function sensu stricto, thereby advancing our understanding of Ehrlichia's infection process. These results suggest that Ehrlichia is able to sense changes in iron concentrations in the environment and to regulate the expression of virulence factors accordingly.

  17. Resin Bonding to Type IV Gold Alloy Conditioned with a Novel Mercapto Silane System: Effect of Incorporation of a Phosphate Monomer.

    Science.gov (United States)

    Kwon, Sung-Min; Min, Bong Ki; Son, Jun Sik; Kwon, Tae-Yub

    2018-02-01

    Self-assembled monolayers of thiols have been used to link a range of materials to planar gold surfaces or gold nanoparticles in nanoscience and nanotechnology. Novel mercapto silane systems are a promising alternative to dental noble metal alloys for enhanced resin bonding durability Goldbased alloys for full-cast restorations contain various base metal elements, which may bond to acidic functional monomers chemically, in addition to noble metal elements. This study examined how the additional incorporation of a phosphate monomer (di-2-hydroxyethyl methacryl hydrogenphosphate, DHP) into novel mercapto silane primer systems affected the resin bond strength to a type IV gold alloy pretreated with the primers. One of three commercial primers (Alloy Primer and M. L. Primer) and three experimental primer systems ((1) blend of γ-mercaptopropyltrimethoxysilane (SPS) and γ-methacryloxypropyltrimethoxysilane (MPS) (both 1.0 wt%), (2) 1.0 wt% DHP-containing primer, and (3) blend of SPS, MPS, and DHP (each 1.0 wt%)) was applied to the alloy surfaces after sandblasting. Resin cylinders (diameter: 2.38 mm) were bonded to the surfaces and light-cured. All bonded specimens were stored in water at 37 °C for 24 h and then half of them additionally water immersed for 7 days (37 °C) and thermocycled 10,000 times before the shear bond strength test (n = 10). The mercapto silane systems (SPS + MPS) were found to show superior resin bonding durability to the commercial primers and the only DHP-containing primer, regardless of additional incorporation of the phosphate monomer.

  18. Animal Protection and Structural Studies of a Consensus Sequence Vaccine Targeting the Receptor Binding Domain of the Type IV Pilus of Pseudomonas aeruginosa

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Daniel J.; Churchill, Mair E.A.; Irvin, Randall T.; Hodges, Robert S. (Alberta); (Colorado)

    2008-09-23

    One of the main obstacles in the development of a vaccine against Pseudomonas aeruginosa is the requirement that it is protective against a wide range of virulent strains. We have developed a synthetic-peptide consensus-sequence vaccine (Cs1) that targets the host receptor-binding domain (RBD) of the type IV pilus of P. aeruginosa. Here, we show that this vaccine provides increased protection against challenge by the four piliated strains that we have examined (PAK, PAO, KB7 and P1) in the A.BY/SnJ mouse model of acute P. aeruginosa infection. To further characterize the consensus sequence, we engineered Cs1 into the PAK monomeric pilin protein and determined the crystal structure of the chimeric Cs1 pilin to 1.35 {angstrom} resolution. The substitutions (T130K and E135P) used to create Cs1 do not disrupt the conserved backbone conformation of the pilin RBD. In fact, based on the Cs1 pilin structure, we hypothesize that the E135P substitution bolsters the conserved backbone conformation and may partially explain the immunological activity of Cs1. Structural analysis of Cs1, PAK and K122-4 pilins reveal substitutions of non-conserved residues in the RBD are compensated for by complementary changes in the rest of the pilin monomer. Thus, the interactions between the RBD and the rest of the pilin can either be mediated by polar interactions of a hydrogen bond network in some strains or by hydrophobic interactions in others. Both configurations maintain a conserved backbone conformation of the RBD. Thus, the backbone conformation is critical in our consensus-sequence vaccine design and that cross-reactivity of the antibody response may be modulated by the composition of exposed side-chains on the surface of the RBD. This structure will guide our future vaccine design by focusing our investigation on the four variable residue positions that are exposed on the RBD surface.

  19. SDSS IV MaNGA: Deep observations of extra-planar, diffuse ionized gas around late-type galaxies from stacked IFU spectra

    Science.gov (United States)

    Jones, A.; Kauffmann, G.; D'Souza, R.; Bizyaev, D.; Law, D.; Haffner, L.; Bahé, Y.; Andrews, B.; Bershady, M.; Brownstein, J.; Bundy, K.; Cherinka, B.; Diamond-Stanic, A.; Drory, N.; Riffel, R. A.; Sánchez, S. F.; Thomas, D.; Wake, D.; Yan, R.; Zhang, K.

    2017-03-01

    We have conducted a study of extra-planar diffuse ionized gas using the first year data from the MaNGA IFU survey. We have stacked spectra from 49 edge-on, late-type galaxies as a function of distance from the midplane of the galaxy. With this technique we can detect the bright emission lines Hα, Hβ, [O II]λλ3726, 3729, [O III]λ5007, [N II]λλ6549, 6584, and [S II]λλ6717, 6731 out to about 4 kpc above the midplane. With 16 galaxies we can extend this analysis out to about 9 kpc, I.e. a distance of 2Re, vertically from the midplane. In the halo, the surface brightnesses of the [O II] and Hα emission lines are comparable, unlike in the disk where Hα dominates. When we split the sample by specific star-formation rate, concentration index, and stellar mass, each subsample's emission line surface brightness profiles and ratios differ, indicating that extra-planar gas properties can vary. The emission line surface brightnesses of the gas around high specific star-formation rate galaxies are higher at all distances, and the line ratios are closer to ratios characteristic of H II regions compared with low specific star-formation rate galaxies. The less concentrated and lower stellar mass samples exhibit line ratios that are more like H II regions at larger distances than their more concentrated and higher stellar mass counterparts. The largest difference between different subsamples occurs when the galaxies are split by stellar mass. We additionally infer that gas far from the midplane in more massive galaxies has the highest temperatures and steepest radial temperature gradients based on their [N II]/Hα and [O II]/Hα ratios between the disk and the halo. SDSS IV.

  20. Q fever in Egypt: Epidemiological survey of Coxiella burnetii specific antibodies in cattle, buffaloes, sheep, goats and camels.

    Directory of Open Access Journals (Sweden)

    Jessica Klemmer

    Full Text Available Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Clinical presentation in humans varies from asymptomatic to flu-like illness and severe sequelae may be seen. Ruminants are often sub-clinically infected or show reproductive disorders such as abortions. In Egypt, only limited data on the epidemiology of Q fever in animals are available. Using a stratified two stage random sampling approach, we evaluated the prevalence of Coxiella burnetii specific antibodies among ruminants and camels in 299 herds. A total of 2,699 blood samples was investigated using enzyme-linked-immunosorbent assay (ELISA. Coxiella burnetii specific antibodies were detected in 40.7% of camels (215/528, 19.3% of cattle (162/840, 11.2% of buffaloes (34/304, 8.9% of sheep (64/716 and 6.8% of goats (21/311, respectively. Odds of seropositivity were significantly higher for cattle (aOR: 3.17; 95% CI: 1.96-5.13 and camels (aOR: 9.75; 95% CI: 6.02-15.78. Significant differences in seropositivity were also found between domains (Western Desert, Eastern Desert and Nile Valley and Delta and 25 governorates (p 0.05. Only 8.7% of the interviewed people living on the farms consumed raw camel milk and none reported prior knowledge on Q fever. Findings from this nationwide study show that exposure to Coxiella burnetii is common in ruminants and camels. Disease awareness among physicians, veterinarians and animal owners has to be raised. Future epidemiological investigations have to elucidate the impact of Q fever on human health and on the economy of Egypt.

  1. Coxiella burnetii Exhibits Morphological Change and Delays Phagolysosomal Fusion after Internalization by J774A.1 Cells†

    OpenAIRE

    Howe, Dale; Mallavia, Louis P.

    2000-01-01

    Coxiella burnetii, the etiological agent of Q fever, is an obligate intracellular bacterium proliferating within the harsh environment of the phagolysosome. Mechanisms controlling trafficking to, and survival of pathogens within, the phagolysosome are unknown. Two distinct morphological variants have been implicated as playing a role in C. burnetii survival. The dormant small-cell variant (SCV) is resistant to extracellular stresses and the more metabolically active large-cell variant (LCV) i...

  2. No excess risk of adverse pregnancy outcomes among women with serological markers of previous infection with Coxiella burnetii

    DEFF Research Database (Denmark)

    Nielsen, Stine Yde; Andersen, Anne-Marie Nybo; Mølbak, Kåre

    2013-01-01

    Q fever caused by Coxiella burnetii is transmitted to humans by inhalation of aerosols from animal birth products. Q fever in pregnancy is suspected to be a potential cause of fetal and maternal morbidity and fetal mortality but the pathogenesis is poorly understood, and even in Q fever endemic...... areas, the magnitude of a potential association is not established.We aimed to examine if presence of antibodies to C. burnetii during pregnancy or seroconversion were associated with adverse pregnancy outcomes....

  3. Substitution of Aspartate for glycine 1018 in the Type III procollagen (COL3AI) gene causes type IV Ehlers-Danlos Syndrome: The mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother

    Energy Technology Data Exchange (ETDEWEB)

    Kontusaari, S.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Stolle, C. (Robert Wood Johnson Medical School, Piscataway, NJ (United States)); Pope, F.M.

    1992-09-01

    A proband with arterial ruptures and skin changes characteristic of the type IV variant of Ehlers-Danlos syndrome was found to have a single-base mutation in the type III procollagen gene, which converted the codon for glycine at amino position 1018 to a codon for aspartate. (Amino acid positions are numbered by the standard convention in which the first glycine of the triple-helical domain of an [alpha] chain is number 1. The numbers of positions in the [alpha]1(III) chains can be converted to positions in the human pro[alpha](III) chain by adding 167.). Nucleotide sequencing of overlapping PCR products in which the two alleles were distinguished demonstrated that the mutation of glycine 1018 was the only mutation that changed the primary structure of type III procollagen. The glycine substitution markedly decreased the amount of type III procollagen secreted into the medium by cultured skin fibroblasts from the proband. It is surprising that the same mutation was found in about 94% of the peripheral blood leukocytes from the proband's asymptomatic 72-year-old mother. Other tissues from the mother contained the mutated allele; it was present in 0%-100% of different samples of hair cells and in about 40% of cells from the oral epithelium. Therefore, the mother was a mosaic for the mutation. Since the mutated allele was present in cells derived from all three germ layers, the results indicated that the mutation arose by the late blastocyst stage of development. The results also indicate that assays of blood leukocytes do not always reveal mosaicism or predict phenotypic involvement of tissues, such as blood vessels, that are derived from the same embryonic cells as are leukocytes. 66 refs., 6 figs., 1 tab.

  4. [The diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis patients].

    Science.gov (United States)

    Park, Jin Hyung; Park, Chang Kun; Kim, Eun Soo; Park, Soo Young; Jo, Chang Min; Tak, Won Young; Kweon, Young Oh; Kim, Sung Kook; Choi, Yong Whan

    2003-06-01

    The prognosis of chronic liver disease is closely related to the development of hepatic fibrosis. Liver biopsy is the gold standard method to assess inflammatory activity and fibrosis stage, but this is associated with morbidity and mortality. This study aimed to evaluate the diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis. This study included 100 patients with chronic hepatitis B and cirrhosis. Liver biopsy and histopathologic classification were done. Serum hyaluronic acid and 7S domain of type IV collagen were measured by one step sandwich binding protein assay and radioimmunoassay using polyclonal antibody to 7S domain of type IV collagen, respectively. The serum concentrations of hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio in the cirrhosis group (139 +/- 98.4 ng/mL, 6.9 +/- 3.5 ng/mL, 1.6 +/- 1.5) were significantly higher (p<0.01) than those in the normal and fatty liver group (20.2 +/- 12.5 ng/mL, 3.5 +/- 0.5 ng/mL, 0.7 +/- 0.3), mild hepatitis group (32.3 +/- 52.7 ng/mL, 3.9 +/- 1.4 ng/mL, 0.7 +/- 0.4), and moderate to severe hepatitis group (68.2 +/- 72.3 ng/mL, 5.3 +/- 2.4 ng/mL, 0.8 +/- 0.4). At the cutoff value of 77 ng/mL for hyaluronic acid and 6.3 ng/mL for 7S domain of type IV collagen and 0.62 for AST/ALT ratio, the sensitivities were 81.8%, 63.6%, 90.9% and specificities were 87.3%, 88.6%, 53.1% for discriminating cirrhosis (fibrosis score: 4) from the mild to severe fibrosis (fibrosis score: 0-3). Serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio measurement may be clinically useful as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.

  5. Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB/D4 type IV secretion system.

    Science.gov (United States)

    Lu, Yun-Yueh; Franz, Bettina; Truttmann, Matthias C; Riess, Tanja; Gay-Fraret, Jérémie; Faustmann, Marco; Kempf, Volkhard A J; Dehio, Christoph

    2013-05-01

    The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in humans. Two pathogenicity factors of B. henselae - each displaying multiple functions in host cell interaction - have been characterized in greater detail: the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of the individual activities of BadA or VirB/D4 it is unknown whether these major virulence factors affect each other in their specific activities. In this study, expression and function of BadA and VirB/D4 were analysed in a variety of clinical B. henselae isolates. Data revealed that most isolates have lost expression of either BadA or VirB/D4 during in vitro passages. However, the phenotypic effects of coexpression of both virulence factors was studied in one clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA, which forms a dense layer on the bacterial surface, negatively affected VirB/D4-dependent Bep translocation and invasome formation by likely preventing close contact between the bacterial cell envelope and the host cell membrane. In contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not affected by a functional VirB/D4 T4SS. The obtained data imply that the essential virulence factors BadA and VirB/D4 are likely differentially expressed during different stages of the infection cycle of

  6. Enterococcus faecalis PcfC, a spatially localized substrate receptor for type IV secretion of the pCF10 transfer intermediate.

    Science.gov (United States)

    Chen, Yuqing; Zhang, Xiaolin; Manias, Dawn; Yeo, Hye-Jeong; Dunny, Gary M; Christie, Peter J

    2008-05-01

    Upon sensing of peptide pheromone, Enterococcus faecalis efficiently transfers plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand-specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we present evidence that PcfF and PcfG spatially coordinate docking of the pCF10 transfer intermediate with PcfC, a membrane-bound putative ATPase related to the coupling proteins of gram-negative T4S machines. PcfC and PcfG fractionated with the membrane and PcfF with the cytoplasm, yet all three proteins formed several punctate foci at the peripheries of pheromone-induced cells as monitored by immunofluorescence microscopy. A PcfC Walker A nucleoside triphosphate (NTP) binding site mutant (K156T) fractionated with the E. faecalis membrane and also formed foci, whereas PcfC deleted of its N-terminal putative transmembrane domain (PcfCDelta N103) distributed uniformly throughout the cytoplasm. Native PcfC and mutant proteins PcfCK156T and PcfCDelta N103 bound pCF10 but not pcfG or Delta oriT mutant plasmids as shown by transfer DNA immunoprecipitation, indicating that PcfC binds only the processed form of pCF10 in vivo. Finally, purified PcfCDelta N103 bound DNA substrates and interacted with purified PcfF and PcfG in vitro. Our findings support a model in which (i) PcfF recruits PcfG to oriT to catalyze T-strand nicking, (ii) PcfF and PcfG spatially position the relaxosome at the cell membrane to stimulate substrate docking with PcfC, and (iii) PcfC initiates substrate transfer through the pCF10 T4S channel by an NTP-dependent mechanism.

  7. Enterococcus faecalis PcfC, a Spatially Localized Substrate Receptor for Type IV Secretion of the pCF10 Transfer Intermediate▿

    Science.gov (United States)

    Chen, Yuqing; Zhang, Xiaolin; Manias, Dawn; Yeo, Hye-Jeong; Dunny, Gary M.; Christie, Peter J.

    2008-01-01

    Upon sensing of peptide pheromone, Enterococcus faecalis efficiently transfers plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand-specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we present evidence that PcfF and PcfG spatially coordinate docking of the pCF10 transfer intermediate with PcfC, a membrane-bound putative ATPase related to the coupling proteins of gram-negative T4S machines. PcfC and PcfG fractionated with the membrane and PcfF with the cytoplasm, yet all three proteins formed several punctate foci at the peripheries of pheromone-induced cells as monitored by immunofluorescence microscopy. A PcfC Walker A nucleoside triphosphate (NTP) binding site mutant (K156T) fractionated with the E. faecalis membrane and also formed foci, whereas PcfC deleted of its N-terminal putative transmembrane domain (PcfCΔN103) distributed uniformly throughout the cytoplasm. Native PcfC and mutant proteins PcfCK156T and PcfCΔN103 bound pCF10 but not pcfG or ΔoriT mutant plasmids as shown by transfer DNA immunoprecipitation, indicating that PcfC binds only the processed form of pCF10 in vivo. Finally, purified PcfCΔN103 bound DNA substrates and interacted with purified PcfF and PcfG in vitro. Our findings support a model in which (i) PcfF recruits PcfG to oriT to catalyze T-strand nicking, (ii) PcfF and PcfG spatially position the relaxosome at the cell membrane to stimulate substrate docking with PcfC, and (iii) PcfC initiates substrate transfer through the pCF10 T4S channel by an NTP-dependent mechanism. PMID:18326569

  8. Raman spectra of Cu{sub 2}B{sup II}C{sup IV}X{sub 4}{sup VI} magnetic quaternary semiconductor compounds with tetragonal stannite type structure

    Energy Technology Data Exchange (ETDEWEB)

    Rincón, C., E-mail: crincon@ula.ve; Quintero, M.; Power, Ch.; Moreno, E.; Quintero, E.; Morocoima, M. [Centro de Estudios de Semiconductores, Departamento de Física, Facultad de Ciencias, Universidad de Los Andes, Mérida (Venezuela, Bolivarian Republic of); Henao, J. A.; Macías, M. A. [Grupo de Investigación en Química Estructural, Facultad de Ciencias, Escuela de Química, Universidad Industrial de Santander, Apartado Aéreo 678, Bucaramanga (Colombia)

    2015-05-28

    A comparative study of the Raman spectra of Cu{sub 2}B{sup II}C{sup IV}S{sub 4}{sup VI} and Cu{sub 2}B{sup II}C{sup IV}Se{sub 4}{sup VI}(where B = Mn or Fe) magnetic quaternary semiconductor compounds with stannite-type structure (I4{sup ¯}2m) has been done. Most of the fourteen Raman lines expected for these materials were observed in the spectra. The two strongest lines observed have been assigned to the IR inactive A{sub 1}{sup 1} and A{sub 1}{sup 2} stannite modes that originated from the motion of the S or Se anion around the Cu and C{sup IV} cations remaining at rest. The shift in the frequency of these two lines of about 150 cm{sup −1} to lower energies observed in Cu{sub 2}B{sup II}C{sup IV}Se{sub 4}{sup VI} compounds as compared to those in Cu{sub 2}B{sup II}C{sup IV}S{sub 4}{sup VI} ones, can then be explained as due to the anion mass effect. Based on the fact that values of these frequencies depend mainly on anion mass and bond-stretching forces between nearest-neighbor atoms, the vibrational frequencies v{sup ¯}(A{sub 1}{sup 2}) and v{sup ¯}(A{sub 1}{sup 2}) of both modes for several Cu{sub 2}B{sup II}C{sup IV}X{sub 4}{sup VI} stannite compounds (where X = S, Se, or Te) very close to the experimental data reported for these materials were calculated from a simple model that relates these stretching forces to the anion-cation bond-distances.

  9. Coxiella-like endosymbiont in argasid ticks (Ornithodoros muesebecki) from a Socotra Cormorant colony in Umm Al Quwain, United Arab Emirates.

    Science.gov (United States)

    Al-Deeb, Mohammad A; Frangoulidis, Dimitrios; Walter, Mathias C; Kömpf, Daniela; Fischer, Silke F; Petney, Trevor; Muzaffar, Sabir Bin

    2016-02-01

    Coxiella burnetii is a pathogen causing Q fever in domestic animals and humans. Seabirds have been implicated as possible reservoirs of this bacterium in the Arabian Gulf and in the Western Indian Ocean. Recently, Coxiella species closely related to C. burnetii was detected from ticks collected from oil rigs used as roosting areas by Socotra Cormorants (Phalacrocorax nigrogularis) in the western Arabian Gulf. We collected ticks from the largest breeding colony of Socotra Cormorants in the United Arab Emirates on the eastern extreme of the species' breeding range to determine the prevalence of C. burnetii and evaluate its role as a wild reservoir. All ticks were identified as Ornithodoros muesebecki and genomic DNA was extracted from larval and nymph/adult tick pools. Multiplex PCR tests were performed targeting three C. burnetii specific genes. C. burnetii was not detected although a Coxiella-like endosymbiont was identified that was closely related to Coxiella symbionts from Ornithodoros capensis ticks. Because domestic and wild ungulates are the primary source of C. burnetii, we suggest that the presence of free-ranging, native and non-native ungulates in some off-shore islands in the Arabian Gulf could disseminate C. burnetii to seabirds. More comprehensive studies on seabird colonies are needed to better understand the diversity and prevalence of Coxiella symbionts and to establish if C. burnetii is endemic on some of these islands. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. Highly sensitive real-time PCR for specific detection and quantification of Coxiella burnetii

    Directory of Open Access Journals (Sweden)

    Linke Sonja

    2006-01-01

    Full Text Available Abstract Background Coxiella burnetii, the bacterium causing Q fever, is an obligate intracellular biosafety level 3 agent. Detection and quantification of these bacteria with conventional methods is time consuming and dangerous. During the last years, several PCR based diagnostic assays were developed to detect C. burnetii DNA in cell cultures and clinical samples. We developed and evaluated TaqMan-based real-time PCR assays that targeted the singular icd (isocitrate dehydrogenase gene and the transposase of the IS1111a element present in multiple copies in the C. burnetii genome. Results To evaluate the precision of the icd and IS1111 real-time PCR assays, we performed different PCR runs with independent DNA dilutions of the C. burnetii Nine Mile RSA493 strain. The results showed very low variability, indicating efficient reproducibility of both assays. Using probit analysis, we determined that the minimal number of genome equivalents per reaction that could be detected with a 95% probability was 10 for the icd marker and 6.5 for the IS marker. Plasmid standards with cloned icd and IS1111 fragments were used to establish standard curves which were linear over a range from 10 to 107 starting plasmid copy numbers. We were able to quantify cell numbers of a diluted, heat-inactivated Coxiella isolate with a detection limit of 17 C. burnetii particles per reaction. Real-time PCR targeting both markers was performed with DNA of 75 different C. burnetii isolates originating from all over the world. Using this approach, the number of IS1111 elements in the genome of the Nine Mile strain was determined to be 23, close to 20, the number revealed by genome sequencing. In other isolates, the number of IS1111 elements varied widely (between seven and 110 and seemed to be very high in some isolates. Conclusion We validated TaqMan-based real-time PCR assays targeting the icd and IS1111 markers of C. burnetii. The assays were shown to be specific, highly

  11. Coxiella burnetii (Q fever) infection in dairy cattle and associated risk factors in Latvia.

    Science.gov (United States)

    Boroduske, A; Trofimova, J; Kibilds, J; Papule, U; Sergejeva, M; Rodze, I; Grantina-Ievina, L

    2017-07-01

    The purpose of this study was to describe prevalence and spatial distribution of Coxiella burnetii infections in dairy cow sheds in Latvia and to investigate risk factors contributing to C. burnetii infections. Blood serum samples from abortion cases from 1010 sheds have been tested by ELISA for the presence of C. burnetii antibodies and bulk tank milk (BTM) samples from 252 sheds have been tested by real time polymerase chain reaction and ELISA for the presence of C. burnetii DNA and antibodies. Prevalence of C. burnetii antibody-positive sheds in cases of abortion was 13·4%. A total of 10·7% and 13·2% of dairy cow sheds tested positive for the presence of C. burnetii DNA and antibodies in BTM, respectively. Two distinct areas of clustering of test-positive dairy cattle sheds were identified by spatial scan statistics of abortion cases and randomly sampled BTM samples. Three factors were identified as significantly contributing to the risk of C. burnetii DNA presence in BTM - number of cattle in shed (>200 animals/shed) (OR 3·93), location of the shed within risk area in Northern Latvia (OR 8·29) and for the first time, purchasing cattle from abroad has been shown to significantly increase risk (OR 2·68) of C. burnetii infection in dairy cows in Latvia.

  12. Coxiella burnetii DNA in goat milk after vaccination with Coxevac(®).

    Science.gov (United States)

    Hermans, Mirjam H A; Huijsmans, C Ronald J J; Schellekens, Jeroen J A; Savelkoul, Paul H M; Wever, Peter C

    2011-03-24

    Q fever is a zoonotic disease caused by Coxiella burnetii, a species of bacteria that is distributed globally. A large Q fever epidemic is currently spreading throughout the Netherlands with more than 3500 human cases notified from 2007 to 2009. Governmental measures to prevent further spread of the disease imposed in December 2009 included vaccination of all dairy goats and sheep and, in parallel, bulk tank milk testing to identify contaminated goat and sheep farms. When bulk tank milk was found to contain C. burnetii DNA, pregnant ruminants were culled. An important, but unsolved issue in this policy was whether vaccine-derived C. burnetii DNA is excreted in milk after vaccination. Using real time PCR and single nucleotide polymorphism (SNP) genotyping techniques, we show here that within hours and up to 9 days after vaccination with Coxevac(®), vaccine-derived C. burnetii DNA can be detected in the milk of dairy goats. This is the first report describing DNAlactia of vaccine-derived DNA after vaccination with a completely inactivated vaccine. This finding had implications for the Dutch policy to combat the Q fever epidemic. A 2-week interval was introduced between vaccination and bulk tank milk testing to identify infected farms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Cell-free propagation of Coxiella burnetii does not affect its relative virulence.

    Directory of Open Access Journals (Sweden)

    Runa Kuley

    Full Text Available Q fever is caused by the obligate intracellular bacterium Coxiella burnetii. In vitro growth of the bacterium is usually limited to viable eukaryotic host cells imposing experimental constraints for molecular studies, such as the identification and characterisation of major virulence factors. Studies of pathogenicity may benefit from the recent development of an extracellular growth medium for C. burnetii. However, it is crucial to investigate the consistency of the virulence phenotype of strains propagated by the two fundamentally different culturing systems. In the present study, we assessed the viability of C. burnetii and the lipopolysaccaride (LPS encoding region of the bacteria in both culture systems as indirect but key parameters to the infection potential of C. burnetii. Propidium monoazide (PMA treatment-based real-time PCR was used for enumeration of viable C. burnetii which were validated by fluorescent infectious focus forming unit counting assays. Furthermore, RNA isolated from C. burnetiipropagated in both the culture systems was examined for LPS-related gene expression. All thus far known LPS-related genes were found to be expressed in early passages in both culturing systems indicating the presence of predominantly the phase I form of C. burnetii. Finally, we used immune-competent mice to provide direct evidence, that the relative virulence of different C. burnetii strains is essentially the same for both axenic and cell-based methods of propagation.

  14. Long-term dynamics of Coxiella burnetii in farmed red deer (Cervus elaphus

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    David eGonzález-Barrio

    2015-12-01

    Full Text Available Several aspects of the dynamics of Coxiella burnetii that are relevant for the implementation of control strategies in ruminant herds with endemic Q-fever are unknown. We designed a longitudinal study to monitor the dynamics of exposure to C. burnetii in a red deer herd with endemic infection in order to allow the design of Q fever specific control approaches. Other relevant aspects of the dynamics of C. burnetii - the effect of herd immune status, age, season and early infection on exposure, the average half-life of antibodies, the presence and duration of maternal humoral immunity and the age of first exposure - were analysed. The dynamics of C. burnetii in deer herds seems to be modulated by host herd and host individual factors and by particular host life history traits. Red deer females become exposed to C. burnetii at the beginning of their second year since maternal antibodies protect them after birth and during the main pathogen shedding season - at the end of spring-early summer. Infection pressure varies between years, probably associated to herd immunity effects, determining inter-annual variation in the risk of exposure. These results suggest that any strategy applied to control C. burnetii in deer herds should be designed to induce immunity in their first year of life immediately after losing maternal antibodies. The short average life of C. burnetii antibodies suggests that any protection based upon humoral immunity would require re-vaccination every 6 months.

  15. Proteomic and systems biology analysis of the monocyte response to Coxiella burnetii infection.

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    Matt Shipman

    Full Text Available Coxiella burnetii is an obligate intracellular bacterial pathogen and the causative agent of Q fever. Chronic Q fever can produce debilitating fatigue and C. burnetii is considered a significant bioterror threat. C. burnetii occupies the monocyte phagolysosome and although prior work has explained features of the host-pathogen interaction, many aspects are still poorly understood. We have conducted a proteomic investigation of human Monomac I cells infected with the Nine Mile Phase II strain of C. burnetii and used the results as a framework for a systems biology model of the host response. Our principal methodology was multiplex differential 2D gel electrophoresis using ZDyes, a new generation of covalently linked fluorescent protein detection dyes under development at Montana State University. The 2D gel analysis facilitated the detection of changes in posttranslational modifications on intact proteins in response to infection. The systems model created from our data a framework for the design of experiments to seek a deeper understanding of the host-pathogen interactions.

  16. Prevalence of Coxiella burnetii in cattle at South Korean national breeding stock farms.

    Science.gov (United States)

    Seo, Min-Goo; Ouh, In-Ohk; Lee, Seung-Hun; Kim, Jong Wan; Rhee, Man Hee; Kwon, Oh-Deog; Kim, Tae-Hwan; Kwak, Dongmi

    2017-01-01

    This is the first study to evaluate the serologic and molecular prevalence of Coxiella burnetii in cattle at national breeding stock farms in South Korea. These government farms have well-organized biosecurity and management systems to prevent livestock diseases. Of the 736 cattle in this study, 77 tested positive for antibodies against C. burnetii antigens (10.5%, 95% CI: 8.3-12.7) and 11 were positive for a C. burnetti infection on PCR analysis (1.5%, 95% CI: 0.6-2.4). Since the 16S rRNA sequences of C. burnetii from all 11 PCR-positive samples were identical, three representative samples (C-CN-3 from the southern region, C-JJ-9 from Jeju Island, and C-CB-37 from the central region) are described in this paper. These three sequences had 99.3-100% identity to those of C. burnetii deposited in GenBank. These sequences clustered with those from USA, Japan, and Greenland, underscoring the sequence similarity among C. burnetii isolates in these countries. Because C. burnetii was detected in cattle at well-managed national breeding stock farms, cattle at non-government operated farms may be more likely to be exposed to C. burnetii in South Korea. Thus, continuous surveillance and control strategies in animals and humans are required to prevent the transmission of C. burnetii to humans.

  17. The potential utility of nested PCR for investigation of Coxiella burnetii in Iranian snails

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    Mina Dehghani-Samani

    2016-03-01

    Full Text Available Objective: To detect the prevalence of Coxiella burnetii (C. burnetii in two species of snails consisted of Lymnaea palustris (L. palustris and Pomacea canaliculata (P. canaliculata by using nested PCR method in Chaharmahel Va Bakhtiari Province which is located in the southwest of Iran. Methods: A total of 160 snail samples consisted of 100 L. palustris and 60 P. canaliculata were collected from 4 rice paddy fields in the southwest of Iran between June and August 2014. Snails' DNA was extracted by a genomic DNA purification kit according to the manufacturer's instructions. Detection of the presence of C. burnetii's DNA was carried out by using a nested PCR assay with [specific primers outer membrane protein 1 (OMP1-OMP2 and OMP3-OMP4] targeting the com1 gene. Results: In this study, a total of 160 snail samples were tested and 15 (9.37% samples were found positive for C. burnetii, 15 samples were positive from the L. palustris and there were no positive samples from P. canaliculata. Conclusions: Snails are kind of gastropods which seem to be harmless in life, but these small gastropods can be very dangerous for farmers, especially in humid climates. Also, C. burnetii in snails showed that this bacterium can be a factor of transmission of contamination to human beings and animals.

  18. In Vitro and In Vivo Infectious Potential of Coxiella burnetii: A Study on Belgian Livestock Isolates

    Science.gov (United States)

    Mori, Marcella; Boarbi, Samira; Michel, Patrick; Bakinahe, Raïssa; Rits, Katleen; Wattiau, Pierre; Fretin, David

    2013-01-01

    Q-fever is a zoonosis caused by the gram-negative obligate intracellular pathogen Coxiella burnetii. Since its discovery, and particularly following the recent outbreaks in the Netherlands, C. burnetii appeared as a clear public health concern. In the present study, the infectious potential displayed by goat and cattle isolates of C. burnetii was compared to a reference strain (Nine Mile) using both in vitro (human HeLa and bovine macrophage cells) and in vivo (BALB/c mice) models. The isolates had distant genomic profiles with one - the goat isolate - being identical to the predominant strain circulating in the Netherlands during the 2007–2010 outbreaks. Infective doses were established with ethidium monoazide-PCR for the first time here applied to C. burnetii. This method allowed for the preparation of reproducible and characterized inocula thanks to its capacity to discriminate between live and dead cells. Globally, the proliferative capacity of the Nine Mile strain in cell lines and mice was higher compared to the newly isolated field strains. In vitro, the bovine C. burnetii isolate multiplied faster in a bovine macrophage cell line, an observation tentatively explained by the preferential specificity of this strain for allogeneic host cells. In the BALB/c mouse model, however, the goat and bovine isolates multiplied at about the same rate indicating no peculiar hypervirulent behavior in this animal model. PMID:23840751

  19. Type III-IV muscle afferents are not required for steady-state exercise hyperpnea in healthy subjects and patients with COPD or heart failure.

    Science.gov (United States)

    Poon, Chi-Sang; Song, Gang

    2015-09-15

    Blockade of group III-IV muscle afferents by intrathecal injection of the μ-opioid agonist fentanyl (IF) in humans has been variously reported to depress exercise hyperpnea in some studies but not others. A key unanswered question is whether such an effect is transient or persists in the steady state. Here we show that in healthy subjects undergoing constant-load cycling exercise IF significantly slows the transient exercise ventilatory kinetics but has no discernible effect on the ventilatory response when exercise is sufficiently prolonged. Thus, the ventilatory response to group III-IV muscle afferents input in healthy subjects is not a simple reflex but acts like a high-pass filter with maximum sensitivity during early-phase exercise and is reset in the late phase. In patients with chronic heart failure (CHF) IF causes sustained CO2 retention not only during exercise but also in the resting state, where muscle afferents feedback is minimal. In patients with chronic obstructive pulmonary disease (COPD), IF also elicits sustained decreases in the exercise ventilatory response but with little or no resultant CO2 retention due to concomitant decreases in physiological VD/VT (dead space-to-ventilation ratio). These results support the proposition that optimal long-term regulation of exercise hyperpnea in health and in disease is determined centrally by the respiratory controller through the continuing adaptation of an internal model which dynamically tracks the metabolic CO2 load and the ventilatory inefficiency 1/1-VD/VT that must be overcome for the maintenance of arterial PCO2 homeostasis, rather than being reflexively driven by group III-IV muscle afferents feedback per se. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. IV treatment at home

    Science.gov (United States)

    ... Other IV treatments you may receive after you leave the hospital include: Treatment for hormone deficiencies Medicines for severe nausea that cancer chemotherapy or pregnancy may cause Patient-controlled analgesia (PCA) for pain (this is IV ...

  1. Múltiplos carcinomas basocelulares na região pubiana em uma paciente fototipo IV: relato de caso Multiple basal cell carcinomas in the pubic area in a patient with skin type IV: case report

    Directory of Open Access Journals (Sweden)

    Cristiani Banhos Ferreira

    2011-06-01

    Full Text Available O carcinoma basocelular é a neoplasia maligna cutânea mais comum em humanos, localizando-se, frequentemente, em áreas expostas e em indivíduos de pele clara. Relata-se o caso de uma paciente de 62 anos, faiodérmica, com múltiplas lesões de bordas discretamente elevadas, eritemato-acastanhadas na região pubiana, cujo diagnóstico clínico foi carcinoma basocelular pigmentado, confirmado através do estudo histopatológico. A imunoistoquímica das lesões foi negativa para a pesquisa de papiloma vírusBasal cell carcinoma is the most common type of malignant cutaneous neoplasm in humans, being more frequently located in exposed areas and in fair-skinned individuals. It is reported the case of a 62-yearold female patient, brown-skinned ,with multiple lesions with edges slightly raised, reddish-brown in the pubic region, whose clinical diagnosis was pigmented basal cell carcinoma, confirmed by histopathology. Immunohistochemistry of the lesions was negative for the detection of papilloma virus

  2. Characterization of a novel arginine catabolic mobile element (ACME) and staphylococcal chromosomal cassette mec composite island with significant homology to Staphylococcus epidermidis ACME type II in methicillin-resistant Staphylococcus aureus genotype ST22-MRSA-IV.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2011-05-01

    The arginine catabolic mobile element (ACME) is prevalent among methicillin-resistant Staphylococcus aureus (MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassette mec (SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7\\/23, 30%) or MRSA genotype ST22-MRSA-IV (16\\/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassette mec (SCCmec) composite island (ACME\\/SCCmec-CI) in ST22-MRSA-IVh isolates (n=15). This ACME\\/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec type I, and a complete SCCmec type IVh element. The composite island has a novel genetic organization, with ACME located within orfX and SCCmec located downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec type IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

  3. Early Diagnosis and Treatment of Coronary Heart Disease in Asymptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound) and Risk Factors.

    Science.gov (United States)

    Adams, Ansgar; Bojara, Waldemar; Schunk, Klaus

    2018-02-01

    A study was conducted as to whether the early diagnosis of coronary heart disease in asymptomatic subjects with advanced atherosclerosis of the carotid artery which additionally shows at least one risk factor is successful using ultrasound technology. Within the scope of an occupational screening program using subjects from diverse employment sectors, people were given the opportunity to determine their risk of heart attack. During the study the total plaque area (TPA), the maximum plaque thickness in the carotid artery and the PROCAM-Scores of 3,748 healthy men and 2,260 healthy women between the ages of 20 and 64 years were determined. During the subsequent follow-up study 94 subjects sickened. An ultrasound examination of the carotid artery of 79 patients revealed a type III or IV b finding. In a pilot study 33 asymptomatic subjects with a type III or IV b finding in the ultrasound examination were assessed using a computed tomography (CT) coronary angiogram. Additional 10 asymptomatic subjects were examined independently to undergo further cardiac examinations. In the final analysis only five patients had entirely smooth coronary arteries, six had coronary sclerosis, eight had a 30% stenosis, one had a 30-50% stenosis and 23 patients had a stenosis ≥ 50%; and in extreme case, a left main coronary artery stenosis with three-vessel disease. Asymptomatic subjects with advanced atherosclerosis of the carotid artery (type III and type IV b findings) had a high risk for coronary heart disease (CHD). Early treatment of the disease improves the patient's prognosis. A screening consisting in the combination of TPA measurement and determining the maximum plaque thickness is recommended.

  4. Crystallization and preliminary X-ray analysis of the type IV restriction endonuclease ScoMcrA from Streptomyces coelicolor, which cleaves both Dcm-methylated DNA and phosphorothioated DNA.

    Science.gov (United States)

    Liu, Guang; Zhang, Zhenyi; Zhao, Gong; Deng, Zixin; Wu, Geng; He, Xinyi

    2015-01-01

    ScoMcrA is a type IV modification-dependent restriction endonuclease found in the model strain Streptomyces coelicolor. Unlike type I, II and III restriction endonucleases, which cleave unmodified DNA, type IV restriction endonucleases cleave modified DNA, including methylated, hydroxymethylated, glucosyl-hydroxymethylated and phosphorothioated DNA. ScoMcrA targets both Dcm-methylated DNA and phosphorothioated DNA, and makes double-strand breaks 16-28 nt away from the modified nucleotides or the phosphorothioate links. However, the mechanism by which ScoMcrA recognizes these two entirely different types of modification remains unclear. In this study, the ScoMcrA protein was overexpressed, purified and crystallized. The crystals diffracted to 3.35 Å resolution and belonged to space group P2(1)2(1)2(1). The unit-cell parameters were determined to be a=130.19, b=139.36, c=281.01 Å, α=β=γ=90°. These results will facilitate the detailed structural analysis of ScoMcrA and further elucidation of its biochemical mechanism.

  5. Development of Tools for Surveillance of Coxiella burnetii in Domestic Ruminants and Australian Marsupials and Their Waste

    Science.gov (United States)

    2009-06-12

    Guatteo, Beaudeau et al. 2006). Indeed, there is evidence that goats and cows preferentially shed in milk while ewes are more likely to shed in...that almost all aborted kids were PCR positive for Coxiella (Arricau Bouvery, Souriau et al. 2003). It has been hypothesised that there might be a...42 months in milk stored at 4–6°C and 12-16 months in wool stored at 4-6°C (PHAC 2001). The resistance of the metabolically active LCV is less

  6. In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetti inactivation and macrophage enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.S.; Kishimoto, R.A.; Canonico, P.G.

    1980-03-01

    The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (uv) light was studied. The effect of uv treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that uv treatment for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension or within guinea pig peritoneal macrophages. Similar uv treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients.

  7. Characterization of a Novel Arginine Catabolic Mobile Element (ACME) and Staphylococcal Chromosomal Cassette mec Composite Island with Significant Homology to Staphylococcus epidermidis ACME type II in Methicillin-Resistant Staphylococcus aureus Genotype ST22-MRSA-IV.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2011-02-22

    The arginine catabolic mobile element (ACME) is prevalent among ST8-MRSA-IVa (USA300) isolates and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME-positive, all were either MRSA genotype ST8-MRSA-IVa (7\\/23, 30%) or ST22-MRSA-IV (16\\/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and SCCmec composite island (ACME\\/SCCmec-CI) in ST22-MRSA-IVh isolates (n = 15). This ACME\\/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec I and a complete SCCmec IVh element. The composite island has a novel genetic organization with ACME located within orfX and SCCmec located downstream of ACME. One pvl-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec IVa as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

  8. Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique.

    Science.gov (United States)

    Huynh, Thien J; Morton, Ryan P; Levitt, Michael R; Ghodke, Basavaraj V; Wink, Onno; Hallam, Danial K

    2017-08-18

    We report successful transvenous treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture. 2017 BMJ Publishing Group Ltd.

  9. The Effect of Wind on Coxiella burnetii Transmission Between Cattle Herds: a Mechanistic Approach.

    Science.gov (United States)

    Nusinovici, S; Hoch, T; Brahim, M L; Joly, A; Beaudeau, F

    2017-04-01

    There is a consensus that wind plays a key role in the transmission of Coxiella burnetii, the causative agent of Q fever, between ruminants and from ruminants to humans. However, no observational study so far has focused on the mechanisms associated with this airborne transmission. This study applied a mechanistic epidemiological approach to investigate the processes underlying the wind effect and to assess its influence on the risk for a dairy herd to become C. burnetii infected. Ninety-five dairy cattle herds located in the Finistère department (western France) were subjected to samplings of bulk tank milk and indoor dust every 4 months over a 1-year period to determine their C. burnetii status using PCR tests. A total of 27 incident herd-periods (negative-tested on both PCR tests and becoming positive-tested at least once at the subsequent sampling time) and 71 negative herd-periods were retained for analysis. Using logistic regression, we assessed the effect of (i) the cumulated number of bacteria in herds located under the main wind direction and (ii) the mean wind speed in this area, on a given herd's risk of becoming incident. Compared to herds in areas with low wind speed (≤5.5 m/s), the risk was significantly higher (OR = 3.7) in herds in areas with high wind speed (>5.5 m/s) and high bacterial load (>10), whereas it was not significantly different from unity in other situations. In agreement with our assumptions, C. burnetii transmission to a previously infection-free herd occurs only when (i) the wind transporting from infected sources and (ii) the load in the contaminated particles/aerosols generated are high enough to act jointly. © 2015 Blackwell Verlag GmbH.

  10. Maternofetal consequences of Coxiella burnetii infection in pregnancy: a case series of two outbreaks

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    Boden Katharina

    2012-12-01

    Full Text Available Abstract Background A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of Coxiella burnetii infection contracted during pregnancy. Methods Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture. Results 11 pregnant women from Soest (screening rate: 49% and 82 pregnant women from Jena (screening rate: 27% participated in the outbreak investigation. 11 pregnant women with an acute C. burnetii infection were diagnosed. Three women had symptomatic disease. Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3, were treated with macrolides for three weeks (n=1 or after delivery (n=1, were given no treatment at all (n=2 or received antibiotics ineffective for Q fever (n=1. One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35th week and one child was born with syndactyly. We found no obvious association between C. burnetii infection and negative pregnancy outcome. Conclusions Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic C. burnetii infections and with chronic Q fever should be treated. The

  11. Prevalence of Coxiella burnetii in Hungary: screening of dairy cows, sheep, commercial milk samples, and ticks.

    Science.gov (United States)

    Gyuranecz, Miklós; Dénes, Béla; Hornok, Sándor; Kovács, Péter; Horváth, Gábor; Jurkovich, Viktor; Varga, Tamás; Hajtós, István; Szabó, Réka; Magyar, Tibor; Vass, Nóra; Hofmann-Lehmann, Regina; Erdélyi, Károly; Bhide, Mangesh; Dán, Ádám

    2012-08-01

    Q fever is an important zoonotic disease caused by Coxiella burnetii. There are few reliable data about C. burnetii infection available. The aim of this study was to assess the importance and potential infectious sources of Q fever in Hungary. A total of 215 milk samples (10 individual samples from each herd and 1 bulk tank milk sample from each cattle herd), and 400 serum samples (20 from each herd) were tested from 15 dairy cattle herds and 5 sheep flocks located in different parts of Hungary. The study found 19.3% (58/300) and 38.0% (57/150) seropositivity in cattle, and 0% (0/100) and 6.0% (3/50) seropositivity in sheep, by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), respectively. C. burnetii DNA was detected by IS1111 element-based TaqMan real-time polymerase chain reaction (PCR) in 8.7% (13/150) of individual dairy cow milk samples, 4.0% (2/50) of individual sheep milk samples, and 66.7% (10/15) of dairy bulk tank milk samples. Samples taken from nine different commercially-available pasteurized cow milk products from different Hungarian producers were also tested for the presence of C. burnetii DNA, and eight of these samples were found to be positive (88.9%). The real-time PCR examination of 5402 ixodid ticks collected from different parts of the country yielded negative results. Knowledge of the true prevalence of Q fever is crucial for policymakers involved in evidence-based decision making.

  12. A survey of Western Australian sheep, cattle and kangaroos to determine the prevalence of Coxiella burnetii.

    Science.gov (United States)

    Banazis, Michael Janis; Bestall, Abbey Simone; Reid, Simon Andrew; Fenwick, Stan Gordon

    2010-07-14

    The objective of this study was to investigate the prevalence of Coxiella burnetii in two domestic ruminant species (cattle and sheep) and the western grey kangaroo (Macropus fuliginosus) in Western Australia (WA). The IDEXX CHEKiT Q Fever ELISA and CFT were used to test sera from 50 sheep and 329 head of cattle for anti-C. burnetii antibodies and 343 kangaroo sera were tested using an indirect ELISA developed specifically for this study. Faecal or urine samples collected from the same animals were tested with two PCR assays to identify active shedding of C. burnetii in excreta. Only two of the 379 ruminant sera had detectable levels of anti-C. burnetii antibodies according to the ELISA while the CFT did not detect any positive samples. In contrast 115 of the 343 western grey kangaroo serum samples were positive when tested with the antibody-ELISA. The first qPCR assay, targeting the IS1111a element, identified 41 of 379 ruminant and 42 of 343 kangaroo DNA samples as positive for C. burnetii DNA. The second qPCR, targeting the JB153-3 gene, identified nine C. burnetii DNA-positive ruminant samples and six positive kangaroo samples. Sequence comparisons showed high degrees of identity with C. burnetii. Isolation of C. burnetii from faeces was also attempted but was not successful. From the results presented here it appears that domestic ruminants may not be the most significant reservoir of C. burnetii in WA and that kangaroos may pose a significant threat for zoonotic transfer of this pathogen. (c) 2009 Elsevier B.V. All rights reserved.

  13. Risk factors of Coxiella burnetii (Q fever) seropositivity in veterinary medicine students.

    Science.gov (United States)

    de Rooij, Myrna M T; Schimmer, Barbara; Versteeg, Bart; Schneeberger, Peter; Berends, Boyd R; Heederik, Dick; van der Hoek, Wim; Wouters, Inge M

    2012-01-01

    Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors. A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in The Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1:32 and above. Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction 'farm animals' (Odds Ratio (OR) 3.27 [95% CI 2.14-5.02]), advanced year of study (OR year 6: 2.31 [1.22-4.39] OR year 3-5 1.83 [1.07-3.10]) having had a zoonosis during the study (OR 1.74 [1.07-2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59-4.67]). Stratified analysis revealed study direction 'farm animals' to be a study-related risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity. C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factors were identified. This indicates Q fever as an occupational risk for veterinary medicine students.

  14. Physicochemical characterization of the endotoxins from Coxiella burnetii strain Priscilla in relation to their bioactivities

    Directory of Open Access Journals (Sweden)

    Hussein Ahmed

    2004-01-01

    Full Text Available Abstract Background Coxiella burnetii is the etiological agent of Q fever found worldwide. The microorganism has like other Gram-negative bacteria a lipopolysaccharide (LPS, endotoxin in its outer membrane, which is important for the pathogenicity of the bacteria. In order to understand the biological activity of LPS, a detailed physico-chemical analysis of LPS is of utmost importace. Results The lipid A moiety of LPS is tetraacylated and has longer (C-16 acyl chains than most other lipid A from enterobacterial strains. The two ester-linked 3-OH fatty acids found in the latter are lacking. The acyl chains of the C. burnetii endotoxins exhibit a broad melting range between 5 and 25°C for LPS and 10 and 40°C for lipid A. The lipid A moiety has a cubic inverted aggregate structure, and the inclination angle of the D-glucosamine disaccharide backbone plane of the lipid A part with respect to the membrane normal is around 40°. Furthermore, the endotoxins readily intercalate into phospholipid liposomes mediated by the lipopolysaccharide-binding protein (LBP. The endotoxin-induced tumor necrosis factor α (TNFα production in human mononuclear cells is one order of magnitude lower than that found for endotoxins from enterobacterial strains, whereas the same activity as in the latter compounds is found in the clotting reaction of the Limulus amebocyte lysate assay. Conclusions Despite a considerably different chemical primary structure of the C. burnetii lipid A in comparison with enterobacterial lipid A, the data can be well understood by applying the previously presented conformational concept of endotoxicity, a conical shape of the lipid A moiety of LPS and a sufficiently high inclination of the sugar backbone plane with respect to the membrane plane. Importantly, the role of the acyl chain fluidity in modulating endotoxicity now becomes more evident.

  15. Emergence of Coxiella burnetii in ruminants on Reunion Island? Prevalence and risk factors.

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    Eric Cardinale

    2014-08-01

    Full Text Available Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii, and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean. A cross-sectional study was undertaken from March 2011 to August 2012 to assess the Q fever prevalence and to identify the major risk factors of C. burnetii infection in ruminants. A total of 516 ruminants (245 cattle, 137 sheep and 134 goats belonging to 71 farms and localized in different ecosystems of the island were randomly selected. Samples of blood, vaginal mucus and milk were concomitantly collected from females, and a questionnaire was submitted to the farmers. Ticks from positively detected farms were also collected. The overall seropositivity was 11.8% in cattle, 1.4% in sheep and 13.4% in goats. C. burnetii DNA was detected by PCR in 0.81%, 4.4% and 20.1% in cow, sheep and goat vaginal swabs, respectively. C. burnetii shedding in milk was observed in 1% of cows, 0% in sheep and 4.7% in goats. None of the ticks were detected to be positive for C. burnetii. C. burnetii infection increased when the farm was exposed to prevailing winds and when there were no specific precautions for a visitor before entering the farm, and they decreased when a proper quarantine was set up for any introduction of a new ruminant and when the animals returned to the farm at night. MLVA genotyping confirmed the role of these risk factors in infection.

  16. Detection of Coxiella burnetii in ticks by PCR and by PCR - Restriction Fragment Length Polymorphism (RFLP)

    International Nuclear Information System (INIS)

    2010-01-01

    Coxiella burnetii, as an obligata intracellular bacterium, is the etiologic agent of Q-fever. It is widely distributed in nature and is responsible for infection in various animals (cattle, sheep, goat) and humans. C. burnetii has been isolated from milk, ticks and human patients with acute and chronic Q fever. Ticks are the principal vectors and reservoirs of C. burnetii. Since over 40 species of ticks have been found to be infected with C. burnetii, ticks can serve as indicators of infection in nature. In this study, total of 2472 ticks (1446 female, 1021 male and 5 nymphs) were collected from 38 provinces of Turkey. The ticks were gathered into groups of 1 to 7 ticks as to the provinces, species and gender for DNA extraction. Following DNA extraction, the groups were examined for the presence of C. burtii by using the CB1and CB2. The ticks collected from the province of Denizli (56 in total) were gathered into 13 groups according to the species and gender. From these groups, 6 were positive for C. burnetii. The ticks collected from Ankara province, total of 160 ticks, were grouped into 53 as to their species and gender, only one group was found to be positive for C. burnetii. The specificities of PCR products were evaluated by restriction analysis. The positive PCR products were digested with the enzyme Taq1 and for bands in order of 118, 57, 43 and 39 bp's were appeared such as seen in the positive control DNA (C. burnetii Nine Mile RSA493)

  17. Coxiella burnetii seroprevalence and associated risk factors in dairy and mixed cattle farms from Ecuador.

    Science.gov (United States)

    Carbonero, Alfonso; Guzmán, Lucía T; Montaño, Karen; Torralbo, Alicia; Arenas-Montes, Antonio; Saa, Luis R

    2015-03-01

    Q fever is a zoonotic disease caused by Coxiella burnetii, a bacterial agent for which ruminants are the main reservoir. An extensive cross-sectional study to determine the seroprevalence of and associated risk factors for Q fever was performed in dairy and mixed (dairy-beef) cattle herds in Ecuador. A total of 2668 serum samples from 386 herds were analyzed using an ELISA. In addition, a questionnaire with 57 variables related to management, feeding, facilities, biosecurity and animal health was completed for every cattle farm. A Generalized Estimating Equations model was used to determine the factors associated with C. burnetii seropositivity. The true prevalence of C. burnetii seropositivity in dairy and mixed cattle from Ecuador reached 12.6% (CI95%: 11.3-13.9%). The herd prevalence was 46.9% (181/386) (CI95%: 41.9-51.9%), and the within herd prevalence ranged between 8% and 100% (mean: 25.0%; Q1: 12.5%, Q2: 25.0%, Q3: 37.5%). Four factors were included in the GEE model for C. burnetii seropositivity: age of the cattle (OR: 1.01; CI95%: 1.006-1.014), feeding of calves with milk replacers (OR: 1.94; CI95%: 1.1-3.3), bovine respiratory syncytial virus seropositivity (OR: 1.54; CI95%: 1.1-2.3), and disinfection of the umbilical cord (OR: 0.60; CI95%: 0.4-0.9). Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Coxiella burnetii transcriptional analysis reveals serendipity clusters of regulation in intracellular bacteria.

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    Quentin Leroy

    Full Text Available Coxiella burnetii, the causative agent of the zoonotic disease Q fever, is mainly transmitted to humans through an aerosol route. A spore-like form allows C. burnetii to resist different environmental conditions. Because of this, analysis of the survival strategies used by this bacterium to adapt to new environmental conditions is critical for our understanding of C. burnetii pathogenicity. Here, we report the early transcriptional response of C. burnetii under temperature stresses. Our data show that C. burnetii exhibited minor changes in gene regulation under short exposure to heat or cold shock. While small differences were observed, C. burnetii seemed to respond similarly to cold and heat shock. The expression profiles obtained using microarrays produced in-house were confirmed by quantitative RT-PCR. Under temperature stresses, 190 genes were differentially expressed in at least one condition, with a fold change of up to 4. Globally, the differentially expressed genes in C. burnetii were associated with bacterial division, (pppGpp synthesis, wall and membrane biogenesis and, especially, lipopolysaccharide and peptidoglycan synthesis. These findings could be associated with growth arrest and witnessed transformation of the bacteria to a spore-like form. Unexpectedly, clusters of neighboring genes were differentially expressed. These clusters do not belong to operons or genetic networks; they have no evident associated functions and are not under the control of the same promoters. We also found undescribed but comparable clusters of regulation in previously reported transcriptomic analyses of intracellular bacteria, including Rickettsia sp. and Listeria monocytogenes. The transcriptomic patterns of C. burnetii observed under temperature stresses permits the recognition of unpredicted clusters of regulation for which the trigger mechanism remains unidentified but which may be the result of a new mechanism of epigenetic regulation.

  19. Persistence of Coxiella burnetii, the agent of Q fever, in murine adipose tissue.

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    Yassina Bechah

    Full Text Available Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the presence of C. burnetii several months after infection. C. burnetii was detected in abdominal, inguinal and dorsal adipose tissue 4 months post-infection, when no bacteria were detected in blood, liver, lungs and spleen, regardless of the inoculation route and independently of mouse strain. The transfer of abdominal adipose tissue from convalescent BALB/c mice to naïve immunodeficient mice resulted in the infection of the recipient animals. It is likely that C. burnetii infects adipocytes in vivo because bacteria were found in adipocytes within adipose tissue and replicated within in vitro-differentiated adipocytes. In addition, C. burnetii induced a specific transcriptional program in in-vivo and in vitro-differentiated adipocytes, which was enriched in categories associated with inflammatory response, hormone response and cytoskeleton. These changes may account for bacterial replication in in-vitro and chronic infection in-vivo. Adipose tissue may be the reservoir in which C. burnetii persists for prolonged periods after apparent clinical cure. The mouse model of C. burnetii infection may be used to understand the relapses of Q fever and provide new perspectives to the follow-up of patients.

  20. Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review.

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    Sky Vanderburg

    2014-04-01

    Full Text Available Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a "One Health" perspective to synthesize the published data and identify knowledge gaps.We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13% among cattle except for studies in Western and Middle Africa (18-55%. Small ruminant seroprevalence ranged from 11-33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10-32%. Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2-9% of febrile illness hospitalizations and 1-3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real

  1. Risk Factors of Coxiella burnetii (Q Fever) Seropositivity in Veterinary Medicine Students

    Science.gov (United States)

    de Rooij, Myrna M. T.; Schimmer, Barbara; Versteeg, Bart; Schneeberger, Peter; Berends, Boyd R.; Heederik, Dick; van der Hoek, Wim; Wouters, Inge M.

    2012-01-01

    Background Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors. Methods A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in the Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1∶32 and above. Results Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction ‘farm animals’ (Odds Ratio (OR) 3.27 [95% CI 2.14–5.02]), advanced year of study (OR year 6: 2.31 [1.22–4.39] OR year 3–5 1.83 [1.07–3.10]) having had a zoonosis during the study (OR 1.74 [1.07–2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59–4.67]). Stratified analysis revealed study direction ‘farm animals’ to be a study-related risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity. Conclusions C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factors were identified. This indicates Q fever as an occupational risk for veterinary medicine students. PMID:22363803

  2. Coxiella burnetii associated reproductive disorders in domestic animals-a critical review

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    Agerholm Jørgen S

    2013-02-01

    Full Text Available Abstract The bacterium Coxiella burnetii has been detected in the fetal membranes, birth fluids and vaginal mucus, as well as in the milk and other excretions of several domestic mammals. The finding of C. burnetii in association with abortion, parturition and in the postpartum period has led to the hypothesis that C. burnetii causes a range of reproductive diseases. This review critically evaluates the scientific basis for this hypothesis in domestic mammals. The review demonstrates a solid evidence for the association between C. burnetii infection and sporadic cases of abortion, premature delivery, stillbirth and weak offspring in cattle, sheep and goats. C. burnetii induced in-herd epidemics of this complete expression of reproductive failure have been reported for sheep and goats, but not for cattle. The single entities occur only as part of the complex and not as single events such as generally increased stillbirth rate. Studies show that C. burnetii initially infects the placenta and that subsequent spread to the fetus may occur either haematogenous or by the amniotic-oral route. The consequences for the equine, porcine, canine and feline conceptus remains to the elucidated but that infection of the conceptus may occur is documented for most species. There is no solid evidence to support a hypothesis of C. burnetii causing disorders such as subfertility, endometritis/metritis, or retained fetal membranes in any kind of domestic animal species. There is a strong need to validate non-pathology based methods such as polymerase chain reaction for their use in diagnostic and research in relation to establishing C. burnetii as the cause of abortion and to adapt an appropriate study design and include adequate control animals when linking epidemiological findings to C. burnetii or when evaluating effects of vaccination in production herds.

  3. A probably minor role for land-applied goat manure in the transmission of Coxiella burnetii to humans in the 2007–2010 Dutch Q fever outbreak

    NARCIS (Netherlands)

    Van den Brom, R.; Roest, H.J.; De Bruin, A.; Dercksen, D.; Santman-Berends, I.; Van der Hoek, W.; Dinkla, A.; Vellema, J.; Vellema, P.

    2015-01-01

    In 2007, Q fever started to become a major public health problem in the Netherlands, with small ruminants as most probable source. In order to reduce environmental contamination, control measures for manure were implemented because of the assumption that manure was highly contaminated with Coxiella

  4. A Probably Minor Role for Land-Applied Goat Manure in the Transmission of Coxiella burnetii to Humans in the 2007-2010 Dutch Q Fever Outbreak

    NARCIS (Netherlands)

    Brom, Van den R.; Roest, H.I.J.; Bruin, de Arnout; Dercksen, D.; Santman-Berends, I.M.G.A.; Hoek, van der Wim; Dinkla, A.; Vellema, Jelmer; Vellema, P.

    2015-01-01

    In 2007, Q fever started to become a major public health problem in the Netherlands, with small ruminants as most probable source. In order to reduce environmental contamination, control measures for manure were implemented because of the assumption that manure was highly contaminated with Coxiella

  5. Use of a Dose-Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii : Analysis of a Multiyear Outbreak of Q Fever

    NARCIS (Netherlands)

    Brooke, R J; Teunis, P F M; Kretzschmar, M E E; Wielders, C C H; Schneeberger, P M; Waller, L A

    The Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of

  6. Culture-independent genome sequencing of Coxiella burnetii from a native heart valve of a Tunisian patient with severe infective endocarditis

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    J. Delaloye

    2018-01-01

    Full Text Available We report draft genome of a Coxiella burnetii strain sequenced from the native valve of a patient presenting with severe endocarditis in Tunisia. The genome could be sequenced without a cellular or axenic culture step. The MST5 strain was demonstrated to be closely related to the published reference genome of C. burnetii CbuK_Q154.

  7. Detection of Coxiella burnetii DNA on Small-Ruminant Farms during a Q Fever Outbreak in the Netherlands

    Science.gov (United States)

    van der Plaats, R. Q. J.; de Heer, L.; Paauwe, R.; Schimmer, B.; Vellema, P.; van Rotterdam, B. J.; van Duynhoven, Y. T. H. P.

    2012-01-01

    During large Q fever outbreaks in the Netherlands between 2007 and 2010, dairy goat farms were implicated as the primary source of human Q fever. The transmission of Coxiella burnetii to humans is thought to occur primarily via aerosols, although available data on C. burnetii in aerosols and other environmental matrices are limited. During the outbreak of 2009, 19 dairy goat farms and one dairy sheep farm were selected nationwide to investigate the presence of C. burnetii DNA in vaginal swabs, manure, surface area swabs, milk unit filters, and aerosols. Four of these farms had a positive status during the Coxiella burnetii bulk milk monitoring program in 2009 and additionally reported abortion waves in 2008 or 2009. Eleven farms were reported as having positive bulk milk only, and five selected (control) farms had a bulk milk-negative status in 2009 and no reported Q fever history. Screening by quantitative PCR (qPCR) revealed that on farms with a history of abortions related to C. burnetii and, to a lesser extent, on farms positive by bulk milk monitoring, generally higher proportions of positive samples and higher levels of C. burnetii DNA within positive samples were observed than on the control farms. The relatively high levels of C. burnetii DNA in surface area swabs and aerosols sampled in stables of bulk milk-positive farms, including farms with a Q fever-related abortion history, support the hypothesis that these farms can pose a risk for the transmission of C. burnetii to humans. PMID:22247143

  8. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Science.gov (United States)

    Clements, Karen M.; Peltz, Gerson; Faries, Douglas E.; Lang, Kathleen; Nyambose, Joshua; Earle, Craig C.; Sugarman, Katherine P.; Taylor, Douglas C. A.; Thompson, David; Marciniak, Martin D.

    2010-01-01

    Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC. PMID:22482053

  9. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Karen M. Clements

    2010-01-01

    Full Text Available Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC. We examined the impact of histology on survival of patients (N=2,644 with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G and cisplatin/carboplatin plus a taxane (C/C+T identified retrospectively in the SEER cancer registry (1997–2002. Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P=.018. No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction =.257. There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.

  10. In vitro effects of bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), or VO(dmpp)2, on insulin secretion in pancreatic islets of type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Pelletier, Julien; Domingues, Neuza; Castro, M Margarida C A; Östenson, Claes-Göran

    2016-01-01

    Vanadium compounds have been explored as therapy of diabetes, and most studies have focussed on insulin mimetic effects, i.e. reducing hyperglycemia by improving glucose sensitivity and thus glucose uptake in sensitive tissues. We have recently shown that bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has promising effects when compared to another vanadium compound, bis(maltolato)oxidovanadium(IV), BMOV, and insulin itself, in isolated adipocytes and in vivo in Goto-Kakizaki (GK) rats, an animal model of hereditary type 2 diabetes (T2D).We now have investigated in GK rats whether VO(dmpp)2 also modulates another important defect in T2D, impaired insulin secretion. VO(dmpp)2, but not BMOV, stimulated insulin secretion from isolated GK rat pancreatic islets at high, 16.7mM, but not at low–normal, 3.3 mM, glucose concentration. Mechanistic studies demonstrate that the insulin releasing effect of VO(dmpp)2 is due to its interaction with several steps in the stimulus-secretion coupling for glucose, including islet glucose metabolism and K-ATP channels, L-type Ca2+ channels, modulation by protein kinases A and C, as well as the exocytotic machinery. In conclusion, VO(dmpp)2 exhibits properties of interest for treatment of the insulin secretory defect in T2D, in addition to its well-described insulin mimetic activity.

  11. Microevolution of the chromosomal region of acute disease antigen A (adaA in the query (Q fever agent Coxiella burnetii.

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    Dimitrios Frangoulidis

    Full Text Available The acute disease antigen A (adaA gene is believed to be associated with Coxiella burnetii strains causing acute Q fever. The detailed analysis of the adaA genomic region of 23 human- and 86 animal-derived C. burnetii isolates presented in this study reveals a much more polymorphic appearance and distribution of the adaA gene, resulting in a classification of C. burnetii strains of better differentiation than previously anticipated. Three different genomic variants of the adaA gene were identified which could be detected in isolates from acute and chronic patients, rendering the association of adaA positive strains with acute Q fever disease disputable. In addition, all adaA positive strains in humans and animals showed the occurrence of the QpH1 plasmid. All adaA positive isolates of acute human patients except one showed a distinct SNP variation at position 431, also predominant in sheep strains, which correlates well with the observation that sheep are a major source of human infection. Furthermore, the phylogenetic analysis of the adaA gene revealed three deletion events and supported the hypothesis that strain Dugway 5J108-111 might be the ancestor of all known C. burnetii strains. Based on our findings, we could confirm the QpDV group and we were able to define a new genotypic cluster. The adaA gene polymorphisms shown here improve molecular typing of Q fever, and give new insights into microevolutionary adaption processes in C. burnetii.

  12. Silicon(IV) phthalocyanines substituted axially with different nucleoside moieties. Effects of nucleoside type on the photosensitizing efficiencies and in vitro photodynamic activities.

    Science.gov (United States)

    Zheng, Bi-Yuan; Shen, Xiao-Min; Zhao, Dong-Mei; Cai, Yi-Bin; Ke, Mei-Rong; Huang, Jian-Dong

    2016-06-01

    A series of new silicon(IV) phthalocyanines (SiPcs) di-substituted axially with different nucleoside moieties have been synthesized and evaluated for their singlet oxygen quantum yields (ΦΔ) and in vitro photodynamic activities. The adenosine-substituted SiPc shows a lower photosensitizing efficiency (ΦΔ=0.35) than the uridine- and cytidine-substituted analogs (ΦΔ=0.42-0.44), while the guanosine-substituted SiPc exhibits a weakest singlet oxygen generation efficiency with a ΦΔ value down to 0.03. On the other hand, replacing axial adenosines with chloro-modified adenosines and purines can result in the increase of photogenerating singlet oxygen efficiencies of SiPcs. The formed SiPcs 1 and 2, which contain monochloro-modified adenosines and dichloro-modified purines respectively, appear as efficient photosensitizers with ΦΔ of 0.42-0.44. Both compounds 1 and 2 present high photocytotoxicities against HepG2 and BGC823 cancer cells with IC50 values ranging from 9nM to 33nM. The photocytotoxicities of these two compounds are remarkably higher than the well-known anticancer photosensitizer, chlorin e6 (IC50=752nM against HepG2 cells) in the same condition. As revealed by confocal microscopy, for both cell lines, compound 1 can essentially bind to mitochondria, while compound 2 is just partially localized in mitochondria. In addition, the two compounds induce cell death of HepG2 cells likely through apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Predominance of Three Closely Related Methicillin-Resistant Staphylococcus aureus Clones Carrying a Unique ccrC-Positive SCCmec type III and the Emergence of spa t304 and t690 SCCmec type IV pvl+MRSA Isolates in Kinta Valley, Malaysia.

    Science.gov (United States)

    Ho, Wai-Yew; Choo, Quok-Cheong; Chew, Choy-Hoong

    2017-03-01

    We investigated the epidemiology and clonality of 175 nonrepetitive methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical specimens collected between 2011 and 2012 in Kinta Valley in Malaysia. Molecular tools such as polymerase chain reaction, pulsed-field gel electrophoresis, and staphylococcal protein A (spa) typing were used. Our study revealed the predominance of three closely related ermA + SCCmec type III pulsotypes belonging to spa type t037 (Brazilian-Hungarian clone), which were deficient in the locus F, but positive for the ccrC gene in majority (65.7%) of the MRSA infections in this region. The first evidence of SCCmec type II MRSA in the country, belonging to spa type t2460, was also noted. Although the carriage of pvl gene was uncommon (8.6%) and mostly confined to either SCCmec type IV or SCCmec type V isolates, most of these isolates belonged to spa types t345 or t657, which are associated with the Bengal-Bay CA-MRSA clone. Interestingly, spa t304 and t690 SCCmec type IV pvl + were also detected among the MRSA isolates. Data from this study show the rise of uncommon clones among MRSA isolates in Malaysia.

  14. SDSS-IV MaNGA: Probing the Kinematic Morphology–Density Relation of Early-type Galaxies with MaNGA

    Science.gov (United States)

    Greene, J. E.; Leauthaud, A.; Emsellem, E.; Goddard, D.; Ge, J.; Andrews, B. H.; Brinkman, J.; Brownstein, J. R.; Greco, J.; Law, D.; Lin, Y.-T.; Masters, K. L.; Merrifield, M.; More, S.; Okabe, N.; Schneider, D. P.; Thomas, D.; Wake, D. A.; Yan, R.; Drory, N.

    2017-12-01

    The “kinematic” morphology–density relation for early-type galaxies posits that those galaxies with low angular momentum are preferentially found in the highest-density regions of the universe. We use a large sample of galaxy groups with halo masses {10}12.5MaNGA) survey to examine whether there is a correlation between local environment and rotational support that is independent of stellar mass. We find no compelling evidence for a relationship between the angular momentum content of early-type galaxies and either local overdensity or radial position within the group at fixed stellar mass.

  15. Stark Broadening of Se IV, Sn IV, Sb IV and Te IV Spectral Lines

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    Milan S. Dimitrijević

    2018-03-01

    Full Text Available Stark broadening parameters, line width and shift, are needed for investigations, analysis and modelling of astrophysical, laboratory, laser produced and technological plasmas. Especially in astrophysics, due to constantly increasing resolution of satellite borne spectrographs, and large terrestrial telescopes, data on trace elements, which were previously insignificant, now have increasing importance. Using the modified semiempirical method of Dimitrijević and Konjević, here, Stark widths have been calculated for 2 Se IV, 6 Sn IV, 2 Sb IV and 1 Te IV transitions. Results have been compared with existing theoretical data for Sn IV. Obtained results will be implemented in the STARK-B database, which is also a part of Virtual atomic and molecular data center (VAMDC.

  16. Q Fever (Coxiella burnetii) Knowledge and Attitudes of Australian Cat Breeders and Their Husbandry Practices.

    Science.gov (United States)

    Shapiro, A J; Norris, J M; Bosward, K L; Heller, J

    2017-06-01

    A Q fever outbreak in a small animal veterinary hospital, associated with a cat caesarean section, initiated a cat seroprevalence study (n = 712) that found circulating antibodies to Coxiella burnetii was highest in cattery-confined breeding cats (9.3%). These findings stimulated interest about potential sources of C. burnetii infection for cats and humans associated with cats. Cat breeders are potentially a group at increased risk of C. burnetii infection, and this study sought to identify potential risk factors. A cross-sectional online survey was conducted targeting all domestic cat breeders registered with an affiliate member body in Australia in 2015. Responses from 177 cat breeders across Australia were analysed. Forty per cent of responding cat breeders had not heard of Q fever. Raw meat was fed as an integral constituent of the diet by 89% of respondents. Eighty per cent of respondents allowed queens access to the home for parturition, and assistance of queens and resuscitation of kittens at the time of birth were reported by 97% of respondents. Respondents who perceived some level of exposure to Q fever through their breeding activities were three times less likely to perform mouth-to-snout resuscitation (OR 0.3 95% CI 0.1-0.9; P = 0.034) than those who did not perceive a risk of exposure. Similarly, respondents who perceived Q fever as a risk through breeding activities were close to eight times more likely to use personal protective equipment during parturition (OR 7.7 95% CI 1.5-39.9; P = 0.015) than those who did not. Husbandry practices of cat breeders that may increase the risk of C. burnetii transmission require further targeted investigations to assess the contribution of these risk factors to the acquisition of disease. Concurrent education forums are recommended to inform Australian cat breeders of the aetiopathogenesis of Q fever. © 2016 Blackwell Verlag GmbH.

  17. Coxiella burnetii Nine Mile II proteins modulate gene expression of monocytic host cells during infection

    Directory of Open Access Journals (Sweden)

    Shaw Edward I

    2010-09-01

    Full Text Available Abstract Background Coxiella burnetii is an intracellular bacterial pathogen that causes acute and chronic disease in humans. Bacterial replication occurs within enlarged parasitophorous vacuoles (PV of eukaryotic cells, the biogenesis and maintenance of which is dependent on C. burnetii protein synthesis. These observations suggest that C. burnetii actively subverts host cell processes, however little is known about the cellular biology mechanisms manipulated by the pathogen during infection. Here, we examined host cell gene expression changes specifically induced by C. burnetii proteins during infection. Results We have identified 36 host cell genes that are specifically regulated when de novo C. burnetii protein synthesis occurs during infection using comparative microarray analysis. Two parallel sets of infected and uninfected THP-1 cells were grown for 48 h followed by the addition of chloramphenicol (CAM to 10 μg/ml in one set. Total RNA was harvested at 72 hpi from all conditions, and microarrays performed using Phalanx Human OneArray™ slides. A total of 784 (mock treated and 901 (CAM treated THP-1 genes were up or down regulated ≥2 fold in the C. burnetii infected vs. uninfected cell sets, respectively. Comparisons between the complementary data sets (using >0 fold, eliminated the common gene expression changes. A stringent comparison (≥2 fold between the separate microarrays revealed 36 host cell genes modulated by C. burnetii protein synthesis. Ontological analysis of these genes identified the innate immune response, cell death and proliferation, vesicle trafficking and development, lipid homeostasis, and cytoskeletal organization as predominant cellular functions modulated by C. burnetii protein synthesis. Conclusions Collectively, these data indicate that C. burnetii proteins actively regulate the expression of specific host cell genes and pathways. This is in addition to host cell genes that respond to the presence of the

  18. Cortactin is involved in the entry of Coxiella burnetii into non-phagocytic cells.

    Directory of Open Access Journals (Sweden)

    Eliana M Rosales

    Full Text Available BACKGROUND: Cortactin is a key regulator of the actin cytoskeleton and is involved in pathogen-host cell interactions. Numerous pathogens exploit the phagocytic process and actin cytoskeleton to infect host cells. Coxiella burnetii, the etiologic agent of Q fever, is internalized by host cells through a molecular mechanism that is poorly understood. METHODOLOGY/PRINCIPAL FINDING: Here we analyzed the role of different cortactin motifs in the internalization of C. burnetii by non-phagocytic cells. C. burnetii internalization into HeLa cells was significantly reduced when the cells expressed GFP-cortactin W525K, which carries a mutation in the SH3 domain that renders the protein unable to bind targets such as N-WASP. However, internalization was unaffected when the cells expressed the W22A mutant, which has a mutation in the N-terminal acidic region that destroys the protein's ability to bind and activate Arp2/3. We also determined whether the phosphorylation status of cortactin is important for internalization. Expression of GFP-cortactin 3F, which lacks phosphorylatable tyrosines, significantly increased internalization of C. burnetii, while expression of GFP-cortactin 3D, a phosphotyrosine mimic, did not affect it. In contrast, expression of GFP-cortactin 2A, which lacks phosphorylatable serines, inhibited C. burnetii internalization, while expression of GFP-cortactin SD, a phosphoserine mimic, did not affect it. Interestingly, inhibitors of Src kinase and the MEK-ERK kinase pathway blocked internalization. In fact, both kinases reached maximal activity at 15 min of C. burnetii infection, after which activity decreased to basal levels. Despite the decrease in kinase activity, cortactin phosphorylation at Tyr421 reached a peak at 1 h of infection. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the SH3 domain of cortactin is implicated in C. burnetii entry into HeLa cells. Furthermore, cortactin phosphorylation at serine and dephosphorylation

  19. Bone Turnover Markers in Patients with Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes during Oral Glucose and Isoglycemic iv Glucose

    DEFF Research Database (Denmark)

    Maagensen, Henrik; Junker, Anders E; Jørgensen, Niklas R

    2018-01-01

    Context: Non-alcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes (T2D) and vice versa, and both conditions are associated with an increased risk of fractures and altered bone turnover. While NAFLD patients typically suffer from decreased bone mineral density (BMD), T2D...... is associated with normal to high BMD. The pathophysiology is uncertain, but may involve the gut-bone axis. Objective: We investigated the influence of the gut on glucose-induced changes in plasma bone turnover markers in healthy controls and patients with T2D and/or biopsy-verified NAFLD. Design: Cross-sectional...... cohort study. Patients: NAFLD patients with normal glucose tolerance, NAFLD patients with T2D, T2D patients without liver disease and healthy controls. Interventions: 4-hour 50g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI). Main Outcome Measures: Collagen type...

  20. X-linked Alport syndrome associated with a synonymous p.Gly292Gly mutation alters the splicing donor site of the type IV collagen alpha chain 5 gene.

    Science.gov (United States)

    Fu, Xue Jun; Nozu, Kandai; Eguchi, Aya; Nozu, Yoshimi; Morisada, Naoya; Shono, Akemi; Taniguchi-Ikeda, Mariko; Shima, Yuko; Nakanishi, Koichi; Vorechovsky, Igor; Iijima, Kazumoto

    2016-10-01

    X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the type IV collagen alpha chain 5 gene (COL4A5). Although many COL4A5 mutations have previously been identified, pathogenic synonymous mutations have not yet been described. A family with XLAS underwent mutational analyses of COL4A5 by PCR and direct sequencing, as well as transcript analysis of potential splice site mutations. In silico analysis was also conducted to predict the disruption of splicing factor binding sites. Immunohistochemistry (IHC) of kidney biopsies was used to detect α2 and α5 chain expression. We identified a hemizygous point mutation, c.876A>T, in exon 15 of COL4A5 in the proband and his brother, which is predicted to result in a synonymous amino acid change, p.(Gly292Gly). Transcript analysis showed that this mutation potentially altered splicing because it disrupted the splicing factor binding site. The kidney biopsy of the proband showed lamellation of the glomerular basement membrane (GBM), while IHC revealed negative α5(IV) staining in the GBM and Bowman's capsule, which is typical of XLAS. This is the first report of a synonymous COL4A5 substitution being responsible for XLAS. Our findings suggest that transcript analysis should be conducted for the future correct assessment of silent mutations.

  1. Dipeptidyl peptidase IV inhibitory activity of protein hydrolyzates ...

    African Journals Online (AJOL)

    Background: Type 2 diabetes is a chronic metabolic disorder. Recently, dipeptidyl peptidase IV (DPP-IV) inhibitors that protect incretin hormones from being cleaved by DPP-IV have been used as drugs to control glycemia. This study examined the potential hypoglycemic effect of amaranth grain storage protein hydrolyzates ...

  2. Traveling-wave solutions of a modified Hodgkin-Huxley type neural model via Novel analytical results for nonlinear transmission lines with arbitrary I(V) characteristics

    OpenAIRE

    Valentino Anthony Simpao

    2000-01-01

    Herein an enhanced Hodgkin-Huxley (H-H) type model of neuron dynamics is solved analytically via formal methods. Our model is a variant of an earlier one by M.A. Mahrous and H.Y. Alkahby [1]. Their modified model is realized by a hyperbolic quasi-linear diffusion operator with time-delay parameters; this compared to the original H-H model with standard parabolic quasi-linear diffusion operator and no time-delay parameters. Besides these features, the present model also incorporates terms desc...

  3. Methicillin-resistant Staphylococcus aureus in Rio de Janeiro hospitals: dissemination of the USA400/ST1 and USA800/ST5 SCCmec type IV and USA100/ST5 SCCmec type II lineages in a public institution and polyclonal presence in a private one.

    Science.gov (United States)

    Caboclo, Roberta Mello Ferreira; Cavalcante, Fernanda Sampaio; Iorio, Natalia Lopes Pontes; Schuenck, Ricardo Pinto; Olendzki, André Nogueira; Felix, Maria José; Chamon, Raiane Cardoso; dos Santos, Kátia Regina Netto

    2013-03-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections have changed since certain non-multiresistant MRSA lineages have emerged in hospitals. In this study, 99 MRSA isolates, 77 from a public and 22 from a private hospital, were characterized. Isolates were tested for antimicrobial susceptibility, whereas staphylococcal chromosomal cassette mec (SCCmec) typing and Panton-Valentine leukocidin genes were assessed by polymerase chain reaction. Pulsed-field gel electrophoresis and multilocus sequence typing analyses were carried out to determine the MRSA lineages. High rates of resistance were found to erythromycin (96%), ciprofloxacin (93%), and clindamycin (90%). The SCCmec types found were as follows: type II (14.2%), III (62.6%), and IV (23.2%). Approximately 85% of type III isolates was related to the Brazilian epidemic clone in both hospitals. For type IV isolates, 94.4% were related to both USA400/ sequence type (ST) 1 and USA800/ST5 lineages in the public hospital, whereas the USA400/ST1, USA800/ST5, USA1100/ST30, and EMRSA (Epidemic MRSA)-15/ST22 lineages were detected in the private hospital. Among the SCCmec II isolates, approximately 85% were related to the USA100/ST5 lineage. Three MRSA isolates were positive to Panton-Valentine leukocidin genes. The study showed that there was an emergence of USA400/ST1, USA800/ST5 SCCmec IV, and USA100/ST5 SCCmec II MRSA lineages in both hospitals. There was a dissemination of them in the public hospital and a polyclonal presence of the MRSA isolates in the private hospital. The spread of these lineages can be facilitated by the characteristics of the health institution. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  4. Detection of Coxiella burnetii in Aborted Fetuses of Cattle and Sheep Using Polymerase Chain Reaction Assay in Mashhad City, Iran

    Directory of Open Access Journals (Sweden)

    Zeinab Abiri

    2016-02-01

    Full Text Available Background: Coxiella burnetii is an important intracellular pathogen that ruminants can act as primary reservoirs. Reservoirs may excrete the bacterium into the placenta, vaginal mucus and feces. Objectives: The aim of this study was to detect C. burnetii in aborted samples from ruminant flocks in Mashhad city, northeast of Iran, using the polymerase chain reaction (PCR assay. Materials and Methods: A total number of 154 fetal tissue samples of cattle, sheep and goat were subjected to nested PCR assay. Results: Sixteen (17.3% out of 92 samples from sheep and 15 (25% from 60 cattle fetuses were positive. Conclusions: The results of this study indicate the presence of C. burnetii in aborted ruminants and these can be the potential reservoirs of C. burnetii in the mentioned area.

  5. Association between antibodies to Coxiella burnetii in bulk tank milk and perinatal mortality of Danish dairy calves

    DEFF Research Database (Denmark)

    Nielsen, Katrine T.; Nielsen, Søren S.; Agger, Jens F.

    2011-01-01

    Background: Coxiella burnetii is a well-known cause of placentitis and subsequent abortion in ruminants, but there are no reports on the relationship with perinatal mortality. The study was performed to determine the influence of level and change of bulk tank milk (BTM) antibodies to C. burnetii...... on two outcomes associated with parturition in cattle: a) stillbirth; and b) stillbirth and neonatal mortality combined (perinatal death). Methods: Twenty-four Danish dairy herds were tested repeatedly for antibodies to C. burnetii in BTM using a commercial ELISA. Samples were collected monthly from July......, but not outside this period. Conclusion: We conclude that the level of antibodies to C. burnetii in BTM may be associated with perinatal mortality, but the association was not persistent and should be investigated further....

  6. Bayesian estimation of sensitivity and specificity of Coxiella burnetii antibody ELISA tests in bovine blood and milk

    DEFF Research Database (Denmark)

    Paul, Suman; Toft, Nils; Agerholm, Jørgen S.

    2013-01-01

    of the ELISA methods on milk and blood were equal at 0.99. No conditional dependence was observed between the specificity estimates of the two test methods. However, the sensitivity estimates of both tests were significantly reduced when conditional covariances ≥40 were used. Collection of milk samples from......Serological tests for Coxiella burnetii (the causative agent of Q fever) antibodies are usually based on enzyme linked immunosorbent assay (ELISA) although this method is not thoroughly evaluated. The objective of this study was to determine the sensitivity and specificity of an ELISA for detection...... of C. burnetii antibodies in milk and blood samples, using latent class models in a Bayesian analysis. Blood and milk samples of 568 lactating cows from 17 Danish dairy cattle herds collected in 2008 were used.The best combination of sensitivity and specificity estimates was revealed at a sample...

  7. Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial.

    Directory of Open Access Journals (Sweden)

    Linong Ji

    Full Text Available Differences exist between treatment recommendations regarding the choice of metformin as first-line therapy for type 2 diabetes patients according to body mass index (BMI. This study compared the efficacy of metformin monotherapy among normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes.In this prospective, multicenter, open-label study in China, patients aged 23-77 years were enrolled 1∶1:1 according to baseline BMI: normal-weight (BMI 18.5-23.9 kg/m(2; n = 125; overweight (BMI 24.0-27.9 kg/m(2; n = 122 or obese (BMI ≥28 kg/m(2; n = 124. Extended-release metformin was administered for 16 weeks (500 mg/day, up-titrated weekly to a maximum 2,000 mg/day. The primary efficacy endpoint was the effect of baseline BMI on glycemic control with metformin monotherapy, measured as the change from baseline in glycosylated hemoglobin (HbA1c at week 16 compared among BMI groups using ANCOVA. Other endpoints included comparisons of metformin's effects on fasting plasma glucose (FPG, lipid levels and body weight.Mean HbA1c decreases at week 16, adjusted for baseline values, were -1.84%, -1.78% and -1.78% in normal-weight, overweight and obese patients, (P = 0.664; body weight decreased by 2.4%, 3.9% and 3.5%, respectively. FPG levels decreased similarly over time in all BMI groups (P = 0.461 and changes from baseline in high-density lipoprotein cholesterol (HDL-C and low-density lipoprotein cholesterol (LDL-C did not differ significantly among BMI groups at week 16 (P = 0.143 and 0.451, respectively.Baseline BMI had no impact on glycemic control, weight change or other efficacy measures with metformin monotherapy. These data suggest that normal-weight type 2 diabetes patients would derive the same benefits from first-line treatment with metformin as overweight and obese patients, and are not at increased risk of excess weight loss.ClinicalTrials.gov NCT00778622.

  8. Cementless total hip arthroplasty for patients with Crowe type III or IV developmental dysplasia of the hip: two-stage total hip arthroplasty following skeletal traction after soft tissue release for irreducible hips.

    Science.gov (United States)

    Yoon, Pil Whan; Kim, Jung Il; Kim, Dong Ok; Yu, Cheol Hwan; Yoo, Jeong Joon; Kim, Hee Joong; Yoon, Kang Sup

    2013-09-01

    Total hip arthroplasty (THA) for severe developmental dysplasia of the hip (DDH) is a technically demanding procedure for arthroplasty surgeons, and it is often difficult to reduce the hip joint without soft tissue release due to severe flexion contracture. We performed two-stage THAs in irreducible hips with expected lengthening of the affected limb after THA of over 2.5 cm or with flexion contractures of greater than 30 degrees in order to place the acetabular cup in the true acetabulum and to prevent neurologic deficits associated with acute elongation of the limb. The purpose of this study is to evaluate the outcomes of cementless THA in patients with severe DDH with a special focus on the results of two-stage THA. Retrospective clinical and radiological evaluations were done on 17 patients with Crowe type III or IV developmental DDH treated by THA. There were 14 women and 3 men with a mean age of 52.3 years. Follow-ups averaged 52 months. Six cases were treated with two-stage THA followed by surgical hip liberalization and skeletal traction for 2 weeks. The mean Harris hip score improved from 40.9 to 89.1, and mean leg length discrepancy (LLD) in 13 unilateral cases was reduced from 2.95 to 0.8 cm. In the patients who underwent two-stage surgery, no nerve palsy was observed, and the single one-stage patient with incomplete peroneal nerve palsy recovered fully 4 weeks postoperatively. The short-term clinical and radiographic outcomes of primary cementless THA for patients with Crowe type III or IV DDH were encouraging. Two-stage THA followed by skeletal traction after soft tissue release could provide alternative solutions to the minimization of limb shortenings or LLD without neurologic deficits in highly selected patients.

  9. The natural infection of birds and ticks feeding on birds with Rickettsia spp. and Coxiella burnetii in Slovakia.

    Science.gov (United States)

    Berthová, Lenka; Slobodník, Vladimír; Slobodník, Roman; Olekšák, Milan; Sekeyová, Zuzana; Svitálková, Zuzana; Kazimírová, Mária; Špitalská, Eva

    2016-03-01

    Ixodid ticks (Acari: Ixodidae) are known as primary vectors of many pathogens causing diseases in humans and animals. Ixodes ricinus is a common ectoparasite in Europe and birds are often hosts of subadult stages of the tick. From 2012 to 2013, 347 birds belonging to 43 species were caught and examined for ticks in three sites of Slovakia. Ticks and blood samples from birds were analysed individually for the presence of Rickettsia spp. and Coxiella burnetii by PCR-based methods. Only I. ricinus was found to infest birds. In total 594 specimens of bird-attached ticks were collected (451 larvae, 142 nymphs, 1 female). Altogether 37.2% (16/43) of bird species were infested by ticks and some birds carried more than one tick. The great tit, Parus major (83.8%, 31/37) was the most infested species. In total, 6.6 and 2.7% of bird-attached ticks were infected with Rickettsia spp. and C. burnetii, respectively. Rickettsia helvetica predominated (5.9%), whereas R. monacensis (0.5%) was only sporadically detected. Coxiella burnetii was detected in 0.9%, Rickettsia spp. in 8.9% and R. helvetica in 4.2% of bird blood samples. The great tit was the bird species most infested with I. ricinus, carried R. helvetica and C. burnetti positive tick larvae and nymphs and was found to be rickettsaemic in its blood. Further studies are necessary to define the role of birds in the circulation of rickettsiae and C. burnetii in natural foci.

  10. Detection of Bartonella tamiae, Coxiella burnetii and rickettsiae in arthropods and tissues from wild and domestic animals in northeastern Algeria.

    Science.gov (United States)

    Leulmi, Hamza; Aouadi, Atef; Bitam, Idir; Bessas, Amina; Benakhla, Ahmed; Raoult, Didier; Parola, Philippe

    2016-01-20

    In recent years, the scope and importance of emergent vector-borne diseases has increased dramatically. In Algeria, only limited information is currently available concerning the presence and prevalence of these zoonotic diseases. For this reason, we conducted a survey of hematophagous ectoparasites of domestic mammals and/or spleens of wild animals in El Tarf and Souk Ahras, Algeria. Using real-time PCR, standard PCR and sequencing, the presence of Bartonella spp., Rickettsia spp., Borrelia spp. and Coxiella burnetii was evaluated in 268/1626 ticks, 136 fleas, 11 Nycteribiidae flies and 16 spleens of domestic and/or wild animals from the El Tarf and Souk Ahras areas. For the first time in Algeria, Bartonella tamiae was detected in 12/19 (63.2%) Ixodes vespertilionis ticks, 8/11 (72.7%) Nycteribiidae spp. flies and in 6/10 (60%) bat spleens (Chiroptera spp.). DNA from Coxiella burnetii, the agent of Q fever, was also identified in 3/19 (15.8%) I. vespertilionis from bats. Rickettsia slovaca, the agent of tick-borne lymphadenopathy, was detected in 1/1 (100%) Haemaphysalis punctata and 2/3 (66.7%) Dermacentor marginatus ticks collected from two boars (Sus scrofa algira) respectively. Ri. massiliae, an agent of spotted fever, was detected in 38/94 (40.4%) Rhipicephalus sanguineus sensu lato collected from cattle, sheep, dogs, boars and jackals. DNA of Ri. aeschlimannii was detected in 6/20 (30%) Hyalomma anatolicum excavatum and 6/20 (30%) Hy. scupense from cattle. Finally, Ri. felis, an emerging rickettsial pathogen, was detected in 80/110 (72.7%) Archaeopsylla erinacei and 2/2 (100%) Ctenocephalides felis of hedgehogs (Atelerix algirus). In this study, we expanded knowledge about the repertoire of ticks and flea-borne bacteria present in ectoparasites and/or tissues of domestic and wild animals in Algeria.

  11. Seroprevalence ofCoxiella burnetiiAntibodies Among Ruminants and Occupationally Exposed People in Thailand, 2012-2013.

    Science.gov (United States)

    Doung-Ngern, Pawinee; Chuxnum, Teerasak; Pangjai, Decha; Opaschaitat, Pattarin; Kittiwan, Nattinee; Rodtian, Pranee; Buameetoop, Noppawan; Kersh, Gilbert J; Padungtod, Pawin

    2017-04-01

    AbstractLittle is known about the burden of Q fever in Thailand. We conducted a serological study to describe the prevalence of anti- Coxiella burnetii antibodies among ruminants and occupationally exposed persons in response to the report of the first two Q fever endocarditis patients in Thailand in 2012. We randomly selected ruminant sera from brucellosis surveillance and examined sera of 661 occupationally exposed subjects from two provinces of Thailand: Chiangmai and Nakornratchasima. Animal and human sera were tested using commercial enzyme-linked immunosorbent assay (ELISA). Environmental samples, vaginal swab, and milk from cows in Chiangmai farms with detectable anti- C. burnetii serum antibodies were tested using polymerase chain reaction (PCR). Among the 1,632 animal sera tested, 64 (3.9%) were seropositive. The prevalence was highest in dairy cattle (4.6%, 45/988), followed by goats (3.5%, 18/516) and sheep (2.1%, 1/48). The prevalence of anti- C. burnetii antibodies in each species varied significantly by province: the prevalence in cattle was higher in Chiangmai (5.5% versus 0%), however, the prevalence in sheep and goats was higher in Nakornratchasima (5.9% versus 1.0%). Four out of 60 milk samples were positive by PCR (6.7%). No environmental samples were positive. Among 661 human samples, 83 (12.6%) were ELISA positive. Seroprevalence was statistically higher in Chiangmai compare with Nakornratchasima (42.8% versus 3.0%). Coxiella burnetii infection exists in Thailand, but the prevalence varies by geographic distribution and animal reservoirs. Further studies focusing on the burden and risk factors of C. burnetii infection among high-risk groups should be conducted.

  12. NNDSS - Table IV. Tuberculosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table IV. Tuberculosis - 2016.This Table includes total number of cases reported in the United States, by region and by states, in accordance with the...

  13. NNDSS - Table IV. Tuberculosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table IV. Tuberculosis - 2014.This Table includes total number of cases reported in the United States, by region and by states, in accordance with the...

  14. NNDSS - Table IV. Tuberculosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table IV. Tuberculosis - 2015.This Table includes total number of cases reported in the United States, by region and by states, in accordance with the...

  15. SAGE IV Pathfinder

    Data.gov (United States)

    National Aeronautics and Space Administration — Utilizing a unique, new occultation technique involving imaging, the SAGE IV concept will meet or exceed the quality of previous SAGE measurements at a small...

  16. SDSS-IV MaNGA: global stellar population and gradients for about 2000 early-type and spiral galaxies on the mass-size plane

    Science.gov (United States)

    Li, Hongyu; Mao, Shude; Cappellari, Michele; Ge, Junqiang; Long, R. J.; Li, Ran; Mo, H. J.; Li, Cheng; Zheng, Zheng; Bundy, Kevin; Thomas, Daniel; Brownstein, Joel R.; Roman Lopes, Alexandre; Law, David R.; Drory, Niv

    2018-05-01

    We perform full spectrum fitting stellar population analysis and Jeans Anisotropic modelling of the stellar kinematics for about 2000 early-type galaxies (ETGs) and spiral galaxies from the MaNGA DR14 sample. Galaxies with different morphologies are found to be located on a remarkably tight mass plane which is close to the prediction of the virial theorem, extending previous results for ETGs. By examining an inclined projection (`the mass-size' plane), we find that spiral and early-type galaxies occupy different regions on the plane, and their stellar population properties (i.e. age, metallicity, and stellar mass-to-light ratio) vary systematically along roughly the direction of velocity dispersion, which is a proxy for the bulge fraction. Galaxies with higher velocity dispersions have typically older ages, larger stellar mass-to-light ratios and are more metal rich, which indicates that galaxies increase their bulge fractions as their stellar populations age and become enriched chemically. The age and stellar mass-to-light ratio gradients for low-mass galaxies in our sample tend to be positive (centre < outer), while the gradients for most massive galaxies are negative. The metallicity gradients show a clear peak around velocity dispersion log10 σe ≈ 2.0, which corresponds to the critical mass ˜3 × 1010 M⊙ of the break in the mass-size relation. Spiral galaxies with large mass and size have the steepest gradients, while the most massive ETGs, especially above the critical mass Mcrit ≳ 2 × 1011 M⊙, where slow rotator ETGs start dominating, have much flatter gradients. This may be due to differences in their evolution histories, e.g. mergers.

  17. SDSS-IV MaNGA: Global stellar population and gradients for about 2000 early-type and spiral galaxies on the mass-size plane

    Science.gov (United States)

    Li, Hongyu; Mao, Shude; Cappellari, Michele; Ge, Junqiang; Long, R. J.; Li, Ran; Mo, HJ; Li, Cheng; Zheng, Zheng; Bundy, Kevin; Thomas, Daniel; Brownstein, Joel R.; Lopes, Alexandre Roman; Law, David R.; Drory, Niv

    2018-02-01

    We perform full spectrum fitting stellar population analysis and Jeans Anisotropic modelling (JAM) of the stellar kinematics for about 2000 early-type galaxies (ETGs) and spiral galaxies from the MaNGA DR14 sample. Galaxies with different morphologies are found to be located on a remarkably tight mass plane which is close to the prediction of the virial theorem, extending previous results for ETGs. By examining an inclined projection (`the mass-size' plane), we find that spiral and early-type galaxies occupy different regions on the plane, and their stellar population properties (i.e. age, metallicity and stellar mass-to-light ratio) vary systematically along roughly the direction of velocity dispersion, which is a proxy for the bulge fraction. Galaxies with higher velocity dispersions have typically older ages, larger stellar mass-to-light ratios and are more metal rich, which indicates that galaxies increase their bulge fractions as their stellar populations age and become enriched chemically. The age and stellar mass-to-light ratio gradients for low-mass galaxies in our sample tend to be positive (centregalaxies are negative. The metallicity gradients show a clear peak around velocity dispersion log10σe ≈ 2.0, which corresponds to the critical mass ˜3 × 1010M⊙ of the break in the mass-size relation. Spiral galaxies with large mass and size have the steepest gradients, while the most massive ETGs, especially above the critical mass M_crit≳ 2× 10^{11} M_{\\odot}, where slow rotator ETGs start dominating, have much flatter gradients. This may be due to differences in their evolution histories, e.g. mergers.

  18. Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

    Science.gov (United States)

    Sethuraman, G; Sreenivas, V; Yenamandra, V K; Gupta, N; Sharma, V K; Marwaha, R K; Bhari, N; Irshad, M; Kabra, M; Thulkar, S

    2015-01-01

    Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis. To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital ichthyosis. In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25(OH)D and PTH showed that a serum level of 25(OH)D 8 ng mL(-1) was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75 pg mL(-1) was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. Serum levels of 25(OH)D ≤ 8 ng mL(-1) and PTH ≥ 75 pg mL(-1) significantly increases the risk for development of rickets [odds ratio (OR) 2·8; 95% confidence interval (CI) 1·05-7·40; P = 0·04] in ichthyosis. Among the different types, patients with ARCI (OR 4·83; 95% CI 1·74-13·45; P < 0·01) and EI (OR 5·71; 95% CI 1·74-18·79; P < 0·01) are at an increased risk of developing rickets. © 2014 British Association of Dermatologists.

  19. Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.

    Directory of Open Access Journals (Sweden)

    Philippe C Morand

    Full Text Available Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and Pil

  20. A new fructose-free, resistant-starch type IV-enriched enteral formula improves glycaemic control and cardiovascular risk biomarkers when administered for six weeks to elderly diabetic patients.

    Science.gov (United States)

    Mesa García, María Dolores; García-Rodríguez, Cruz Erika; Rico, María de la Cruz; Aguilera, Concepción María; Pérez-Rodríguez, Milagros; Pérez-de-la-Cruz, Antonio Jesús; Gil, Ángel

    2017-02-01

    Reducing the dietary glycaemic response has been proposed as a way to reduce the risk of diabetes complications. The aim of the present study was to evaluate the glycaemic control and cardiovascular risk biomarkers in fragile, elderly type 2 diabetes patients after the intake of a new fructose-free diabetes-specific formula enriched with resistant-starch type IV and high in monounsaturated fatty acids. Forty-one type 2 diabetes patients aged 78.9 ± 2.8 years were fed exclusively with an enteral diabetes-specific formula for 6 weeks. Data were collected at baseline and after 6 weeks of feeding. Carbohydrate and lipid metabolism and inflammatory and cardiovascular risk biomarkers were measured to evaluated the course of diabetes complications. Blood glycated haemoglobin significantly decreased after the intervention (6.1 ± 0.1 vs. 5.8 ± 0.1 %; pcardiovascular risk without altering lipid metabolism, which is useful for the prevention of diabetic complications. Longer intervention studies are needed in order to validate these results in a larger population.

  1. Creating standards for absolute quantification of Coxiella burnetii in real-time PCR--a comparative study based on transmission electron microscopy.

    Science.gov (United States)

    Sting, Reinhard; Molz, Kerstin; Hoferer, Marc

    2015-01-01

    Quantitative standards are a prerequisite for quality control and quantification of pathogens. In this study the creation of quantitative standards for use in qPCR is described using the pathogen Coxiella burnetii. Quantification of Coxiella burnetii particles by transmission electron microscopy (TEM) was used as primary standard and compared with data obtained by light microscopy as well as genome equivalents (GE) and plasmid units (recombinant plasmid). Based on pathogen quantification using TEM and light microscopy, pathogen detection limits of 6 and 2 C. burnetii particles could be determined per com1 qPCR reaction, respectively. In comparison, the detection limits were 17 and 13 pathogen units using GE and plasmid units, respectively. The standard generated by TEM can be used as gold standard for universal application due to high accuracy, quantitative control of the producing process and supplying intact pathogen particles. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  2. Modifications in the glycerophospholipid composition between the Coxiella burnetii phase I and phase II cells suggest an association with phase variation of the bacterium

    Czech Academy of Sciences Publication Activity Database

    Frimmelová, M.; Toman, R.; Pompach, Petr; Škultéty, L'udovít

    2016-01-01

    Roč. 60, č. 1 (2016), s. 27-33 ISSN 0001-723X R&D Projects: GA MŠk(CZ) LO1509; GA MŠk(CZ) EE2.3.30.0003; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Coxiella burnetii * glycerophospholipids * FT-ICR MS Subject RIV: EE - Microbiology, Virology Impact factor: 0.673, year: 2016

  3. Long-term outcomes of tension band wiring with a single K-wire in Rockwood type IV/V acute acromio-clavicular dislocations: 25 cases.

    Science.gov (United States)

    Lateur, G; Boudissa, M; Rubens-Duval, B; Mader, R; Rouchy, R C; Pailhé, R; Saragaglia, D

    2016-09-01

    Our objective was to evaluate the long-term functional and radiological outcomes of tension band wiring with a single K-wire for acute Rockwood types IV and V acromio-clavicular dislocation (ACD). Single-centre cross-sectional non-randomised observational cohort study of 25 shoulders treated surgically between January 2002 and December 2004, in 25 patients, 23 males and 2 females, with a mean age of 35±11years (24-46). The evaluation criteria were the absolute and weighted Constant scores, QuickDASH score, subjective shoulder value (SSV), visual analogue scale (VAS) pain score at rest and during activities, and radiographic features in clinically symptomatic patients. Mean values were as follows: follow-up, 150±17months (133-167); absolute Constant score, 88±17 (71-105); weighted Constant score, 92.5±12.5 (80-105); QuickDASH, 15.5±7 (8.5-22.5); SSV, 88±17% (71-105); VAS pain score at rest, 0.2±0.7 (0-0.9); and VAS pain score while active, 1.4±2.3 (0-3.7). The weighted Constant score was less than 70% in only 8% of patients. Of the 17 patients for whom radiographs were obtained, 8 had acromio-clavicular osteoarthritis. Mean coraco-clavicular distance was 12.3±4.3mm (8-16.6) and mean acromio-clavicular distance was 5±5mm (0-10). The recurrence rate was 8%. Tension band wiring with a single K-wire for acute acromio-clavicular dislocation reliably provides good long-term functional outcomes. Recurrences are uncommon and few patients experience symptoms (8%). IV, retrospective study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Arthroscopic repair of traumatic isolated subscapularis tendon lesions (Lafosse Type III or IV): a prospective magnetic resonance imaging-controlled case series with 1 year of follow-up.

    Science.gov (United States)

    Grueninger, Patrick; Nikolic, Nikola; Schneider, Joerg; Lattmann, Thomas; Platz, Andreas; Chmiel, Corinne; Meier, Christoph

    2014-06-01

    The purpose of this study was to prospectively assess the efficacy of arthroscopic repair of isolated high-grade subscapularis (SSC) tendon lesions by means of clinical follow-up combined with magnetic resonance imaging investigations. Between January 2008 and September 2010, 11 patients (9 men and 2 women; mean age, 45 ± 10 years) with Lafosse type III or IV traumatic isolated SSC tendon lesions underwent arthroscopic repair including tenodesis of the long head of the biceps tendon. All patients were preoperatively assessed by clinical examination (Constant-Murley score [CMS]) and contrast-enhanced magnetic resonance arthrography. At 1 year of follow-up, specific clinical SSC tests, the CMS, and the loss of external rotation were evaluated. A native magnetic resonance investigation was performed to assess the structural integrity of the repair. The SSC muscle was compared with its preoperative condition regarding fatty infiltration and size (cross-sectional area). Patient satisfaction was graded from 1 (poor) to 4 (excellent). The mean time interval from trauma to surgery was 3.7 months. A concomitant lesion of the biceps tendon was observed in 10 patients (91%). The mean CMS improved from 44 to 89 points (P lift-off test, 4.8 v 2.9). The mean loss of external rotation at 0° of abduction was 10° compared with the contralateral side (P Magnetic resonance imaging evaluation showed complete structural integrity of the tendon repair in all studies. The SSC showed a significant decrease in fatty infiltration and increase in the cross-sectional area. Arthroscopic repair of higher-grade isolated SSC lesions provides reliable tendon healing accompanied by excellent functional results 1 year after surgery. Level IV, prospective therapeutic case series. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  5. The All-Alpha Domains of Coupling Proteins from the Agrobacterium tumefaciens VirB/VirD4 and Enterococcus faecalis pCF10-Encoded Type IV Secretion Systems Confer Specificity to Binding of Cognate DNA Substrates.

    Science.gov (United States)

    Whitaker, Neal; Chen, Yuqing; Jakubowski, Simon J; Sarkar, Mayukh K; Li, Feng; Christie, Peter J

    2015-07-01

    Bacterial type IV coupling proteins (T4CPs) bind and mediate the delivery of DNA substrates through associated type IV secretion systems (T4SSs). T4CPs consist of a transmembrane domain, a conserved nucleotide-binding domain (NBD), and a sequence-variable helical bundle called the all-alpha domain (AAD). In the T4CP structural prototype, plasmid R388-encoded TrwB, the NBD assembles as a homohexamer resembling RecA and DNA ring helicases, and the AAD, which sits at the channel entrance of the homohexamer, is structurally similar to N-terminal domain 1 of recombinase XerD. Here, we defined the contributions of AADs from the Agrobacterium tumefaciens VirD4 and Enterococcus faecalis PcfC T4CPs to DNA substrate binding. AAD deletions abolished DNA transfer, whereas production of the AAD in otherwise wild-type donor strains diminished the transfer of cognate but not heterologous substrates. Reciprocal swaps of AADs between PcfC and VirD4 abolished the transfer of cognate DNA substrates, although strikingly, the VirD4-AADPcfC chimera (VirD4 with the PcfC AAD) supported the transfer of a mobilizable plasmid. Purified AADs from both T4CPs bound DNA substrates without sequence preference but specifically bound cognate processing proteins required for cleavage at origin-of-transfer sequences. The soluble domains of VirD4 and PcfC lacking their AADs neither exerted negative dominance in vivo nor specifically bound cognate processing proteins in vitro. Our findings support a model in which the T4CP AADs contribute to DNA substrate selection through binding of associated processing proteins. Furthermore, MOBQ plasmids have evolved a docking mechanism that bypasses the AAD substrate discrimination checkpoint, which might account for their capacity to promiscuously transfer through many different T4SSs. For conjugative transfer of mobile DNA elements, members of the VirD4/TraG/TrwB receptor superfamily bind cognate DNA substrates through mechanisms that are largely undefined. Here

  6. Fratura extra-articular da extremidade medial da clavícula associada à luxação acromioclavicular tipo IV: relato de caso Extra-articular fracture of the medial end of the clavicle associated with type IV acromioclavicular dislocation: case report

    Directory of Open Access Journals (Sweden)

    Mário Chaves Correa

    2011-10-01

    Full Text Available Ocorrendo isoladamente, as fraturas da clavícula e as luxações acromioclaviculares são lesões muito comuns. A combinação de uma luxação acromioclavicular e de uma fratura do terço lateral da clavícula não é rara. Entretanto, existem muito poucos casos descritos de luxações acromioclaviculares associadas a fraturas do terço médio da clavícula; aquelas associadas a fraturas do terço medial são ainda mais raras. Nós reportamos o caso de um indivíduo adulto do sexo masculino que sofreu uma luxação acromioclavicular (tipo IV associada a uma fratura extra-articular desviada da extremidade medial da clavícula (grupo 3 de Almann em um acidente ciclístico. O paciente foi tratado na fase aguda com redução aberta e fixação interna das duas lesões. Na avaliação clínica, 12 meses após a cirurgia, o paciente apresentava-se assintomático, com mobilidade ativa e passiva completa, força e resistência normais e simetria das cinturas escapulares. As radiografias e a tomografia computadorizada tridimensional mostravam subluxação posterossuperior persistente da articulação acromioclavicular e consolidação anatômica da fratura clavicular.Fractures of the clavicle and acromioclavicular dislocations are very common injuries when they occur separately. The combination of an acromioclavicular dislocation and a fracture of the lateral third of the clavicle is not rare. However, there are very few reported cases of acromioclavicular dislocations associated with fractures of the middle third of the clavicle; those associated with fractures of the medial third are even rarer. We report the case of an adult male who suffered an acromioclavicular dislocation (type IV associated with a displaced extra-articular fracture of the medial end of the clavicle (Almann group 3 in a cycling accident. The patient was treated during the acute phase with open reduction and internal fixation of the two lesions. At the clinical evaluation 12

  7. IV access in dental practice.

    LENUS (Irish Health Repository)

    Fitzpatrick, J J

    2009-04-01

    Intravenous (IV) access is a valuable skill for dental practitioners in emergency situations and in IV sedation. However, many people feel some apprehension about performing this procedure. This article explains the basic principles behind IV access, and the relevant anatomy and physiology, as well as giving a step-by-step guide to placing an IV cannula.

  8. Brucellosis and Coxiella burnetii Infection in Householders and Their Animals in Secure Villages in Herat Province, Afghanistan: A Cross-Sectional Study

    Science.gov (United States)

    Akbarian, Zarif; Ziay, Ghulam; Schauwers, Willy; Noormal, Bashir; Saeed, Islam; Qanee, Abul Hussain; Shahab, Zabiullah; Dennison, Tania; Dohoo, Ian; Jackson, Ronald

    2015-01-01

    Background Brucellosis and coxiellosis are known to be endemic in ruminant populations throughout Afghanistan, but information about their prevalence and factors that affect prevalence in householders and livestock under diverse husbandry systems and pastoral settings is sparse. Methods/Principal Findings We conducted a cross-sectional survey to investigate the seroprevalence of brucellosis and Coxiella burnetii in humans and livestock in six secure districts in Herat from 26th December 2012–17th January 2013. A total of 204 households with livestock were surveyed in six Kuchi and five sedentary type villages. Blood samples from 1,017 humans, 1,143 sheep, 876 goats and 344 cattle were tested for brucellosis and Q fever. About one in six households (15.7%) had at least one Brucella seropositive person, about one in eight households (12.3%) had at least one Brucella seropositive animal and about one in four (24.5%) had either seropositive animals or humans. Ninety-seven percent of households had at least one C. burnetii seropositive person and 98.5% of households had one or more C. burnetii seropositive animals. Forty- seven householders had serological evidence of exposure to both C. burnetii and Brucella and eight animals were serologically positive for both diseases. Drinking unpasteurised milk (OR 1.6), treating animals for ticks (OR 1.4), milking sheep (OR 1.4), male gender (OR 1.4) and seropositivity to Brucella (OR 4.3) were identified as risk factors for seropositivity to C. burnetii in householders. Household factors associated with households having either Brucella seropositive animals or humans were Kuchi households (OR 2.5), having ≤4 rooms in the house (OR 2.9) and not owning land (OR 2.9). Conclusions The results from this study provide baseline information for the planning and monitoring of future interventions against these diseases. The implementation of this study greatly improved collaboration, coordination and capability of veterinary and

  9. Brucellosis and Coxiella burnetii Infection in Householders and Their Animals in Secure Villages in Herat Province, Afghanistan: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Zarif Akbarian

    Full Text Available Brucellosis and coxiellosis are known to be endemic in ruminant populations throughout Afghanistan, but information about their prevalence and factors that affect prevalence in householders and livestock under diverse husbandry systems and pastoral settings is sparse.We conducted a cross-sectional survey to investigate the seroprevalence of brucellosis and Coxiella burnetii in humans and livestock in six secure districts in Herat from 26th December 2012-17th January 2013. A total of 204 households with livestock were surveyed in six Kuchi and five sedentary type villages. Blood samples from 1,017 humans, 1,143 sheep, 876 goats and 344 cattle were tested for brucellosis and Q fever. About one in six households (15.7% had at least one Brucella seropositive person, about one in eight households (12.3% had at least one Brucella seropositive animal and about one in four (24.5% had either seropositive animals or humans. Ninety-seven percent of households had at least one C. burnetii seropositive person and 98.5% of households had one or more C. burnetii seropositive animals. Forty- seven householders had serological evidence of exposure to both C. burnetii and Brucella and eight animals were serologically positive for both diseases. Drinking unpasteurised milk (OR 1.6, treating animals for ticks (OR 1.4, milking sheep (OR 1.4, male gender (OR 1.4 and seropositivity to Brucella (OR 4.3 were identified as risk factors for seropositivity to C. burnetii in householders. Household factors associated with households having either Brucella seropositive animals or humans were Kuchi households (OR 2.5, having ≤ 4 rooms in the house (OR 2.9 and not owning land (OR 2.9.The results from this study provide baseline information for the planning and monitoring of future interventions against these diseases. The implementation of this study greatly improved collaboration, coordination and capability of veterinary and public health professionals from government

  10. Current status of NPP generation IV

    International Nuclear Information System (INIS)

    Yohanes Dwi Anggoro; Dharu Dewi; Nurlaila; Arief Tris Yuliyanto

    2013-01-01

    Today development of nuclear technology has reached the stage of research and development of Generation IV nuclear power plants (advanced reactor systems) which is an innovative development from the previous generation of nuclear power plants. There are six types of power generation IV reactors, namely: Very High Temperature Reactor (VHTR), Sodium-cooled Fast Reactor (SFR), Gas-cooled Fast Reactor (GFR), Lead-cooled Fast Reactor (LFR), Molten Salt Reactor (MSR), and Super Critical Water-cooled Reactor (SCWR). The purpose of this study is to know the development of Generation IV nuclear power plants that have been done by the thirteen countries that are members of the Gen IV International Forum (GIF). The method used is review study and refers to various studies related to the current status of research and development of generation IV nuclear power. The result of this study showed that the systems and technology on Generation IV nuclear power plants offer significant advances in sustainability, safety and reliability, economics, and proliferation resistance and physical protection. In addition, based on the research and development experience is estimated that: SFR can be used optimally in 2015, VHTR in 2020, while NPP types GFR, LFR, MSR, and SCWR in 2025. Utilization of NPP generation IV said to be optimal if fulfill the goal of NPP generation IV, such as: capable to generate energy sustainability and promote long-term availability of nuclear fuel, minimize nuclear waste and reduce the long term stewardship burden, has an advantage in the field of safety and reliability compared to the previous generation of NPP and VHTR technology have a good prospects in Indonesia. (author)

  11. Dibromidodimethyldipyridineplatinum(IV

    Directory of Open Access Journals (Sweden)

    Mairéad E. Kelly

    2008-11-01

    Full Text Available In the title complex, [PtBr2(CH32(C5H5N2], the PtIV metal centre lies on a twofold rotation axis and adopts a slightly distorted octahedral coordination geometry. The structure displays weak intramolecular C—H...Br hydrogen-bonding interactions.

  12. Synthesis and Characterization of Organ Tin (IV) Complexes ...

    African Journals Online (AJOL)

    User

    2012-08-21

    Aug 21, 2012 ... the reference drug. In addition, within the diorganotin(IV) complexes, monomeric type (3) exhibited a slightly better activity as compared to the organodistannoxane dimer types (1 and 4). Key words: Preliminary in vitro cytotoxic assay, organotin(IV) complexes, comparison study. INTRODUCTION. Although ...

  13. Enhanced Design Alternative IV

    International Nuclear Information System (INIS)

    Kramer, N.E.

    1999-01-01

    This report evaluates Enhanced Design Alternative (EDA) IV as part of the second phase of the License Application Design Selection (LADS) effort. The EDA IV concept was compared to the VA reference design using criteria from the Design Input Request for LADS Phase II EDA Evaluations (CRWMS M and O 1999b) and (CRWMS M and O 1999f). Briefly, the EDA IV concept arranges the waste packages close together in an emplacement configuration known as line load. Continuous pre-closure ventilation keeps the waste packages from exceeding their 350 C cladding and 200 C (4.3.6) drift wall temperature limits. This EDA concept keeps relatively high, uniform emplacement drift temperatures (post-closure) to drive water away from the repository and thus dry out the pillars between emplacement drifts. The waste package is shielded to permit human access to emplacement drifts and includes an integral filler inside the package to reduce the amount of water that can contact the waste form. Closure of the repository is desired 50 years after first waste is emplaced. Both backfill and drip shields will be emplaced at closure to improve post-closure performance. The EDA IV concept includes more defense-in-depth layers than the VA reference design because of its backfill, drip shield, waste package shielding, and integral filler features. These features contribute to the low dose-rate to the public achieved during the first 10,000 years of repository life as shown in Figure 3. Investigation of the EDA IV concept has led to the following general conclusions: (1) The total life cycle cost for EDA IV is about $21.7 billion which equates to a $11.3 billion net present value (both figures rounded up). (2) The incidence of design basis events for EDA IV is similar to the VA reference design. (3) The emplacement of the waste packages in drifts will be similar to the VA reference design. However, heavier equipment may be required because the shielded waste package will be heavier. (4) The heavier

  14. Pr{sub 2}Te{sub 2}O{sub 7}: a praseodymium(III) oxide oxotellurate(IV) according to Pr{sub 2}O(TeO{sub 3}){sub 2} with pyrochlore-type crystal structure

    Energy Technology Data Exchange (ETDEWEB)

    Weber, F.A.; Schleid, T. [Stuttgart Univ. (Germany). Inst. fuer Anorganische Chemie

    2000-06-01

    Regardless of their composition all rare-earth(III) oxotellurates(IV) structurally known so far e.g. Nd{sub 2}Te{sub 4}O{sub 11} and Ho{sub 2}Te{sub 5}O{sub 13} exhibit {psi}{sup 1}-coordination geometries for the involved Te{sup 4+} cations according to the valence shell electron pair repulsion (VSEPR) model, attesting for a strong stereochemical activity of non-binding electron lone pairs. Considering the large number of missing links within the phase diagrams of the M{sub 2}O{sub 3}-TeO{sub 2} systems (M = Sc, Y; La-Lu) at the tellurium-dioxide-poor region (e. g. M{sub 2}TeO{sub 5}, M{sub 2}Te{sub 2}O{sub 7}, and M{sub 2}Te{sub 3}O{sub 9}) a lot more preparative and analytical work seems to be necessary in order to confirm (or falsify) this apparently obvious regularity. The serendipitous formation of single-crystalline Pr{sub 2}Te{sub 2}O{sub 7} during attempts to synthesize Pr{sub 2}O{sub 2}Te with Nd{sub 2}O{sub 2}Te-type structure has now revealed an unexpected elucidation at least for the composition M{sub 2}Te{sub 2}O{sub 7} with M = Pr. (orig.)

  15. Antibodies against the majority subunit of type IV Pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media.

    Science.gov (United States)

    Novotny, Laura A; Jurcisek, Joseph A; Ward, Michael O; Jordan, Zachary B; Goodman, Steven D; Bakaletz, Lauren O

    2015-04-01

    Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual 'top-down' dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT and delivered via a noninvasive transcutaneous immunization route induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI. © 2015 John Wiley & Sons Ltd.