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Sample records for acquire distinct activation

  1. Evidence for distinct modes of solar activity

    Usoskin, I G; Gallet, Y; Roth, R; Licht, A; Joos, F; Kovaltsov, G A; Thebault, E; Khokhlov, A

    2014-01-01

    Aims. The Sun shows strong variability in its magnetic activity, from Grand minima to Grand maxima, but the nature of the variability is not fully understood, mostly because of the insufficient length of the directly observed solar activity records and of uncertainties related to long-term reconstructions. Here we present a new adjustment-free reconstruction of solar activity over three millennia and study its different modes. Methods. We present a new adjustment-free, physical reconstruction of solar activity over the past three millennia, using the latest verified carbon cycle, 14C production, and archeomagnetic field models. This great improvement allowed us to study different modes of solar activity at an unprecedented level of details. Results. The distribution of solar activity is clearly bi-modal, implying the existence of distinct modes of activity. The main regular activity mode corresponds to moderate activity that varies in a relatively narrow band between sunspot numbers about 20 and 67. The exist...

  2. Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias.

    Dicke, Christina; Schneppenheim, Sonja; Holstein, Katharina; Spath, Brigitte; Bokemeyer, Carsten; Dittmer, Rita; Budde, Ulrich; Langer, Florian

    2016-05-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may cause life-threatening hemorrhages in patients with plasma cell dyscrasias (PCDs). Early diagnosis and treatment require a thorough understanding of its underlying pathophysiology. Two patients with IgG MGUS presented with dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1 pattern on multimer analysis. A prompt response to intravenous immunoglobulins (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a less pronounced response to IVIG, suggesting that additional mechanism(s) contributed to AVWS evolution. In a patient with Waldenström's macroglobulinemia and severe depletion of plasma VWF, multimer analysis indicated association of the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in destruction of the agarose gel and a characteristically distorted band structure of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and laboratory evidence of excessive fibrinolytic activity suggested that plasmin-mediated VWF degradation contributed to AVWS in a patient with multiple myeloma (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged PFA-100® closure times and a specific defect in ristocetin-induced platelet agglutination, both of which resolved after remission induction, indicated interference of the paraprotein with VWF binding to platelet GPIb. Importantly, in none of the six patients, circulating autoantibodies to VWF were detected by a specific in-house ELISA. In summary, when evaluating PCD patients with severe bleeding symptoms, AVWS due to various pathogenic mechanisms should be considered. PMID:27040683

  3. Multinational Exploration of Acquired R&D Activities

    Gammelgård, Jens

    2004-01-01

    This paper presents the results of a survey of 54 Danish multinational corporations that have acquired activities abroad. The role of the acquired R&D units was the focus of the survey, particularly with respect to the schism between basic and applied R&D, and the schism between autonomous and network R&D. This paper establishes the connection between a multinational corporation that follows a capability-motivated acquisition strategy and the R&D role new subsidiaries should pl...

  4. Distinct neuropsychological correlates of cognitive, behavioural and affective apathy sub-domains in acquired brain injury.

    Progress eNjomboro; Shoumitro eDeb

    2014-01-01

    Apathy has a high prevalence and a significant contribution to treatment and rehabilitation outcomes in acquired brain damage. Research on the disorder’s neuropsychological correlates has produced mixed results. While the mixed picture may be due to the use of varied assessment tools on different patient populations, it’s also the case that most studies treat apathy as a unitary syndrome. This is in spite of evidence that apathy is a multifaceted and multidimensional syndrome. This study inve...

  5. Soft tissue sarcoma subtypes exhibit distinct patterns of acquired uniparental disomy

    Tuna Musaffe

    2012-12-01

    Full Text Available Abstract Background Soft tissue sarcomas (STS are heterogeneous mesenchymal tumors with diverse subtypes. STS can be classified into two main categories according to the type of genomic alteration: recurrent translocation driven STS, and non-recurrent translocations. However, little has known about acquired uniparental disomy in STS. Methods In this study, we analyzed SNP microarray data to determine the frequency and distribution patterns of acquired uniparental disomy (aUPD in major soft tissue sarcoma (STS subtypes using CNAG and R softwares. Results We identified recurrent aUPD regions specific to alveolar rhabdomyosarcoma with the most frequent at 11p15.4, gastrointestinal stromal tumor at 1p36.11-p35.3, leiomyosarcoma at 17p13.3-p13.1, myxofibrosarcoma at 1p35.1-p34.2 and 16q23.3-q24.1, and pleomorphic liposarcoma at 13q13.2-q13.3 and 13q14.11-q14.2. In contrast, specific recurrent aUPD regions were not identified in dedifferentiated liposarcoma, Ewing sarcoma, myxoid/round cell liposarcoma, and synovial sarcoma. Strikingly total, centromeric and segmental aUPD regions are more frequent in STS that do not exhibit recurrent translocation events. Conclusions Our study yields a detailed map of aUPD across 9 diverse STS subtypes and suggests the potential location of several novel tumor suppressor genes and oncogenes.

  6. Multinational Exploration of Acquired R&D Activities

    Gammelgaard, Jens

    2004-01-01

    This paper presents the results of a survey of 54 Danish multinational corporations that haveacquired activities abroad. The role of the acquired R&D units was the focus of the survey,particularly with respect to the schism between basic and applied R&D, and the schismbetween autonomous and netwo...... combination of basic andnetwork-oriented R&D activities when focusing on capability development.Keywords: Acquisition; Research and Development (R&D), Basic R&D, Applied R&D,Autonomy, Network, Capabilities....

  7. Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation

    Jennifer R. Molina

    2010-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core and invasive (Inv cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.

  8. Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development.

    Cherilyn A Elwell

    2011-09-01

    Full Text Available The strain designated Chlamydia trachomatis serovar that was used for experiments in this paper is Chlamydia muridarum, a species closely related to C. trachomatis (and formerly termed the Mouse Pneumonitis strain of C. trachomatis. [corrected]. The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM, a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM, for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic

  9. Ecological Insights from Pelagic Habitats Acquired Using Active Acoustic Techniques

    Benoit-Bird, Kelly J.; Lawson, Gareth L.

    2016-01-01

    Marine pelagic ecosystems present fascinating opportunities for ecological investigation but pose important methodological challenges for sampling. Active acoustic techniques involve producing sound and receiving signals from organisms and other water column sources, offering the benefit of high spatial and temporal resolution and, via integration into different platforms, the ability to make measurements spanning a range of spatial and temporal scales. As a consequence, a variety of questions concerning the ecology of pelagic systems lend themselves to active acoustics, ranging from organism-level investigations and physiological responses to the environment to ecosystem-level studies and climate. As technologies and data analysis methods have matured, the use of acoustics in ecological studies has grown rapidly. We explore the continued role of active acoustics in addressing questions concerning life in the ocean, highlight creative applications to key ecological themes ranging from physiology and behavior to biogeography and climate, and discuss emerging avenues where acoustics can help determine how pelagic ecosystems function.

  10. Different bacteriocin activities of Streptococcus mutans reflect distinct phylogenetic lineages

    Balakrishnan, M; Simmonds, RS; Kilian, Mogens;

    2002-01-01

    Bacteriocins produced by mutans streptococci are known as mutacins. In this study 16 broadly active mutacin-producing Streptococcus mutans strains from New Zealand, North America and Europe were classified into four groups (A-D) on the basis of differences in their activity in deferred antagonism...

  11. Distinct Biochemical Activities of Eyes absent During Drosophila Eye Development.

    Jin, Meng; Mardon, Graeme

    2016-01-01

    Eyes absent (Eya) is a highly conserved transcriptional coactivator and protein phosphatase that plays vital roles in multiple developmental processes from Drosophila to humans. Eya proteins contain a PST (Proline-Serine-Threonine)-rich transactivation domain, a threonine phosphatase motif (TPM), and a tyrosine protein phosphatase domain. Using a genomic rescue system, we find that the PST domain is essential for Eya activity and Dac expression, and the TPM is required for full Eya function. We also find that the threonine phosphatase activity plays only a minor role during Drosophila eye development and the primary function of the PST and TPM domains is transactivation that can be largely substituted by the heterologous activation domain VP16. Along with our previous results that the tyrosine phosphatase activity of Eya is dispensable for normal Eya function in eye formation, we demonstrate that a primary function of Eya during Drosophila eye development is as a transcriptional coactivator. Moreover, the PST/TPM and the threonine phosphatase activity are not required for in vitro interaction between retinal determination factors. Finally, this work is the first report of an Eya-Ey physical interaction. These findings are particularly important because they highlight the need for an in vivo approach that accurately dissects protein function. PMID:26980695

  12. Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

    Droemann Daniel

    2008-08-01

    Full Text Available Abstract Background Neutrophil products like matrix metalloproteinases (MMP, involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP. In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMPconcentration in human pneumonia. Methods In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL. Results MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 ± 41 vs. 34 ± 11, p Conclusion Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation.

  13. Distinct Biochemical Activities of Eyes absent During Drosophila Eye Development

    Meng Jin; Graeme Mardon

    2016-01-01

    Eyes absent (Eya) is a highly conserved transcriptional coactivator and protein phosphatase that plays vital roles in multiple developmental processes from Drosophila to humans. Eya proteins contain a PST (Proline-Serine-Threonine)-rich transactivation domain, a threonine phosphatase motif (TPM), and a tyrosine protein phosphatase domain. Using a genomic rescue system, we find that the PST domain is essential for Eya activity and Dac expression, and the TPM is required for full Eya function. ...

  14. IAEA standard syllabus of a course to acquire competence on ionizing radiation sources activities

    The specialized training for Ionizing Radiation Sources (IRS) activities is conducted according to educational syllabuses developed for every job position in compliance with art. 12, (3) of new Regulation of the conditions and procedure for acquiring professional qualification and for the procedure for issuing licenses for specialized training and certificates for qualification for use of nuclear energy. A brief review of the modular structure of the standard syllabus of the Postgraduate Educational Course in Radiation Protection and the Safe Use of Radiation Sources is presented in this paper. The content and level of training for categories of persons engaged in different practices are also listed

  15. Molecular characteristics of Illicium verum extractives to activate acquired immune response.

    Peng, Wanxi; Lin, Zhi; Wang, Lansheng; Chang, Junbo; Gu, Fangliang; Zhu, Xiangwei

    2016-05-01

    Illicium verum, whose extractives can activate the demic acquired immune response, is an expensive medicinal plant. However, the rich extractives in I. verum biomass were seriously wasted for the inefficient extraction and separation processes. In order to further utilize the biomedical resources for the good acquired immune response, the four extractives were obtained by SJYB extraction, and then the immunology moleculars of SJYB extractives were identified and analyzed by GC-MS. The result showed that the first-stage extractives contained 108 components including anethole (40.27%), 4-methoxy-benzaldehyde (4.25%), etc.; the second-stage extractives had 5 components including anethole (84.82%), 2-hydroxy-2-(4-methoxy-phenyl)-n-methyl-acetamide (7.11%), etc.; the third-stage extractives contained one component namely anethole (100%); and the fourth-stage extractives contained 5 components including cyclohexyl-benzene (64.64%), 1-(1-methylethenyl)-3-(1-methylethyl)-benzene (17.17%), etc. The SJYB extractives of I. verum biomass had a main retention time between 10 and 20 min what's more, the SJYB extractives contained many biomedical moleculars, such as anethole, eucalyptol, [1S-(1α,4aα,10aβ)]-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-1-phenanthrenecarboxylic acid, stigmast-4-en-3-one, γ-sitosterol, and so on. So the functional analytical results suggested that the SJYB extractives of I. verum had a function in activating the acquired immune response and a huge potential in biomedicine. PMID:27081359

  16. Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan

    Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

  17. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan.

    Masanori Matsumoto

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a type of thrombotic microangiopathy (TMA. Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai ADAMTS13-deficient TTP (ADAMTS13 activity <5% were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01, while older patients were more likely to die during the TTP hospitalization (p<0.05. Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort and gender composition (60% to 100% female in the other cohort. We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed.

  18. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance.

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-11-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  19. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance12

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-01-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  20. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance

    Euan A. Stronach

    2011-11-01

    Full Text Available Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinumresistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK, and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Re-sensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage–mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors.

  1. The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct.

    Kyra Y L Chua

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159 to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total. These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300 share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2. This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid

  2. Selectively Acquiring Customer Information: A New Data Acquisition Problem and an Active Learning-Based Solution

    Zhiqiang Zheng; Balaji Padmanabhan

    2006-01-01

    This paper presents a new information acquisition problem motivated by business applications where customer data has to be acquired with a specific modeling objective in mind. In the last two decades, there has been substantial work in two different fields--optimal experimental design and machine learning--that has addressed the issue of acquiring data in a selective manner with a specific objective in mind. We show that the problem presented here is different from the classic model-based dat...

  3. Arousal and locomotion make distinct contributions to cortical activity patterns and visual encoding

    Vinck, Martin; Batista-Brito, Renata; Knoblich, Ulf; Cardin, Jessica A.

    2015-01-01

    Spontaneous and sensory-evoked cortical activity is highly state-dependent, yet relatively little is known about transitions between distinct waking states. Patterns of activity in mouse V1 differ dramatically between quiescence and locomotion, but this difference could be explained by either motor feedback or a change in arousal levels. We recorded single cells and local field potentials from area V1 in mice head-fixed on a running wheel and monitored pupil diameter to assay arousal. Using n...

  4. Selected Laws, Rules and State-Level Activities in Wisconsin Related to Acquired Immunodeficiency Syndrome. Information Memorandum 87-4.

    Sweet, Richard

    This information memorandum describes the selected laws, rules, and state-level activities in Wisconsin related to acquired immunodeficiency syndrome (AIDS) and tests for antibodies to the virus (HIV) that causes AIDS. A section on current state laws on AIDS and HIV antibody testing describes laws related to informed consent for testing,…

  5. Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels.

    Kapoor, Vikrant; Provost, Allison C; Agarwal, Prateek; Murthy, Venkatesh N

    2016-02-01

    The serotonergic raphe nuclei are involved in regulating brain states over timescales of minutes and hours. We examined more rapid effects of raphe activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels. PMID:26752161

  6. Computer-Aided Relearning Activity Patterns for People with Acquired Brain Injury

    Montero, Francisco; Lopez-Jaquero, Victor; Navarro, Elena; Sanchez, Enriqueta

    2011-01-01

    People with disabilities constitute a collective that requires continuous and customized attention, since their conditions or abilities are affected with respect to specific standards. People with "Acquired Brain Injury" (ABI), or those who have suffered brain injury at some stage after birth, belong to this collective. The treatment these people…

  7. Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase

    Shimizu, M.; Wang, W.; Walch, E. T.; Dunne, P. W.; Epstein, H. F.

    2000-01-01

    Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

  8. Distinct mechanisms for DNA cleavage by myoglobin with a designed heme active center.

    Zhao, Yuan; Du, Ke-Jie; Gao, Shu-Qin; He, Bo; Wen, Ge-Bo; Tan, Xiangshi; Lin, Ying-Wu

    2016-03-01

    Heme proteins perform diverse biological functions, of which myoglobin (Mb) is a representative protein. In this study, the O2 carrier Mb was shown to cleave double stranded DNA upon aerobic dithiothreitol-induced reduction, which is fine-tuned by an additional distal histidine, His29 or His43, engineered in the heme active center. Spectroscopic (UV-vis and EPR) and inhibition studies suggested that free radicals including singlet oxygen and hydroxyl radical are responsible for efficient DNA cleavage via an oxidative cleavage mechanism. On the other hand, L29E Mb, with a distinct heme active center involving three water molecules in the met form, was found to exhibit an excellent DNA cleavage activity that was not depending on O2. Inhibition and ligation studies demonstrated for the first time that L29E Mb cleaves double stranded DNA into both the nicked circular and linear forms via a hydrolytic cleavage mechanism, which resembles native endonucleases. This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can be fine-tuned by rational design of the heme active center with a hydrogen-bonding network. PMID:26775281

  9. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype

    Guiliano David

    2002-07-01

    Full Text Available Abstract Background "Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. Results We have used murine macrophages elicited by nematode infection (NeMφ as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. Conclusions Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.

  10. Distinctive microstructural features of aged sodium silicate-activated slag concretes

    San Nicolas, Rackel [Department of Chemical and Biomolecular Engineering, University of Melbourne, Victoria 3010 (Australia); Bernal, Susan A. [Department of Materials Science and Engineering, University of Sheffield, Sir Robert Hadfield Building, Mappin St, Sheffield S1 3JD (United Kingdom); School of Materials Engineering, Composite Materials Group, Universidad del Valle, Cali (Colombia); Mejía de Gutiérrez, Ruby [School of Materials Engineering, Composite Materials Group, Universidad del Valle, Cali (Colombia); Deventer, Jannie S.J. van [Department of Chemical and Biomolecular Engineering, University of Melbourne, Victoria 3010 (Australia); Zeobond Pty Ltd, P.O. Box 23450, Docklands, Victoria 8012 (Australia); Provis, John L., E-mail: j.provis@sheffield.ac.uk [Department of Materials Science and Engineering, University of Sheffield, Sir Robert Hadfield Building, Mappin St, Sheffield S1 3JD (United Kingdom)

    2014-11-15

    Electron microscopic characterisation of 7-year old alkali-activated blast-furnace slag concretes enabled the identification of distinct microstructural features, providing insight into the mechanisms by which these materials evolve over time. Backscattered electron images show the formation of Liesegang-type ring formations, suggesting that the reaction at advanced age is likely to follow an Oswald supersaturation–nucleation–depletion cycle. Segregation of Ca-rich veins, related to the formation of Ca(OH){sub 2}, is observed in microcracked regions due to the ongoing reaction between the pore solution and available calcium from remnant slag grains. A highly dense and uniform interfacial transition zone is identified between siliceous aggregate particles and the alkali activated slag binders, across the concretes assessed. Alkali-activated slag concretes retain a highly dense and stable microstructure at advanced ages, where any microcracks induced at early ages seem to be partially closing, and the remnant slag grains continue reacting.

  11. Arousal and locomotion make distinct contributions to cortical activity patterns and visual encoding.

    Vinck, Martin; Batista-Brito, Renata; Knoblich, Ulf; Cardin, Jessica A

    2015-05-01

    Spontaneous and sensory-evoked cortical activity is highly state-dependent, yet relatively little is known about transitions between distinct waking states. Patterns of activity in mouse V1 differ dramatically between quiescence and locomotion, but this difference could be explained by either motor feedback or a change in arousal levels. We recorded single cells and local field potentials from area V1 in mice head-fixed on a running wheel and monitored pupil diameter to assay arousal. Using naturally occurring and induced state transitions, we dissociated arousal and locomotion effects in V1. Arousal suppressed spontaneous firing and strongly altered the temporal patterning of population activity. Moreover, heightened arousal increased the signal-to-noise ratio of visual responses and reduced noise correlations. In contrast, increased firing in anticipation of and during movement was attributable to locomotion effects. Our findings suggest complementary roles of arousal and locomotion in promoting functional flexibility in cortical circuits. PMID:25892300

  12. Distinct developmental defense activations in barley embryos identified by transcriptome profiling

    Nielsen, ME; Lok, F; Nielsen, Henrik Bjørn

    2006-01-01

    analyses of > 22,000 genes, which together with measurements of jasmonic acid and salicylic acid during embryo development provide new information on the initiation in the developing barley embryo of at least two distinct types of developmental defense activation (DDA). Early DDA is characterized by the up......-regulation of several PR genes is notable. Throughout barley embryo development, there are no indications of an increased biosynthesis of either jasmonic acid or salicylic acid. Collectively, the results help explain how the proposed DDA enables protection of the developing barley embryo and grain for purposes...

  13. Activated Ras alters lens and corneal development through induction of distinct downstream targets

    Reneker Lixing

    2010-01-01

    Full Text Available Abstract Background Mammalian Ras genes regulate diverse cellular processes including proliferation and differentiation and are frequently mutated in human cancers. Tumor development in response to Ras activation varies between different tissues and the molecular basis for these variations are poorly understood. The murine lens and cornea have a common embryonic origin and arise from adjacent regions of the surface ectoderm. Activation of the fibroblast growth factor (FGF signaling pathway induces the corneal epithelial cells to proliferate and the lens epithelial cells to exit the cell cycle. The molecular mechanisms that regulate the differential responses of these two related tissues have not been defined. We have generated transgenic mice that express a constitutively active version of human H-Ras in their lenses and corneas. Results Ras transgenic lenses and corneal epithelial cells showed increased proliferation with concomitant increases in cyclin D1 and D2 expression. This initial increase in proliferation is sustained in the cornea but not in the lens epithelial cells. Coincidentally, cdk inhibitors p27Kip1 and p57Kip2 were upregulated in the Ras transgenic lenses but not in the corneas. Phospho-Erk1 and Erk2 levels were elevated in the lens but not in the cornea and Spry 1 and Spry 2, negative regulators of Ras-Raf-Erk signaling, were upregulated more in the corneal than in the lens epithelial cells. Both lens and corneal differentiation programs were sensitive to Ras activation. Ras transgenic embryos showed a distinctive alteration in the architecture of the lens pit. Ras activation, though sufficient for upregulation of Prox1, a transcription factor critical for cell cycle exit and initiation of fiber differentiation, is not sufficient for induction of terminal fiber differentiation. Expression of Keratin 12, a marker of corneal epithelial differentiation, was reduced in the Ras transgenic corneas. Conclusions Collectively, these

  14. Peroxidatic activity distinct from myeloperoxidase in human monocytes cultured in vitro and in alveolar macrophages.

    Breton-Gorius, J; Vildé, J L; Guichard, J; Vainchenker, W; Basset, F

    1982-01-01

    Human monocytes develop a peroxidatic activity (PA) in rough endoplasmic reticulum (RER) after adherence or after culture in semi-solid medium. This enzyme activity disappears after three days of culture in the majority of macrophages derived from adult monocytes but persists for one week in macrophages derived from neonatal monocytes. The PA is due to an enzyme distinct from myeloperoxidase (MPO), since monocytes from a patient with MPO deficiency develop the same PA as that of normal monocytes after adherence. By its localization and other characteristics, PA of adherent monocytes resembles that of rodent macrophages. We therefore investigated whether human alveolar macrophages exhibit PA, using a sensitive cytochemical method which prevents inhibition by aldehyde in adherent monocytes. In various pathological cases, four types of macrophages could be identified: the majority were peroxidase-negative, a small percentage was of exudate type exhibiting a PA in granules as blood monocytes, while few macrophages were intermediate, possessing only PA in RER i.e. of type resident and a smaller proportion had PA in RER and in granules i.e. exudate-resident macrophages. These findings demonstrate that human macrophages and adherent monocytes may exhibit PA in RER as has been reported for rodent macrophages. The true nature and function of the enzyme responsible for this PA, which is distinct from MPO, remains unknown, but some arguments seem to suggest its role in prostaglandin synthesis. PMID:6283838

  15. Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers.

    Drath, D B; Do, C; Burd, T; Hong, L L

    1994-03-01

    A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers. PMID:8194852

  16. Antimicrobial activity of tigecycline against community-acquired methicillin-resistant Staphylococcus aureus isolates recovered from North American medical centers.

    Mendes, Rodrigo E; Sader, Helio S; Deshpande, Lalitagauri; Jones, Ronald N

    2008-04-01

    A total of 1989 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were susceptibility tested by broth microdilution. Pulsed-field gel electrophoresis, SCCmec type, and polymerase chain reaction for Panton-Valentine leukocidin (PVL) genes were also performed. The overall tigecycline susceptibility rate was 98.2%. Glycopeptides, quinupristin/dalfopristin, linezolid, and chloramphenicol were also active against this collection (< or =0.7% resistant). The vast majority (70.8%) of the CA-MRSA was SCCmec type IV, from which 88.4% belonged to the USA300-0114 clone and 94.7% were PVL positive. Tigecycline showed in vitro activity comparable with other highly active parenteral agents and represents an option for treating complicated infections caused by CA-MRSA. PMID:18068326

  17. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  18. Caste-specific visual adaptations to distinct daily activity schedules in Australian Myrmecia ants.

    Narendra, Ajay; Reid, Samuel F; Greiner, Birgit; Peters, Richard A; Hemmi, Jan M; Ribi, Willi A; Zeil, Jochen

    2011-04-22

    Animals are active at different times of the day and their activity schedules are shaped by competition, time-limited food resources and predators. Different temporal niches provide different light conditions, which affect the quality of visual information available to animals, in particular for navigation. We analysed caste-specific differences in compound eyes and ocelli in four congeneric sympatric species of Myrmecia ants, with emphasis on within-species adaptive flexibility and daily activity rhythms. Each caste has its own lifestyle: workers are exclusively pedestrian; alate females lead a brief life on the wing before becoming pedestrian; alate males lead a life exclusively on the wing. While workers of the four species range from diurnal, diurnal-crepuscular, crepuscular-nocturnal to nocturnal, the activity times of conspecific alates do not match in all cases. Even within a single species, we found eye area, facet numbers, facet sizes, rhabdom diameters and ocelli size to be tuned to the distinct temporal niche each caste occupies. We discuss these visual adaptations in relation to ambient light levels, visual tasks and mode of locomotion. PMID:20926444

  19. Soft skills: an important asset acquired from organizing regional student group activities.

    de Ridder, Jeroen; Meysman, Pieter; Oluwagbemi, Olugbenga; Abeel, Thomas

    2014-07-01

    Contributing to a student organization, such as the International Society for Computational Biology Student Council (ISCB-SC) and its Regional Student Group (RSG) program, takes time and energy. Both are scarce commodities, especially when you are trying to find your place in the world of computational biology as a graduate student. It comes as no surprise that organizing ISCB-SC-related activities sometimes interferes with day-to-day research and shakes up your priority list. However, we unanimously agree that the rewards, both in the short as well as the long term, make the time spent on these extracurricular activities more than worth it. In this article, we will explain what makes this so worthwhile: soft skills. PMID:24992198

  20. The mature activating natural killer cell immunologic synapse is formed in distinct stages.

    Orange, Jordan S; Harris, K Eliza; Andzelm, Milena M; Valter, Markus M; Geha, Raif S; Strominger, Jack L

    2003-11-25

    Natural killer (NK) cells form a structure at their interface with a susceptible target cell called the activating NK cell immunologic synapse (NKIS). The mature activating NKIS contains a central and peripheral supramolecular activation cluster (SMAC), and includes polarized surface receptors, filamentous actin (F-actin) and perforin. Evaluation of the NKIS in human NK cells revealed CD2, CD11a, CD11b and F-actin in the peripheral SMAC (pSMAC) with perforin in the central SMAC. The accumulation of F-actin and surface receptors was rapid and depended on Wiskott-Aldrich syndrome protein-driven actin polymerization. The accumulation at and arrangement of these molecules in the pSMAC was not affected by microtubule depolymerization. The polarization of perforin, however was slower and required intact actin, Wiskott-Aldrich syndrome protein, and microtubule function. Thus the process of CD2, CD11a, CD11b, and F-actin accumulation in the pSMAC and perforin accumulation in the central SMAC of the NKIS are sequential processes with distinct cytoskeletal requirements. PMID:14612578

  1. Soft Skills: An Important Asset Acquired from Organizing Regional Student Group Activities

    De Ridder, J.; Meysman, P.; Oluwagbemi, O.; Abeel, T.

    2014-01-01

    Contributing to a student organization, such as the International Society for Computational Biology Student Council (ISCB-SC) and its Regional Student Group (RSG) program, takes time and energy. Both are scarce commodities, especially when you are trying to find your place in the world of computational biology as a graduate student. It comes as no surprise that organizing ISCB-SC-related activities sometimes interferes with day-to-day research and shakes up your priority list. However, we una...

  2. Acquired Techniques

    Lunde Nielsen, Espen; Halse, Karianne

    2013-01-01

    Acquired Techniques - a Leap into the Archive, at Aarhus School of Architecture. In collaboration with Karianne Halse, James Martin and Mika K. Friis. Following the footsteps of past travelers this is a journey into tools and techniques of the architectural process. The workshop will focus upon...

  3. Acquired blepharoptosis

    Oosterhuis, HJGH

    1996-01-01

    A review is given of the aetiology and possible treatment of acquired (non-congenital) blepharoptosis, which is a common but not specific sign of neurological disease: The diagnostic categories of upper eyelid drooping are scheduled as (a) pseudo-ptosis due to a local process or overactivity of eye

  4. In Vitro Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms.

    Arendrup, Maiken Cavling; Jensen, Rasmus Hare; Cuenca-Estrella, Manuel

    2016-01-01

    ASP2397 is a new compound with a novel and as-yet-unknown target different from that of licensed antifungal agents. It has activity against Aspergillus and Candida glabrata. We compared its in vitro activity against wild-type and azole-resistant A. fumigatus and A. terreus isolates with that of amphotericin B, itraconazole, posaconazole, and voriconazole. Thirty-four isolates, including 4 wild-type A. fumigatus isolates, 24 A. fumigatus isolates with alterations in CYP51A TR/L98H (5 isolates), M220 (9 isolates), G54 (9 isolates), and HapE (1 isolate), and A. terreus isolates (2 wild-type isolates and 1 isolate with an M217I CYP51A alteration), were analyzed. EUCAST E.Def 9.2 and CLSI M38-A2 MIC susceptibility testing was performed. ASP2397 MIC50 values (in milligrams per liter, with MIC ranges in parentheses) determined by EUCAST and CLSI were 0.5 (0.25 to 1) and 0.25 (0.06 to 0.25) against A. fumigatus CYP51A wild-type isolates and were similarly 0.5 (0.125 to >4) and 0.125 (0.06 to >4) against azole-resistant A. fumigatus isolates, respectively. These values were comparable to those for amphotericin B, which were 0.25 (0.125 to 0.5) and 0.25 (0.125 to 0.25) against wild-type isolates and 0.25 (0.125 to 1) and 0.25 (0.125 to 1) against isolates with azole resistance mechanisms, respectively. In contrast, MICs for the azole compounds were elevated and highest for itraconazole: >4 (1 to >4) and 4 (0.5 to >4) against isolates with azole resistance mechanisms compared to 0.125 (0.125 to 0.25) and 0.125 (0.06 to 0.25) against wild-type isolates, respectively. ASP2397 was active against A. terreus CYP51A wild-type isolates (MIC 0.5 to 1), whereas MICs of both azole and ASP2397 were elevated for the mutant isolate. ASP2397 displayed in vitro activity against A. fumigatus and A. terreus isolates which was independent of the presence or absence of azole target gene resistance mutations in A. fumigatus. The findings are promising at a time when azole-resistant A. fumigatus

  5. Molecular changes in mitochondrial respiratory activity and metabolic enzyme activity in muscle of four pig breeds with distinct metabolic types.

    Liu, Xuan; Trakooljul, Nares; Muráni, Eduard; Krischek, Carsten; Schellander, Karl; Wicke, Michael; Wimmers, Klaus; Ponsuksili, Siriluck

    2016-02-01

    Skeletal muscles are metabolically active and have market value in meat-producing farm animals. A better understanding of biological pathways affecting energy metabolism in skeletal muscle could advance the science of skeletal muscle. In this study, comparative pathway-focused gene expression profiling in conjunction with muscle fiber typing were analyzed in skeletal muscles from Duroc, Pietrain, and Duroc-Pietrain crossbred pigs. Each breed type displayed a distinct muscle fiber-type composition. Mitochondrial respiratory activity and glycolytic and oxidative enzyme activities were comparable among genotypes, except for significantly lower complex I activity in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. At the transcriptional level, lactate dehydrogenase B showed breed specificity, with significantly lower expression in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. A similar mRNA expression pattern was shown for several subunits of oxidative phosphorylation complexes, including complex I, complex II, complex IV, and ATP synthase. Significant correlations were observed between mRNA expression of genes in focused pathways and enzyme activities in a breed-dependent manner. Moreover, expression patterns of pathway-focused genes were well correlated with muscle fiber-type composition. These results stress the importance of regulation of transcriptional rate of genes related to oxidative and glycolytic pathways in the metabolic capacity of muscle fibers. Overall, the results further the breed-specific understanding of the molecular basis of metabolic enzyme activities, which directly impact meat quality. PMID:26759028

  6. Human activities cause distinct dissolved organic matter composition across freshwater ecosystems.

    Williams, Clayton J; Frost, Paul C; Morales-Williams, Ana M; Larson, James H; Richardson, William B; Chiandet, Aisha S; Xenopoulos, Marguerite A

    2016-02-01

    Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by the interactions among physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic-like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic-rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in

  7. Human activities cause distinct dissolved organic matter composition across freshwater ecosystems

    Williams, Clayton J.; Frost, Paul C.; Morales-Williams, Ana M.; Larson, James H.; Richardson, William B.; Chiandet, Aisha S.; Xenopoulos, Marguerite A.

    2016-01-01

    Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by interactions between physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes Region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic-like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic-rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in

  8. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

    Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis

  9. Insulin activation of mouse diaphragm glycogen synthase (GS) involves generation of electrophoretically distinct subunit species

    Glycogen synthase, the rate limiting enzyme for glycogen synthesis, was analyzed in mouse diaphragm extracts both by immunoprecipitation and immunoblotting using specific antibodies raised to the rabbit muscle enzyme. Diaphragms, with the supporting ribs attached, were incubated either with or without [32P]P/sub i/ in the medium. In extracts from unincubated, rapidly frozen diaphragms, immunoblotting indicated the presence of 3 distinct species, separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). In addition, phosphorylation of immunoprecipitated GS with the kinase F/sub A//GSK-3 converted the higher mobility forms into the low mobility species. In diaphragms incubated with [32P]P/sub i/, 32P was incorporated only into one of the GS species, that of lowest mobility, indicating differential labelling among the multiple subunit forms. Insulin action, which increased the -/+ glucose-6-P activity ratio from 0.2 to 0.4, converted the low mobility species to the two higher mobility forms. The authors propose that this effect of insulin can be explained by dephosphorylation in the proline/serine rich site 3 region of GS, which has potent influence on both mobility on SDS-PAGE and activity

  10. Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome

    Diness, Thomas G; Yeh, Yung-Hsin; Qi, Xiao Yan; Chartier, Denis; Tsuji, Yukiomi; Hansen, Rie S; Olesen, Søren-Peter; Grunnet, Morten; Nattel, Stanley

    2008-01-01

    AIMS: Impaired repolarization in cardiac myocytes can lead to long QT syndrome (LQTS), with delayed repolarization and increased susceptibility to Torsades de Pointes (TdP) arrhythmias. Current pharmacological treatment of LQTS is often inadequate. This study sought to evaluate the antiarrhythmic...... effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, I(Kr), in two rabbit models of acquired LQTS. METHODS AND RESULTS: We used two clinically relevant in vivo rabbit models of TdP in which we infused NS1643 or vehicle: (i) three-week atrioventricular block with...... ventricular bradypacing; (ii) dofetilide-induced I(Kr) inhibition in methoxamine-sensitized rabbits. In addition, we studied effects on ionic currents in cardiomyocytes with I(Kr) suppressed by bradycardia remodelling or dofetilide exposure. Bradypaced rabbits developed QT interval prolongation, spontaneous...

  11. Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece.

    Karageorgopoulos, D E; Maraki, S; Vatopoulos, A C; Samonis, G; Schito, G C; Falagas, M E

    2013-11-01

    Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates. PMID:23686506

  12. Epidermal β-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages

    Lichtenberger, Beate M.; Mastrogiannaki, Maria; Watt, Fiona M.

    2016-01-01

    Sustained epidermal Wnt/β-catenin signalling expands the stem cell compartment and induces ectopic hair follicles (EFs). This is accompanied by extensive fibroblast proliferation and extracellular matrix (ECM) remodelling in the underlying dermis. Here we show that epidermal Hedgehog (Hh) and Transforming growth factor-beta (TGF-β) signalling mediate the dermal changes. Pharmacological inhibition or genetic deletion of these pathways prevents β-catenin-induced dermal reprogramming and EF formation. Epidermal Shh stimulates proliferation of the papillary fibroblast lineage, whereas TGF-β2 controls proliferation, differentiation and ECM production by reticular fibroblasts. Hh inhibitors do not affect TGF-β target gene expression in reticular fibroblasts, and TGF-β inhibition does not prevent Hh target gene induction in papillary fibroblasts. However, when Hh signalling is inhibited the reticular dermis does not respond to epidermal β-catenin activation. We conclude that the dermal response to epidermal Wnt/β-catenin signalling depends on distinct fibroblast lineages responding to different paracrine signals. PMID:26837596

  13. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny.

    Suda, Kenichi; Mizuuchi, Hiroshi; Maehara, Yoshihiko; Mitsudomi, Tetsuya

    2012-12-01

    Lung cancers that harbor somatic activating mutations in the gene for the epidermal growth factor receptor (EGFR) depend on mutant EGFR for their proliferation and survival; therefore, lung cancer patients with EGFR mutations often dramatically respond to orally available EGFR tyrosine kinase inhibitors (TKIs). However, emergence of acquired resistance is virtually inevitable, thus limiting improvement in patient outcomes. To elucidate and overcome this acquired resistance, multidisciplinary basic and clinical investigational approaches have been applied, using in vitro cell line models or samples obtained from lung cancer patients treated with EGFR-TKIs. These efforts have revealed several acquired resistance mechanisms and candidates, including EGFR secondary mutations (T790M and other rare mutations), MET amplification, PTEN downregulation, CRKL amplification, high-level HGF expression, FAS-NFκB pathway activation, epithelial-mesenchymal transition, and conversion to small cell lung cancer. Interestingly, cancer cells harbor potential destiny and ductility together in acquiring resistance to EGFR-TKIs, as shown in in vitro acquired resistance models. Molecular mechanisms of "reversible EGFR-TKI tolerance" that occur in early phase EGFR-TKI exposure have been identified in cell line models. Furthermore, others have reported molecular markers that can predict response to EGFR-TKIs in clinical settings. Deeper understanding of acquired resistance mechanisms to EGFR-TKIs, followed by the development of molecular target drugs that can overcome the resistance, might turn this fatal disease into a chronic disorder. PMID:22736441

  14. Antitumor activity of sorafenib in human cancer cell lines with acquired resistance to EGFR and VEGFR tyrosine kinase inhibitors.

    Floriana Morgillo

    Full Text Available Treatment of non small cell lung cancer (NSCLC and colorectal cancer (CRC have substantially changed in the last years with the introduction of epidermal growth factor receptor (EGFR inhibitors in the clinical practice. The understanding of mechanisms which regulate cells sensitivity to these drugs is necessary for their optimal use.An in vitro model of acquired resistance to two tyrosine kinase inhibitors (TKI targeting the EGFR, erlotinib and gefitinib, and to a TKI targeting EGFR and VEGFR, vandetanib, was developed by continuously treating the human NSCLC cell line CALU-3 and the human CRC cell line HCT116 with escalating doses of each drug. MTT, western blot analysis, migration, invasion and anchorage-independent colony forming assays were conducted in vitro and experiments with established xenografts in athymic nude mice were performed in vivo in sensitive, wild type (WT and TKI-resistant CALU-3 and HCT116 cell lines.As compared to WT CALU-3 and HCT116 human cancer cells, TKI-resistant cell lines showed a significant increase in the levels of activated, phosphorylated AKT, MAPK, and of survivin. Considering the role of RAS and RAF as downstream signals of both the EGFR and VEGFR pathways, we treated resistant cells with sorafenib, an inhibitor of C-RAF, B-RAF, c-KIT, FLT-3, RET, VEGFR-2, VEGFR-3, and PDGFR-β. Sorafenib reduced the activation of MEK and MAPK and caused an inhibition of cell proliferation, invasion, migration, anchorage-independent growth in vitro and of tumor growth in vivo of all TKI-resistant CALU-3 and HCT116 cell lines.These data suggest that resistance to EGFR inhibitors is predominantly driven by the RAS/RAF/MAPK pathway and can be overcame by treatment with sorafenib.

  15. 75 FR 71130 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    2010-11-22

    .... Linwood Gill, III, Vice President) 701 East Byrd Street, Richmond, Virginia 23261-4528: 1. Royal Bank of Canada, Montreal, Canada; to acquire BlueBay Asset Management plc, London, England, and...

  16. Bovine NK cells acquire cytotoxic activity and produce IFN-gamma after stimulation by Mycobacterium bovis BCG- or Babesia bovis-exposed splenic dendritic cells

    Early interactions of innate immune cell populations such as DC, monocytes/macrophages and NK cells, can affect the ability of the acquired immune response to control infection of intracellular microorganisms. In this study, we investigated the activation of bovine NK cells by CD13+ splenic DC or CD...

  17. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

    Lanz, Rainer B.; Razani, Bahram; Goldberg, Aaron D.; O'Malley, Bert W.

    2002-01-01

    Steroid receptor RNA activator (SRA) is an RNA transcript that functions as a eukaryotic transcriptional coactivator for steroid hormone receptors. We report here the isolation and functional characterization of distinct RNA substructures within the SRA molecule that constitute its coactivation function. We used comparative sequence analysis and free energy calculations to systematically study SRA RNA subdomains for identification of structured regions and base pairings, and we used site-dire...

  18. Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis.

    Gieseck, Richard L; Ramalingam, Thirumalai R; Hart, Kevin M; Vannella, Kevin M; Cantu, David A; Lu, Wei-Yu; Ferreira-González, Sofía; Forbes, Stuart J; Vallier, Ludovic; Wynn, Thomas A

    2016-07-19

    Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis. VIDEO ABSTRACT. PMID:27421703

  19. Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways.

    Sengupta, T K; Schmitt, E M; Ivashkiv, L B

    1996-01-01

    An important component of cytokine regulation of cell growth and differentiation is rapid transcriptional activation of genes by the JAK-STAT (signal transducer and activator of transcription) signaling pathway. Ligation of cytokine receptors results in tyrosine phosphorylation and activation of receptor-associated Jak protein tyrosine kinases and cytoplasmic STAT transcription factors, which then translocate to the nucleus. We describe the interruption of cytokine triggered JAK-STAT signals ...

  20. Why p-OMe- and p-Cl-β-Methylphenethylamines Display Distinct Activities upon MAO-B Binding

    Celis-Barros, Cristian; Zapata-Torres, Gerald

    2016-01-01

    Despite their structural and chemical commonalities, p-chloro-β-methylphenethylamine and p-methoxy-β-methylphenethylamine display distinct inhibitory and substrate activities upon MAO-B binding. Density Functional Theory (DFT) quantum chemical calculations reveal that β-methylation and para-substitution underpin the observed activities sustained by calculated transition state energy barriers, attained conformations and key differences in their interactions in the enzyme’s substrate binding site. Although both compounds meet substrate requirements, it is clear that β-methylation along with the physicochemical features of the para-substituents on the aromatic ring determine the activity of these compounds upon binding to the MAO B-isoform. While data for a larger set of compounds might lend generality to our conclusions, our experimental and theoretical results strongly suggest that the contrasting activities displayed depend on the conformations adopted by these compounds when they bind to the enzyme. PMID:27152414

  1. Distinct Kinetics Features of LFA-1 and Mac-1 in Neutrophil Activation

    LI Ning; MAO De-bin; GONG Yi-xin; LV Shou-qin; ZHANG Yan; LONG Mian

    2015-01-01

    LFA-1 and Mac-1, two β2 integrin members constitutively expressed on neutrophils, mediate leukocyte recruitment cascade by binding to the same ligand of ICAM-1The slow rolling and firm adhesion of leukocytes rely on LFA-1 while the cell crawling is dependent on Mac-1We hypothesized that their distinct roles are likely attributed to the differences in the binding kinetics or in the diverse responses of outside-in and inside-out signalingIn this study, we compared the ICAM-1 binding features between soluble or membrane-expressed LFA-1 and Mac-1 with different affinity conformation using optical trap techniqueOur data indicated that the affinity up-regulation from wide type (WT) to high affinity (HA) is off-rate dependent for LFA-1 but on-rate dependent for Mac-1The structural bases of this new finding were found to be consistent with our previous simulationsThese results furthered our understanding in their function differences under shear flow.

  2. An Acidic Thermostable Recombinant Aspergillus nidulans Endoglucanase Is Active towards Distinct Agriculture Residues

    Marcio Jose Poças-Fonseca; Ildinete Silva-Pereira; Cynthia Maria Kyaw; Edivaldo Ximenes Ferreira Filho; Fabrícia Paula de Faria; Gilvan Caetano Duarte; Marciano Regis Rubini; Thiago Machado Mello-de-Sousa; Eveline Queiroz de Pinho Tavares

    2013-01-01

    Aspergillus nidulans is poorly exploited as a source of enzymes for lignocellulosic residues degradation for biotechnological purposes. This work describes the A. nidulans Endoglucanase A heterologous expression in Pichia pastoris, the purification and biochemical characterization of the recombinant enzyme. Active recombinant endoglucanase A (rEG A) was efficiently secreted as a 35 kDa protein which was purified through a two-step chromatography procedure. The highest enzyme activity was dete...

  3. Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    glycine-free or a glycine-bound subunit. Agonist-free subunits were created by incorporating T204A and R65K mutations, which disrupted glycine binding to both (+) and (-) subunit interfaces. In heteromeric receptors comprising wild-type and R65K,T204A,R271C triple-mutant subunits, the fluorescence...... response exhibited a drastically reduced glycine sensitivity relative to the current response. Two conclusions can be drawn from this. First, because the labeled glycine-free subunits were activated by glycine binding to neighboring wild-type subunits, our results provide evidence for a cooperative...... activation mechanism. However, because the fluorescent label on glycine-free subunits does not reflect movements at the channel gate, we conclude that glycine binding also produces a local non-concerted conformational change that is not essential for receptor activation....

  4. Cyclic lipopeptides from Bacillus subtilis activate distinct patterns of defence responses in grapevine.

    Farace, Giovanni; Fernandez, Olivier; Jacquens, Lucile; Coutte, François; Krier, François; Jacques, Philippe; Clément, Christophe; Barka, Essaid Ait; Jacquard, Cédric; Dorey, Stéphan

    2015-02-01

    Non-self-recognition of microorganisms partly relies on the perception of microbe-associated molecular patterns (MAMPs) and leads to the activation of an innate immune response. Bacillus subtilis produces three main families of cyclic lipopeptides (LPs), namely surfactins, iturins and fengycins. Although LPs are involved in induced systemic resistance (ISR) activation, little is known about defence responses induced by these molecules and their involvement in local resistance to fungi. Here, we showed that purified surfactin, mycosubtilin (iturin family) and plipastatin (fengycin family) are perceived by grapevine plant cells. Although surfactin and mycosubtilin stimulated grapevine innate immune responses, they differentially activated early signalling pathways and defence gene expression. By contrast, plipastatin perception by grapevine cells only resulted in early signalling activation. Gene expression analysis suggested that mycosubtilin activated salicylic acid (SA) and jasmonic acid (JA) signalling pathways, whereas surfactin mainly induced an SA-regulated response. Although mycosubtilin and plipastatin displayed direct antifungal activity, only surfactin and mycosubtilin treatments resulted in a local long-lasting enhanced tolerance to the necrotrophic fungus Botrytis cinerea in grapevine leaves. Moreover, challenge with specific strains overproducing surfactin and mycosubtilin led to a slightly enhanced stimulation of the defence response compared with the LP-non-producing strain of B. subtilis. Altogether, our results provide the first comprehensive view of the involvement of LPs from B. subtilis in grapevine plant defence and local resistance against the necrotrophic pathogen Bo. cinerea. Moreover, this work is the first to highlight the ability of mycosubtilin to trigger an immune response in plants. PMID:25040001

  5. Etiopathology of acquired cholesteatoma

    Prabodh Karnik

    2011-01-01

    Full Text Available The etiopathology of acquired cholesteatoma has undergone numerous changes over the past 150 years. However, certain facts stand out with clarity. The presence of cytokeratins in acquired cholesteatoma, which are akin to those found in the tympanic membrane and external auditory canal, shows that these are probably the site of origin of acquired cholesteatoma. The cholesteatoma sac also shows its greatest growth at its tympanic membrane attachment into the middle ear. Implantations of squamous epithelium due to trauma or surgery could be another originating factor. The basic pathology is the formation of papillary cones from the tympanic membrane or external auditory canal, which progress from microcholesteatoma to frank cholesteatoma with keratin collections. There is an altered matrix metalloproteinase pathway. Tumor necrosis factor activation with altered wound healing process contributes to the collateral destruction of bone. Trisomy and aneuploidy of chromosome 8 predispose to cholesteatoma formation in affected individuals. In this article, we present the etiopathology of acquired cholesteatoma as it stands today.

  6. Distinctive role of activated tumor-associated macrophages in photosensitizer accumulation

    Korbelik, Mladen; Krosl, Gorazd

    1995-05-01

    Cells dissociated from tumors (carcinomas and sarcomas) growing subcutaneously in mice that have been administered Photofrin or other photosensitizers were analyzed by flow cytometry. Monoclonal antibodies were used for identification of major cellular populations contained in these tumors. The results demonstrate that a subpopulation of tumor-associated macrophages (TAMs) is unique among tumor cell populations in that it excels in the accumulation of very high levels of photosensitizers. These macrophages showed an increased expression of interleukin 2 receptor, which is indicative of their activated state. since macrophages were reported to concentrate in the periphery of human neoplasms, it is suggested that activates TAMs are the determinants of tumor-localized photosensitizer fluorescence.

  7. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions...

  8. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  9. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  10. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    Abdallah, Abdallah

    2011-09-28

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5 - two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators - during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. Copyright © 2011 by The American Association of Immunologists, Inc.

  11. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation.

    Abdallah, Abdallah M; Bestebroer, Jovanka; Savage, Nigel D L; de Punder, Karin; van Zon, Maaike; Wilson, Louis; Korbee, Cees J; van der Sar, Astrid M; Ottenhoff, Tom H M; van der Wel, Nicole N; Bitter, Wilbert; Peters, Peter J

    2011-11-01

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5--two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators--during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1β activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. PMID:21957139

  12. Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3

    Wang, Wei; Yan ZHANG; Lv, Ming; Feng, Jiannan; Peng, Hui; Geng, Jing; Lin, Zhou; Zhou, Tingting; Li, Xinying; Shen, Beifen; Ma, Yuanfang; Qiao, Chunxia

    2014-01-01

    Background Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival. Methods IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1...

  13. A systematic review of the efficacy of self-management programs for increasing physical activity in community-dwelling adults with acquired brain injury (ABI)

    Jones, Taryn M; Dean, Catherine M.; Hush, Julia M.; Dear, Blake F.; Titov, Nickolai

    2015-01-01

    Background Individuals living with acquired brain injury, typically caused by stroke or trauma, are far less likely to achieve recommended levels of physical activity for optimal health and well-being. With a growing number of people living with chronic disease and disability globally, self-management programs are seen as integral to the management of these conditions and the prevention of secondary health conditions. However, to date, there has been no systematic review of the literature exa...

  14. Common and distinct mechanisms of activation of rhodopsin and other G protein-coupled receptors

    Sumire Nakamura; Takeshi Itabashi; Daisuke Ogawa; Tetsuji Okada

    2013-01-01

    Detailed and systematic examination of high-resolution structural data is a rational strategy for understanding the function of biological macromolecules. G protein-coupled receptors (GPCRs) are an exceptionally valuable superfamily of proteins for such analysis. The most intriguing question is how a variety of extracellular stimuli evoke structural changes in the intracellular surface of the receptors. The recent active-like crystal structures of GPCRs provide information for uncovering comm...

  15. Differential Activation of Innate Immune Pathways by Distinct Islet Amyloid Polypeptide (IAPP) Aggregates.

    Westwell-Roper, Clara; Denroche, Heather C; Ehses, Jan A; Verchere, C Bruce

    2016-04-22

    Aggregation of islet amyloid polypeptide (IAPP) contributes to beta cell dysfunction in type 2 diabetes and islet transplantation. Like other amyloidogenic peptides, human IAPP induces macrophage IL-1β secretion by stimulating both the synthesis and processing of proIL-1β, a pro-inflammatory cytokine that (when chronically elevated) impairs beta cell insulin secretion. We sought to determine the specific mechanism of IAPP-induced proIL-1β synthesis. Soluble IAPP species produced early during IAPP aggregation provided a Toll-like-receptor-2- (TLR2-) dependent stimulus for NF-κB activation in HEK 293 cells and bone marrow-derived macrophages (BMDMs). Non-amyloidogenic rodent IAPP and thioflavin-T-positive fibrillar amyloid produced by human IAPP aggregation failed to activate TLR2. Blockade of TLR6 but not TLR1 prevented hIAPP-induced TLR2 activation, consistent with stimulation of a TLR2/6 heterodimer. TLR2 and its downstream adaptor protein MyD88 were required for IAPP-induced cytokine production by BMDMs, a process that is partially dependent on autoinduction by IL-1. BMDMs treated with soluble but not fibrillar IAPP provided a TLR2-dependent priming stimulus for ATP-induced IL-1β secretion, whereas late IAPP aggregates induced NLRP3-dependent IL-1β secretion by LPS-primed macrophages. Moreover, inhibition of TLR2 and depletion of islet macrophages prevented up-regulation of Il1b and Tnf expression in human IAPP-expressing transgenic mouse islets. These data suggest participation by both soluble and fibrillar aggregates in IAPP-induced islet inflammation. IAPP-induced activation of TLR2 and secretion of IL-1 may be important therapeutic targets to prevent amyloid-associated beta cell dysfunction. PMID:26786104

  16. Cytokinin and Auxin Display Distinct but Interconnected Distribution and Signaling Profiles to Stimulate Cambial Activity.

    Immanen, Juha; Nieminen, Kaisa; Smolander, Olli-Pekka; Kojima, Mikiko; Alonso Serra, Juan; Koskinen, Patrik; Zhang, Jing; Elo, Annakaisa; Mähönen, Ari Pekka; Street, Nathaniel; Bhalerao, Rishikesh P; Paulin, Lars; Auvinen, Petri; Sakakibara, Hitoshi; Helariutta, Ykä

    2016-08-01

    Despite the crucial roles of phytohormones in plant development, comparison of the exact distribution profiles of different hormones within plant meristems has thus far remained scarce. Vascular cambium, a wide lateral meristem with an extensive developmental zonation, provides an optimal system for hormonal and genetic profiling. By taking advantage of this spatial resolution, we show here that two major phytohormones, cytokinin and auxin, display different yet partially overlapping distribution profiles across the cambium. In contrast to auxin, which has its highest concentration in the actively dividing cambial cells, cytokinins peak in the developing phloem tissue of a Populus trichocarpa stem. Gene expression patterns of cytokinin biosynthetic and signaling genes coincided with this hormonal gradient. To explore the functional significance of cytokinin signaling for cambial development, we engineered transgenic Populus tremula × tremuloides trees with an elevated cytokinin biosynthesis level. Confirming that cytokinins function as major regulators of cambial activity, these trees displayed stimulated cambial cell division activity resulting in dramatically increased (up to 80% in dry weight) production of the lignocellulosic trunk biomass. To connect the increased growth to hormonal status, we analyzed the hormone distribution and genome-wide gene expression profiles in unprecedentedly high resolution across the cambial zone. Interestingly, in addition to showing an elevated cambial cytokinin content and signaling level, the cambial auxin concentration and auxin-responsive gene expression were also increased in the transgenic trees. Our results indicate that cytokinin signaling specifies meristematic activity through a graded distribution that influences the amplitude of the cambial auxin gradient. PMID:27426519

  17. Distinct neural activity associated with focused-attention meditation and loving-kindness meditation

    Lee, Tatia M. C.; Leung, Mei-Kei; Hou, Wai-Kai; Tang, Joey C. Y.; Yin, Jing; So, Kwok-Fai; Lee, Chack-Fan; Chan, Chetwyn C. H.

    2012-01-01

    This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monito...

  18. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression

    Chavali, Arvind K.; Wong, Victor C.; Miller-Jensen, Kathryn

    2015-12-01

    Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a ‘molecular switch’ controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi-state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance.

  19. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  20. EGF AND TGF-α motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms

    EGF and TGF-α induce an equipotent stimulation of fibroblast migration and proliferation. In spite of their homologous structure and ligation by the same receptor (EGFR), we report that their respective motogenic activities are mediated by different signal transduction intermediates, with p70S6K participating in EGF signalling and phospholipase Cγ in TGF-α signalling. We additionally demonstrate that EGF and TGF-α motogenic activities may be resolved into two stages: (a) cell 'activation' by a transient exposure to either cytokine, and (b) the subsequent 'manifestation' of an enhanced migratory phenotype in the absence of cytokine. The cell activation and manifestation stages for each cytokine are mediated by distinct matrix-dependent mechanisms: motogenetic activation by EGF requires the concomitant functionality of EGFR and the hyaluronan receptor CD44, whereas activation by TGF-α requires EGFR and integrin αvβ3. Manifestation of elevated migration no longer requires the continued presence of exogenous cytokine and functional EGFR but does require the above mentioned matrix receptors, as well as their respective ligands, i.e., hyaluronan in the case of EGF, and vitronectin in the case of TGF-α. In contrast, the mitogenic activities of EGF and TGF-α are independent of CD44 and αvβ3 functionality. These results demonstrate clear qualitative differences between EGF and TGF-α pathways and highlight the importance of the extracellular matrix in regulating cytokine bioactivity

  1. Convergence on a Distinctive Assembly Mechanism by Unrelated Families of Activating Immune Receptors

    Feng, Jianwen; Garrity, David; Call, Matthew E.; Moffett, Howell; Wucherpfennig, Kai W.

    2005-01-01

    Activating receptors in cells of hematopoetic origin include members of two unrelated protein families, the immunoglobulin (Ig) and C type lectins, which differ even in the orientation of the transmembrane (TM) domains. We examined assembly of four receptors with diverse function: the NK receptors KIR2DS and NKG2C/CD94, the Fc receptor for IgA, and the GPVI collagen receptor. For each of the four different receptors studied here, assembly results in the formation of a three-helix interface in...

  2. Distinct and common cerebral activation changes during mental time travel in relapsing-remitting multiple sclerosis patients.

    Ernst, A; Noblet, V; Denkova, E; Blanc, F; De Seze, J; Gounot, D; Manning, L

    2016-03-01

    Mental time travel (MTT) entails the ability to mentally travel into autobiographical memory (AM) and episodic future thinking (EFT). While AM and EFT share common phenomenological and cerebral functional properties, distinctive characteristics have been documented in healthy and clinical populations. No report, to our knowledge, has informed on the functional underpinnings of MTT impairment in multiple sclerosis (MS) patients, hence the aim of this work. We studied 22 relapsing-remitting MS patients and 22 matched controls. Participants underwent an AM/EFT assessment using the Autobiographical Interview (Levine et al. 2002), followed by a functional MRI session. The latter consisted in AM and EFT tasks, distinguishing the construction and elaboration phases of events. The results showed impaired performance for AM and EFT in patients, accompanied by increased cerebral activations mostly located in the frontal regions, which extended to the parietal, lateral temporal and posterior regions during AM/EFT tasks, relative to healthy controls. Enhanced brain activations in MS patients were particularly evident during the EFT task and involved the hippocampus, frontal, external temporal, and cingulate regions. The construction phase required greater fronto-parieto-temporal activations in MS patients relative to both healthy controls, and the elaboration phase. Taking together, our results suggested the occurrence of cerebral activation changes in the context of MTT in MS patients, expressed by distinct and common mechanisms for AM and EFT. This study may provide new insights in terms of cerebral activation changes in brain lesion and their application to clinical settings, considering AM/EFT's central role in everyday life. PMID:25972116

  3. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  4. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Lucy Matthews

    Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  5. Distinct Expression Levels of ALS, LIP, and SAP Genes in Candida tropicalis with Diverse Virulent Activities.

    Yu, Shuanbao; Li, Wenge; Liu, Xiaoshu; Che, Jie; Wu, Yuan; Lu, Jinxing

    2016-01-01

    Candia tropicalis is an increasingly important human pathogen, causing nosocomial fungemia among patients with neutropenia or malignancy. However, limited research has been published concerning its pathogenicity. Based on the phenotypes of C. tropicalis in our previous study, we selected nine representative strains with different activities of virulence factors (adhesion, biofilm formation, secreted aspartic proteinases, and hemolysins), and one reference strain, ATCC750. The present study aimed to investigate the filamentation ability, the expression of virulence genes (ALST1-3, LIP1, LIP4, and SAPT1-4) and the cell damage of C. tropicalis strains with diverse virulences. C. tropicalis exhibited strain-dependent filamentation ability, which was positively correlated with biofilm formation. Reverse transcriptase PCR analysis showed that the ALST3 and SAPT3 genes had the highest expression in their corresponding genes for most C. tropicalis. The expressions of virulence genes, except ALST3 on polystyrene, were upregulated compared with growth in the planktonic and on human urinary bladder epithelial cell line (TCC-SUP) surface. Clustering analysis of virulence genes showed that isolates had a high biofilm forming ability on polystyrene formed a group. Lactate dehydrogenase assays showed that the cell damage induced by C. tropicalis markedly increased with longer infection time (24 and 48 h). Strain FXCT01, isolated from blood, caused the most serious cell damage; while ZRCT52, which had no filamentation ability, caused the least cell damage. Correlation analysis demonstrated significant correlation existed between adhesion on epithelial cells or the expression of ALST2-3 and cell damage. Overall, our results supported the view that adhesion and filamentation may play significant roles in the cell damage caused by C. tropicalis. PMID:27524980

  6. Hypoxia-Inducible Factor 3 Is an Oxygen-Dependent Transcription Activator and Regulates a Distinct Transcriptional Response to Hypoxia

    Peng Zhang

    2014-03-01

    Full Text Available Hypoxia-inducible factors (HIFs play key roles in the cellular response to hypoxia. It is widely accepted that whereas HIF-1 and HIF-2 function as transcriptional activators, HIF-3 inhibits HIF-1/2α action. Contrary to this idea, we show that zebrafish Hif-3α has strong transactivation activity. Hif-3α is degraded under normoxia. Mutation of P393, P493, and L503 inhibits this oxygen-dependent degradation. Transcriptomics and chromatin immunoprecipitation analyses identify genes that are regulated by Hif-3α, Hif-1α, or both. Under hypoxia or when overexpressed, Hif-3α binds to its target gene promoters and upregulates their expression. Dominant-negative inhibition and knockdown of Hif-3α abolish hypoxia-induced Hif-3α-promoter binding and gene expression. Hif-3α not only mediates hypoxia-induced growth and developmental retardation but also possesses hypoxia-independent activities. Importantly, transactivation activity is conserved and human HIF-3α upregulates similar genes in human cells. These findings suggest that Hif-3 is an oxygen-dependent transcription factor and activates a distinct transcriptional response to hypoxia.

  7. Activation of resting T cells: distinct roles of intact accessory cells, phorbol myristate acetate and interleukin 1

    Davis, L.; Lipsky, P.E.

    1986-03-05

    The accessory cell (AC) signals involved in the activation of resting guinea pig T lymphocytes stimulated with mitogen (PHA), or the calcium ionophore, ionomycin (Ion) were examined. Activation of T cells was assessed by cell cycle analysis after acridine orange staining and /sup 3/H-thymidine incorporation. PHA-stimulated T cells depleted of all AC were unable to respond in the presence of phorbol myristate acetate (PMA), and/or interleukin 1 (IL 1). With suboptimal numbers of AC, PMA greatly augmented the number of T cells activated by PHA to enter and progress through the cell cycle, but only when present during the first few hours of culture. By contrast, IL 1 had little effect on the number of cells entering the cell cycle, although it enhanced S phase entry of the activated cells. IL 1 augmented DNA synthesis when added initially or later in culture. In contrast to the effects noted with PHA, PMA promoted activation and DNA synthesis of the majority of Ion stimulated cells in the complete absence of AC. IL 1 alone could not support Ion induced T cell activation although it enhanced T cell DNA synthesis in cultures stimulated by PMA and Ion. These studies indicate that intact AC, IL 1 and PMA-like signals play distinct roles in the progression of T cells through the initial cell cycle. Stimulation by Ion requires only PMA whereas PHA responses require intact AC and can be amplified by PMA. The major effect of IL 1 is to promote S phase entry of activated T cells.

  8. Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

    Rebecca L Schmidt

    Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.

  9. Dynamic Recruitment of Functionally Distinct Swi/Snf Chromatin Remodeling Complexes Modulates Pdx1 Activity in Islet β Cells

    Brian McKenna

    2015-03-01

    Full Text Available Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β cell function. However, little is known about the positive- and negative-acting coregulators recruited to mediate transcriptional control. Here, we isolated numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf core ATPase subunits, Brg1 and Brm, distinctly affected target gene expression in β cells. Furthermore, physiological and pathophysiological conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes in vivo. We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity.

  10. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

    2016-01-01

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

  11. Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

    The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

  12. Acquired deficiencies of protein S. Protein S activity during oral anticoagulation, in liver disease, and in disseminated intravascular coagulation.

    D'Angelo, A.; Vigano-D'Angelo, S; Esmon, C T; Comp, P C

    1988-01-01

    Protein S is a vitamin K-dependent plasma protein which serves as the cofactor for activated protein C. Protein S circulates in both an active, free form and in an inactive complex with C4b-binding protein. To elucidate the role of protein S in disease states and during oral anticoagulation, we developed a functional assay for protein S that permits evaluation of the distribution of protein S between free and bound forms and permits determination of the specific activity of the free protein S...

  13. Recursive Distinctioning

    Isaacson, Joel

    2016-01-01

    Recursive distinctioning (RD) is a name coined by Joel Isaacson in his original patent document describing how fundamental patterns of process arise from the systematic application of operations of distinction and description upon themselves. Recursive distinctioning means just what it says. A pattern of distinctions is given in a space based on a graphical structure (such as a line of print or a planar lattice or given graph). Each node of the graph is occupied by a letter from some arbitrary alphabet. A specialized alphabet is given that can indicate distinctions about neighbors of a given node. The neighbors of a node are all nodes that are connected to the given node by edges in the graph. The letters in the specialized alphabet (call it SA) are used to describe the states of the letters in the given graph and at each stage in the recursion, letters in SA are written at all nodes in the graph, describing its previous state. The recursive structure that results from the iteration of descriptions is called ...

  14. Maitotoxin activates cation channels distinct from the receptor-activated non-selective cation channels of HL-60 cells

    Musgrave, I. F.; Seifert, Roland; Schultz, Günter

    1994-01-01

    We investigated whether maitotoxin activates non-selective cation channels, as was recently proposed [Soergel, Yasumoto, Daly and Gusovsky (1992) Mol. Pharmacol. 41, 487-493]. Stimulation of dibutyryl cyclic AMP-differentiated HL-60 cells with the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 0.1 microM), the Ca(2+)-ATPase inhibitor thapsigargin (0.1 microM) or maitotoxin (25 ng/ml) resulted in an increase in cytoplasmic free calcium concentration ([Ca2+]i). Unlike ...

  15. RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.

    Glatzer, Timor; Killig, Monica; Meisig, Johannes; Ommert, Isabelle; Luetke-Eversloh, Merlin; Babic, Marina; Paclik, Daniela; Blüthgen, Nils; Seidl, Rainer; Seifarth, Claudia; Gröne, Jörn; Lenarz, Minoo; Stölzel, Katharina; Fugmann, Dominik; Porgador, Angel; Hauser, Anja; Karlas, Alexander; Romagnani, Chiara

    2013-06-27

    RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus. PMID:23791642

  16. Protein arginine methyltransferase 1 may be involved in pregnane x receptor-activated overexpression of multidrug resistance 1 gene during acquired multidrug resistant

    Li, Tingting; Kong, Ah-Ng Tony; Ma, Zhiqiang; Liu, Haiyan; Liu, Pinghua; Xiao, Yu; Jiang, Xuehua; Wang, Ling

    2016-01-01

    Purpose Pregnane x receptor (PXR) - activated overexpression of the multidrug resistance 1 (MDR1) gene is an important way for tumor cells to acquire drug resistance. However, the detailed mechanism still remains unclear. In the present study, we aimed to investigate whether protein arginine methyl transferase 1(PRMT1) is involved in PXR - activated overexpression of MDR1 during acquired multidrug resistant. Experimental Design Arginine methyltransferase inhibitor 1 (AMI-1) was used to pharmacologically block PRMT1 in resistant breast cancer cells (MCF7/adr). The mRNA and protein levels of MDR1 were detected by real-time PCR and western blotting analysis. Immunofluorescence microscopy and co-immunoprecipitation were used to investigate the physical interaction between PXR and PRMT1. Then, 136 candidate compounds were screened for PRMT1 inhibitors. Lastly, luciferase reporter gene and nude mice bearing resistant breast cancer xenografts were adopted to investigate the anti-tumor effect of PRMT1 inhibitors when combined with adriamycin. Results AMI-1 significantly suppressed the expression of MDR1 in MCF7/adr cells and increased cells sensitivity of MCF7/adr to adriamycin. Physical interaction between PRMT1 and PXR exists in MCF7/adr cells, which could be disrupted by AMI-1. Those results suggest that PRMT1 may be involved in PXR-activated overexpression of MDR1 in resistant breast cancer cells, and AMI-1 may suppress MDR1 by disrupting the interaction between PRMT1 and PXR. Then, five compounds including rutin, isoquercitrin, salvianolic acid A, naproxen, and felodipline were identified to be PRMT1 inhibitors. Finally, those PRMT1 inhibitors were observed to significantly decrease MDR1 promoter activity in vitro and enhance the antitumor effect of adriamycin in nude mice that bearing resistant breast cancer xenografts. Conclusions PRMT1 may be an important co-activator of PXR in activating MDR1 gene during acquired resistance, and PRMT1 inhibitor combined with

  17. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    Illemann, Martin; Bird, Nigel; Majeed, Ali;

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1......). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14......, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings...

  18. The Nudix Hydrolase CDP-Chase, a CDP-Choline Pyrophosphatase, Is an Asymmetric Dimer with Two Distinct Enzymatic Activities

    Duong-Ly, Krisna C.; Gabelli, Sandra B.; Xu, WenLian; Dunn, Christopher A.; Schoeffield, Andrew J.; Bessman, Maurice J.; Amzel, L. Mario (Loyola); (JHU)

    2011-09-06

    A Nudix enzyme from Bacillus cereus catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. Here, we show that in addition, the enzyme has a 3{prime} {yields} 5{prime} RNA exonuclease activity. The structure of the free enzyme, determined to a 1.8-{angstrom} resolution, shows that the enzyme is an asymmetric dimer. Each monomer consists of two domains, an N-terminal helical domain and a C-terminal Nudix domain. The N-terminal domain is placed relative to the C-terminal domain such as to result in an overall asymmetric arrangement with two distinct catalytic sites: one with an 'enclosed' Nudix pyrophosphatase site and the other with a more open, less-defined cavity. Residues that may be important for determining the asymmetry are conserved among a group of uncharacterized Nudix enzymes from Gram-positive bacteria. Our data support a model where CDP-choline hydrolysis is catalyzed by the enclosed Nudix site and RNA exonuclease activity is catalyzed by the open site. CDP-Chase is the first identified member of a novel Nudix family in which structural asymmetry has a profound effect on the recognition of substrates.

  19. Distinctive Citizenship

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  20. Comparative in vitro activity of oral antimicrobial agents against Enterobacteriaceae from patients with community-acquired urinary tract infections in three European countries.

    Kresken, M; Körber-Irrgang, B; Biedenbach, D J; Batista, N; Besard, V; Cantón, R; García-Castillo, M; Kalka-Moll, W; Pascual, A; Schwarz, R; Van Meensel, B; Wisplinghoff, H; Seifert, H

    2016-01-01

    Enterobacteriaceae causing community-acquired urinary tract infections were examined in selected outpatient clinics and hospitals in Belgium, Germany and Spain using EUCAST breakpoints for susceptibility. A total of 1190 isolates were collected. Escherichia coli isolates were resistant to amoxicillin-clavulanic acid (28.1%), ciprofloxacin (23.4%) and trimethoprim-sulfamethoxazole (21.4%) compared with fosfomycin and nitrofurantoin (each, <1.5%). Ceftibuten (MIC50/90 0.25/0.5 mg/L) and ceftriaxone activity (MIC50/90 ≤0.25 mg/L) was comparable. Ceftibuten (MIC90 ≤0.25 mg/L) was also active against Proteus mirabilis and Klebsiella spp. Extended-spectrum β-lactamase phenotypes were 7.1% for E. coli, 5.6% for Klebsiella pneumoniae and 0.4% for P. mirabilis. Resistance was common among men and elderly women. PMID:26321667

  1. Hospital-acquired pneumonia

    ... this page: //medlineplus.gov/ency/article/000146.htm Hospital-acquired pneumonia To use the sharing features on this page, please enable JavaScript. Hospital-acquired pneumonia is an infection of the lungs ...

  2. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans

    Petrie, Michael A.; Kimball, Amy L.; McHenry, Colleen L.; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K.

    2016-01-01

    Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. Purpose: The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Methods: Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. Results: We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05). Conclusion: These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative

  3. Distinct parts of leukotriene C{sub 4} synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein

    Strid, Tobias; Svartz, Jesper; Franck, Niclas; Hallin, Elisabeth; Ingelsson, Bjoern; Soederstroem, Mats [Division of Cell biology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-58185 Linkoeping (Sweden); Hammarstroem, Sven, E-mail: sven.hammarstrom@liu.se [Division of Cell biology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-58185 Linkoeping (Sweden)

    2009-04-17

    Leukotriene C{sub 4} is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP) and leukotriene C{sub 4} synthase (LTC{sub 4}S) participate in its biosynthesis. We report evidence that LTC{sub 4}S interacts in vitro with both FLAP and 5-LO and that these interactions involve distinct parts of LTC{sub 4}S. FLAP bound to the N-terminal part/first hydrophobic region of LTC{sub 4}S. This part did not bind 5-LO which bound to the second hydrophilic loop of LTC{sub 4}S. Fluorescent FLAP- and LTC{sub 4}S-fusion proteins co-localized at the nuclear envelope. Furthermore, GFP-FLAP and GFP-LTC{sub 4}S co-localized with a fluorescent ER marker. In resting HEK293/T or COS-7 cells GFP-5-LO was found mainly in the nuclear matrix. Upon stimulation with calcium ionophore, GFP-5-LO translocated to the nuclear envelope allowing it to interact with FLAP and LTC{sub 4}S. Direct interaction of 5-LO and LTC{sub 4}S in ionophore-stimulated (but not un-stimulated) cells was demonstrated by BRET using GFP-5-LO and Rluc-LTC{sub 4}S.

  4. Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation.

    Liu, Jeff C; Wang, Dong-Yu; Egan, Sean E; Zacksenhaus, Eldad

    2016-02-23

    PTEN loss and PIK3CA activation both promote the accumulation of phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). While these proteins also have distinct biochemical functions, beyond the regulation of PIP3, little is known about the consequences of these differences in vivo. Here, we directly compared cancer signalling in mammary tumors from MMTV-Cre:Ptenf/f and MMTV-Cre:Pik3caLSL-H1047R mice. Using unsupervised hierarchical clustering we found that whereas MMTV-Cre:Pik3caLSL-H1047R-derived tumors fall into two separate groups, designated squamous-likeEx and class14Ex, MMTV-Cre:Ptenf/f tumors cluster as one group together with PIK3CAH1047R class14Ex, exhibiting a 'luminal' expression profile. Gene Set Enrichment Analysis (GSEA) of Pten∆ and PIK3CAH1047R class14Ex tumors revealed very similar profiles of signalling pathways as well as some interesting differences. Analysis of 18 signalling signatures revealed that PI3K signalling is significantly induced whereas EGFR signalling is significantly reduced in Pten∆ versus PIK3CAH1047R tumors. Thus, Pten∆ and PIK3CAH1047R tumors exhibit discernable differences that may impact tumorigenesis and response to therapy. PMID:26814435

  5. HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

    Freya M Mowat

    Full Text Available BACKGROUND: Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO. CONCLUSIONS/SIGNIFICANCE: Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation

  6. An enriched rearing environment calms adult male rat sexual activity: implication for distinct serotonergic and hormonal responses to females.

    Susumu Urakawa

    Full Text Available Early life events induce alterations in neural function in adulthood. Although rearing in an enriched environment (EE has a great impact on behavioral development, the effects of enriched rearing on sociosexual behavior remain unclear. In this study, we investigated the effects of rearing in an EE on male copulatory behavior and its underlying neurobiological mechanisms in Wistar-Imamichi rats. Three-week-old, recently weaned rats were continuously subjected to a standard environment (SE or an EE comprised of a large cage with several objects, such as toys, tunnels, ladders, and a running wheel. After 6 weeks, rats reared in an EE (EE rats showed decreased sexual activity compared with rats reared in a SE (SE rats. This included a lower number of ejaculations and longer latencies in three consecutive copulatory tests. In addition, EE rats showed decreased emotional responsiveness and less locomotor behavior in an open field. In a runway test, on the other hand, sexual motivation toward receptive females in EE males was comparable to that of SE males. Furthermore, following exposure to a female, increases in serotonin levels in the nucleus accumbens and the striatum were significantly suppressed in EE males, whereas dopaminergic responses were similar between the groups. Female-exposure-induced increases in the levels of plasma corticosterone and testosterone were also suppressed in EE rats compared to SE rats. These data suggest that rearing in an EE decreases male copulatory behavior, and serotonin and hormonal regulating systems may regulate the differences in sociosexual interactions that result from distinct rearing environments.

  7. An enriched rearing environment calms adult male rat sexual activity: implication for distinct serotonergic and hormonal responses to females.

    Urakawa, Susumu; Mitsushima, Dai; Shimozuru, Michito; Sakuma, Yasuo; Kondo, Yasuhiko

    2014-01-01

    Early life events induce alterations in neural function in adulthood. Although rearing in an enriched environment (EE) has a great impact on behavioral development, the effects of enriched rearing on sociosexual behavior remain unclear. In this study, we investigated the effects of rearing in an EE on male copulatory behavior and its underlying neurobiological mechanisms in Wistar-Imamichi rats. Three-week-old, recently weaned rats were continuously subjected to a standard environment (SE) or an EE comprised of a large cage with several objects, such as toys, tunnels, ladders, and a running wheel. After 6 weeks, rats reared in an EE (EE rats) showed decreased sexual activity compared with rats reared in a SE (SE rats). This included a lower number of ejaculations and longer latencies in three consecutive copulatory tests. In addition, EE rats showed decreased emotional responsiveness and less locomotor behavior in an open field. In a runway test, on the other hand, sexual motivation toward receptive females in EE males was comparable to that of SE males. Furthermore, following exposure to a female, increases in serotonin levels in the nucleus accumbens and the striatum were significantly suppressed in EE males, whereas dopaminergic responses were similar between the groups. Female-exposure-induced increases in the levels of plasma corticosterone and testosterone were also suppressed in EE rats compared to SE rats. These data suggest that rearing in an EE decreases male copulatory behavior, and serotonin and hormonal regulating systems may regulate the differences in sociosexual interactions that result from distinct rearing environments. PMID:24505330

  8. Distinct Mechanisms of Receptor and Nonreceptor Tyrosine Kinase Activation by Reactive Oxygen Species in Vascular Smooth Muscle Cells: Role of Metalloprotease and Protein Kinase C-δ

    Frank, Gerald D.; Mifune, Mizuo; Inagami, Tadashi; Ohba, Motoi; Sasaki, Terukatsu; Higashiyama, Shigeki; Dempsey, Peter J; Eguchi, Satoru

    2003-01-01

    Reactive oxygen species (ROS) are implicated in cardiovascular diseases. ROS, such as H2O2, act as second messengers to activate diverse signaling pathways. Although H2O2 activates several tyrosine kinases, including the epidermal growth factor (EGF) receptor, JAK2, and PYK2, in vascular smooth muscle cells (VSMCs), the intracellular mechanism by which ROS activate these tyrosine kinases remains unclear. Here, we identified two distinct signaling pathways required for receptor and nonreceptor...

  9. Signals involved in T cell activation. II. Distinct roles of intact accessory cells, phorbol esters, and interleukin 1 in activation and cell cycle progression of resting T lymphocytes

    Davis, L.; Lipsky, P.E.

    1986-05-15

    The signals involved in the initiation of mitogen-induced activation of resting guinea pig T cells were examined. The combination of phytohemagglutinin (PHA) and 4..beta..-phorbol 12-myristate 13-acetate (PMA) stimulated DNA synthesis by accessory cell (AC)-depleted T cells cultured at high density, but the use of low density cultures indicated that intact AC were absolutely necessary for PHA-stimulated T cell DNA synthesis even in the presence of PMA, interleukin 1 (IL 1), or interleukin 2 (IL 2). In contrast, AC-depleted T cells were able to respond to the combination of the calcium ionophore, ionomycin, and PMA regardless of the cell density at which they were cultured. Results of cell cycle analysis support the conclusion that intact AC, IL 1, and a PMA-like signal play distinct roles in the progression of mitogen stimulated T cells through the first round of the cell cycle.

  10. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Abu Lila, Amr S. [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Sharqia Governorate, Zagazig 44519 (Egypt); Ishida, Tatsuhiro, E-mail: ishida@tokushima-u.ac.jp [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Kiwada, Hiroshi [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan)

    2014-05-15

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal

  11. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG2000 conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH2CH2) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG IgMs were

  12. Bacillus cereus AR156 activates PAMP-triggered immunity and induces a systemic acquired resistance through a NPR1-and SA-dependent signaling pathway.

    Niu, Dongdong; Wang, Xiujuan; Wang, Yanru; Song, Xiaoou; Wang, Jiansheng; Guo, Jianhua; Zhao, Hongwei

    2016-01-01

    Induced resistance responses play a potent role in plant defense system against pathogen attack. Bacillus cereus AR156 is a plant growth promoting rhizobacterium (PGPR) that installs induced systemic resistance (ISR) to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis. Here, we show that AR156 leaf infiltration enhances disease resistance in Arabidopsis through the activation of a systemic acquired resistance (SAR). PR1 protein expression and reactive oxygen species (ROS) burst are strongly induced in plants treated with AR156 and inoculated with Pst than that in plants inoculated with Pst only. Moreover, AR156 can trigger SAR in jar1 or ein2 mutants, but not in the NahG transgenic and NPR1 mutant plants. Our results indicate that AR156-induced SAR depends on SA-signaling pathway and NPR1, but not JA and ET. Also, AR156-treated plants are able to rapidly activate MAPK signaling and FRK1 gene expression, which are involved in pathogen associated molecular pattern (PAMP)-triggered immunity (PTI). Altogether, our results indicate that AR156 can induce SAR by the SA-signaling pathways in an NPR1-dependent manner and involves multiple PTI components. PMID:26616055

  13. Distinctly December.

    Instructor, 1982

    1982-01-01

    This special section presents Christmas and Hanukkah holiday activities and describes decorations and gifts that children can make. Other seasonal ideas include a Christmas luau dance, a magic Christmas tree, and Christmas and Hanukkah games and stories. (PP)

  14. Intercontrole acquiring by Framatome

    The Framatome group, as the worldwide leader in nuclear power plant construction, has reinforced his competences in nuclear services thanks to the acquiring of the Intercontrole company, specialized in non-destructive testing in nuclear and industrial environments. After a presentation of the functioning principle and of the safety aspects of a PWR reactor, this press dossier presents in a first part the role of nuclear services and in particular of non-destructive testing in nuclear power plants (in-service inspection, regulatory aspects, testing processes). This part is illustrated with some examples of inspection performed on some components of the primary coolant loop (steam generators, reactor vessel, pressurizer, pipes, primary pumps). A second part presents the technical centres and units of Framatome in charge of performing non-destructive inspections, while a third part describes the industrial policy and strategy of the group in this domain (market of nuclear park maintenance in France, in the USA and worldwide, creation of the 'inspection and control' centre of Framatome). A last part presents the activities of the Intercontrole company and of its daughter companies with some examples of actions realized in the nuclear and natural gas domains. (J.S.)

  15. Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells.

    Firtina Karagonlar, Zeynep; Koc, Dogukan; Iscan, Evin; Erdal, Esra; Atabey, Neşe

    2016-04-01

    Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Limitations in HCC treatment result due to poor prognosis and resistance against traditional radiotherapy and chemotherapies. The multikinase inhibitor sorafenib is the only FDA approved drug available for advanced HCC patients, and development of second-line treatment options for patients who cannot tolerate or develop resistance to sorafenib is an urgent medical need. In this study, we established sorafenib-resistant cells from Huh7 and Mahlavu cell lines by long-term sorafenib exposure. Sorafenib-resistant HCC cells acquired spindle-shape morphology, upregulated mesenchymal markers, and showed significant increase in both migration and invasion abilities compared to their parental counterparts. Moreover, after long-term sorafenib treatment, HCC cells showed induction of hepatocyte growth factor (HGF) synthesis and secretion along with increased levels of c-Met kinase and its active phosphorylated form, indicating autocrine activation of HGF/c-Met signaling. Importantly, the combined treatment of the resistant cells with c-Met kinase inhibitor SU11274 and HGF neutralizing antibody significantly reversed the increased invasion ability of the cells. The combined treatment also significantly augmented sorafenib-induced apoptosis, suggesting restoration of sorafenib sensitivity. These results describe, for the first time, compensatory upregulation of HGF synthesis leading to autocrine activation of HGF/c-Met signaling as a novel cellular strategy in the acquisition of sorafenib resistance. Therefore, we suggest that combinatorial therapeutic strategies with HGF and c-Met inhibitors comprise promising candidates for overcoming sorafenib resistance. PMID:26790028

  16. Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera

    Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with 201Tl (84 patients) or 99mTc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for 201Tl (78 patients) or 99mTc-sestamibi (80 patients) exercise CZT SPECT. The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for 201Tl than for 99mTc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26 % error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for 99mTc-sestamibi and 30.5 and 13.1ppm for 201Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for 99mTc-sestamibi and 39 and 91 MBq for 201Tl, respectively. Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for 99mTc-sestamibi and in non-obese subjects. (orig.)

  17. Immunomodulation in community-acquired pneumonia

    Remmelts, H.H.F.

    2013-01-01

    Community-acquired pneumonia (CAP) is a common disease with considerable morbidity and mortality, despite effective antibiotic treatment. In this thesis, we showed that the major causative microorganisms in CAP trigger distinct inflammatory response profiles in the host. While an inflammatory respon

  18. Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

    Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

    2009-01-01

    Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morpholo...

  19. Genetic Susceptibility and Caspase Activation in Mouse and Human Macrophages Are Distinct for Legionella longbeachae and L. pneumophila▿

    Asare, Rexford; Santic, Marina; Gobin, Ivana; Doric, Miljenko; Suttles, Jill; Graham, James E.; Price, Christopher D.; Abu Kwaik, Yousef

    2007-01-01

    Legionella pneumophila is the predominant cause of Legionnaires' disease in the United States and Europe, while Legionella longbeachae is the common cause of the disease in Western Australia. Although clinical manifestations by both intracellular pathogens are very similar, recent studies have shown that phagosome biogeneses of both species within human macrophages are distinct (R. Asare and Y. Abu Kwaik, Cell. Microbiol., in press). Most inbred mouse strains are resistant to infection by L. ...

  20. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine

    Barington, T; Gyhrs, A; Kristensen, Kim;

    1994-01-01

    factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One...... than infants with low prevaccination levels after the first (P = 0.0001) and the second (P = 0.01) doses of HibCP-TT. In contrast, active priming with TT at 4 months resulted in a threefold-higher median level of anti-HibCP (group C; 1.34 micrograms/ml) than in the unprimed group (group A; 0.......40 microgram/ml) after the first dose of HibCP-TT (P = 0.01). Coadministration of TT had no enhancing effect (group B; 0.58 microgram/ml). No significant differences between the median anti-HibCP levels were seen after the second HibCP-TT dose (6.72, 9.63, and 11.44 micrograms/ml in groups A, B, and C...

  1. Ground Deformation Associated With Post-Mining Activity at the French-German Border Revealed by Multidimensional Time Series Analysis of SAR Data Acquired in Various Orbital Geometries

    Smets, B.; Samsonov, S. V.; d'Oreye, N.

    2012-12-01

    We present the application of an innovative methodology for producing multidimensional time series of ground deformation from satellite radar data acquired by sensors with various acquisition geometry, ground resolution, and wave band (Samsonov and d'Oreye, Resubmitted). This technique is based on the Small Baseline Subset (SBAS) method that is modified to produce horizontal and vertical time series of ground deformation. Produced time series have combined coverage, improved temporal resolution and lower noise level. We apply this methodology for mapping coal mining related ground subsidence and heave in the Greater Region of Luxembourg along the French-German border. For this we processed 167 Synthetic Aperture Radar ERS-1/2 and ENVISAT images acquired between 1995 and 2009 from one ascending (track 29) and one descending (track 337) tracks and created over five hundred interferograms that were used for time series analysis. Produced vertical and east-west linear deformation rates show with remarkable precision region of localized ground deformation located above and caused by mining and post-mining activities. Time series of ground de- formation display temporal variability: reversal from subsidence to uplift and acceleration of subsidence on the vertical component and horizontal motion towards the center of the subsidence on the east-west component. InSAR results are successfully validated by leveling measurements performed by the French Geological Survey (BRGM) during 2006-2008. We determined that deformation rate changes are mainly caused by water level variations in the mines. Due to higher temporal and spatial resolution the proposed space-born method detected a larger number of subsidence and uplift areas in comparison to leveling measurements restricted to annual monitoring of benchmark points along roads. We also identified deformation regions that are not precisely located above the mining sites. Comparison of InSAR measurements with the water levels

  2. Laboratory-acquired brucellosis

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  3. A distinct and active bacterial community in cold oxygenated fluids circulating beneath the western flank of the Mid-Atlantic ridge

    Meyer, Julie L.; Jaekel, Ulrike; Tully, Benjamin J.; Glazer, Brian T.; Wheat, C. Geoffrey; Lin, Huei-Ting; Hsieh, Chih-Chiang; Cowen, James P.; Hulme, Samuel M.; Girguis, Peter R.; Huber, Julie A.

    2016-03-01

    The rock-hosted, oceanic crustal aquifer is one of the largest ecosystems on Earth, yet little is known about its indigenous microorganisms. Here we provide the first phylogenetic and functional description of an active microbial community residing in the cold oxic crustal aquifer. Using subseafloor observatories, we recovered crustal fluids and found that the geochemical composition is similar to bottom seawater, as are cell abundances. However, based on relative abundances and functional potential of key bacterial groups, the crustal fluid microbial community is heterogeneous and markedly distinct from seawater. Potential rates of autotrophy and heterotrophy in the crust exceeded those of seawater, especially at elevated temperatures (25 °C) and deeper in the crust. Together, these results reveal an active, distinct, and diverse bacterial community engaged in both heterotrophy and autotrophy in the oxygenated crustal aquifer, providing key insight into the role of microbial communities in the ubiquitous cold dark subseafloor biosphere.

  4. Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera

    Verger, Antoine; Karcher, Gilles [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); INSERM U947 and Universite de Lorraine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Imbert, Laetitia [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Centre Alexis Vautrin, Department of Radiotherapy, Vandoeuvre (France); Yagdigul, Yalcine; Roch, Veronique [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Fay, Renaud [INSERM, Centre d' Investigation Clinique CIC-P 9501, Nancy (France); Djaballah, Wassila [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); INSERM U947 and Universite de Lorraine, Nancy (France); Rouzet, Francois; Le Guludec, Dominique [AP-HP, Hopital Bichat, Department of Nuclear Medicine, Paris (France); INSERM U 773 and Denis Diderot University, Paris (France); Fourquet, Nicolas [Clinique Pasteur, Toulouse (France); Poussier, Sylvain [INSERM U947 and Universite de Lorraine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Marie, Pierre-Yves [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); INSERM U1116 and Universite de Lorraine, Nancy (France); CHU-Nancy, Allee du Morvan, Medecine Nucleaire, Hopital de Brabois, Vandoeuvre-les-Nancy (France)

    2014-03-15

    Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with {sup 201}Tl (84 patients) or {sup 99m}Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for {sup 201}Tl (78 patients) or {sup 99m}Tc-sestamibi (80 patients) exercise CZT SPECT. The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for {sup 201}Tl than for {sup 99m}Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26 % error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for {sup 99m}Tc-sestamibi and 30.5 and 13.1ppm for {sup 201}Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for {sup 99m}Tc-sestamibi and 39 and 91 MBq for {sup 201}Tl, respectively. Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for {sup 99m}Tc-sestamibi and in non-obese subjects. (orig.)

  5. Aluminum-activated citrate and malate transporters encoded by distinct Al tolerance genes function independently in Arabidopsis

    Aluminum (Al) -activated malate and citrate exudation from roots plays an important role in conferring Al tolerance to many plant species. Here, we report on the identification and characterization of AtMATE, the gene encoding an Al-activated root citrate efflux transporter that functions in Arabid...

  6. Pneumonia - adults (community acquired)

    ... breathing (respiratory) condition in which there is an infection of the lung. This article covers community-acquired pneumonia (CAP). This type of pneumonia is found in persons who have not recently been in the hospital or another health care facility such as a ...

  7. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms

    Chiang, Wen-Chi; Pamp, Sünje Johanna; Nilsson, Martin;

    2012-01-01

    Biofilms are reported to be inherently refractory toward antimicrobial attack and, therefore, cause problems in industrial and medical settings. Pseudomonas aeruginosa biofilms contain subpopulations that exhibit high metabolic activity and subpopulations that exhibit low metabolic activity. We...... have found that membrane-targeting antimicrobials such as colistin, EDTA, SDS, and chlorhexidine specifically kill the inactive subpopulation in P. aeruginosa biofilms, whereas the active subpopulation survives exposure to these compounds. Because treatment of P. aeruginosa biofilms with the membrane......, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes. Our data suggest that the active subpopulation in P...

  8. Self-enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia

    Geng, Huimin; Hurtz, Christian; Lenz, Kyle B.; Chen, Zhengshan; Baumjohann, Dirk; Thompson, Sarah; Goloviznina, Natalya; Chen, Wei-Yi; Huan, Jianya; LaTocha, Dorian; Ballabio, Erica; Xiao, Gang; Lee, Jae-Woong; Deucher, Anne; Qi, Zhongxia; Park, Eugene; Huang, Chuanxin; Nahar, Rahul; Kweon, Soo-Mi; Shojaee, Seyedmehdi; Chan, Lai N.; Yu, Jingwei; Kornblau, Steven M.; Bijl, Janetta J.; Ye, B. Hilda; Ansel, Mark; Paietta, Elisabeth; Melnick, Ari; Hunger, Stephen P.; Kurre, Peter; Tyner, Jeffrey W.; Loh, Mignon L.; Roeder, Robert G.; Druker, Brian J.; Burger, Jan. A.; Milne, Thomas A.; Chang, Bill H.; Müschen, Markus

    2015-01-01

    SUMMARY Studying 830 pre-B ALL cases from four clinical trials, we found that human ALL can be divided into two fundamentally distinct subtypes based on pre-BCR function. While absent in the majority of ALL cases, tonic pre-BCR signaling was found in 112 cases (13.5%). In these cases, tonic pre-BCR signaling induced activation of BCL6, which in turn increased pre-BCR signaling output at the transcriptional level. Interestingly, inhibition of pre-BCR-related tyrosine kinases reduced constitutive BCL6 expression and selectively killed patient-derived pre-BCR+ ALL cells. These findings identify a genetically and phenotypically distinct subset of human ALL that critically depends on tonic pre-BCR signaling. In vivo treatment studies suggested that pre-BCR tyrosine kinase inhibitors are useful for the treatment of patients with pre-BCR+ ALL. PMID:25759025

  9. G0 B cells activated by anti-μ acquire the ability to proliferate in response to B cell-activating factors independently from entry into G1 phase

    The early steps in B cell activation were investigated and it was determined that activation could be separated from entry into cell cycle. Purified B cells from BALB/c nu/nu mice, activated under controlled conditions by affinity-purified rabbit IgG anti-μ or F(ab')2 fragments prepared from the same antibodies, were sorted according to size by flow cytometry. Approximately 80% of the B cells were small and were shown to be in G0 state by quantitative RNA analysis and by [3H]uridine and [3H]thymidine incorporation studies. The sorted G0 B cells, when again incubated in serum-free medium with the appropriate anti-μ preparations, remained in G0. However, G0 B cells in the presence of anti-μ have undergone significant change(s), in as much as they were now able to proliferate in response to soluble mediators. The ability to develop a proliferative response to B cell-activating factor(s), acquired independently from entry into cell cycle, characterizes another important step in early B cell activation and also indicates that G0 B cells characterized on the basis of cell size, density, and/or RNA content may be in an activated state

  10. Two distinct regions of the BPV1 E1 replication protein interact with the activation domain of E2.

    Moscufo, N; Sverdrup, F; Breiding, D E; Androphy, E J

    1999-12-15

    Papillomavirus E1 and E2 proteins co-operation in viral DNA replication is mediated by protein-protein interactions that lead to formation of an E1-E2 complex. To identify the domains involved, portions of the two proteins were expressed as fusions to the DNA-binding protein LexA or the transactivation domain of VP16 and analyzed by the yeast two-hybrid system. The C-terminal 266 amino acids of BPV1 E1 (E1C266) interacted strongly with E2 in the yeast system and in a mammalian two-hybrid assay. VP16-E1C266 interacted with a region encompassing amino acids 1-200 of the transactivation domain of E2 that was fused to LexA. The interaction between E1 full length and E2 was clearly observed only when E1 was expressed as LexA-E1 chimera. In addition, we found that in the LexA context also the N-terminal region encompassing the first 340 amino acids of E1 (E1N340) interacted with E2 full length. The interactions of E1N340 and E1C266 with E2 were confirmed also by in vitro binding studies. These observations demonstrate that two distinct regions of E1 mediate the interaction with E2 in vivo. PMID:10581387

  11. DMPD: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activit...Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity... IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. Authors Solis M, Goubau

  12. In Vitro Activity of the Quinolone WCK 771 against Recent U.S. Hospital and Community-Acquired Staphylococcus aureus Pathogens with Various Resistance Types▿

    Bhagwat, Sachin S.; McGhee, Pamela; Kosowska-Shick, Klaudia; Patel, Mahesh V.; Appelbaum, Peter C.

    2008-01-01

    WCK 771 demonstrated MIC50 and MIC90s of 0.03 and 1 μg/ml, respectively, against 297 recent U.S. community-acquired and hospital strains of Staphylococcus aureus, irrespective of quinolone or glycopeptide resistance. Against quinolone-resistant strains, MIC90s of WCK 771 and moxifloxacin were 1 and 16 μg/ml, respectively.

  13. Distinct Polymer Architecture Mediates Switching of Complement Activation Pathways at the Nanosphere-Serum Interface: Implications for Stealth Nanoparticle Engineering

    Hamad, I.; Al-Hanbali, O.; Hunter, A.C.;

    2010-01-01

    Nanoparticles with surface projected polyethyleneoxide (PEO) chains in 'mushroom-brush' and "brush" configurations display stealth properties in systemic circulation and have numerous applications in site specific targeting for controlled drug delivery and release as well as diagnostic Imaging. We...... reactions in some individuals Conformational states of surface chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only....... Notably, the role properdin mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom-brush configuration Since nanoparticle-mediated complement activation is of clinical concern our findings provide a rational basis for improved surface...

  14. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization

    Reinhardt, H Christian; Hasskamp, Pia; Schmedding, Ingolf;

    2010-01-01

    Following genotoxic stress, cells activate a complex kinase-based signaling network to arrest the cell cycle and initiate DNA repair. p53-defective tumor cells rewire their checkpoint response and become dependent on the p38/MK2 pathway for survival after DNA damage, despite a functional ATR-Chk1...... pathway. We used functional genetics to dissect the contributions of Chk1 and MK2 to checkpoint control. We show that nuclear Chk1 activity is essential to establish a G(2)/M checkpoint, while cytoplasmic MK2 activity is critical for prolonged checkpoint maintenance through a process of...... posttranscriptional mRNA stabilization. Following DNA damage, the p38/MK2 complex relocalizes from nucleus to cytoplasm where MK2 phosphorylates hnRNPA0, to stabilize Gadd45α mRNA, while p38 phosphorylates and releases the translational inhibitor TIAR. In addition, MK2 phosphorylates PARN, blocking Gadd45α m...

  15. INFLUENCE OF SOCIAL ACTIVITY ON FUNCTIONING OF POLITICAL SYSTEM: DISTINCTIONS BETWEEN CLAN ISLAMIC AND WESTERN INDIVIDUALISTIC SOCIETIES

    Semenov Vitaly Andriyovych

    2012-01-01

    In this article the mechanism of influence of social activity on process of functioning of political system is considered. Within the limits of the structural functionalism comparison of concepts «political regime» and «political system» is undertaken. Building upon the L.N.Gumilev’s concept of passionarity, dependence of political regime type on level of social activity of a society is investigated. The main aim of this work is to discover why introduction of western political practices into...

  16. Acquired cystic kidney disease

    Choyke, P.L. [National Institutes of Health, Bethesda, MD (United States). Dept. of Diagnostic Radiology

    2000-11-01

    Acquired cystic kidney disease (ACKD), also known as acquired renal cystic disease (ARCD,) occurs in patients who are on dialysis for end-stage renal disease. It is generally accepted that ACKD develops as a consequence of sustained uremia and can first manifest even before dialysis is initiated while the patient is still in chronic renal failure. The role of immune suppression, particularly in transplant recipients, in the development of ACKD, is still under investigation. The prevalence of ACKD is directly related to the duration of dialysis and the risk of cancer is directly related to the presence of cysts. Herein we review the current understanding of the pathophysiology and imaging implications of ACKD. (orig.)

  17. Acquired cystic kidney disease

    Acquired cystic kidney disease (ACKD), also known as acquired renal cystic disease (ARCD,) occurs in patients who are on dialysis for end-stage renal disease. It is generally accepted that ACKD develops as a consequence of sustained uremia and can first manifest even before dialysis is initiated while the patient is still in chronic renal failure. The role of immune suppression, particularly in transplant recipients, in the development of ACKD, is still under investigation. The prevalence of ACKD is directly related to the duration of dialysis and the risk of cancer is directly related to the presence of cysts. Herein we review the current understanding of the pathophysiology and imaging implications of ACKD. (orig.)

  18. Acquired epidermolysis bullosa

    Maricel Sucar Batista; Yanier Serrano García; Taimí Miranda Vergara

    2015-01-01

    Epidermolysis bullosa is a group of diseases or skin disorders genetically transmitted and it is characterized by the appearance of bullae, ulcers and skin wounds. It usually appears at birth or in the first months of life. This is a case of a 72-year-old female patient who comes to the dermatology department with skin lesions of 6 months of evolution. A skin biopsy was performed, taking a sample for direct and indirect immunofluorescence. Acquired epidermolysis bullosa of unknown etiology wa...

  19. Acquired hypertrichosis lanuginosa

    Kumar Pramod

    1993-01-01

    Full Text Available Acquired hypertirichosis lanuginose developed rapidly in a patient with no detectable malignancy. Soft, fine, downy hair growth was noticed on the face, ears, limbs and trunk. Bilaterally symmetrical vitiliginous macules were present on the ear and preauricular region. This case is reported because of its rarity, absence of any detectable malignancy and development of vitiligo, which to our knowledge has not been reported earlier.

  20. AIDS: acquired immunodeficiency syndrome

    Gilmore, N. J.; Beaulieu, R.; Steben, M.; Laverdière, M.

    2002-01-01

    Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi's sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Ca...

  1. Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.

    Simon, Bertrand; Huart, Anne-Sophie; Temmerman, Koen; Vahokoski, Juha; Mertens, Haydyn D T; Komadina, Dana; Hoffmann, Jan-Erik; Yumerefendi, Hayretin; Svergun, Dmitri I; Kursula, Petri; Schultz, Carsten; McCarthy, Andrew A; Hart, Darren J; Wilmanns, Matthias

    2016-06-01

    The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation. PMID:27133022

  2. Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells.

    Toivonen, Raine; Kong, Lingjia; Rasool, Omid; Lund, Riikka J; Lahesmaa, Riitta; Hänninen, Arno

    2016-06-01

    Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis. PMID:27183629

  3. Human B lymphoblastoid cells contain distinct patterns of cathepsin activity in endocytic compartments and regulate MHC class II transport in a cathepsin S-independent manner.

    Lautwein, Alfred; Kraus, Marianne; Reich, Michael; Burster, Timo; Brandenburg, J; Overkleeft, Herman S; Schwarz, Gerold; Kammer, Winfried; Weber, Ekkehard; Kalbacher, Hubert; Nordheim, Alfred; Driessen, Christoph

    2004-05-01

    Endocytic proteolysis represents a major functional component of the major histocompatibility complex class II antigen-presentation machinery. Although transport and assembly of class II molecules in the endocytic compartment are well characterized, we lack information about the pattern of endocytic protease activity along this pathway. Here, we used chemical tools that visualize endocytic proteases in an activity-dependent manner in combination with subcellular fractionation to dissect the subcellular distribution of the major cathepsins (Cat) CatS, CatB, CatH, CatD, CatC, and CatZ as well as the asparagine-specific endoprotease (AEP) in human B-lymphoblastoid cells (BLC). Endocytic proteases were distributed in two distinct patterns: CatB and CatZ were most prominent in early and late endosomes but absent from lysosomes, and CatH, CatS, CatD, CatC, and AEP distributed between late endosomes and lysosomes, suggesting that CatB and CatZ might be involved in the initial proteolytic attack on a given antigen. The entire spectrum of protease activity colocalized with human leukocyte antigen-DM and the C-terminal and N-terminal processing of invariant chain (Ii) in late endosomes. CatS was active in all endocytic compartments. Surprisingly and in contrast with results from dendritic cells, inhibition of CatS activity by leucine-homophenylalanine-vinylsulfone-phenol prevented N-terminal processing of Ii but did not alter the subcellular trafficking or surface delivery of class II complexes, as deferred from pulse-chase analysis in combination with subcellular fractionation and biotinylation of cell-surface protein. Thus, BLC contain distinct activity patterns of proteases in endocytic compartments and regulate the intracellular transport and surface-delivery of class II in a CatS-independent manner. PMID:14966190

  4. Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling.

    Gaykema, Ronald P A; Daniels, Teresa E; Shapiro, Nathan J; Thacker, Gregory C; Park, Su-Mi; Goehler, Lisa E

    2009-10-19

    Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge

  5. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

    Brigitte Teissedre

    Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

  6. Early Adolescence as a Critical Window During Which Social Stress Distinctly Alters Behavior and Brain Norepinephrine Activity

    Bingham, Brian; McFadden, Kile; Zhang, Xiaoyan; Bhatnagar, Seema; Beck, Sheryl; Valentino, Rita

    2010-01-01

    Many neural programs that shape behavior become established during adolescence. Adverse events at this age can have enduring consequences for both adolescent and adult mental health. Here we show that repeated social stress at different stages of adolescent development differentially affects rat behavior and neuronal activity. Early-adolescent (PND 28, EA), mid-adolescent (PND 42, MA), and adult (PND 63) rats were subjected to resident-intruder social stress (7 days) and behavior was examined...

  7. Analysis of Thalassiosira pseudonana Silicon Transporters Indicates Distinct Regulatory Levels and Transport Activity through the Cell Cycle▿

    Thamatrakoln, Kimberlee; Hildebrand, Mark

    2006-01-01

    An analysis of the expression and activity of silicon transporters (SITs) was done on synchronously growing cultures of the diatom Thalassiosira pseudonana to provide insight into the role these proteins play in cellular silicon metabolism during the cell cycle. The first SIT-specific polyclonal peptide antibody was generated and used in the immunoblot analysis of whole-cell protein lysates to monitor SIT protein levels during synchronized progression through the cell cycle. Peaks in SIT prot...

  8. Distinct and cooperative activities of HESO1 and URT1 nucleotidyl transferases in microRNA turnover in Arabidopsis.

    Bin Tu

    2015-04-01

    Full Text Available 3' uridylation is increasingly recognized as a conserved RNA modification process associated with RNA turnover in eukaryotes. 2'-O-methylation on the 3' terminal ribose protects micro(miRNAs from 3' truncation and 3' uridylation in Arabidopsis. Previously, we identified HESO1 as the nucleotidyl transferase that uridylates most unmethylated miRNAs in vivo, but substantial 3' tailing of miRNAs still remains in heso1 loss-of-function mutants. In this study, we found that among nine other potential nucleotidyl transferases, UTP:RNA uridylyltransferase 1 (URT1 is the single most predominant nucleotidyl transferase that tails miRNAs. URT1 and HESO1 prefer substrates with different 3' end nucleotides in vitro and act cooperatively to tail different forms of the same miRNAs in vivo. Moreover, both HESO1 and URT1 exhibit nucleotidyl transferase activity on AGO1-bound miRNAs. Although these enzymes are able to add long tails to AGO1-bound miRNAs, the tailed miRNAs remain associated with AGO1. Moreover, tailing of AGO1-bound miRNA165/6 drastically reduces the slicing activity of AGO1-miR165/6, suggesting that tailing reduces miRNA activity. However, monouridylation of miR171a by URT1 endows the miRNA the ability to trigger the biogenesis of secondary siRNAs. Therefore, 3' tailing could affect the activities of miRNAs in addition to leading to miRNA degradation.

  9. Role of the Epstein-Barr Virus Rta Protein in Activation of Distinct Classes of Viral Lytic Cycle Genes

    Ragoczy, Tobias; Miller, George

    1999-01-01

    Initiation of the Epstein-Barr virus (EBV) lytic cycle is controlled by two immediate-early genes, BZLF1 and BRLF1. In certain epithelial and B-cell lines, their protein products, ZEBRA and Rta, stimulate their own expression, reciprocally stimulate each other’s expression, and activate downstream viral targets. It has been difficult to examine the individual roles of these two transactivators in EBV-infected lymphocytes, as they are expressed simultaneously upon induction of the lytic cycle....

  10. Distinct activation of primary human BDCA1(+) dendritic cells upon interaction with stressed or infected β cells.

    Schulte, B M; Kers-Rebel, E D; Bottino, R; Piganelli, J D; Galama, J M D; Engelse, M A; de Koning, E J P; Adema, G J

    2016-06-01

    Derailment of immune responses can lead to autoimmune type 1 diabetes, and this can be accelerated or even induced by local stress caused by inflammation or infection. Dendritic cells (DCs) shape both innate and adaptive immune responses. Here, we report on the responses of naturally occurring human myeloid BDCA1(+) DCs towards differentially stressed pancreatic β cells. Our data show that BDCA1(+) DCs in human pancreas-draining lymph node (pdLN) suspensions and blood-derived BDCA1(+) DCs both effectively engulf β cells, thus mimicking physiological conditions. Upon uptake of enterovirus-infected, but not mock-infected cells, BDCA1(+) DCs induced interferon (IFN)-α/β responses, co-stimulatory molecules and proinflammatory cytokines and chemokines. Notably, induction of stress in β cells by ultraviolet irradiation, culture in serum-free medium or cytokine-induced stress did not provoke strong DC activation, despite efficient phagocytosis. DC activation correlated with the amount of virus used to infect β cells and required RNA within virally infected cells. DCs encountering enterovirus-infected β cells, but not those incubated with mock-infected or stressed β cells, suppressed T helper type 2 (Th2) cytokines and variably induced IFN-γ in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed β cells have little effect on human BDCA1(+) DC activation and function, while enterovirus-infected β cells impact these cells significantly, which could help to explain their role in development of autoimmune diabetes in individuals at risk. PMID:26888163

  11. Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation

    Fuda, Nicholas J.; Mahat, Dig B.; Core, Leighton J.; Guertin, Michael J.

    2016-01-01

    The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS. We identify the primary HS response genes and the rate-limiting steps in the transcription cycle that GAGA-associated factor (GAF) and HS factor (HSF) regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA polymerase II (Pol II) formation (likely at the step of chromatin opening) and that GAF-facilitated Pol II pausing is critical for HS activation. In contrast, HSF is dispensable for establishing or maintaining Pol II pausing but is critical for the release of paused Pol II into the gene body at a subset of highly activated genes. Additionally, HSF has no detectable role in the rapid HS repression of thousands of genes. PMID:27492368

  12. Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence.

    Yannis Guillemin

    Full Text Available BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.

  13. Different synchronization characteristics of distinct types of traveling waves in a model of active medium with periodic boundary conditions

    Shepelev, Igor A.; Slepnev, Andrei V.; Vadivasova, Tatiana E.

    2016-09-01

    The model of a one-dimensional active medium, which cells are the FitzHugh-Nagumo oscillators, is studied for periodical boundary conditions. The medium possesses three different regimes in dependence on the parameter values. The regimes correspond to the self-sustained oscillations, excitable dynamics or bistability of the medium cells. Periodic boundary conditions provide the existence of traveling wave modes in all mentioned cases without any deterministic or stochastic excitation. The spatial waveforms and the character of oscillations in time can be similar in the different cases, but the properties of wave modes depend considerably on the medium regime. So, the dispersion characteristics and the synchronization phenomena are essentially different for bistable and excitable media on the one hand, and for the self-sustained oscillatory medium on the other hand. The local and distributed periodic influence on the medium are studied. The phenomenon of the traveling wave frequency locking is observed for all three regimes of the active medium. The comparison of synchronization effects in self-oscillatory, excitable and bistable regimes of the active medium is carried out.

  14. Learning-By-Being-Acquired

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    -categorization theories, we argue that R&D team reorganization increases the acquired inventors’ use of the prior stock of technological knowledge of the acquiring firm after the acquisition. Furthermore, this effect is enhanced if acquired inventors have higher innovation ability relative to their acquiring peers but is...

  15. Mechanism of action of ferrocene derivatives on the catalytic activity of topoisomerase IIalpha and beta--distinct mode of action of two derivatives.

    Sai Krishna, A D; Panda, Gayatri; Kondapi, Anand K

    2005-06-15

    Topoisomerase II is found to be present in two isoforms alpha and beta, and both the isoforms are regulated in cancerous tissue. Development of isoform-specific topoisomerase II poisons has been of great interest for cancer-specific drug targeting. In the present investigation using quantitative structure-activity analysis of ferrocene derivatives, we show that two derivatives of ferrocene, azalactone ferrocene and thiomorpholide amido methyl ferrocene, can preferentially inhibit topoisomerase IIbeta activity. Thiomorpholide amido methyl ferrocene shows higher inhibition of catalytic activity (IC(50) = 50 microM) against topoisomerase IIbeta compared to azalactone ferrocene (IC(50) = 100 microM). The analysis of protein DNA intermediates formed in the presence of these two compounds suggests that azalactone ferrocene readily induces formation of cleavable complex in a dose-dependent manner, in comparison with thiomorpholide amido methyl ferrocene. Both the compounds show significant inhibition of DNA-dependent ATPase activity of enzyme. These results suggest that azalactone ferrocene inhibits DNA passage activity of enzyme leading to the formation of cleavable complex, while thiomorpholide amido methyl ferrocene competes with ATP binding resulting in the inhibition of catalytic activity of enzyme. In summary, thiomorpholide amido methyl ferrocene and azalactone ferrocene show distinctly different mechanisms in inhibition of catalytic activity of topoisomerase IIbeta. PMID:15907782

  16. Distinct expression of alkaline phosphatase activity in epilimnetic bacteria: Implication for persistent DOC consumption in a P-limited reservoir

    Tseng, Y.; Kao, S.; Shiah, F.

    2013-12-01

    In a P-deficient system, P availability usually controls the microbial activity and thus the ecosystem function. Thingstad et al. (1997) first addressed a 'Malfunctioning Microbial-loop' theory, which stated that low bacterial production (BP) caused by insufficient nutrient supply would result in DOC accumulation in an oligotrophic ecosystem. In this study we re-examined the theory by conducting seasonal patterns and correlations among soluble reactive phosphate (SRP) and DOC, microbial abundances (picocyanobacteria, bacteria, and heterotrophic nanoflagellate; HNF) and activities (primary production, bacterial production, and alkaline phosphatase activity; APA) coupled with enzyme-labeled fluorescence (ELF) assays on bacterioplankton in a subtropical reservoir sharing the common features, nitrate-replete and P-deficient, with most natural freshwater system during Oct 2007-Oct 2008. Persistently high APA was recorded during most of time, implying that the system was P-deficient. Size fractionated APA and ELF assay revealed that bacteria were the major APA contributor. However, significantly low epilimnion DOC was recorded during the stratified summer season accompanying with high BP and APA as well as high PP, implying that heterotrophic bacteria can well sustain in P-deficient system by utilizing DOP to rapidly lower down DOC under relatively high PP. Such findings oppose the 'Malfunctioning Microbial-loop' theory. On the other hand, strong epilimnetic DOC accumulation occurred in Oct 2007 under low light and low PP condition accompanying with high abundance of HNF, implying that HNF grazing may contribute to a certain degree of DOC accumulation. Correlation matrix supported our suggestions. This study testified the DOC dynamics in P-deficient ecosystem are tightly coupled with the source (PP and grazing) and sink (BP). We also suggested that in SRP-limited freshwater systems bacteria are capable of breaking down autochthonous DOC to reduce the chance of DOC

  17. Studies of adhesion-dependent platelet activation: distinct roles for different participating receptors can be dissociated by proteolysis of collagen.

    Siljander, P; Lassila, R

    1999-12-01

    The molecular differences between native-type collagen type I fibrils (NC) and their pepsinated monomers (PC) were used to uncover receptors involved in platelet-collagen interaction along the adhesion-activation axis. The platelet-depositing capacity of NC and PC under blood flow and their adhesive properties and respective morphologies, aggregation, procoagulant capacity, and tyrosine phosphorylation were compared under different cationic milieus, including or excluding the glycoprotein (GP) Ia/IIa. NC was consistently a more preferable and activating substrate than PC during flow (5 minutes) and in platelet aggregation. In PPACK-treated blood, both NC (3.3-fold) and PC (2.7-fold) increased platelet attachment on elevation of the shear rate from 500 to 1640 s(-1), whereas in citrated blood, adhesion and thrombus growth on PC were negligible under the high shear rate, unlike on NC (1.9-fold increase). The complete lack of platelet deposition on PC in citrated blood could be overcome by restoring physiological Mg(2+) concentration, and in contrast to NC, platelets interacting with PC were highly dependent on Mg(2+) during adhesion, aggregation, and procoagulant response. Monoclonal antibody (mAb 131.7) against GP IV inhibited platelet deposition to NC in citrated blood (2 minutes) by 49%, which was not further increased by coincubation with mAb against GP Ia (6F1). These results stress the importance of GP Ia/IIa in shear-resistant platelet deposition on collagen monomers. In native fibers, however, the preserved quaternary structure with telopeptides activates additional platelet receptors capable of substituting GP Ia/IIa and GP IV. PMID:10591685

  18. Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

    Hanselman Keaton B

    2006-10-01

    Full Text Available Abstract Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109 animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C phenotype of age-1(mg109. Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109;akt-1(mg247 animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109;pdk-1(mg261 animals was dependent on akt-1. However, reproductive development in age-1(mg109; mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109 animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247 and pdk-1(mg261 did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these

  19. The Structure of the GM-CSF Receptor Complex Reveals a Distinct Mode of Cytokine Receptor Activation

    Hansen, Guido; Hercus, Timothy R.; McClure, Barbara J.; Stomski, Frank C.; Dottore, Mara; Powell, Jason; Ramshaw, Hayley; Woodcock, Joanna M.; Xu, Yibin; Guthridge, Mark; McKinstry, William J.; Lopez, Angel F.; Parker, Michael W. (SVIMR-A); (Hanson)

    2008-08-11

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific {alpha} subunit and a {beta}c subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface and functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.

  20. Discrete levels of Twist activity are required to direct distinct cell functions during gastrulation and somatic myogenesis.

    Ming-Ching Wong

    Full Text Available Twist (Twi, a conserved basic helix-loop-helix transcriptional regulator, directs the epithelial-to-mesenchymal transition (EMT, and regulates changes in cell fate, cell polarity, cell division and cell migration in organisms from flies to humans. Analogous to its role in EMT, Twist has been implicated in metastasis in numerous cancer types, including breast, pancreatic and prostate. In the Drosophila embryo, Twist is essential for discrete events in gastrulation and mesodermal patterning. In this study, we derive a twi allelic series by examining the various cellular events required for gastrulation in Drosophila. By genetically manipulating the levels of Twi activity during gastrulation, we find that coordination of cell division is the most sensitive cellular event, whereas changes in cell shape are the least sensitive. Strikingly, we show that by increasing levels of Snail expression in a severe twi hypomorphic allelic background, but not a twi null background, we can reconstitute gastrulation and produce viable adult flies. Our results demonstrate that the level of Twi activity determines whether the cellular events of ventral furrow formation, EMT, cell division and mesodermal migration occur.

  1. Acquired von Willebrand Syndrome

    郭涛

    2005-01-01

    @@ Acquired von Willebrand syndrome (AvWS) is kind of bleeding disorder with laboratory findings similar to those in congenital yon Willebrand disease (vWD).AvWS doesn's have any personal or family history of bleeding, but is associated with certain diseases or abnormal conditions or drugs. Although AvWS is being stated as a rare disease, it has gained more and more attention during the past years. Not because of the severity of the disease, but it is more common than we thought and most patients don' t have a proper diagnosis.

  2. Acquired epidermolysis bullosa

    Maricel Sucar Batista

    2015-12-01

    Full Text Available Epidermolysis bullosa is a group of diseases or skin disorders genetically transmitted and it is characterized by the appearance of bullae, ulcers and skin wounds. It usually appears at birth or in the first months of life. This is a case of a 72-year-old female patient who comes to the dermatology department with skin lesions of 6 months of evolution. A skin biopsy was performed, taking a sample for direct and indirect immunofluorescence. Acquired epidermolysis bullosa of unknown etiology was diagnosed. Treatment was started with low-dose colchicine to increase it later, according to the patient’s tolerance and disease progression.

  3. Erythropoietin activates two distinct signaling pathways required for the initiation and the elongation of c-myc

    Chen, C.; Sytkowski, A. J.

    2001-01-01

    Erythropoietin (Epo) stimulation of erythroid cells results in the activation of several kinases and a rapid induction of c-myc expression. Protein kinase C is necessary for Epo up-regulation of c-myc by promoting elongation at the 3'-end of exon 1. PKCepsilon mediates this signal. We now show that Epo triggers two signaling pathways to c-myc. Epo rapidly up-regulated Myc protein in BaF3-EpoR cells. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked Myc up-regulation in a concentration-dependent manner but had no effect on the Epo-induced phosphorylation of ERK1 and ERK2. LY294002 also had no effect on Epo up-regulation of c-fos. MEK1 inhibitor PD98059 blocked both the c-myc and the c-fos responses to Epo. PD98059 and the PKC inhibitor H7 also blocked the phosphorylation of ERK1 and ERK2. PD98059 but not LY294002 inhibited Epo induction of ERK1 and ERK2 phosphorylation in normal erythroid cells. LY294002 blocked transcription of c-myc at exon 1. PD98059 had no effect on transcription from exon 1 but, rather, blocked Epo-induced c-myc elongation at the 3'-end of exon 1. These results identify two Epo signaling pathways to c-myc, one of which is PI3K-dependent operating on transcriptional initiation, whereas the other is mitogen-activated protein kinase-dependent operating on elongation.

  4. 获得性再生障碍性贫血患者端粒-端粒酶活性的变化及其意义%Changes of telomere-telomerase activity in patients with acquired aplastic anemia

    宋佳音; 王耀春; 肖扬

    2013-01-01

    Summary To summarize (he research progress of iclomcrc length and telomerase activity in acquired aplastic anemia(Aaa). A full text database system based on PUBMED and CNK1 was adopted for searching relevant literature from 1996 to 2012 with the key words of "telomere.telomerase and acquired aplastic anemia". Criterion for data selection-The literature about advances of telomere, telomerase and acquired aplastic anemia was selected for a-nalysis. According to the standard.236 articles were analyzed. Acquired aplastic anemia is hone marrow failure syndromes that mainly results from immune-mediated destruction of hematopoiesis. About one-third of patients with Aaa have short telomeres in peripheral white blood cells.some of which have heterozygous mutations in genes encoding the telomerase components of TERT or TERC Clinical observation found that most Aaa patients with telomere shortening were insensitive to immunosuppressive therapy;the disease duration increased and the prognosis was poor. Short telomeres may cause malignant clonal diseases in the advanced .stage.such as MDS.AML. Treatment plan for these Aaa patients with shortening telomere should he adjusted. They must undergo haematopoietic stem cell transplant ( HSCT) as soon as possible,and family donors with relevant mutations must he avoided. The Aaa patients with telomere related abnormality are different from other patients regarding pathological mechanism,disease progress, treatment and prognosis. Only a small proportion of these eases could be explained by TERT or TERC mutation. Other mutation or causes may remain unknown .

  5. Osmosensitivity of transient receptor potential vanilloid 1 is synergistically enhanced by distinct activating stimuli such as temperature and protons.

    Eri Nishihara

    Full Text Available In animals, body-fluid osmolality is continuously monitored to keep it within a narrow range around a set point (∼300 mOsm/kg. Transient receptor potential vanilloid 1 (TRPV1, a cation channel, has been implicated in body-fluid homeostasis in vivo based on studies with the TRPV1-knockout mouse. However, the response of TRPV1 to hypertonic stimuli has not been demonstrated with heterologous expression systems so far, despite intense efforts by several groups. Thus, the molecular entity of the hypertonic sensor in vivo still remains controversial. Here we found that the full-length form of TRPV1 is sensitive to an osmotic increase exclusively at around body temperature using HEK293 cells stably expressing rat TRPV1. At an ambient temperature of 24°C, a slight increase in the intracellular calcium concentration ([Ca(2+](i was rarely observed in response to hypertonic stimuli. However, the magnitude of the osmosensitive response markedly increased with temperature, peaking at around 36°C. Importantly, the response at 36°C showed a robust increase over a hypertonic range, but a small decrease over a hypotonic range. A TRPV1 antagonist, capsazepine, and a nonspecific TRP channel inhibitor, ruthenium red, completely blocked the increase in [Ca(2+](i. These results endorse the view that the full-length form of TRPV1 is able to function as a sensor of hypertonic stimuli in vivo. Furthermore, we found that protons and capsaicin likewise synergistically potentiated the response of TRPV1 to hypertonic stimuli. Of note, HgCl(2, which blocks aquaporins and inhibits cell-volume changes, significantly reduced the osmosensitive response. Our findings thus indicate that TRPV1 integrates multiple different types of activating stimuli, and that TRPV1 is sensitive to hypertonic stimuli under physiologically relevant conditions.

  6. Distinct ensembles of medial prefrontal cortex neurons are activated by threatening stimuli that elicit excitation vs. inhibition of movement.

    Halladay, Lindsay R; Blair, Hugh T

    2015-08-01

    Neural circuits controlling defensive behavior were investigated by recording single units in medial prefrontal cortex (mPFC) and dorsolateral periaqueductal gray (dlPAG) while rats expressed conditioned fear responses to an auditory conditioned stimulus (CS; 20-s train of white noise pips) previously paired with an aversive unconditioned stimulus (US; 2-s train of periorbital shocks). The CS elicited conditioned movement inhibition (CMI; characterized by decreased movement speed and freezing) when rats had not recently encountered the US, whereas the CS elicited conditioned movement excitation (CME; characterized by increased movement speed and flight behavior) after recent US encounters. Many mPFC neurons were "strategy-selective" cells that changed their firing rates only when the CS elicited CME (15/71) or CMI (13/71) responses, whereas few mPFC cells (4/71) responded nonselectively to the CS during either response. By contrast, many dlPAG neurons (20/74) responded nonselectively to the CS, but most (40/74) were excited by the CS selectively during CME trials (and none during CMI trials). CME-selective neurons in dlPAG responded phasically after CS pips that elicited CME responses, whereas CME-selective neurons in mPFC showed tonically elevated activity before and after pips that evoked CME responses. These findings suggest that, at the time when the CS occurs, tonic firing rates of CME- and CMI-selective mPFC neurons may bias the rat's choice of whether to express CME vs. CMI responses, perhaps via projections to downstream structures (such as amygdala and PAG) that influence how sensory stimuli are mapped onto motor circuits that drive the expression of competing behaviors. PMID:25972588

  7. MRI active guidewire with an embedded temperature probe and providing a distinct tip signal to enhance clinical safety

    Sonmez Merdim

    2012-06-01

    Full Text Available Abstract Background The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035” (0.89 mm guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility. Methods The design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire. Results The solenoid displaced the point of maximal heating (“hot spot” from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes. Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45°; SAR, 1.01 W/kg; the temperature increased by 4.2°C only during high RF power mode (flip angle, 90°; SAR, 3.96 W/kg and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire. Conclusions We integrated a fiberoptic temperature probe inside

  8. Trade-offs between acquired and innate immune defenses in humans

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  9. Trade-offs between acquired and innate immune defenses in humans.

    McDade, Thomas W; Georgiev, Alexander V; Kuzawa, Christopher W

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  10. Acquired Blaschkoid dermatitis

    Mercy P

    2007-01-01

    Full Text Available Acquired Blaschkoid dermatitis characterised by unilateral relapsing inflammatory disease along the lines of Blaschko. A 40-year-old Indian male presented with unilateral erythematous, itchy grouped papules on the left side of the chest, abdomen, back and left arm of 15 days duration. The eruption stopped abruptly at the midline of the torso, completely sparing the right side of the body. The lesions were arranged in whorls and streaks corresponding to the lines of Blaschko. Skin biopsy showed hyperkeratosis and features suggestive of sub-acute spongiotic dermatitis with lymphocytic infiltrate around the blood vessels in the dermis. Patient was diagnosed as a case of Blaschkoid dermatitis. To the best of our knowledge, this is the first case of this condition being reported from India.

  11. Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

    Matthijs A A Van Der Meer

    2009-06-01

    Full Text Available Local field potential (LFP oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson’s disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45-55 Hz and gamma-80 (70-85 Hz oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

  12. Two distinct modes of metal ion binding in the nuclease active site of a viral DNA-packaging terminase: insight into the two-metal-ion catalytic mechanism.

    Zhao, Haiyan; Lin, Zihan; Lynn, Anna Y; Varnado, Brittany; Beutler, John A; Murelli, Ryan P; Le Grice, Stuart F J; Tang, Liang

    2015-12-15

    Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg(2+). A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 Å. Such proximity of the two metal ions may play an essential role in catalysis by generating a highly positive electrostatic niche to enable formation of the negatively charged pentacovalent phosphate transition state, and provides the structural basis for distinguishing Mg(2+) from Ca(2+). Using a metal ion chelator β-thujaplicinol as a molecular probe, we observed a second mode of metal ion binding at the active site, mimicking the DNA binding state. Arrangement of the active site residues differs drastically from those in RNase H-like nucleases, suggesting a drifting of the active site configuration during evolution. The two distinct metal ion binding modes unveiled mechanistic details of the two-metal-ion catalysis at atomic resolution. PMID:26450964

  13. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; Baelum, Jacob; Tas, Neslihan; Elberling, Bo; Jansson, Janet K.; Semenchuk, Phillip; Prieme, Anders

    2015-04-30

    The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78°N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below -10°C. Multivariate statistical analysis of the bacterial diversity data (DNA and cDNA libraries) revealed a season-based clustering of the samples, and, e.g., the relative abundance of potentially active Cyanobacteria peaked in June and Alphaproteobacteria increased over the summer and then declined from October to November. The structure of the bulk (DNA-based) community was significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface.

  14. ECoG high gamma activity reveals distinct cortical representations of lyrics passages, harmonic and timbre-related changes in a rock song

    Irene Sturm

    2014-10-01

    Full Text Available Listening to music moves our minds and moods, stirring interest in its neural underpinnings. A multitude of compositional features drives the appeal of natural music. How such original music, where a composer's opus is not manipulated for experimental purposes, engages a listener's brain has not been studied until recently. Here, we report an in-depth analysis of two electrocorticographic (ECoG data sets obtained over the left hemisphere in ten patients during presentation of either a rock song or a read-out narrative. First, the time courses of five acoustic features (intensity, presence/absence of vocals with lyrics, spectral centroid, harmonic change, and pulse clarity were extracted from the audio tracks and found to be correlated with each other to varying degrees. In a second step, we uncovered the specific impact of each musical feature on ECoG high-gamma power (70-170 Hz by calculating partial correlations to remove the influence of the other four features. In the music condition, the onset and offset of vocal lyrics in ongoing instrumental music was consistently within the subject group identified as the dominant driver for ECoG high-gamma power changes over temporal auditory areas, while concurrently subject-individual activation spots were identified for sound intensity, timbral and harmonic features. The distinct cortical activations to vocal speech-related content embedded in instrumental music directly demonstrate that song overlaid on instrumental music represents a distinct dimension in complex music. In contrast, in the speech condition, the full sound envelope was reflected in the high gamma response rather than the onset or offset of the vocal lyrics. This demonstrates how the contributions of stimulus features that modulate the brain response differ across the two examples of a full-length natural stimulus, which suggests a context-dependent feature selection in the processing of complex auditory stimuli.

  15. ECoG high gamma activity reveals distinct cortical representations of lyrics passages, harmonic and timbre-related changes in a rock song.

    Sturm, Irene; Blankertz, Benjamin; Potes, Cristhian; Schalk, Gerwin; Curio, Gabriel

    2014-01-01

    Listening to music moves our minds and moods, stirring interest in its neural underpinnings. A multitude of compositional features drives the appeal of natural music. How such original music, where a composer's opus is not manipulated for experimental purposes, engages a listener's brain has not been studied until recently. Here, we report an in-depth analysis of two electrocorticographic (ECoG) data sets obtained over the left hemisphere in ten patients during presentation of either a rock song or a read-out narrative. First, the time courses of five acoustic features (intensity, presence/absence of vocals with lyrics, spectral centroid, harmonic change, and pulse clarity) were extracted from the audio tracks and found to be correlated with each other to varying degrees. In a second step, we uncovered the specific impact of each musical feature on ECoG high-gamma power (70-170 Hz) by calculating partial correlations to remove the influence of the other four features. In the music condition, the onset and offset of vocal lyrics in ongoing instrumental music was consistently identified within the group as the dominant driver for ECoG high-gamma power changes over temporal auditory areas, while concurrently subject-individual activation spots were identified for sound intensity, timbral, and harmonic features. The distinct cortical activations to vocal speech-related content embedded in instrumental music directly demonstrate that song integrated in instrumental music represents a distinct dimension in complex music. In contrast, in the speech condition, the full sound envelope was reflected in the high gamma response rather than the onset or offset of the vocal lyrics. This demonstrates how the contributions of stimulus features that modulate the brain response differ across the two examples of a full-length natural stimulus, which suggests a context-dependent feature selection in the processing of complex auditory stimuli. PMID:25352799

  16. Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity.

    Kourtidis, Antonis; Ngok, Siu P; Pulimeno, Pamela; Feathers, Ryan W; Carpio, Lomeli R; Baker, Tiffany R; Carr, Jennifer M; Yan, Irene K; Borges, Sahra; Perez, Edith A; Storz, Peter; Copland, John A; Patel, Tushar; Thompson, E Aubrey; Citi, Sandra; Anastasiadis, Panos Z

    2015-09-01

    E-cadherin and p120 catenin (p120) are essential for epithelial homeostasis, but can also exert pro-tumorigenic activities. Here, we resolve this apparent paradox by identifying two spatially and functionally distinct junctional complexes in non-transformed polarized epithelial cells: one growth suppressing at the apical zonula adherens (ZA), defined by the p120 partner PLEKHA7 and a non-nuclear subset of the core microprocessor components DROSHA and DGCR8, and one growth promoting at basolateral areas of cell-cell contact containing tyrosine-phosphorylated p120 and active Src. Recruitment of DROSHA and DGCR8 to the ZA is PLEKHA7 dependent. The PLEKHA7-microprocessor complex co-precipitates with primary microRNAs (pri-miRNAs) and possesses pri-miRNA processing activity. PLEKHA7 regulates the levels of select miRNAs, in particular processing of miR-30b, to suppress expression of cell transforming markers promoted by the basolateral complex, including SNAI1, MYC and CCND1. Our work identifies a mechanism through which adhesion complexes regulate cellular behaviour and reveals their surprising association with the microprocessor. PMID:26302406

  17. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism.

    Pinkosky, Stephen L; Filippov, Sergey; Srivastava, Rai Ajit K; Hanselman, Jeffrey C; Bradshaw, Cheryl D; Hurley, Timothy R; Cramer, Clay T; Spahr, Mark A; Brant, Ashley F; Houghton, Jacob L; Baker, Chris; Naples, Mark; Adeli, Khosrow; Newton, Roger S

    2013-01-01

    ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. However, the molecular mechanism(s) mediating these activities remained undefined. Studies described here show that ETC-1002 free acid activates AMP-activated protein kinase in a Ca(2+)/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. These distinct molecular mechanisms are complementary in their beneficial effects on lipid and carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms, ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body weight and improved glycemic control in a mouse model of diet-induced obesity. ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk factors associated with metabolic syndrome and benefit patients with cardiovascular disease. PMID:23118444

  18. Sperm surface protein PH-20 is bifunctional: one activity is a hyaluronidase and a second, distinct activity is required in secondary sperm-zona binding.

    Hunnicutt, G R; Primakoff, P; Myles, D G

    1996-07-01

    In previous studies, we have found that the sperm membrane protein PH-20 acts during two different stages of fertilization. On acrosome-intact sperm, PH-20 has a hyaluronidase activity that is required for sperm penetration through the cumulus cell layer that surrounds the oocyte. On acrosome-reacted sperm, PH-20 has a required function in sperm-zona binding (secondary binding). Because hyaluronic acid (HA) has been detected in the zona pellucida, secondary sperm-zona adhesion could depend on repetitive binding and hydrolysis of HA by PH-20 acting as a hyaluronidase. Alternatively, PH-20 may be bifunctional and have a second, different activity required for secondary binding. To distinguish between these two possibilities, in this study we used reagents that inhibit either PH-20's function in sperm-zona binding or its hyaluronidase activity. We found that an anti-PH-20 monoclonal antibody that inhibited sperm-zona binding (approximately 90%) had no effect on hyaluronidase activity. Conversely, apigenin, a hyaluronidase inhibitor, blocked PH-20 hyaluronidase activity 93% without inhibiting sperm-zona binding. Similarly, another anti-PH-20 monoclonal antibody that inhibited hyaluronidase activity 95% only partially inhibited sperm-zona binding (approximately 45%). We also extensively pretreated oocytes with hyaluronidase to remove all accessible HA on or in the zona pellucida and found little or no effect on secondary sperm-zona binding. Our results suggest that PH-20 is bifunctional and has two activities: a hyaluronidase activity and a second, separate activity required for secondary sperm-zona binding. PMID:8793062

  19. High-rate activated sludge communities have a distinctly different structure compared to low-rate sludge communities, and are less sensitive towards environmental and operational variables.

    Meerburg, Francis A; Vlaeminck, Siegfried E; Roume, Hugo; Seuntjens, Dries; Pieper, Dietmar H; Jauregui, Ruy; Vilchez-Vargas, Ramiro; Boon, Nico

    2016-09-01

    High-rate activated sludge processes allow for the recovery of organics and energy from wastewaters. These systems are operated at a short sludge retention time and high sludge-specific loading rates, which results in a higher sludge yield and better digestibility than conventional, low-rate activated sludge. Little is known about the microbial ecology of high-rate systems. In this work, we address the need for a fundamental understanding of how high-rate microbial communities differ from low-rate communities. We investigated the high-rate and low-rate communities in a sewage treatment plant in relation to environmental and operational variables over a period of ten months. We demonstrated that (1) high-rate and low-rate communities are distinctly different in terms of richness, evenness and composition, (2) high-rate community dynamics are more variable and less shaped by deterministic factors compared to low-rate communities, (3) sub-communities of continuously core and transitional members are more shaped by deterministic factors than the continuously rare members, both in high-rate and low-rate communities, and (4) high-rate community members showed a co-occurrence pattern similar to that of low-rate community members, but were less likely to be correlated to environmental and operational variables. These findings provide a basis for further optimization of high-rate systems, in order to facilitate resource recovery from wastewater. PMID:27183209

  20. cAMP response element binding protein (CREB activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene

    Stefano Luisa

    2005-01-01

    Full Text Available Abstract Background The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE. Results The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2, known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene. Conclusions Using a constitutively active CREB2

  1. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer.

    Park, Ji Hyun; Choi, Yun Jung; Kim, Seon Ye; Lee, Jung-Eun; Sung, Ki Jung; Park, Sojung; Kim, Woo Sung; Song, Joon Seon; Choi, Chang-Min; Sung, Young Hoon; Rho, Jin Kyung; Lee, Jae Cheol

    2016-04-19

    Mutant-selective, 3rd-generation EGFR-TKIs were recently developed to control lung cancer cells harboring T790M-mediated resistance. However, the development of resistance to these novel drugs seems inevitable. Thus, we investigated the mechanism of acquired resistance to the mutant-selective EGFR-TKI WZ4002. We established five WZ4002-resistant cells, derived from cells harboring both EGFR and T790M mutations by long-term exposure to increasing doses of WZ4002. Compared with the parental cells, all resistant cells showed 10-100-folds higher resistance to WZ4002, as well as cross-resistance to other mutant-selective inhibitors. Among them, three resistant cells (HCC827/WR, PC-9/WR and H1975/WR) showed dependency on EGFR signaling, but two other cells (PC-9/GR/WR and PC-9/ER/WR) were not. Notably, insulin-like growth factor-1 receptor (IGF1R) was aberrantly activated in PC-9/GR/WR cells in phospho-receptor tyrosine kinase array, consistently accompanied by loss of IGF binding protein-3 (IGFBP3). Down-regulation of IGF1R by shRNA, as well as inhibition of IGF1R activity either by AG-1024 (a small molecule IGF1R inhibitor) or BI 836845 (a monoclonal anti-IGF1/2 blocking antibody), restored the sensitivity to WZ4002 both in vitro and xenograft. Taken together, these results suggest that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. PMID:26980747

  2. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

    Park, Ji Hyun; Choi, Yun Jung; Kim, Seon Ye; Lee, Jung-Eun; Sung, Ki Jung; Park, Sojung; Kim, Woo Sung; Song, Joon Seon; Choi, Chang-Min; Sung, Young Hoon; Rho, Jin Kyung; Lee, Jae Cheol

    2016-01-01

    Mutant-selective, 3rd-generation EGFR-TKIs were recently developed to control lung cancer cells harboring T790M-mediated resistance. However, the development of resistance to these novel drugs seems inevitable. Thus, we investigated the mechanism of acquired resistance to the mutant-selective EGFR-TKI WZ4002. We established five WZ4002-resistant cells, derived from cells harboring both EGFR and T790M mutations by long-term exposure to increasing doses of WZ4002. Compared with the parental cells, all resistant cells showed 10–100-folds higher resistance to WZ4002, as well as cross-resistance to other mutant-selective inhibitors. Among them, three resistant cells (HCC827/WR, PC-9/WR and H1975/WR) showed dependency on EGFR signaling, but two other cells (PC-9/GR/WR and PC-9/ER/WR) were not. Notably, insulin-like growth factor-1 receptor (IGF1R) was aberrantly activated in PC-9/GR/WR cells in phospho-receptor tyrosine kinase array, consistently accompanied by loss of IGF binding protein-3 (IGFBP3). Down-regulation of IGF1R by shRNA, as well as inhibition of IGF1R activity either by AG-1024 (a small molecule IGF1R inhibitor) or BI 836845 (a monoclonal anti-IGF1/2 blocking antibody), restored the sensitivity to WZ4002 both in vitro and xenograft. Taken together, these results suggest that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. PMID:26980747

  3. Acquired Dyslexia in Japanese: Implications for Reading Theory

    Sato, H

    2007-01-01

    Acquired dyslexia research has been conducted mainly on English neurological patients. A limited number of dyslexia studies on non-alphabetic orthographies are available. Classical case studies for acquired dyslexia in Japanese, which has two distinctive scripts (morphographic Kanji and phonographic Kana), reported 'script-dependent' dyslexia patterns. Although recent case studies showed 'script-independent' dyslexia patterns for surface and phonological dyslexia, a 'script-independent'...

  4. The in vitro anti-viral potential of Setarud (IMOD™, a commercial herbal medicine with protective activity against acquired immune deficiency syndrome in clinical trials

    Rezvan Zabihollahi

    2012-01-01

    Conclusions: Data from this study indicate that IMOD has significant anti-viral activity against HIV, HSV and MLV. Setarud could be subjected to further investigation after isolation of the constituents and determination of the toxic components.

  5. Antifungal activity of Arctotis arctotoides (L.f. O. Hoffm. and Gasteria bicolor Haw. against opportunistic fungi associated with human immunodeficiency virus/acquired immunodeficiency syndrome

    Wilfred M Otang

    2012-01-01

    Full Text Available Background : In South Africa where many patients are immunocompromised as a result of the AIDS pandemic, opportunistic fungal infections such as candidiasis caused mainly by Candida albicans are common. Arctotis arctotoides and Gasteria bicolor are two plants which are frequently and commonly used in traditional medicine in the treatment of HIV patients. Aim: The aim of this study was to investigate the antifungal activity of A. arctotoides and G. bicolor against opportunistic fungi common in HIV/AIDS patients. Materials and Methods: The agar diffusion and micro-dilution methods were used to determine the antifungal activities of the medicinal plant extracts against 10 opportunistic fungi. Results: All the hexane and acetone extracts were active against at least one of the fungi with zones of inhibition varying from 8 to 32 mm, while none of the aqueous extracts was active against any of the fungi. The inhibitory activity of the active extracts, based on the overall mean inhibition diameters, was in the order: A. arctotoides (hexane > A. arctotoides (acetone > G. bicolor (hexane > G. bicolor (acetone. The most susceptible fungi, based on the overall mean diameter of growth inhibition, were Candida glabrata, C. krusei, and Microsporum canis, while Cyptococcus neoformans, Trycophyton tonsurans, and Microsporum gypseum were not susceptible to any of the extracts even at 5 mg/ml which was the highest concentration used. Conclusion: This study validates the use of these plants in traditional medicine in the treatment of secondary fungal infections in HIV/AIDS patients.

  6. Assessment of coupling between trans-abdominally acquired fetal ECG and uterine activity by bivariate phase-rectified signal averaging analysis.

    Daniela Casati

    Full Text Available Couplings between uterine contractions (UC and fetal heart rate (fHR provide important information on fetal condition during labor. At present, couplings between UC and fHR are assessed by visual analysis and interpretation of cardiotocography. The application of computerized approaches is restricted due to the non-stationarity of the signal, missing data and noise, typical for fHR. Herein, we propose a novel approach to assess couplings between UC and fHR, based on a signal-processing algorithm termed bivariate phase-rectified signal averaging (BPRSA.Electrohysterogram (EHG and fetal electrocardiogram (fECG were recorded non-invasively by a trans-abdominal device in 73 women at term with uneventful singleton pregnancy during the first stage of labor. Coupling between UC and fHR was analyzed by BPRSA and by conventional cross power spectral density analysis (CPSD. For both methods, degree of coupling was assessed by the maximum coefficient of coherence (CPRSA and CRAW, respectively in the UC frequency domain. Coherence values greater than 0.50 were consider significant. CPRSA and CRAW were compared by Wilcoxon test.At visual inspection BPRSA analysis identified coupled periodicities in 86.3% (63/73 of the cases. 11/73 (15% cases were excluded from further analysis because no 30 minutes of fECG recording without signal loss was available for spectral analysis. Significant coupling was found in 90.3% (56/62 of the cases analyzed by BPRSA, and in 24.2% (15/62 of the cases analyzed by CPSD, respectively. The difference between median value of CPRSA and CRAW was highly significant (0.79 [IQR 0.69-0.90] and 0.29 [IQR 0.17-0.47], respectively; p<0.0001.BPRSA is a novel computer-based approach that can be reliably applied to trans-abdominally acquired EHG-fECG. It allows the assessment of correlations between UC and fHR patterns in the majority of labors, overcoming the limitations of non-stationarity and artifacts. Compared to standard techniques of

  7. Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

    Kakuta, Hirotoshi; Kurosaki, Eiji; Niimi, Tatsuya; Gato, Katsuhiko; Kawasaki, Yuko; Suwa, Akira; Honbou, Kazuya; Yamaguchi, Tomohiko; Okumura, Hiroyuki; Sanagi, Masanao; Tomura, Yuichi; Orita, Masaya; Yonemoto, Takako; Masuzaki, Hiroaki

    2014-04-01

    A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement. PMID:24424487

  8. GABAB receptors inhibit low-voltage activated and high-voltage activated Ca(2+) channels in sensory neurons via distinct mechanisms.

    Huang, Dongyang; Huang, Sha; Peers, Chris; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

    2015-09-18

    Growing evidence suggests that mammalian peripheral somatosensory neurons express functional receptors for gamma-aminobutyric acid, GABAA and GABAB. Moreover, local release of GABA by pain-sensing (nociceptive) nerve fibres has also been suggested. Yet, the functional significance of GABA receptor triggering in nociceptive neurons is not fully understood. Here we used patch-clamp recordings from small-diameter cultured DRG neurons to investigate effects of GABAB receptor agonist baclofen on voltage-gated Ca(2+) currents. We found that baclofen inhibited both low-voltage activated (LVA, T-type) and high-voltage activated (HVA) Ca(2+) currents in a proportion of DRG neurons by 22% and 32% respectively; both effects were sensitive to Gi/o inhibitor pertussis toxin. Inhibitory effect of baclofen on both current types was about twice less efficacious as compared to that of the μ-opioid receptor agonist DAMGO. Surprisingly, only HVA but not LVA current modulation by baclofen was partially prevented by G protein inhibitor GDP-β-S. In contrast, only LVA but not HVA current modulation was reversed by the application of a reducing agent dithiothreitol (DTT). Inhibition of T-type Ca(2+) current by baclofen and the recovery of such inhibition by DTT were successfully reconstituted in the expression system. Our data suggest that inhibition of LVA current in DRG neurons by baclofen is partially mediated by an unconventional signaling pathway that involves a redox mechanism. These findings reinforce the idea of targeting peripheral GABA receptors for pain relief. PMID:26239659

  9. Quantum Distinction: Quantum Distinctiones!

    Dainis ZEPS

    2009-07-01

    Full Text Available How many distinctions, in Latin, quantum distinctions have? We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking should be equated with subject of physics (that of nature. For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinction may be considered as freedom of motion.

  10. Hyperosmotic stress memory in Arabidopsis is mediated by distinct epigenetically labile sites in the genome and is restricted in the male germline by DNA glycosylase activity.

    Wibowo, Anjar; Becker, Claude; Marconi, Gianpiero; Durr, Julius; Price, Jonathan; Hagmann, Jorg; Papareddy, Ranjith; Putra, Hadi; Kageyama, Jorge; Becker, Jorg; Weigel, Detlef; Gutierrez-Marcos, Jose

    2016-01-01

    Inducible epigenetic changes in eukaryotes are believed to enable rapid adaptation to environmental fluctuations. We have found distinct regions of the Arabidopsis genome that are susceptible to DNA (de)methylation in response to hyperosmotic stress. The stress-induced epigenetic changes are associated with conditionally heritable adaptive phenotypic stress responses. However, these stress responses are primarily transmitted to the next generation through the female lineage due to widespread DNA glycosylase activity in the male germline, and extensively reset in the absence of stress. Using the CNI1/ATL31 locus as an example, we demonstrate that epigenetically targeted sequences function as distantly-acting control elements of antisense long non-coding RNAs, which in turn regulate targeted gene expression in response to stress. Collectively, our findings reveal that plants use a highly dynamic maternal 'short-term stress memory' with which to respond to adverse external conditions. This transient memory relies on the DNA methylation machinery and associated transcriptional changes to extend the phenotypic plasticity accessible to the immediate offspring. PMID:27242129

  11. Learning to Acquire

    Henningsson, Stefan

    2015-01-01

    This paper develops a knowledge-based model of information systems (IS) integration in acquisition-based growth programs. Previous research has found important differences in the acquirers’ abilities for acquisition IS integration, and that these differences play key roles in explaining the...... Trelleborg. The analyses yield five propositions that explain the building of knowledge for acquisition IS integration by the mechanisms of routine refinement, superstitious learning, expertise building, sub-activity refinement and related expertise building. Together, the five propositions form a knowledge...

  12. Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice

    Toh, Shen Yon; Gong, Jingyi; Du, Guoli; Li, John Zhong; Yang, Shuqun; Ye, Jing; Yao, Huilan; Zhang, Yinxin; Xue, Bofu; Li, Qing; Yang, Hongyuan; Wen, Zilong; Li, Peng

    2008-01-01

    Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27 −/− mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse st...

  13. Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice

    Shen Yon Toh; Jingyi Gong; Guoli Du; John Zhong Li; Shuqun Yang; Jing Ye; Huilan Yao; Yinxin Zhang; Bofu Xue; Qing Li; Hongyuan Yang; Zilong Wen; Peng Li

    2008-01-01

    Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/-) mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse s...

  14. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    Majowicz Anna; van der Marel Sander; te Velde Anje A; Meijer Sybren L; Petry Harald; van Deventer Sander J; Ferreira Valerie

    2012-01-01

    Abstract Background Induced regulatory T (iTreg) lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg) cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore ...

  15. Antifungal activity of Arctotis arctotoides (L.f.) O. Hoffm. and Gasteria bicolor Haw. against opportunistic fungi associated with human immunodeficiency virus/acquired immunodeficiency syndrome

    Wilfred M. Otang; Grierson, Donald S.; Ndip, Roland N.

    2012-01-01

    Background : In South Africa where many patients are immunocompromised as a result of the AIDS pandemic, opportunistic fungal infections such as candidiasis caused mainly by Candida albicans are common. Arctotis arctotoides and Gasteria bicolor are two plants which are frequently and commonly used in traditional medicine in the treatment of HIV patients. Aim: The aim of this study was to investigate the antifungal activity of A. arctotoides and G. bicolor against opportunistic fungi common in...

  16. Highly Efficient F, Cu doped TiO2 anti-bacterial visible light active photocatalytic coatings to combat hospital-acquired infections

    Leyland, Nigel S.; Podporska-Carroll, Joanna; Browne, John; Hinder, Steven J.; Quilty, Brid; Pillai, Suresh C.

    2016-04-01

    Bacterial infections are a major threat to the health of patients in healthcare facilities including hospitals. One of the major causes of patient morbidity is infection with Staphylococcus aureus. One of the the most dominant nosocomial bacteria, Methicillin Resistant Staphylococcus aureus (MRSA) have been reported to survive on hospital surfaces (e.g. privacy window glasses) for up to 5 months. None of the current anti-bacterial technology is efficient in eliminating Staphylococcus aureus. A novel transparent, immobilised and superhydrophilic coating of titanium dioxide, co-doped with fluorine and copper has been prepared on float glass substrates. Antibacterial activity has demonstrated (by using Staphylococcus aureus), resulting from a combination of visible light activated (VLA) photocatalysis and copper ion toxicity. Co-doping with copper and fluorine has been shown to improve the performance of the coating, relative to a purely fluorine-doped VLA photocatalyst. Reductions in bacterial population of log10 = 4.2 under visible light irradiation and log10 = 1.8 in darkness have been achieved, compared with log10 = 1.8 under visible light irradiation and no activity, for a purely fluorine-doped titania. Generation of reactive oxygen species from the photocatalytic coatings is the major factor that significantly reduces the bacterial growth on the glass surfaces.

  17. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice.

    Shen Yon Toh

    Full Text Available Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/- mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs from wildtype and Fsp27(-/- mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT and white adipose tissue (WAT and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/- mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/- mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/- mice. Remarkably, Fsp27(-/- MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3. Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.

  18. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    Majowicz Anna

    2012-12-01

    Full Text Available Abstract Background Induced regulatory T (iTreg lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance. Methods Using phorbol myristate acetate (PMA/ionomycin and anti-CD3 activation of CD4+CD25- cells we generated in vitro functional CD4+CD25+ iTreg (TregPMA cells. Functionality of the generated TregPMA cells was tested in vivo in a mouse model of inflammatory bowel disease (IBD - CD45RB transfer colitis model. Results TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group. Conclusions This study identifies a new method to generate in vitro iTreg cells (TregPMA cells which physiological efficacy has been demonstrated in vivo.

  19. Optimizing the function of upstanding activities in adult patients with acquired lesions of the central nervous system by using the Bobath concept approach - A case report.

    Jelica, Stjepan; Seper, Vesna; Davidović, Erna; Bujisić, Gordana

    2011-01-01

    Nonspecific medical gymnastic therapy may help patients after stroke achieve certain results in terms of efficiency but not in terms of quality of movement. The goal of treatment by Bobath concept is development of movement (effectiveness) and optimization of movement (efficiency). This article presents the case of a 62-year old patient who had experienced a stroke and has difficulties with standing up activities. It underscores the importance of not only recovery of function but also optimization of the function in such patients. PMID:21648353

  20. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

    Frogne, Thomas; Benjaminsen, Rikke V; Sonne-Hansen, Katrine; Sorensen, Boe S; Nexo, Ebba; Laenkholm, Anne-Vibeke; Rasmussen, Louise M; Riese, David J; de Cremoux, Patricia; Stenvang, Jan; Lykkesfeldt, Anne

    2008-01-01

    Seven fulvestrant resistant cell lines derived from the estrogen receptor alpha positive MCF-7 human breast cancer cell line were used to investigate the importance of epidermal growth factor receptor (ErbB1-4) signaling. We found an increase in mRNA expression of EGFR and the ErbB3/ErbB4 ligand...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2....... Our data support that a concerted action against EGFR, ErbB2 and ErbB3 may be required to obtain complete growth suppression of fulvestrant resistant cells....

  1. Infections Acquired in the Garden.

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis. PMID:26542044

  2. CovS simultaneously activates and inhibits the CovR-mediated repression of distinct subsets of group A Streptococcus virulence factor-encoding genes.

    Treviño, Jeanette; Perez, Nataly; Ramirez-Peña, Esmeralda; Liu, Zhuyun; Shelburne, Samuel A; Musser, James M; Sumby, Paul

    2009-08-01

    To colonize and cause disease at distinct anatomical sites, bacterial pathogens must tailor gene expression in a microenvironment-specific manner. The molecular mechanisms that control the ability of the human bacterial pathogen group A Streptococcus (GAS) to transition between infection sites have yet to be fully elucidated. A key regulator of GAS virulence gene expression is the CovR-CovS two-component regulatory system (also known as CsrR-CsrS). covR and covS mutant strains arise spontaneously during invasive infections and, in in vivo models of infection, rapidly become dominant. Here, we compared wild-type GAS with covR, covS, and covRS isogenic mutant strains to investigate the heterogeneity in the types of natural mutations that occur in covR and covS and the phenotypic consequences of covR or covS mutation. We found that the response regulator CovR retains some regulatory function in the absence of CovS and that CovS modulates CovR to significantly enhance repression of one group of genes (e.g., the speA, hasA, and ska genes) while it reduces repression of a second group of genes (e.g., the speB, grab, and spd3 genes). We also found that different in vivo-induced covR mutations can lead to strikingly different transcriptomes. While covS mutant strains show increased virulence in several invasive models of infection, we determined that these mutants are significantly outcompeted by wild-type GAS during growth in human saliva, an ex vivo model of upper respiratory tract infection. We propose that CovS-mediated regulation of CovR activity plays an important role in the ability of GAS to cycle between pharyngeal and invasive infections. PMID:19451242

  3. Normal mouse kidneys contain activated and CD3+CD4−CD8− double-negative T lymphocytes with a distinct TCR repertoire

    Ascon, Dolores B.; Ascon, Miguel; Satpute, Shailesh; Lopez-Briones, Sergio; Racusen, Lorraine; Colvin, Robert B.; Soloski, Mark J.; Rabb, Hamid

    2008-01-01

    Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3int T cells). Similar to liver and lung, a high percentage of unconventional CD3+CD4−CD8− double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4+ and CD8+ T lymphocytes in the kidney had a high proportion of activated CD69+ and effector/memory CD44CD62L ligand phenotypes. Also, a small percentage of CD4+CD25+forkhead box p3+ and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-γ and TNF-α by CD4+ and CD8+ T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process. PMID:18765477

  4. And the Winner is - Acquired

    Henkel, Joachim; Rønde, Thomas; Wagner, Marcus

    2015-01-01

    New entrants to a market tend to be superior to incumbents in originating radical innovations. We provide a new explanation for this phenomenon, based on markets for technology. It applies in industries where successful entrepreneurial firms, or their technologies, are acquired by incumbents that...... lower probability accompanies higher value in case of success—that is, a more radical innovation. In the second stage, successful entrants bid to be acquired by the incumbent. We assume that entrants cannot survive on their own, so being acquired amounts to a prize in a contest. We identify an...

  5. Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors.

    Guofeng Qian

    Full Text Available Ossification defects leading to craniofacial dysmorphism or rhizomelia are typical phenotypes in patients and corresponding knockout mouse models with distinct peroxisomal disorders. Despite these obvious skeletal pathologies, to date no careful analysis exists on the distribution and function of peroxisomes in skeletal tissues and their alterations during ossification. Therefore, we analyzed the peroxisomal compartment in different cell types of mouse cartilage and bone as well as in primary cultures of calvarial osteoblasts. The peroxisome number and metabolism strongly increased in chondrocytes during endochondral ossification from the reserve to the hypertrophic zone, whereas in bone, metabolically active osteoblasts contained a higher numerical abundance of this organelle than osteocytes. The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11β gene expression. During culture, calvarial pre-osteoblasts differentiated into secretory osteoblasts accompanied by peroxisome proliferation and increased levels of peroxisomal genes and proteins. Since many peroxisomal genes contain a PPAR-responsive element, we analyzed the gene expression of PPARɑ/ß/ɣ in calvarial osteoblasts and MC3T3-E1 cells, revealing higher levels for PPARß than for PPARɑ and PPARɣ. Treatment with different PPAR agonists and antagonists not only changed the peroxisomal compartment and associated gene expression, but also induced complex alterations of the gene expression patterns of the other PPAR family members. Studies in M3CT3-E1 cells showed that the PPARß agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat, whereas the PPARß antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and

  6. Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature

    Marcelo Corti

    2014-01-01

    Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.

  7. Immature myeloid Gr-1+ CD11b+ cells from lipopolysaccharide-immunosuppressed mice acquire inhibitory activity in the bone marrow and migrate to lymph nodes to exert their suppressive function.

    Landoni, Veronica I; Martire-Greco, Daiana; Rodriguez-Rodrigues, Nahuel; Chiarella, Paula; Schierloh, Pablo; Isturiz, Martin A; Fernández, Gabriela C

    2016-02-01

    Secondary infections due to post-sepsis immunosuppression are a major cause of death in patients with sepsis. Repetitive inoculation of increasing doses of lipopolysaccharide (LPS) into mice mimics the immunosuppression associated with sepsis. Myeloid-derived suppressor cells (MDSCs, Gr-1(+) CD11b(+)) are considered a major component of the immunosuppressive network, interfering with T-cell responses in many pathological conditions. We used LPS-immunosuppressed (IS) mice to address whether MDSCs acquired their suppressive ability in the bone marrow (BM) and whether they could migrate to lymph nodes (LNs) to exert their suppressive function. Our results showed that Gr-1(+) CD11b(+) cells of IS mice already had the potential to inhibit T-cell proliferation in the BM. Moreover, soluble factors present in the BM from IS mice were responsible for inducing this inhibitory ability in control BM cells. In addition, migration of Gr-1(+) CD11b(+) to LNs in vivo was maximal when cells obtained from the BM of IS mice were inoculated into an IS context. In this regard, we found chemoattractant activity in cell-free LN extracts (LNEs) from IS mice and an increased expression of the LN-homing chemokine receptor C-C chemokine receptor type 7 (CCR7) in IS BM Gr-1(+) CD11b(+) cells. These results indicate that Gr-1(+) CD11b(+) cells found in BM from IS mice acquire their suppressive activity in the same niche where they are generated, and migrate to LNs to exert their inhibitory role. A better understanding of MDSC generation and/or regulation of factors able to induce their inhibitory function may provide new and more effective tools for the treatment of sepsis-associated immunosuppression. PMID:26582821

  8. Earth Knowledge Acquired by Middle School Students

    Ride, Sally

    2008-01-01

    Earth Knowledge Acquired by Middle School Students (EarthKAM), an education activity, allows middle school students to program a digital camera on board the International Space Station to photograph a variety of geographical targets for study in the classroom. Photos are made available on the web for viewing and study by participating schools around the world. Educators use the images for projects involving Earth Science, geography, physics, and social science.

  9. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes

    Petrovic, Natasa; Walden, Tomas B; Shabalina, Irina G;

    2009-01-01

    The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain...... physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis...... factors now associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing...

  10. Substance, Reality, and Distinctness

    Boris Hennig

    2008-01-01

    Descartes claims that God is a substance and that mind and body are two different and separable substances. This paper provides some background that renders these claims intelligible. For Descartes, that something is real means that it can exist in separation, and something is a substance if it does not depend on other substances for its existence. Further, separable objects are correlates of distinct ideas, since an idea is distinct (in an objective sense) if its object may be easily and cle...

  11. Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

    Gilbert, Frédéric; Focquaert, Farah

    2015-01-01

    This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. PMID:25725545

  12. 33 CFR 211.2 - Authority to acquire real estate.

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional...

  13. Acquiring taste in home economics?

    Stenbak Larsen, Christian

    2015-01-01

    that the pupils were encouraged to use their senses: listen to things frying, touch the meat to check if it was done and taste the food in the process of seasoning it. But while some children learned what the teachers expected: to produce well tasting food, others learned to cook very salty and hot food...... appreciated by the group of boys, and others again learned to stick with their idiosyncrasies when pressured by the teacher. Conclusions: Children were acquiring taste in the home economic lessons, but not only the kind of tastes that the teacher had planned for. This leads to reflections on the very complex...... process of taste acquiring and to a call for further research into taste acquiring in complex real life contexts as home economics lessons....

  14. Clinicopathological correlation of acquired hyperpigmentary disorders

    Anisha B Patel

    2013-01-01

    Full Text Available Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseases have varying etiologies that need to be addressed in order to effectively treat the dyspigmentation. In this review, we describe and discuss the utility of histology in the diagnostic work of hyperpigmentary disorders, and how, in many cases, it can lead to targeted and more effective therapy. We focus on the most common acquired pigmentary disorders seen in Indian patients as well as a few uncommon diseases with distinctive histological traits. Facial melanoses, including mimickers of melasma, are thoroughly explored. These diseases include lichen planus pigmentosus, discoid lupus erythematosus, drug-induced melanoses, hyperpigmentation due to exogenous substances, acanthosis nigricans, and macular amyloidosis.

  15. Clinicopathological correlation of acquired hyperpigmentary disorders.

    Patel, Anisha B; Kubba, Raj; Kubba, Asha

    2013-01-01

    Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseases have varying etiologies that need to be addressed in order to effectively treat the dyspigmentation. In this review, we describe and discuss the utility of histology in the diagnostic work of hyperpigmentary disorders, and how, in many cases, it can lead to targeted and more effective therapy. We focus on the most common acquired pigmentary disorders seen in Indian patients as well as a few uncommon diseases with distinctive histological traits. Facial melanoses, including mimickers of melasma, are thoroughly explored. These diseases include lichen planus pigmentosus, discoid lupus erythematosus, drug-induced melanoses, hyperpigmentation due to exogenous substances, acanthosis nigricans, and macular amyloidosis. PMID:23619441

  16. Benefits and costs of clearer distinction between networks and sales activities; Nytte og kostnader ved klarere skille mellom nett- og omsetningsvirksomhet

    2008-12-15

    There will be substantial socio-economic cost connected to an introduction to a stronger distinction between the grid company and power provider in the vertically integrated companies or companies in the same group, provided information from a variety of network companies and suppliers. Full separation will result in additional costs to society in the order of 300 to 500 million kroner per year. The rewards for society can be expected to be modest, a maximum of two million per year. It may therefore be useful to consider other measures that can help to increase companies 'net neutrality, such as measures that restrict net companies' direct contact with end customers, clearer distinction between the operator and electricity supplier in the communication that takes place and strengthen NVE regulator's role. (AG)

  17. Acquired Factor VIII Inhibitors: Three Cases

    Tay Za Kyaw

    2013-03-01

    Full Text Available Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients’ ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.

  18. Acquired Aplastic Anemia in Children

    Hartung, Helge D.; Olson, Timothy S.; Bessler, Monica

    2013-01-01

    This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.

  19. Acquired anhidrosis a case report

    Nair Laxmi

    1992-01-01

    Full Text Available A 30-year -old man was seen for acquired anhidrosis. There was no systemic disease. Vasomotor functions were normal. Biopsy showed normal sweat glands and ducts. Intravenous injection of neostigmine could produce profuse sweating on the face, trunk and arms. The disorder is likely to be due to a peripheral dysautonomia selectively affecting the sudomotor function.

  20. Acquired anhidrosis a case report

    Nair Laxmi; Beena D; Manohar S

    1992-01-01

    A 30-year -old man was seen for acquired anhidrosis. There was no systemic disease. Vasomotor functions were normal. Biopsy showed normal sweat glands and ducts. Intravenous injection of neostigmine could produce profuse sweating on the face, trunk and arms. The disorder is likely to be due to a peripheral dysautonomia selectively affecting the sudomotor function.

  1. Substance, Reality, and Distinctness

    Boris Hennig

    2008-04-01

    Full Text Available Descartes claims that God is a substance, and that mind and body are two different and separable substances. This paper provides some background that renders these claims intelligible. For Descartes, that something is real means it can exist in separation, and something is a substance if it does not depend on other substances for its existence. Further, separable objects are correlates of distinct ideas, for an idea is distinct (in an objective sense if its object may be easily and clearly separated from everything that is not its object. It follows that if our idea of God is our most distinct idea, as Descartes claims, then God must be a substance in the Cartesian sense of the term. Also, if we can have an idea of a thinking subject which does not in any sense refer to bodily things, and if bodily things are substances, then mind and body must be two different substances.

  2. Kita zadnje golenične mišice pri nastanku pridobljenega ploskega stopala odraslih: The role of the posterior tibial tendon in the adult acquired flatfoot:

    Antolič, Vane; Drobnič, Matej

    2002-01-01

    Flatfoot involves a complex change in the foot architecture with a lowered medial longitudinal arch and a hindfoot eversion. It is observed in one fifth of the adult population. A distinction should be made between a flexible and arigid form. The major cause of an acquired adult flatfoot deformity is degeneration of the tibialis posterior tendon. The tendon dysfunction results in diminished active support to the medial foot arch. There are four clinical stages of tendon dysfunction which requ...

  3. Occupationally Acquired American Cutaneous Leishmaniasis

    Maria Edileuza Felinto de Brito

    2012-01-01

    Full Text Available We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL: one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples and characterized as Leishmania (Viannia naiffi through an indirect immunofluorescence assay (IFA with species-specific monoclonal antibodies (mAbs and by multilocus enzyme electrophoresis (MLEE. Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis.

  4. CNOOC Acquires Oversea Assets Successfully

    Hu Senlin

    2006-01-01

    @@ After last year CNOOC's bidding for buy the US energy company Unocal Corp lost out to the Chevron Corporation, it conducted the crossing-border asset-acquirement again in the beginning of this year. On Jan. 9, 2006,CNOOC Ltd signed a definitive agreement with Nigeria South Atlantic Petroleum Limited (SAPETRO) to acquire a 45 % working interest in an offshore oil developing license OML 130 in Nigeria for US$2.268 billion cash. The purchase will be funded by the internal capital resources of CNOOC Ltd. In which, US$1.75 billion will pay for buying SAPETRO, and the remaining cash will be used to pay for the early operation cost.

  5. Cogema acquires TOTAL's uranium assets

    On April 28, France's nuclear fuel cycle conglomerate Cogema and petroleum group TOTAL announced a plan in which Cogema will assume ownership of TOTAL's uranium assets worldwide, and as part of the deal, each firm will acquire shares of the other. On June 2, the agreement will be submitted to shareholders and, assuming it is approved, will go into effect this year. The agreement calls for TOTAL to acquire a 10.8-percent share in Cogema, thus becoming its first private sector shareholder, by underwriting a reserve capital increase of FF1.5 billion (approximately US$283 million). In return, Cogema will pay FF2.52 billion for approximately 4.3 percent of TOTAL, as part of a reserve capital increase totalling FF4.07 billion

  6. Acquired causes of intestinal malabsorption.

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  7. A shared neural ensemble links distinct contextual memories encoded close in time

    Cai, Denise J.; Aharoni, Daniel; Shuman, Tristan; Shobe, Justin; Biane, Jeremy; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Lou, Jerry; Flores, Sergio E.; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Baumgaertel, Karsten; Lavi, Ayal; Kamata, Masakazu; Tuszynski, Mark; Mayford, Mark; Golshani, Peyman; Silva, Alcino J.

    2016-06-01

    Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information.

  8. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.;

    2015-01-01

    The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78º...

  9. Inhibitors against the coagulation factors spontaneously acquired: Acquired B Hemophilia

    Claudia Lucía Sossa Melo; Sara Inés Jiménez Sanguino; Pilar Rodríguez

    2003-01-01

    Spontaneously acquired inhibitors to factor IX, are extremely rare. A 70-year-old male, presented with major continuous post-orthopedic surgery bleeding. His initial APTT was 77.4 s (normal range, 25-36) and normal PT. Expanded APTT corrects, results in favor of deficit of factor IX, confirming the level of dose of IX factor: 52% (NR 70–125%) with normal factor VIII. It was realized with fresh frozen plasma, and by the fifth day of treatment, he presents a bruise in the surgery bed with radic...

  10. Knowledge transfer - Acquiring implicit knowledge

    Many organisations have recognised the problem of experts taking home a huge amount of specific knowledge, which they have gathered in their department, when they leave. The successor is capable only of acquiring explicit expertise because implicit experiences are not documented and therefore no more available. That is why we have started this pilot study in order to try to conserve the above mentioned tacit and implicit knowledge and to make it available to other colleagues. Using a semi-standardised interview we elicit tacit knowledge from the expert and summarise it in a report. This interview-guideline forms the basis of in-depth investigation for implicit knowledge. (author)

  11. Regulator of G protein signaling 8 inhibits protease-activated receptor 1/Gi/o signaling by forming a distinct G protein-dependent complex in live cells.

    Lee, Jinyong; Ghil, Sungho

    2016-05-01

    Activation of seven-transmembrane-domain-possessing G protein-coupled receptors (GPCRs) by extracellular stimuli elicits intracellular responses. One class of GPCRs-protease-activated receptors (PARs)-is activated by endogenous proteases, such as thrombin and trypsin. Members of the regulator of G protein signaling (RGS) family stimulate GTP hydrolysis of G protein alpha (Gα) subunits, thereby inhibiting GPCR/Gα-mediated signaling. We previously reported that RGS2 and RGS4 inhibit PAR1/Gα-mediated signaling by interacting with PAR1 in a Gα-dependent manner. Here, employing the bioluminescence resonance energy transfer (BRET) technique, we identified RGS8 as a novel PAR1-interacting protein. Very little BRET activity was observed between PAR1-Venus (PAR1-Ven) and RGS8-Luciferase (RGS8-Luc) in the absence of Gα. However, in the presence of Gαo, BRET activity was specifically and significantly increased. This interaction was confirmed by biochemical and immunofluorescence assays. Notably, RGS8 inhibited PAR1/Gαi/o-mediated adenylyl cyclase and ERK activation, and prevented Gαo-induced neurite outgrowth and activation of Necdin protein, a downstream target of Gαo. Our findings suggest a novel function of RGS8 and reveal cellular mechanisms by which RGS8 mediates PAR1 inhibition. PMID:26829215

  12. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael;

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains obs...... obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component...

  13. Mining multidimensional distinct patterns

    Kubendranathan, Thusjanthan

    2010-01-01

    How do we find the dominant groups of customers in age, sex and location that were responsible for at least 85% of the sales of iPad, Macbook and iPhone? To answer such types of questions we introduce a novel data mining task – mining multidimensional distinct patterns (DPs). Given a multidimensional data set where each tuple carries some attribute values and a transaction, multidimensional DPs are itemsets whose absolute support ratio in a group-by on the attributes against the rest of the d...

  14. High-rate activated sludge communities have a distinctly different structure compared to low-rate sludge communities, and are less sensitive towards environmental and operational variables.

    Meerburg, Francis A; Vlaeminck, Siegfried E.; Roume, Hugo; Seuntjens, Dries; Dietmar H. Pieper; Jauregui, Ruy; Vilchez-Vargas, Ramiro; Boon, Nico

    2016-01-01

    High-rate activated sludge processes allow for the recovery of organics and energy from wastewaters. These systems are operated at a short sludge retention time and high sludge-specific loading rates, which results in a higher sludge yield and better digestibility than conventional, low-rate activated sludge. Little is known about the microbial ecology of high-rate systems. In this work, we address the need for a fundamental understanding of how high-rate microbial communities differ from low...

  15. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  16. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO2). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis

  17. Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.

    Barbara L Bernardo

    Full Text Available BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516 and a myostatin antibody and resistance training mimetic (PF-879 on metabolic and performance outcomes in obese insulin resistant mice. METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.

  18. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; Bælum, Jacob; Tas, Neslihan; Elberling, Bo; Jansson, Janet K.; Semenchuk, Philipp; Prieme, Anders

    2015-01-01

    The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78º...... phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface.......N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable...... significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and...

  19. A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of Toll-like receptor activation in irritable bowel syndrome

    GerardClarke

    2012-05-01

    Full Text Available Irritable bowel syndrome (IBS, a disorder of the brain-gut axis, is characterised by the absence of reliable biological markers. Tryptophan is an essential amino acid that serves as a precursor to serotonin but which can alternatively be metabolised along the kynurenine pathway leading to the production of other neuroactive agents. We previously reported an increased degradation of tryptophan along this immunoresponsive pathway in IBS. Recently, altered cytokine production following activation of specific members of the toll-like receptor (TLR family (TLR1-9 has also been demonstrated in IBS. However, the relationship between TLR activation and kynurenine pathway activity in IBS is unknown. In this study, we investigated whether activation of specific TLRs elicits exaggerated kynurenine production in IBS patients compared to controls. Whole blood from IBS patients and healthy controls was cultured with a panel of nine different TLR agonists for 24 hours. Cell culture supernatants were then analysed for both tryptophan and kynurenine concentrations, as were plasma samples from both cohorts. IBS subjects had an elevated plasma kynurenine:tryptophan ratio compared to healthy controls. Furthermore, we demonstrated a differential downstream profile of kynurenine production subsequent to TLR activation in IBS patients compared to healthy controls. This profile included alterations at TLR1/2, TLR2, TLR3, TLR5, TLR7 and TLR8. Our data expands on our previous understanding of altered tryptophan metabolism in IBS and suggests that measurement of tryptophan metabolites downstream of TLR activation may ultimately find utility as components of a biomarker panel to aid gastroenterologists in the diagnosis of IBS. Furthermore, these studies implicate the modulation of TLRs as means through which aberrant tryptophan metabolism along the kynurenine pathway can be controlled, a novel potential therapeutic strategy in this and other disorders.

  20. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous......, however, in the nature of the fragments deposited as a result of CP and AP activation: C3b fragments deposited via the CP were extensively ( approximately 90%) converted to the terminal degradation product, C3dg, whereas about 50% of those deposited by the AP persisted as C3b/iC3b fragments. The extent of...

  1. Pseudomona pseudomallei community acquired pneumonia

    This is the first published case report en Colombia about pseudomona pseudomallei community acquired pneumonia. This uncommon pathogen is from the epidemiological standpoint a very important one and medical community should be aware to look after it in those patients where no other etiological pathogen is recovered. A brief summary about epidemiology is showed, emphasizing those regions where it can be found. Likewise, comments about the differential diagnosis are important since it should be considered in those patients where tuberculosis is suspected. This is particularly representative for countries with high tuberculosis rates. Furthermore, a microbiological review is shown, emphasizing on isolation techniques, descriptions about therapeutics and other regarding treatment issues according international standards. Finally; a description about the clinical picture, laboratory findings, treatment and evolution of the case reported are shown for discussion

  2. Complement's participation in acquired immunity

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

    2002-01-01

    B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses.......The preliminary evidence for the involvement of complement in promoting primary humoral responses dates back over a quarter of a century. However, it is only in the course of the past decade or so that the detailed mechanisms underlying complement's influence have been characterized in depth. It is...

  3. Verum and sham acupuncture exert distinct cerebral activation in pain processing areas: a crossover fMRI investigation in healthy volunteers.

    Usichenko, Taras I; Wesolowski, Toni; Lotze, Martin

    2015-06-01

    Although acupuncture is effective for treating pain, its site-specificity is questioned. The aim was to compare the cerebral responses of needling applied to an acupuncture point to the needling of a sham point, using functional magnetic resonance imaging (fMRI). Twenty-one healthy male volunteers were enrolled. Manual stimulation of the acupuncture (ST44) and sham points on the dorsum of the left foot was applied during fMRI in a crossover manner. fMRI data analysis was performed contrasting the ST44 and the sham conditions. Stimulation intensity, subjective discrimination of the needling site and the incidence of "Qi" sensation were additionally recorded. Stimulation of ST44 acupoint, in comparison to the sham procedure, was associated with an increased fMRI-activation in the primary somatosensory, the inferior parietal and the prefrontal cortex and the posterior insula. Sham needling was associated with increased activation in the anterior cingulate cortex and the anterior insula. Verum acupuncture increased the activity of discriminative somatosensory and cognitive pain processing areas of the brain, whereas sham needling activated the areas responsible for affective processing of pain. This may explain favorable effects of verum acupuncture in clinical studies about treatment of chronic pain patients. PMID:24728839

  4. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement.

    Wang, Min; Qu, Qingyang; He, Tingting; Li, Min; Song, Zhimin; Chen, Feiyu; Zhang, Xiao; Xie, Jinlu; Geng, Xiwen; Yang, Maoquan; Wang, Xiusong; Lei, Chengdong; Hou, Yabing

    2016-08-25

    Several studies have suggested that the thalamic centromedian-parafascicular (CM/PF or the PF in rodents) is implicated in the pathophysiology of Parkinson's disease (PD). However, inconsistent changes in the neuronal firing rate and pattern have been reported in parkinsonian animals. To investigate the impact of a dopaminergic cell lesion on PF extracellular discharge in behaving rats, the PF neural activities in the spike and local field potential (LFP) were recorded in unilaterally 6-hydroxydopamine- (6-OHDA) lesioned and neurologically intact control rats during rest and limb movement. During rest, the two PF neuronal subtypes was less spontaneously active, with no difference in the spike firing rates between the control and lesioned rats; only the lesioned rats reshaped their spike firing pattern. Furthermore, the simultaneously recorded LFP in the lesioned rats exhibited a significant increase in power at 12-35 and 35-70Hz and a decrease in power at 0.7-12Hz. During the execution of a voluntary movement, two subtypes of PF neurons were identified by a rapid increase in the discharge activity in both the control and lesioned rats. However, dopamine lesioning was associated with a decrease in neuronal spiking fire rate and reshaping in the firing pattern in the PF. The simultaneously recorded LFP activity exhibited a significant increase in power at 12-35Hz and a decrease in power at 0.7-12Hz compared with the control rats. These findings indicate that 6-OHDA induces modifications in PF spike and LFP activities in rats during rest and movement and suggest that PF dysfunction may be an important contributor to the pathophysiology of parkinsonian motor impairment. PMID:27238892

  5. Distinct inhibition of acute cocaine-stimulated motor activity following microinjection of a group III metabotropic glutamate receptor agonist into the dorsal striatum of rats.

    Mao, L; Wang, J Q

    2000-09-01

    Group III metabotropic glutamate receptors (mGluRs) are negatively coupled to adenylate cyclase through G-proteins. Activation of this group of mGluRs shows an inhibition of dopaminergic transmission in the forebrain. To define the role of striatal group III mGluRs in the regulation of basal and dopamine-stimulated motor behavior, the recently developed agonist and antagonist relatively selective for group III mGluRs were utilized to pharmacologically enhance and reduce group III mGluR glutamatergic tone in the dorsal striatum of chronically cannulated rats. Bilateral injections of a group III agonist, L-2-amino-4-phosphonobutyrate (L-AP4), did not alter basal levels of motor activity at three doses surveyed (1, 10, and 100 nmol). Neither did intracaudate injection of a group III antagonist, alpha-methyl-4-phosphonophenylglycine (MPPG), at 10, 30, and 100 nmol. However, pretreatment with L-AP4 (10 and 100 nmol) dose dependently blocked hyperlocomotion induced by acute injection of cocaine (20 mg/kg, i.p.), amphetamine (2.5 mg/kg, i.p.), or apomorphine (1 mg/kg, s.c.). The behavioral activity induced by cocaine was much more sensitive to L-AP4 than that induced by amphetamine and apomorphine. At 100 nmol, L-AP4 completely blocked cocaine effect whereas amphetamine- and apomorphine-stimulated behaviors were blocked only by 28% and 31%, respectively. The blocking effect of L-AP4 on cocaine action was reversed by pretreatment with MPPG. MPPG itself did not modify behavioral responses to cocaine, amphetamine, or apomorphine. These data indicate that the glutamatergic tone on the group III mGluRs is not active in the regulation of basal and acute dopamine-stimulated motor activity. However, enhanced group III mGluR glutamatergic transmission by an exogenous ligand is capable of suppressing behavioral responses to acute exposure of dopamine stimulants. PMID:11113488

  6. Touch communicates distinct emotions.

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. PMID:16938094

  7. Study on safety classifications of software used in nuclear power plants and distinct applications of verification and validation activities in each class

    This paper describes the safety classification regarding instrumentation and control (I and C) systems and their software used in nuclear power plants, provides regulatory positions for software important to safety, and proposes verification and validation (V and V) activities applied differently in software classes which are important elements in ensuring software quality assurance. In other word, the I and C systems important to safety are classified into IC-1, IC-2, IC-3, and Non-IC and their software are classified into safety-critical, safety-related, and non-safety software. Based upon these safety classifications, the extent of software V and V activities in each class is differentiated each other. In addition, the paper presents that the software for use in I and C systems important to safety is divided into newly-developed and previously-developed software in terms of design and implementation, and provides the regulatory positions on each type of software

  8. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous...... serum in the absence and presence of selective inhibitors of the AP and CP, respectively. While the total amount of C3 fragments deposited was relatively unaffected by blocking either pathway individually, deposition was virtually abrogated by their combined blockade. A marked difference was observed......, however, in the nature of the fragments deposited as a result of CP and AP activation: C3b fragments deposited via the CP were extensively ( approximately 90%) converted to the terminal degradation product, C3dg, whereas about 50% of those deposited by the AP persisted as C3b/iC3b fragments. The extent of...

  9. Successful control of juvenile dermatomyositis-associated macrophage activation syndrome and interstitial pneumonia: distinct kinetics of interleukin-6 and -18 levels

    Wakiguchi, Hiroyuki; Hasegawa, Shunji; Hirano, Reiji; Kaneyasu, Hidenobu; Wakabayashi-Takahara, Midori; Ohga, Shouichi

    2015-01-01

    Background Macrophage activation syndrome (MAS) is the secondary hemophagocytic lymphohistiocytosis associated with rheumatic diseases. Recently, the different cytokine profiles between systemic juvenile idiopathic arthritis (sJIA)-associated MAS (sJIA-MAS) and juvenile systemic lupus erythematosus (JSLE)-associated MAS (JSLE-MAS) were reported. However, there is little information about juvenile dermatomyositis (JDM)-associated MAS (JDM-MAS). Case presentation A 4-year-old girl with JDM was ...

  10. Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

    Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J.; Kraus, Felix; Tattermusch, Anna; Cerase, Andrea; Sterr, Michael; Fiedler, Susanne; Demmerle, Justin; Popken, Jens; Leonhardt, Heinrich; Brockdorff, Neil; Cremer, Thomas; Schermelleh, Lothar; Cremer, Marion

    2014-01-01

    Background A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs)...

  11. Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

    Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J.; Kraus, Felix; Tattermusch, Anna; Cerase, Andrea; Sterr, Michael; Fiedler, Susanne; Demmerle, Justin; Popken, Jens; Leonhardt, Heinrich; Brockdorff, Neil; Cremer, Thomas; Schermelleh, Lothar; Cremer, Marion

    2014-01-01

    Background: A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs...

  12. Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating

    Wicks, Nadine L.; Wong, Tammy; Sun, Jinyi; Madden, Zarina; Young, Edgar C.

    2010-01-01

    Voltage gating of hyperpolarization-activated cation (HCN) channels is potentiated by direct binding of cAMP to a cytoplasmic cAMP-sensing domain (CSD). When unliganded, the CSD inhibits hyperpolarization-dependent opening of the HCN channel gate; cAMP binding relieves this autoinhibition so that opening becomes more favorable thermodynamically. This autoinhibition-relief mechanism is conserved with that of several other cyclic nucleotide receptors using the same ligand-binding fold. Besides ...

  13. Pleiotropic effects of the yeast Sal1 and Aac2 carriers on mitochondrial function via an activity distinct from adenine nucleotide transport

    Kucejova, Blanka; Li, Li; Wang, Xiaowen; Giannattasio, Sergio; Chen, Xin Jie

    2009-01-01

    In Saccharomyces cerevisiae, SAL1 encodes a Ca2+-binding mitochondrial carrier. Disruption of SAL1 is synthetically lethal with the loss of a specific function associated with the Aac2 isoform of the ATP/ADP translocase. This novel activity of Aac2 is defined as the V function (for Viability of aac2 sal1 double mutant), which is independent of the ATP/ADP exchange activity required for respiratory growth (the R function). We found that co-inactivation of SAL1 and AAC2 leads to defects in mitochondrial translation and mitochondrial DNA (mtDNA) maintenance. Additionally, sal1Δ exacerbates the respiratory deficiency and mtDNA instability of ggc1Δ, shy1Δ and mtg1Δ mutants, which are known to reduce mitochondrial protein synthesis or protein complex assembly. The V function is complemented by the human Short Ca2+-binding Mitochondrial Carrier (SCaMC) protein, SCaMC-2, a putative ATP-Mg/Pi exchangers on the inner membrane. However, mitochondria lacking both Sal1p and Aac2p are not depleted of adenine nucleotides. The Aac2R252I and Aac2R253I variants mutated at the R252-254 triplet critical for nucleotide transport retain the V function. Likewise, Sal1p remains functionally active when the R479I and R481I mutations were introduced into the structurally equivalent R479-T480-R481 motif. Finally, we found that the naturally occurring V-R+ Aac1 isoform of adenine nucleotide translocase partially gains the V function at the expense of the R function by introducing the mutations P89L and A96V. Thus, our data support the view that the V function is independent of adenine nucleotide transport associated with Sal1p and Aac2p and this evolutionarily conserved activity affects multiple processes in mitochondria. PMID:18431598

  14. Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. I. Distinctions between volume- activated Cl- and K+ conductance pathways

    1984-01-01

    Human peripheral blood lymphocytes (PBL), when placed into hypotonic media, first swell and then shrink back to their original volumes because of a rapid KCl leakage via volume-activated K+ and anion permeation pathways. By using gramicidin, a cation channel-forming ionophore, cation transport through the cell membrane can be shunted so that the salt fluxes and thus the volume changes are limited by the rate of the net anion movements. The "gramicidin method," supplemented with direct measure...

  15. The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

    Akwa, Yvette; Ladurelle, Nathalie; Covey, Douglas F.; Baulieu, Etienne-Emile

    2001-01-01

    The demonstration that the neurosteroid pregnenolone sulfate (PREGS) is active on memory function at both the physiological and pharmacological levels led to us examining in detail the effects of the steroid on spatial working memory by using a two-trial recognition task in a Y-maze, a paradigm based on the natural drive in rodents to explore a novel environment. Dose–response studies in young male adult Sprague–Dawley rats and Swiss mice, after the postacquisition intracerebroventricular inj...

  16. Acquired vulval lymphangiectases mimicking genital warts

    Sharma Rajeev; Tomar Sudarshan; Chandra Mithilesh

    2002-01-01

    Acquired lymphangiectasia can sometimes occur on the vulva and cause diagnostic difficulties especially if they have a warty appearance. We report a case of acquired vulva I lymphangiectasia which mimicked genital warts.

  17. Acquired vulval lymphangiectases mimicking genital warts

    Sharma Rajeev

    2002-01-01

    Full Text Available Acquired lymphangiectasia can sometimes occur on the vulva and cause diagnostic difficulties especially if they have a warty appearance. We report a case of acquired vulva I lymphangiectasia which mimicked genital warts.

  18. Two distinct functions of ComW in stabilization and activation of the alternative sigma factor ComX in Streptococcus pneumoniae.

    Sung, Chang Kyoo; Morrison, Donald A

    2005-05-01

    Natural genetic transformation in Streptococcus pneumoniae is controlled by a quorum-sensing system, which acts through the competence-stimulating peptide (CSP) for transient activation of genes required for competence. More than 100 genes have been identified as CSP regulated by use of DNA microarray analysis. One of the CSP-induced genes required for genetic competence is comW. As the expression of this gene depended on the regulator ComE, but not on the competence sigma factor ComX (sigma(X)), and as expression of several genes required for DNA processing was affected in a comW mutant, comW appears to be a new regulatory gene. Immunoblotting analysis showed that the amount of the sigma(X) protein is dependent on ComW, suggesting that ComW may be directly or indirectly involved in the accumulation of sigma(X). As sigma(X) is stabilized in clpP mutants, a comW mutation was introduced into the clpP background to ask whether the synthesis of sigma(X) depends on ComW. The clpP comW double mutant accumulated an amount of sigma(X) higher (threefold) than that seen in the wild type but was not transformable, suggesting that while comW is not needed for sigma(X) synthesis, it acts both in stabilization of sigma(X) and in its activation. Modification of ComW with a histidine tag at its C or N terminus revealed that both amino and carboxyl termini are important for increasing the stability of sigma(X), but only the N terminus is important for stimulating its activity. PMID:15838032

  19. The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex.

    R. Jiang; Carlson, M

    1997-01-01

    The Snf1 protein kinase plays a central role in the response to glucose starvation in the yeast Saccharomyces cerevisiae. Previously, we showed that two-hybrid interaction between Snf1 and its activating subunit, Snf4, is inhibited by high levels of glucose. These findings, together with biochemical evidence that Snf1 and Snf4 remain associated in cells grown in glucose, suggested that another protein (or proteins) anchors Snf1 and Snf4 into a complex. Here, we examine the possibility that a ...

  20. Coordination polymers of Fe(iii) and Al(iii) ions with TCA ligand: distinctive fluorescence, CO2 uptake, redox-activity and oxygen evolution reaction.

    Dhara, Barun; Sappati, Subrahmanyam; Singh, Santosh K; Kurungot, Sreekumar; Ghosh, Prasenjit; Ballav, Nirmalya

    2016-04-19

    Fe and Al belong to different groups in the periodic table, one from the p-block and the other from the d-block. In spite of their different groups, they have the similarity of exhibiting a stable 3+ oxidation state. Here we have prepared Fe(iii) and Al(iii) based coordination polymers in the form of metal-organic gels with the 4,4',4''-tricarboxyltriphenylamine (TCA) ligand, namely Fe-TCA and Al-TCA, and evaluated some important physicochemical properties. Specifically, the electrical conductivity, redox-activity, porosity, and electrocatalytic activity (oxygen evolution reaction) of the Fe-TCA system were noted to be remarkably higher than those of the Al-TCA system. As for the photophysical properties, almost complete quenching of the fluorescence originating from TCA was observed in case of the Fe-TCA system, whereas for the Al-TCA system a significant retention of fluorescence with red-shifted emission was observed. Quantum mechanical calculations based on density functional theory (DFT) were performed to unravel the origin of such discriminative behaviour of these coordination polymer systems. PMID:26961352

  1. Structural characteristics of two wheat histone H2A genes encoding distinct types of variants and functional differences in their promoter activity.

    Huh, G H; Nakayama, T; Meshi, T; Iwabuchi, M

    1997-03-01

    To investigate the regulation of plant histone H2A gene expression, we isolated two H2A genes (TH254 and TH274) from wheat, which encode two variants of H2A. Both genes had an intron in the coding region. In the promoters, some characteristic sequences, such as Oct and Nona motifs, which are conserved among plant histone genes, were located in a short region (about 120 bp) upstream from the putative TATA box. Transient expression analyses of promoter activity with H2A-GUS fusion genes using tobacco protoplasts revealed novel types of positive cis-acting sequences in the TH254 promoter: a direct repeat of a 13 bp sequence (AGTTACATTATTG) and a stretch composed of an AT-rich sequence (ATATAGAAAATTAAAA) and a G-box (CACGTG). Quantitative S1 assay of the mRNA amounts from the TH254/GUS and TH274/GUS chimeric genes in stably transformed and cell cycle-synchronized tobacco cell lines showed that the promoters of both genes contained at least one cis-acting element responsible for S phase-specific expression. Histochemical analysis of transgenic tobacco plants carrying the chimeric genes showed that the promoters of the two H2A genes were active in developing seedlings and flower organs but were regulated in a different manner. PMID:9106503

  2. Changes to gonadotropin-releasing hormone (GnRH) receptor extracellular loops differentially affect GnRH analog binding and activation: evidence for distinct ligand-stabilized receptor conformations.

    Pfleger, Kevin D G; Pawson, Adam J; Millar, Robert P

    2008-06-01

    GnRH and its structural variants bind to GnRH receptors from different species with different affinities and specificities. By investigating chimeric receptors that combine regions of mammalian and nonmammalian GnRH receptors, a greater understanding of how different domains influence ligand binding and receptor activation can be achieved. Using human-catfish and human-chicken chimeric receptors, we demonstrate the importance of extracellular loop conformation for ligand binding and agonist potency, providing further evidence for GnRH and GnRH II stabilization of distinct active receptor conformations. We demonstrate examples of GnRH receptor gain-of-function mutations that apparently improve agonist potency independently of affinity, implicating a role for extracellular loops in stabilizing the inactive receptor conformation. We also show that entire extracellular loop substitution can overcome the detrimental effects of localized mutations, thereby demonstrating the importance of considering the conformation of entire domains when drawing conclusions from point-mutation studies. Finally, we present evidence implicating the configuration of extracellular loops 2 and 3 in combination differentiating GnRH analog binding modes. Because there are two endogenous forms of GnRH ligand but only one functional form of full-length GnRH receptor in humans, understanding how GnRH and GnRH II can elicit distinct functional effects through the same receptor is likely to provide important insights into how these ligands can have differential effects in both physiological and pathological situations. PMID:18356273

  3. Distinctive binding modes and inhibitory mechanisms of two peptidic inhibitors of urokinase-type plasminogen activator with isomeric P1 residues

    Jiang, Longguang; Zhao, Baoyu; Xu, Peng;

    2015-01-01

    Two isomeric piperidine derivatives (meta and para isomers) were used as arginine mimics in the P1 position of a cyclic peptidic inhibitor (CPAYSRYLDC) of urokinase-type plasminogen activator. The two resulting cyclic peptides showed vastly different affinities (~70 fold) to the target enzyme. X......-ray crystal structure analysis showed that the two P1 residues were inserted into the S1 specificity pocket in indistinguishable manners. However, the rest of the peptides bound in entirely different ways on the surface of the enzyme, and the two peptides have different conformations, despite the highly...... similar sequence. These results demonstrate how the subtle difference in P1 residue can dictate the exosite interactions and the potencies of peptidic inhibitors, and highlight the importance of P1 residue for protease inhibition. This study provides important information for the development of peptidic...

  4. Alanine scan and (2)H NMR analysis of the membrane-active peptide BP100 point to a distinct carpet mechanism of action.

    Zamora-Carreras, Héctor; Strandberg, Erik; Mühlhäuser, Philipp; Bürck, Jochen; Wadhwani, Parvesh; Jiménez, M Ángeles; Bruix, Marta; Ulrich, Anne S

    2016-06-01

    The short membrane-active peptide BP100 [KKLFKKILKYL-NH2] is known as an effective antimicrobial and cell penetrating agent. For a functional alanine scan each of the 11 amino acids was replaced with deuterated Ala-d3, one at a time. MIC assays showed that a substitution of Lys did not affect the antimicrobial activity, but it decreased when a hydrophobic residue was replaced. In most cases, a reduction in hydrophobicity led to a decrease in hemolysis, and some peptide analogues had an improved therapeutic index. Circular dichroism showed that BP100 folds as an amphiphilic α-helix in a bilayer. Its alignment was determined from (2)H NMR in oriented membranes of different composition. The azimuthal rotation angle was the same under all conditions, but the average helix tilt angle and the dynamical behavior of the peptide varied in a systematic manner. In POPC/POPG bilayers, with a negative spontaneous curvature, the peptide was found to lie flat on the bilayer surface, and with little wobble. In DMPC/DMPG, with a positive spontaneous curvature, BP100 at higher concentrations became tilted obliquely into the membrane, with the uncharged C-terminus inserted more deeply into the lipid bilayer, experiencing significant fluctuations in tilt angle. In DMPC/DMPG/lyso-MPC, with a pronounced positive spontaneous curvature, the helix tilted even further and became even more mobile. The 11-mer BP100 is obviously too short to form transmembrane pores. We conclude that BP100 operates via a carpet mechanism, whereby the C-terminus gets inserted into the hydrophobic core of the bilayer, which leads to membrane perturbation and induces transient permeability. PMID:26975251

  5. Characterization of two activated mutants of human pp60c-src that escape c-Src kinase regulation by distinct mechanisms.

    Bjorge, J D; Bellagamba, C; Cheng, H C; Tanaka, A; Wang, J H; Fujita, D J

    1995-10-13

    Two activated transforming mutants of human pp60c-src were found to possess single point mutations within the regulatory carboxyl terminus (E527K in CY CST201) and the kinase domain (E381G in WO CST1), respectively, that do not directly interfere with either the regulatory c-Src kinase (CSK) phosphorylation site (Tyr530) or the SH2/3 domains. In vivo, both mutant proteins are hypophosphorylated on their carboxyl-terminal regulatory tyrosines and are hyperactive. In an in vitro Src kinase inactivation assay, both mutant Src proteins exhibited resistance to inactivation by CSK relative to wild-type Src. Under these in vitro conditions, E381G c-Src was found to be phosphorylated by CSK to wild-type levels, while E527K c-Src was not detectably phosphorylated. The ability of CSK to phosphorylate a carboxyl-terminal peptide modelled against E527K c-Src was also impaired, suggesting that CSK is unable to recognize E527K c-Src as an efficient substrate. In the case of E381G c-Src, examination of whether its SH2/3 domains were accessible to the carboxyl-terminal regulatory phosphotyrosine revealed a highly reduced ability of autophosphorylated E381G c-Src to bind to a synthetic phosphopeptide modelled from the SH2-binding region of polyoma middle-T antigen which binds to Src SH2 with high affinity. This suggests that the E381G c-Src mutation results in an altered or reduced accessibility of the SH2 domain of the autophosphorylated form of E381G c-Src and may represent a previously undescribed mode of Src activation. Further study of these and other Src mutants may offer additional new insights into the regulation of "Src family" kinases. PMID:7592628

  6. CARRAGEENAN-INDUCED NFκB ACTIVATION DEPENDS ON DISTINCT PATHWAYS MEDIATED BY REACTIVE OXYGEN SPECIES AND HSP27 OR BY BCL10

    Bhattacharyya, Sumit; Dudeja, Pradeep K.; Tobacman, Joanne K.

    2013-01-01

    Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/lymphoma 10). However, increases in phospho-IκBα and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFκB (p65), phospho-IκBα, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38γ), MAPK 13 (p38δ), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IκBα kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKγ (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome. PMID:18452717

  7. In vivo mechanisms of acquired thymic tolerance

    Chen, W; Issazadeh-Navikas, Shohreh; Sayegh, M H; Khoury, S J

    1997-01-01

    Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen......-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized...... expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect of...

  8. Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus) show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi.

    Peña-Espinoza, Miguel; Boas, Ulrik; Williams, Andrew R; Thamsborg, Stig M; Simonsen, Henrik T; Enemark, Heidi L

    2015-12-01

    The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars 'Spadona' and 'Puna II' were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC). O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA), while cultured L3 were used in a larval exsheathment inhibition assay (LEIA). Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA). Electron microscopy (EM) was performed on adult O. ostertagi exposed to 1000 μg extract mL(-1) of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO) were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P = 0.01), while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P  0.05). In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P inhibit feeding of free-living larvae and exert direct effects against parasitic stages of O. ostertagi. Our results may contribute to the identification of natural anti-parasitic compounds and to interpret the in vivo anthelmintic effects of forage chicory. PMID:27120066

  9. Surface Sampler Arm Acquiring Sample

    1976-01-01

    Operation of the surface sampler in obtaining Martian soil for Viking 2's molecular analysis experiment last Saturday (September 25) was closely monitored by one of the Lander cameras because of the precision required in trenching the small area--8 by 9 inches-surrounded by rocks. Dubbed 'Bonneville Salt Flats,' the exposure of thin crust appeared unique in contrast with surrounding materials and became a prime target for organic analysis in spite of potential hazards. Large rock in foreground is 8 inches high. At left, the sampler scoop has touched the surface, missing the rock at upper left by a comfortable 6 inches, and the backhoe has penetrated the surface about one-half inch. The scoop was then pulled back to sample the desired point and (second photo) the backhoe furrowed the surface pulling a piece of thin crust toward the spacecraft. The initial touchdown and retraction sequence was used to avoid a collision between a rock in the shadow of the arm and a plate joining the arm and scoop. The rock was cleared by 2 to 3 inches. The third picture was taken 8 minutes after the scoop touched the surface and shows that the collector head has acquired a quantity of soil. With surface sampler withdrawn (right), the foot-long trench is seen between the rocks. The trench is three inches wide and about 1 1/2 to 2 inches deep. The scoop reached to within 3 inches of the rock at far end of trench. Penetration appears to have left a cavernous opening roofed by the crust and only about one inch of undisturbed crust separates the deformed surface and the rock.

  10. Acquired vulvar lymphangioma circumscriptum after cervical cancer treatment: Case report.

    Valente, Kari; Montgomery, Kathleen; Schultenover, Stephen; Desouki, Mohamed Mokhtar

    2016-04-01

    Vulvar lymphangioma circumscriptum (LC) is a rare entity which may present as a painful, warty lesion. In contrast to the congenital form, which occurs in children, the acquired form arises in older adults and may be associated with infection, Crohn's disease, or prior pelvic/regional surgery. We present a case of acquired LC of the vulva in a 55-year-old woman who presented with a 3-4 year history of vulvar pain following chemotherapy, radiation, and brachytherapy for cervical cancer. Vulvar shave biopsies followed by excision revealed a thickened dermis with epidermal hyperkeratosis, parakeratosis, elongated rete ridges and dilated lymphatic channels containing eosinophilic material and scattered thrombi. The differential diagnosis for this unusual lesion includes more common conditions such as condyloma acuminatum, fungating squamous cell carcinoma and molluscum contagiosum. It is important to recognize the clinical presentation as well as the distinct histological appearance of this rare benign entity. PMID:27331134

  11. Community-acquired Acinetobacter baumannii: clinical characteristics, epidemiology and pathogenesis.

    Dexter, Carina; Murray, Gerald L; Paulsen, Ian T; Peleg, Anton Y

    2015-05-01

    Community-acquired Acinetobacter baumannii (CA-Ab) is a rare but serious cause of community-acquired pneumonia in tropical regions of the world. CA-Ab infections predominantly affect individuals with risk factors, which include excess alcohol consumption, diabetes mellitus, smoking and chronic lung disease. CA-Ab pneumonia presents as a surprisingly fulminant course and is characterized by a rapid onset of fever, severe respiratory symptoms and multi-organ dysfunction, with a mortality rate reported as high as 64%. It is unclear whether the distinct clinical syndrome caused by CA-Ab is because of host predisposing factors or unique bacterial characteristics, or a combination of both. Deepening our understanding of the drivers of overwhelming CA-Ab infection will provide important insights into preventative and therapeutic strategies. PMID:25850806

  12. Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi

    Miguel Peña-Espinoza

    2015-12-01

    Full Text Available The study investigated direct anthelmintic effects of sesquiterpene lactones (SL-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars ‘Spadona’ and ‘Puna II’ were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC. O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA, while cultured L3 were used in a larval exsheathment inhibition assay (LEIA. Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA. Electron microscopy (EM was performed on adult O. ostertagi exposed to 1000 μg extract mL−1 of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P = 0.01, while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P  0.05. In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P < 0.0001. No cuticular damage was observed by EM in worms exposed to any of the extracts. We have demonstrated that SL-containing extracts from forage chicory can inhibit feeding of free-living larvae and exert direct effects against parasitic stages of O. ostertagi. Our results may contribute to the identification of natural anti-parasitic compounds and to interpret the in vivo anthelmintic effects of forage chicory.

  13. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired....

  14. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  15. [Merits of acquiring ISO15189 accreditation].

    Kitagawa, Masami

    2010-01-01

    In Japan, an ISO15189 accreditation system was started in 2005. To date, 47 hospitals have been accredited. In this session, I will present the merits of acquiring accreditation regarding ISO15189 based on our experience. Our hospital has 263 beds. The Clinical Examination Section consists of 12 staff (including 5 part-time workers): 7 in change of sample examination and 5 in charge of physiological examination. The annual number of samples is approximately 150,000. Samples collected on health checkups account for 90%. To improve the quality and service, assessment by third persons has been positively utilized in our hospital. Accreditation regarding ISO9001, ISO14001, ISO27001, privacy mark, hospital function assessment, the functional assessment of "ningen-dock"/health checkup hospitals, labor/hygiene service function assessment, and ISO15189 has been acquired. Patients may not recognize ISO. So, it must be utilized, considering that the acquisition of accreditation is not a goal but a starting point. Furthermore, cost-performance should be improved to achieve utilization-related merits. It is important to not only acquire accreditation but also help clinical staff and patients become aware of some changes/merits. Patients may consult a hospital for the following reasons: confidence in the hospital, and the staffs kind/polite attitudes. Long-term management strategies should be established without pursuing only short-term profits. I will introduce several merits of acquiring accreditation regarding ISO15189. Initially, incidental conditions for bids and appeal points include accreditation regarding ISO15189. Our corporation has participated in some competitive bids regarding health checkup business. In some companies, the bid conditions included ISO acquisition. In our hospital, clinical trials have been positively carried out. For participation in trials, hospitals must pass an institutional examination. However, ISO acquisition facilitates the preparation of

  16. Guidelines for prevention of hospital acquired infections

    Yatin Mehta

    2014-01-01

    Full Text Available These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.

  17. Characteristics of Individuals with Congenital and Acquired Deaf-Blindness

    Dalby, Dawn M.; Hirdes, John P.; Stolee, Paul; Strong, J. Graham; Poss, Jeff; Tjam, Erin Y.; Bowman, Lindsay; Ashworth, Melody

    2009-01-01

    Using a standardized assessment instrument, the authors compared 182 adults with congenital deaf-blindness and those with acquired deaf-blindness. They found that those with congenital deaf-blindness were more likely to have impairments in cognition, activities of daily living, and social interactions and were less likely to use speech for…

  18. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism[S

    Pinkosky, Stephen L.; Filippov, Sergey; Srivastava, Rai Ajit K.; Hanselman, Jeffrey C.; Bradshaw, Cheryl D.; Hurley, Timothy R.; Cramer, Clay T.; Spahr, Mark A.; Brant, Ashley F.; Houghton, Jacob L.; Baker, Chris; Naples, Mark; Adeli, Khosrow; Newton, Roger S.

    2013-01-01

    ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. However, the molecular mechanism(s) mediating these activities remained undefined. Studies described here show that ETC-1002 free acid activates AMP-activated protein kinase in a Ca2+/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. These distinct molecular mechanisms are complementary in their beneficial effects on lipid and carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms, ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body weight and improved glycemic control in a mouse model of diet-induced obesity. ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk factors associated with metabolic syndrome and benefit patients with cardiovascular disease. PMID:23118444

  19. Sym004, a novel EGFR antibody mixture, can overcome acquired resistance to cetuximab.

    Iida, Mari; Brand, Toni M; Starr, Megan M; Li, Chunrong; Huppert, Evan J; Luthar, Neha; Pedersen, Mikkel W; Horak, Ivan D; Kragh, Michael; Wheeler, Deric L

    2013-10-01

    The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in a variety of human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for head and neck and colorectal cancer treatment, but many patients treated with cetuximab don't respond or eventually acquire resistance. To determine how tumor cells acquire resistance to cetuximab, we previously developed a model of acquired resistance using the non-small cell lung cancer line NCI-H226. These cetuximab-resistant (Ctx(R)) cells exhibit increased steady-state EGFR expression secondary to alterations in EGFR trafficking and degradation and, further, retained dependence on EGFR signaling for enhanced growth potential. Here, we examined Sym004, a novel mixture of antibodies directed against distinct epitopes on the extracellular domain of EGFR, as an alternative therapy for Ctx(R) tumor cells. Sym004 treatment of Ctx(R) clones resulted in rapid EGFR degradation, followed by robust inhibition of cell proliferation and down-regulation of several mitogen-activated protein kinase pathways. To determine whether Sym004 could have therapeutic benefit in vivo, we established de novo Ctx(R) NCI-H226 mouse xenografts and subsequently treated Ctx(R) tumors with Sym004. Sym004 treatment of mice harboring Ctx(R) tumors resulted in growth delay compared to mice continued on cetuximab. Levels of total and phospho-EGFR were robustly decreased in Ctx(R) tumors treated with Sym004. Immunohistochemical analysis of these Sym004-treated xenograft tumors further demonstrated decreased expression of Ki67, and phospho-rpS6, as well as a modest increase in cleaved caspase-3. These results indicate that Sym004 may be an effective targeted therapy for Ctx(R) tumors. PMID:24204198

  20. Sym004, a Novel EGFR Antibody Mixture, Can Overcome Acquired Resistance to Cetuximab

    Mari Iida

    2013-10-01

    Full Text Available The epidermal growth factor receptor (EGFR is a central regulator of tumor progression in a variety of human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for head and neck and colorectal cancer treatment, but many patients treated with cetuximab don't respond or eventually acquire resistance. To determine how tumor cells acquire resistance to cetuximab, we previously developed a model of acquired resistance using the non-small cell lung cancer line NCI-H226. These cetuximab-resistant (CtxR cells exhibit increased steady-state EGFR expression secondary to alterations in EGFR trafficking and degradation and, further, retained dependence on EGFR signaling for enhanced growth potential. Here, we examined Sym004, a novel mixture of antibodies directed against distinct epitopes on the extracellular domain of EGFR, as an alternative therapy for CtxR tumor cells. Sym004 treatment of CtxR clones resulted in rapid EGFR degradation, followed by robust inhibition of cell proliferation and down-regulation of several mitogen-activated protein kinase pathways. To determine whether Sym004 could have therapeutic benefit in vivo, we established de novo CtxR NCI-H226 mouse xenografts and subsequently treated CtxR tumors with Sym004. Sym004 treatment of mice harboring CtxR tumors resulted in growth delay compared to mice continued on cetuximab. Levels of total and phospho-EGFR were robustly decreased in CtxR tumors treated with Sym004. Immunohistochemical analysis of these Sym004-treated xenograft tumors further demonstrated decreased expression of Ki67, and phospho-rpS6, as well as a modest increase in cleaved caspase-3. These results indicate that Sym004 may be an effective targeted therapy for CtxR tumors.

  1. Acquired Zinc Deficiency in an Adult Female

    Mohanan Saritha; Divya Gupta; Laxmisha Chandrashekar; Devinder M Thappa; Nachiappa G Rajesh

    2012-01-01

    Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. Acquired cases are reported occasionally in patients with eating disorders or Crohn′s disease. We report a 24-year-old housewife with acquired isolated severe zinc deficiency with no other comorbidities to highlight the rare occurrence of isolated nutritional zinc deficiency in an otherwise normal patient.

  2. And the Winner is – Acquired

    Henkel, Joachim; Rønde, Thomas; Wagner, Marcus

    value in case of success—that is, a more radical innovation. In the second stage, successful entrants bid to be acquired by the incumbent. We assume that entrants cannot survive on their own, so being acquired amounts to a ‘prize’ in a contest. We identify an equilibrium in which the incumbent chooses...

  3. Acquired intrathoracic kidney in thoracic kyphosis

    Two cases of acquired intrathoracic kidney associated with thoracic kyphosis are reported, with emphasis on the radiographic manifestations. A search of the scientific literature disclosed that the acquired type of this abnormality is rare. The importance of recognizing this entity from a differential diagnostic standpoint is underscored. (author)

  4. Optimal Distinctiveness Signals Membership Trust.

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

    According to optimal distinctiveness theory, sufficiently small minority groups are associated with greater membership trust, even among members otherwise unknown, because the groups are seen as optimally distinctive. This article elaborates on the prediction's motivational and cognitive processes and tests whether sufficiently small minorities (defined by relative size; for example, 20%) are associated with greater membership trust relative to mere minorities (45%), and whether such trust is a function of optimal distinctiveness. Two experiments, examining observers' perceptions of minority and majority groups and using minimal groups and (in Experiment 2) a trust game, revealed greater membership trust in minorities than majorities. In Experiment 2, participants also preferred joining minorities over more powerful majorities. Both effects occurred only when minorities were 20% rather than 45%. In both studies, perceptions of optimal distinctiveness mediated effects. Discussion focuses on the value of relative size and optimal distinctiveness, and when membership trust manifests. PMID:27140657

  5. Community-Acquired Methicillin-Resistant "Staphylococcus aureus": Considerations for School Nurses

    Alex, Aniltta; Letizia, MariJo

    2007-01-01

    Methicillin-resistant "Staphylococcus aureus" (MRSA) is a disease-causing organism that has been present in hospital settings since the 1960s. However, a genetically distinct strain of MRSA, called community-acquired methicillin-resistant "Staphylococcus aureus" (CA-MRSA), has emerged in recent years in community settings among healthy…

  6. Distinction

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  7. Enhancing Medicares Hospital Acquired Conditions Policy

    U.S. Department of Health & Human Services — The current Medicare policy of non-payment to hospitals for Hospital Acquired Conditions (HAC) seeks to avoid payment for preventable complications identified...

  8. Hospital-Acquired Condition Reduction Program

    U.S. Department of Health & Human Services — In October 2014, CMS began reducing Medicare payments for subsection (d) hospitals that rank in the worst performing quartile with respect to hospital-acquired...

  9. Acquired Inventors’ Productivity after Horizontal Acquisition

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    Effective integration of the R&D functions of the acquired and acquiring firms is essential for knowledge recombination after acquisition. However, prior research suggests that the post-acquisition integration process often damages the inventive labor force. We argue that an examination of the mu......Effective integration of the R&D functions of the acquired and acquiring firms is essential for knowledge recombination after acquisition. However, prior research suggests that the post-acquisition integration process often damages the inventive labor force. We argue that an examination...... of the multifaceted nature of the integration process further enhances our understanding of which conditions will be more or less detrimental for corporate inventors. We focus on R&D teams which are the immediate organizational context in which inventors operate and drawing on insights from learning theory...

  10. Infections acquired in clinical laboratories in Utah.

    Jacobson, J.T.; Orlob, R B; Clayton, J L

    1985-01-01

    We reviewed laboratory-acquired infections occurring in Utah from 1978 through 1982. Written and telephone interviews of supervisors of 1,191 laboratorians revealed an estimated annual incidence of 3 laboratory-acquired infections per 1,000 employees. Infections, in order of frequency, included hepatitis B (clinical cases), shigellosis, pharyngitis, cellulitis, tuberculosis (skin test conversion), conjunctivitis, and non-A, non-B hepatitis. One-half of large laboratories (over 25 employees), ...

  11. The Acquired Immunodeficiency Syndrome: current status.

    Quagliarello, V.

    1982-01-01

    A recently recognized syndrome of acquired immunodeficiency (Acquired Immunodeficiency Syndrome-AIDS) has arisen since June 1981. It has received international attention. The clinical spectrum consists of repeated opportunistic infections, rare malignancies, and autoimmune phenomena, occurring in previously healthy adults with no history of an immunologic disorder. The population subset at risk for this syndrome appears to be predominantly homosexual American males and intravenous drug abuser...

  12. Intensive Care Unit–Acquired Weakness: Implications for Physical Therapist Management

    Nordon-Craft, Amy; Moss, Marc; Quan, Dianna; Schenkman, Margaret

    2012-01-01

    Patients admitted to the intensive care unit (ICU) can develop a condition referred to as “ICU-acquired weakness.” This condition is characterized by profound weakness that is greater than might be expected to result from prolonged bed rest. Intensive care unit–acquired weakness often is accompanied by dysfunction of multiple organ systems. Individuals with ICU-acquired weakness typically have significant activity limitations, often requiring physical assistance for even the...

  13. Seeing the eyes in acquired prosopagnosia.

    Pancaroglu, Raika; Hills, Charlotte S; Sekunova, Alla; Viswanathan, Jayalakshmi; Duchaine, Brad; Barton, Jason J S

    2016-08-01

    Case reports have suggested that perception of the eye region may be impaired more than that of other facial regions in acquired prosopagnosia. However, it is unclear how frequently this occurs, whether such impairments are specific to a certain anatomic subtype of prosopagnosia, and whether these impairments are related to changes in the scanning of faces. We studied a large cohort of 11 subjects with this rare disorder, who had a variety of occipitotemporal or anterior temporal lesions, both unilateral and bilateral. Lesions were characterized by functional and structural imaging. Subjects performed a perceptual discrimination test in which they had to discriminate changes in feature position, shape, or external contour. Test conditions were manipulated to stress focused or divided attention across the whole face. In a second experiment we recorded eye movements while subjects performed a face memory task. We found that greater impairment for eye processing was more typical of subjects with occipitotemporal lesions than those with anterior temporal lesions. This eye selectivity was evident for both eye position and shape, with no evidence of an upper/lower difference for external contour. A greater impairment for eye processing was more apparent under attentionally more demanding conditions. Despite these perceptual deficits, most subjects showed a normal tendency to scan the eyes more than the mouth. We conclude that occipitotemporal lesions are associated with a partially selective processing loss for eye information and that this deficit may be linked to loss of the right fusiform face area, which has been shown to have activity patterns that emphasize the eye region. PMID:27288649

  14. Response to mTOR inhibition: activity of eIF4E predicts sensitivity in cell lines and acquired changes in eIF4E regulation in breast cancer

    Bartlett John MS

    2011-02-01

    Full Text Available Abstract Background Inhibitors of the kinase mTOR, such as rapamycin and everolimus, have been used as cancer therapeutics with limited success since some tumours are resistant. Efforts to establish predictive markers to allow selection of patients with tumours likely to respond have centred on determining phosphorylation states of mTOR or its targets 4E-BP1 and S6K in cancer cells. In an alternative approach we estimated eIF4E activity, a key effector of mTOR function, and tested the hypothesis that eIF4E activity predicts sensitivity to mTOR inhibition in cell lines and in breast tumours. Results We found a greater than three fold difference in sensitivity of representative colon, lung and breast cell lines to rapamycin. Using an assay to quantify influences of eIF4E on the translational efficiency specified by structured 5'UTRs, we showed that this estimate of eIF4E activity was a significant predictor of rapamycin sensitivity, with higher eIF4E activities indicative of enhanced sensitivity. Surprisingly, non-transformed cell lines were not less sensitive to rapamycin and did not have lower eIF4E activities than cancer lines, suggesting the mTOR/4E-BP1/eIF4E axis is deregulated in these non-transformed cells. In the context of clinical breast cancers, we estimated eIF4E activity by analysing expression of eIF4E and its functional regulators within tumour cells and combining these scores to reflect inhibitory and activating influences on eIF4E. Estimates of eIF4E activity in cancer biopsies taken at diagnosis did not predict sensitivity to 11-14 days of pre-operative everolimus treatment, as assessed by change in tumour cell proliferation from diagnosis to surgical excision. However, higher pre-treatment eIF4E activity was significantly associated with dramatic post-treatment changes in expression of eIF4E and 4E-binding proteins, suggesting that eIF4E is further deregulated in these tumours in response to mTOR inhibition. Conclusions

  15. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    Yeh, Jun-Jun [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Section of Thoracic Imaging, Department of Chest Medicine and Family Medicine, Chiayi City (China); Chia Nan University of Pharmacy and Science, Tainan (China); Meiho University, Pingtung (China); Pingtung Christian Hospital, Pingtung (China); Chen, Solomon Chih-Cheng; Chen, Cheng-Ren [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Medical Research, Chiayi City (China); Yeh, Ting-Chun; Lin, Hsin-Kai; Hong, Jia-Bin; Wu, Bing-Tsang [Ditmanson Medical Foundation Chia-Yi Christian Hospital, Department of Family Medicine, Chiayi City (China); Wu, Ming-Ting [Department of Radiology, Kaohsiung Veterans General Hospital, Section of Thoracic and Circulation Imaging, Kaohsiung (China); School of Medicine, National Yang Ming University, Faculty of Medicine, Taipei (China)

    2014-10-15

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  16. A high-resolution computed tomography-based scoring system to differentiate the most infectious active pulmonary tuberculosis from community-acquired pneumonia in elderly and non-elderly patients

    The objective of this study was to use high-resolution computed tomography (HRCT) imaging to predict the presence of smear-positive active pulmonary tuberculosis (PTB) in elderly (at least 65 years of age) and non-elderly patients (18-65 years of age). Patients with active pulmonary infections seen from November 2010 through December 2011 received HRCT chest imaging, sputum smears for acid-fast bacilli and sputum cultures for Mycobacterium tuberculosis. Smear-positive PTB was defined as at least one positive sputum smear and a positive culture for M. tuberculosis. Multivariate logistic regression analyses were performed to determine the HRCT predictors of smear-positive active PTB, and a prediction score was developed on the basis of receiver operating characteristic curve analysis. Of 1,255 patients included, 139 were diagnosed with smear-positive active PTB. According to ROC curve analysis, the sensitivity, specificity, positive predictive value, negative predictive value, false positive rates and false negative rates were 98.6 %, 95.8 %, 78.5 %, 99.8 %, 4.2 % and 1.4 %, respectively, for diagnosing smear-positive active PTB in elderly patients, and 100.0 %, 96.9 %, 76.5 %, 100.0 %, 3.1 % and 0.0 %, respectively, for non-elderly patients. HRCT can assist in the early diagnosis of the most infectious active PTB, thereby preventing transmission and minimizing unnecessary immediate respiratory isolation. (orig.)

  17. Do Acquirer Capabilities Affect Acquisition Performance? Examining Strategic and Effectiveness Capabilities in Acquirers

    Mudde, Paul A.; Brush, Thomas

    2006-01-01

    This paper examines acquisition performance from the perspective of acquirer capabilities. It argues that the strategic capabilities underpinning a firm’s competitive strategy can be utilized to create economic value in acquisitions. Acquirers with strong cost leadership capabilities are expected to leverage these capabilities to reduce post-acquisition costs as they integrate acquisition targets. Acquirers with strong differentiation capabilities are expected to utilize their strategic capab...

  18. Defining poverty as distinctively human

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  19. Acquired angioedema secondary to hormone replacement therapy

    Malani Kumar

    2005-10-01

    Full Text Available Angioedema is a potentially life threatening condition and may be either inherited or acquired. The latter is rare with only a handful of cases reported in the world literature. Presenting complaints are often vague. Those most commonly described include swelling in the subcutaneous and submucosal tissues. Patients presenting with laryngeal edema have high mortality, and high clinical suspicion is necessary to avoid instrumentation, which can precipitate laryngeal spasm. We present a review of reported cases of hormonally induced hereditary angioedema, along with a report of a patient with acquired angioedema secondary to hormone replacement therapy. To the best of our knowledge, this case probably represents the first reported case of acquired angioedema secondary to hormone replacement therapy.

  20. Educational Psychology: The Distinctive Contribution

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  1. Group Treatment in Acquired Brain Injury Rehabilitation

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  2. Sexually acquired Salmonella Typhi urinary tract infection.

    Wielding, Sally; Scott, Gordon

    2016-05-01

    We report a case of isolated urinarySalmonella entericaserotype Typhi in an HIV-positive man who has sex with men. He was clinically well and blood and stool cultures were negative, indicating that this may have been a sexually acquired urinary tract infection. PMID:25953964

  3. Acquired secondary Grynfeltt's hernia: a case report

    Lumbar hernia is a rare condition whose diagnosis is hardly achieved. The prevalence is higher in elderly men. The present case report describes the case of a male, 78-year-old patient who underwent pleural effusion drainage 17 years before presenting with clinical manifestations and tomographic findings compatible with acquired secondary Grynfeltt's hernia. (author)

  4. Prevention of hospital-acquired hyponatraemia

    Lunøe, Mathilde; Overgaard-Steensen, C

    2015-01-01

    prevention of hospital-acquired hyponatraemia is an understanding of what determines plasma sodium concentration (P-[Na(+) ]) in the individual patient. P-[Na(+) ] is determined by balances of water and cations according to Edelman. This paper discusses the mechanisms influencing water and cation balances...

  5. Support Network Responses to Acquired Brain Injury

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  6. Interviewing Children with Acquired Brain Injury (ABI)

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  7. Monitoring Agitated Behavior After acquired Brain Injury

    Aadal, Lena; Mortensen, Jesper; Nielsen, Jørgen Feldbaek

    2015-01-01

    Purpose: To describe the onset, duration, intensity, and nursing shift variation of agitated behavior in patients with acquired brain injury (ABI) at a rehabilitation hospital. Design: Prospective descriptive study. Methods: A total of 11 patients with agitated behavior were included. Agitated...

  8. Acquiring Word-Meaning Mappings for Natural Language Interfaces

    Thompson, C

    2011-01-01

    This paper focuses on a system, WOLFIE (WOrd Learning From Interpreted Examples), that acquires a semantic lexicon from a corpus of sentences paired with semantic representations. The lexicon learned consists of phrases paired with meaning representations. WOLFIE is part of an integrated system that learns to transform sentences into representations such as logical database queries. Experimental results are presented demonstrating WOLFIE's ability to learn useful lexicons for a database interface in four different natural languages. The usefulness of the lexicons learned by WOLFIE are compared to those acquired by a similar system, with results favorable to WOLFIE. A second set of experiments demonstrates WOLFIE's ability to scale to larger and more difficult, albeit artificially generated, corpora. In natural language acquisition, it is difficult to gather the annotated data needed for supervised learning; however, unannotated data is fairly plentiful. Active learning methods attempt to select for annotation...

  9. Hemofilia A adquirida Acquired hemophilia A

    Delfina Almagro Vázquez

    2010-12-01

    Full Text Available La hemofilia A adquirida (HAA es un trastorno hemorrágico poco frecuente caracterizado por la presencia de autoanticuerpos contra el factor VIII (FVIII circulante. Aproximadamente en la mitad de los casos se ha observado un grupo heterogéneo de procesos patológicos que incluyen, entre otros, enfermedades autoinmunes y malignas y durante el embarazo, parto y puerperio. Las manifestaciones hemorrágicas son variables y fundamentalmente de tipo cutáneo mucoso. El diagnóstico se basa en el hallazgo en un paciente con manifestaciones hemorrágicas, prolongación del tiempo parcial de tromboplastina activado (TPTA, disminución de la actividad del FVIII y presencia de inhibidores del FVIII. El tratamiento de HAA incluye el control de las manifestaciones hemorrágicas y la supresión de la producción del anticuerpo. El concentrado de factor VIIa recombinante (FVIIar y el concentrado de complejo protrombínico (CCPA se consideran el tratamiento antihemorrágico de primera línea. Como terapéutica alternativa, en algunos casos puede utilizarse el concentrado de FVIII, la plasmaféresis y la inmunoadsorción extracorpórea. La prednisona sola o asociada con la ciclofosfamida, constituye el tratamiento inmunosupresor de primera línea. En pacientes refractarios puede administrarse como terapéutica de segunda línea, el rituximab (anti-CD20. Con la azatiopina, la ciclosporina, la vincristina y el micofenolato de mofetil, se han obtenido resultados variables.Acquired hemophilia A (AHA is an uncommon hemorrhagic disorder characterized by presence of autoantibodies to circulating factor VIII. Approximately in half of cases it is noted a heterogeneous group of pathological processes including among others, autoimmune and malignant diseases and during pregnancy, labor and puerperium. Hemorrhagic manifestations are variable and mainly of mucous cutaneous type. Diagnosis is based on the finding of a patient presenting with hemorrhagic manifestations

  10. Processed pseudogenes acquired somatically during cancer development

    Cooke, Susanna L.; Shlien, Adam; Marshall, John; Pipinikas, Christodoulos P; Martincorena, Inigo; Tubio, Jose M. C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R; Tarpey, Patrick S.

    2014-01-01

    Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotransp...

  11. Brucella abortus Infection Acquired in Microbiology Laboratories

    Fiori, Pier Luigi; Mastrandrea, Scilla; Rappelli, Paola; Cappuccinelli, Piero

    2000-01-01

    We report an outbreak of laboratory-acquired Brucella abortus infection originating in the accidental breakage of a centrifuge tube. A total of 12 laboratory workers were infected (attack rate of 31%), with an incubation time ranging from 6 weeks to 5 months. Antibody titers were evaluated weekly in all personnel exposed, allowing the diagnosis of the infection in most cases before the onset of clinical symptoms, so that specific therapy could be administrated.

  12. Acquired resistance to immunotherapy and future challenges.

    Restifo, Nicholas P; Smyth, Mark J; Snyder, Alexandra

    2016-02-01

    Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID:26822578

  13. Molecular biological aspects of acquired bullous diseases

    Dabelsteen, Erik

    1998-01-01

    genes have been cloned. The antigens which react with autoantibodies from patients with bullous pemphigoid, cicatricial pemphigoid, acquired epidermolysis bullosa, and linear IgA disease are all proteins of the hemidesmosome basement membrane complex. Interestingly, most of the antigens also appear to...... be the target for mutations seen in patients with the inherited type of epidermolysis bullosa in which bullous lesions are a prominent clinical feature....

  14. Economics and Preventing Hospital-acquired Infection

    Graves, Nicholas

    2004-01-01

    The economics of preventing hospital-acquired infections is most often described in general terms. The underlying concepts and mechanisms are rarely made explicit but should be understood for research and policy-making. We define the key economic concepts and specify an illustrative model that uses hypothetical data to identify how two related questions might be addressed: 1) how much should be invested for infection control, and 2) what are the most appropriate infection-control programs? We...

  15. Immunological memory and acquired immunodeficiency syndrome pathogenesis.

    Kaur, A; Rosenzweig, M; Johnson, R. P.

    2000-01-01

    Infection with the human immunodeficiency virus results in profound perturbations in immunological memory, ultimately resulting in increased susceptibility to opportunistic infections and acquired immunodeficiency syndrome (AIDS). We have used rhesus macaques infected with the simian immunodeficiency virus (SIV) as a model to understand better the effects of AIDS virus infection on immunological memory. Acute infection with SIV resulted in significant deficits in CD4+ helper responses to cyto...

  16. A CMA position. Acquired immunodeficiency syndrome.

    1989-01-01

    The following general principles serve as guidelines for various bodies, health care professionals and the general public. Specific aspects of infection with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) that relate to physicians' ethical responsibilities as well as society's moral obligations are discussed. Such matters include the need for education, research and treatment resources; the patient's right to investigation and treatment and to refusal of eith...

  17. Clinicopathological correlation of acquired hyperpigmentary disorders

    Anisha B Patel; Raj Kubba; Asha Kubba

    2013-01-01

    Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseas...

  18. MRI of fetal acquired brain lesions

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images

  19. MRI of fetal acquired brain lesions

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: daniela.prayer@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)

    2006-02-15

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

  20. Differential Protein Expression in Congenital and Acquired Cholesteatomas.

    Seung-Ho Shin

    Full Text Available Congenital cholesteatomas are epithelial lesions that present as an epithelial pearl behind an intact eardrum. Congenital and acquired cholesteatomas progress quite differently from each other and progress patterns can provide clues about the unique origin and pathogenesis of the abnormality. However, the exact pathogenic mechanisms by which cholesteatomas develop remain unknown. In this study, key proteins that directly affect cholesteatoma pathogenesis are investigated with proteomics and immunohistochemistry. Congenital cholesteatoma matrices and retroauricular skin were harvested during surgery in 4 patients diagnosed with a congenital cholesteatoma. Tissue was also harvested from the retraction pocket in an additional 2 patients during middle ear surgery. We performed 2-dimensional (2D electrophoresis to detect and analyze spots that are expressed only in congenital cholesteatoma and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS to separate proteins by molecular weight. Protein expression was confirmed by immunohistochemical staining. The image analysis of 2D electrophoresis showed that 4 congenital cholesteatoma samples had very similar protein expression patterns and that 127 spots were exclusively expressed in congenital cholesteatomas. Of these 127 spots, 10 major spots revealed the presence of titin, forkhead transcription activator homolog (FKH 5-3, plectin 1, keratin 10, and leucine zipper protein 5 by MALDI-TOF/MS analysis. Immunohistochemical staining showed that FKH 5-3 and titin were expressed in congenital cholesteatoma matrices, but not in acquired cholesteatomas. Our study shows that protein expression patterns are completely different in congenital cholesteatomas, acquired cholesteatomas, and skin. Moreover, non-epithelial proteins, including FKH 5-3 and titin, were unexpectedly expressed in congenital cholesteatoma tissue. Our data indicates that congenital cholesteatoma origins

  1. The Distinction Between English Synonyms

    段佳

    2012-01-01

      A large number of new words and terms flock in the English vocabulary and English has a variety of expressive methods making it possible to express the same meaning by different words. Therefore English synonyms are so abundant that it is possible to describe the colorful world and to express the complicated, delicate human thought and emotions. But they bring people many problems such as the correct choice of words from synonyms. The reason for this problem is the insufficient knowledge of the distinction of English synonyms, which have differences in many aspects. This paper offers three main aspects in distinguishing English synonyms that include words’ meaning, coloring and usage.

  2. Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

    Marta Di Pasquale

    2016-02-01

    Full Text Available Hospital-acquired pneumonia (HAP is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU, as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.

  3. Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

    Di Pasquale, Marta; Aliberti, Stefano; Mantero, Marco; Bianchini, Sonia; Blasi, Francesco

    2016-01-01

    Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP. PMID:26927074

  4. Integrating New Technical Staff: Implications for Acquiring New Technology

    Lee, Denis M. S.; Allen, Thomas J. (Thomas John), 1931-

    1982-01-01

    Hiring new staff in R&D provides an important opportunity for a firm to acquire new technological knowledge. It also takes a considerable length of time before new R&D staff become fully integrated into the organization. This study compares the communication patterns of new and veteran R&D staff as a function of their work activities. The results suggest that both the benefits and problems in the hiring and integration of new R&D staff is moderated by the type of research, development or tech...

  5. Radiologic diagnosis and treatment of iatrogenic acquired uterine arteriovenous malformation

    To analyze gray-scale US, color and duplex Doppler US, and angiographic findings in patients with acquired uterine arteriovenous malformations (AVMs), and to evaluate the usefulness of these modalities in the diagnosis of this disease and the effect of transcatheter arterial embolization in its treatment. During a recent seven-year period, we diagnosed 21 cases of acquired uterine AVM. Nineteen of these patients had a history of causative D and C (between one and seven D and C procedures per patient), one had a history of causative cesarean section, and one had cervical conization. All patients underwent transabdominal and endovaginal gray-scale, color Doppler, and duplex Doppler US and angiography, with therapeutic embolization of bilateral uterine arteries. The majority underwent follow-up Doppler US after embolization. The gray-scale US morphology of uterine AVMs included subtle myometrial inhomogeneity and multiple distinct, small anechoic spaces in the thickened myometrium or endometrium. Color Doppler US showed a tangle of tortuous vessels with multidirectional, high-velocity arterial flow, which was focally or asymmetrically distributed. Duplex Doppler US depicted a waveform of fast arterial flow with low resistance, while angiography demonstrated a complex tangle of vessels supplied by enlarged uterine arteries, in association with early venous drainage during the arterial phase, and staiss of contrast medium within abnormal vasculature. Where AVMs were combined with a pseudoaneurysm, this finding was observed. Transcatheter arterial embolization provided a complete cure, without recurrence. Color and duplex Doppler US in an appropriate modality for the detection and diagnosis of uterine AVMs and for follow-up after embolization. Transcatheter arterial embolization is a safe and effective method of treating this disease

  6. Genomic and metabolic comparison with Dickeya dadantii 3937 reveals the emerging Dickeya solani potato pathogen to display distinctive metabolic activities and T5SS/T6SS-related toxin repertoire

    Pedron, Jacques; Mondy, Samuel; des Essarts, Yannick Raoul; Van Gijsegem, Frederique; Faure, Denis

    2014-01-01

    Background: The pectinolytic enterobacteria of the Pectobacterium and Dickeya genera are causative agents of maceration-associated diseases affecting a wide variety of crops and ornamentals. For the past decade, the emergence of a novel species D. solani was observed in potato fields in Europe and the Mediterranean basin. The purpose of this study is to search by comparative genomics the genetic traits that could be distinctive to other Dickeya species and be involved in D. solani adaptation ...

  7. Two novel ALK mutations mediate acquired resistance to the next generation ALK inhibitor alectinib

    Katayama, Ryohei; Friboulet, Luc; Koike, Sumie; Lockerman, Elizabeth L.; Khan, Tahsin M.; Gainor, Justin F.; Iafrate, A. John; Takeuchi, Kengo; Taiji, Makoto; Okuno, Yasushi; Fujita, Naoya; Engelman, Jeffrey A.; Shaw, Alice T.

    2014-01-01

    Purpose The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged NSCLC. Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance. Experimental Design We established a cell line model of alectinib resistance, and analyzed a resistant tumor specimen from a patient who had relapsed on alectinib. We developed Ba/F3 models harboring alectinib-resistant ALK mutations and evaluated the potency of other next-generation ALK-TKIs in these models. We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. To elucidate structure-activity-relationships of ALK mutations, we performed computational thermodynamic simulation with MP-CAFEE. Results We identified a novel V1180L gatekeeper mutation from the cell line model and a second novel I1171T mutation from the patient who developed resistance to alectinib. Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response. Thermodynamics simulation suggests that both mutations lead to distinct structural alterations that decrease the binding affinity with alectinib. Conclusions We have identified two novel ALK mutations arising after alectinib exposure which are sensitive to other next generation ALK-TKIs. The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs. PMID:25228534

  8. Evaluation of Serratia and Pseudomonas in hospital acquired infection

    Etemadi H; Zahedani Sh

    1996-01-01

    Hospital acquired infection have 2 origins: 1) Infections acquired from the hospitalization. 2) Infections that transmit from hospital personnel and those who referred to a hospital. According to the studies approximately half of hospital acquired infection is under the first group. Gram-negative bacilli is of prime importance from all bacteries that caused hospital acquired infection. There are 3 main ways spreading hospital acquired infections include: 1) Auto infections 2) Transmit infecti...

  9. Sigmoid plate dehiscence: Congenital or acquired condition?

    Liu, Zhaohui, E-mail: lzhtrhos@163.com [Capital Medical University, Beijing Tongren Hospital, No 1 Dong Jiao Min Street, Dongcheng District, Beijing 100730 (China); Li, Jing, E-mail: lijingxbh@yahoo.com.cn [Capital Medical University, Beijing Tongren Hospital, No 1 Dong Jiao Min Street, Dongcheng District, Beijing 100730 (China); Zhao, Pengfei, E-mail: zhaopengf05@163.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Lv, Han, E-mail: chrislvhan@126.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Dong, Cheng, E-mail: derc007@sina.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China); Liu, Wenjuan, E-mail: wenjuanliu@163.com [Jining No. 1 People' s Hospital, No. 6 Health Street, Jining 272100 (China); Wang, Zhenchang, E-mail: cjr.wzhch@vip.163.com [Capital Medical University, Beijing Friendship Hospital, No 95 Yongan Road, Xicheng District, Beijing 100050 (China)

    2015-05-15

    Highlights: • CT with multiplanar reformations can accurately display the sigmoid platet dehiscence. • The prevalence of sigmoid plate dehiscence was no significant difference among different age groups. • The size of sigmoid plate bony defects were not statistically different among different age groups. • The sigmoid plate dehiscence is more commonly a congenital than an acquired condition. - Abstract: Background and purpose: The imaging features of sigmoid plate dehiscence-induced pulsatile tinnitus have been presented. The origin of the sigmoid plate dehiscence, however, remains unclear. Our aim was to assess the prevalence and extent of sigmoid plate dehiscence on computed tomography (CT) images in multiple age groups to determine whether this condition is more likely to be congenital or acquired. Materials and methods: We retrospectively reviewed contrast-enhanced CT images of sigmoid plates of temporal bones in 504 patients. Each temporal bone was characterized as normal or dehiscent. Patients were then subcategorized into four age groups, and the prevalence and extent of dehiscent sigmoid plates in each group were calculated and compared. Results: Overall, 80 patients had sigmoid plate dehiscence, nine of whom had it bilaterally. In successively older age groups, the prevalences of sigmoid plate dehiscence were 18.9%, 20.1%, 14.5%, and 12.7%, respectively. Respective average anteroposterior bony defect diameters were 3.7 ± 1.7, 3.0 ± 1.3, 3.1 ± 1.5, and 3.0 ± 1.1 mm. Respective average vertical bony defect diameters were 3.6 ± 2.3, 2.6 ± 1.2, 3.2 ± 1.5, and 3.0 ± 1.7 mm. The prevalence and extent of sigmoid plate dehiscence were not statistically different among the four age groups. Conclusions: The similar radiologic prevalence and extent of dehiscent sigmoid plates among the age groups suggest that the dehiscence is more commonly a congenital than an acquired condition.

  10. Sigmoid plate dehiscence: Congenital or acquired condition?

    Highlights: • CT with multiplanar reformations can accurately display the sigmoid platet dehiscence. • The prevalence of sigmoid plate dehiscence was no significant difference among different age groups. • The size of sigmoid plate bony defects were not statistically different among different age groups. • The sigmoid plate dehiscence is more commonly a congenital than an acquired condition. - Abstract: Background and purpose: The imaging features of sigmoid plate dehiscence-induced pulsatile tinnitus have been presented. The origin of the sigmoid plate dehiscence, however, remains unclear. Our aim was to assess the prevalence and extent of sigmoid plate dehiscence on computed tomography (CT) images in multiple age groups to determine whether this condition is more likely to be congenital or acquired. Materials and methods: We retrospectively reviewed contrast-enhanced CT images of sigmoid plates of temporal bones in 504 patients. Each temporal bone was characterized as normal or dehiscent. Patients were then subcategorized into four age groups, and the prevalence and extent of dehiscent sigmoid plates in each group were calculated and compared. Results: Overall, 80 patients had sigmoid plate dehiscence, nine of whom had it bilaterally. In successively older age groups, the prevalences of sigmoid plate dehiscence were 18.9%, 20.1%, 14.5%, and 12.7%, respectively. Respective average anteroposterior bony defect diameters were 3.7 ± 1.7, 3.0 ± 1.3, 3.1 ± 1.5, and 3.0 ± 1.1 mm. Respective average vertical bony defect diameters were 3.6 ± 2.3, 2.6 ± 1.2, 3.2 ± 1.5, and 3.0 ± 1.7 mm. The prevalence and extent of sigmoid plate dehiscence were not statistically different among the four age groups. Conclusions: The similar radiologic prevalence and extent of dehiscent sigmoid plates among the age groups suggest that the dehiscence is more commonly a congenital than an acquired condition

  11. Acquired prosopagnosia without word recognition deficits.

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  12. [Acquired immunodeficiency syndrome in pediatric patients].

    Molina Moguel, J L; Ruiz Illezcas, R; Forsbach Sánchez, S; Carreño Alvarez, S; Picco Díaz, I

    1990-12-01

    The object of this study was to determine how many of the patients treated at the Pediatric Odontology Clinic, a branch of the Maxillo-Facial Surgery Service at the Veinte de Noviembre Regional Hospital, ISSSTE, are VIH-positive of show serious manifestations of Acquired Immuno-Deficiency Syndrome (AIDS). For such purpose, 100 pediatric patients suffering from different systemic or local diseases were evaluated, the most common being hematological alterations. Results evidenced the presence of VIH in the blood of five of the pediatric subjects, all suffering from Hemophilia. PMID:2132469

  13. Acquired CNS lesions in fetal MRI

    Acquired central nervous system (CNS) lesions are often subtle; therefore, the prenatal diagnosis of these lesions is extremely important. The fetal ultrasound examination and magnetic resonance imaging (MRI) are two important imaging methods that give an insight into these types lesions. The method of choice during pregnancy is still fetal ultrasound; however, fetal MRI is important when there are certain pathologies, e.g. periventricular leukomalacia (PVL) or malformations of the vein of Galen. In this manner clinicians can plan further therapy after childbirth in advance (e.g. cerebral angiography or embolization). (orig.)

  14. Cerebral involvement in acquired immunodeficiency syndrome (AIDS)

    Involvement of the central nervous system in acquired immune deficiency syndrome (AIDS) is usually due to opportunistic infections; these frequently offer a difficult differential diagnostic problem. Imaging methods play an important part in the elucidation of symptoms. CT and MR findings were analysed in 13 patients with AIDS and neurological symptoms. Some infections of the central nervous system (encephalitis of unknown aetiology, cytomegalic encephalitis, meningitis) may show cerebral atrophy or even no morphological changes. Toxoplasmosis and PML are the most common opportunistic infections typical changes on CT and MR may lead to diagnosis. MR offers advantages compared with CT in its higher sensitivity for the demonstration even of small lesions. (orig.)

  15. Expert games: means to acquire expert knowledge

    G. Ginkul

    1993-06-01

    Full Text Available This article describes the idea and use of non-traditional technique designed to acquire Expert's knowledge for Expert Systems. The procedures, called "Expert Games", look outwardly as well-known computer "playthings" and at the same time are strong means for Knowledge Acquisition. If Expert wants to succeed, he must to use his professional knowledge. After analyzing game operations of an Expert it is possible to resolve reverse problem - to define which what kind of knowledge have been used for making Expert's decision during the game.

  16. Psychological issues in acquired facial trauma

    De Sousa Avinash

    2010-01-01

    Full Text Available The face is a vital component of one′s personality and body image. There are a vast number of variables that influence recovery and rehabilitation from acquired facial trauma many of which are psychological in nature. The present paper presents the various psychological issues one comes across in facial trauma patients. These may range from body image issues to post-traumatic stress disorder symptoms accompanied by anxiety and depression. Issues related to facial and body image affecting social life and general quality of life are vital and the plastic surgeon should be aware of such issues and competent to deal with them in patients and families.

  17. Acquired Congenital Malalignment of the Great Toenails

    Decker, Ashley; Scher, Richard K.; Avarbock, Andrew

    2016-01-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  18. Asian elephants acquire inaccessible food by blowing.

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication. PMID:26541597

  19. Tetracycline resistance genes acquired at birth.

    Alicea-Serrano, Angela M; Contreras, Mónica; Magris, Magda; Hidalgo, Glida; Dominguez-Bello, Maria G

    2013-06-01

    Newborns acquire their first microbiota at birth. Maternal vaginal or skin bacteria colonize newborns delivered vaginally or by C-section, respectively (Dominguez-Bello et al. 2010 #884). We aimed to determine differences in the presence of four tetracycline (tet) resistance genes, in the microbes of ten newborns and in the mouth and vagina of their mothers, at the time of birth. DNA was amplified by PCR with primers specific for [tet(M), tet(O), tet(Q), and tet(W)]. Maternal vaginas harbored all four tet resistance genes, but most commonly tet(M) and tet(O) (63 and 38 %, respectively). Genes coding for tet resistance differed by birth mode, with 50 % of vaginally delivered babies had tet(M) and tet(O) and 16 and 13 % of infants born by C-section had tet(O) and tet(W), respectively. Newborns acquire antibiotic resistance genes at birth, and the resistance gene profile varies by mode of delivery. PMID:23483141

  20. Acquired Muscle Weakness in the Surgical Intensive Care Unit: Nosology, Epidemiology, Diagnosis, and Prevention.

    Farhan, Hassan; Moreno-Duarte, Ingrid; Latronico, Nicola; Zafonte, Ross; Eikermann, Matthias

    2016-01-01

    Muscle weakness is common in the surgical intensive care unit (ICU). Low muscle mass at ICU admission is a significant predictor of adverse outcomes. The consequences of ICU-acquired muscle weakness depend on the underlying mechanism. Temporary drug-induced weakness when properly managed may not affect outcome. Severe perioperative acquired weakness that is associated with adverse outcomes (prolonged mechanical ventilation, increases in ICU length of stay, and mortality) occurs with persistent (time frame: days) activation of protein degradation pathways, decreases in the drive to the skeletal muscle, and impaired muscular homeostasis. ICU-acquired muscle weakness can be prevented by early treatment of the underlying disease, goal-directed therapy, restrictive use of immobilizing medications, optimal nutrition, activating ventilatory modes, early rehabilitation, and preventive drug therapy. In this article, the authors review the nosology, epidemiology, diagnosis, and prevention of ICU-acquired weakness in surgical ICU patients. PMID:26445385

  1. HOW ROMANIAN FINANCIAL AND INTERNAL AUDITORS ACQUIRE ACCOUNTING INFORMATION SYSTEMS KNOWLEDGE AND COMPETENCES?

    Cardos Vasile-Daniel

    2011-01-01

    Research theme - in this article we investigate how Romanian financial and internal auditors acquire accounting information systems knowledge and competences and how they use this knowledge to improve their activity in order to fulfill their mission as required by the professional standards. Objectives - our main purpose is to establish through what type of courses Romanian financial and internal auditors acquiring accounting information systems knowledge and competences and how useful these ...

  2. Penoscrotal porokeratosis: A distinct entity

    Rajiv Joshi

    2015-01-01

    Full Text Available A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition.

  3. The acquired hyperostosis syndrome. Pt. 2

    In the second part of this publication, we describe some additional findings in cases of sternocostoclavicular hyperostosis (SCCH). These include focal hyperostosis of the spine, in the pelvis and in the extremities and psoriatric skin lesions and severe forms of acne (acne conglobata, acne fulminans). An analysis of our 13 patients and of the relevant literature indicates that the hyperostosis is due to increased bone metabolism and heterotopic ossification of fibrous tissue and that these are the pathogenic bases of the changes in the axial skeleton, the pelvis and the bones of the extremities. We have suggested a scheme which would categorise the syndrom into complete, incomplete and possibly acquired forms. (orig./GDG)

  4. How to divest acquired physician practices.

    O'Hare, P K

    1999-02-01

    When an integrated delivery system (IDS) determines it must divest itself of a previously acquired physician practice, it must manage the transaction with care. The IDS most likely will want to maintain a positive ongoing relationship with the physician practice, while avoiding concessions to the practice that could be construed as violations of state and Federal laws. Before proceeding, the IDS should evaluate the reasons for divesting the practice, assess legal issues involved in terminating contracts with the practice, decide how to deal with the practice's assets and office facilities, consider whether covenants not to compete should be enforced, ensure continued access to essential medical records, consider whether to incorporate a "non-disparagement" clause in the termination agreement, and determine what mutual general releases may be necessary. PMID:10345614

  5. Human temporal bone findings in acquired hypothyroidism.

    Hald, J; Milroy, C M; Jensen, K D; Parving, A

    1991-11-01

    Histological studies of the auditory organ in patients with acquired hypothyroidism are scarce. Thus the aim of the present study was to examine the temporal bones and the brain in subjects with hypothyroidism. Four temporal bones and two brains from clinically and biochemically hypothyroid subjects were removed and evaluated by light microscopy determine to the morphological changes and deposition of neutral and acid glycosaminoglycans. An audiogram from one of the patients showed a sensorineural hearing loss, which could be ascribed to occupational noise exposure. The study revealed histological changes compatible with age and infectious disease. No accumulation of neutral or acid glycosaminoglycans could be demonstrated in the temporal bones, or in the brains. PMID:1761939

  6. Time dysperception perspective for acquired brain injury

    Federica ePiras

    2014-01-01

    Full Text Available Distortions of time perception are presented by a number of neuropsychiatric disorders. Here we survey timing abilities in clinical populations with acquired brain injuries in key cerebral areas recently implicated in human studies of timing. We purposely analyzed the complex relationship between cognitive and contextual factors involved in time estimation, as to characterize the correlation between timed and other cognitive behaviors in each group. We assume that interval timing is a solid construct to study cognitive dysfunctions following brain injury, as timing performance is a sensitive metric of information processing, while temporal cognition has the potential of influencing a wide range of cognitive processes. Moreover, temporal performance is a sensitive assay of damage to the underlying neural substrate after a brain insult. Further research in neurological and psychiatric patients will definitively answer the question of whether time distortions are manifestations of cognitive and behavioral symptoms of brain damage and definitively clarify their mechanisms.

  7. Covalent targeting of acquired cysteines in cancer.

    Visscher, Marieke; Arkin, Michelle R; Dansen, Tobias B

    2016-02-01

    The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened the Catalog of Somatic Mutations in Cancer for frequently acquired cysteines. Here, we describe the most common mutations and discuss how these mutations could be potential targets for cysteine-directed personalized therapeutics. PMID:26629855

  8. Acquired methaemoglobinaemia related to phenazopyridine ingestion.

    Shahani, Lokesh; Sattovia, Stacy

    2012-01-01

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population. PMID:22987905

  9. The acquired immunodeficiency syndrome in gay men.

    Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

    1985-11-01

    The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men. PMID:2996396

  10. Acquiring Correct Knowledge for Natural Language Generation

    Reiter, E; Sripada, S G; 10.1613/jair.1176

    2011-01-01

    Natural language generation (NLG) systems are computer software systems that produce texts in English and other human languages, often from non-linguistic input data. NLG systems, like most AI systems, need substantial amounts of knowledge. However, our experience in two NLG projects suggests that it is difficult to acquire correct knowledge for NLG systems; indeed, every knowledge acquisition (KA) technique we tried had significant problems. In general terms, these problems were due to the complexity, novelty, and poorly understood nature of the tasks our systems attempted, and were worsened by the fact that people write so differently. This meant in particular that corpus-based KA approaches suffered because it was impossible to assemble a sizable corpus of high-quality consistent manually written texts in our domains; and structured expert-oriented KA techniques suffered because experts disagreed and because we could not get enough information about special and unusual cases to build robust systems. We bel...

  11. Acquiring neural signals for developing a perception and cognition model

    Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

    2012-06-01

    The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

  12. Does Acquired Hypothyroidism Affect the Hearing Functions?

    Ayşe Arduç

    2015-12-01

    Full Text Available Purpose: It is well known that congenital hypothyroidism can cause hearing loss. However, conflicting results were found in studies investigating hearing functions in acquired hypothyroidism. Therefore, we evaluated the audiometric findings in patients with acquired hypothyroidism. Material and Method: The study included 58 patients with hypothyroidism and age- and gender-matched 34 healthy controls. Twenty eight (48.27% patients had subclinical hypothyroidism, and 30 (51.73% had obvious hypothyroidism. All subjects had a normal otoscopic examination and tympanometry. Pure tone audiometry at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz was performed in both groups. Blood pressure measurements and the levels of plasma electrolytes, lipids and vitamin B12 were available in all subjects. Results: Hypothyroidism group and control group were similar with respect to systolic and diastolic blood pressures and plasma glucose, lipid, vitamin B12, calcium, sodium, potassium, and chloride levels. Significantly higher audiometric thresholds (dB at 250 (10 (0-45 vs. 5 (0-15, p<0.001 and 500 Hz (10 (0-40 vs. 10 (-5-15, p=0.003 were recorded in hypothyroid patients compared to that in healthy controls. Hearing thresholds at 250 and 500 Hz correlated positively with thyroid-stimulating hormone (TSH, and negatively with free triiodothyronine and free thyroxine. Subclinical hypothyroid patients had a higher hearing threshold at 250 Hz than healthy controls (p=0.001. Discussion: Our study demonstrated that hearing ability decreases in hypothyroidism, even in subclinical hypothyroidism. The changes in TSH and thyroid hormone levels seem to be directly related to the hearing loss in this population of patients.

  13. Hematopoietic Stem Cell Regulation by Type I and II Interferons in the Pathogenesis of Acquired Aplastic Anemia.

    Smith, Julianne N P; Kanwar, Vikramjit S; MacNamara, Katherine C

    2016-01-01

    Aplastic anemia (AA) occurs when the bone marrow fails to support production of all three lineages of blood cells, which are necessary for tissue oxygenation, infection control, and hemostasis. The etiology of acquired AA is elusive in the vast majority of cases but involves exhaustion of hematopoietic stem cells (HSC), which are usually present in the bone marrow in a dormant state, and are responsible for lifelong production of all cells within the hematopoietic system. This destruction is immune mediated and the role of interferons remains incompletely characterized. Interferon gamma (IFNγ) has been associated with AA and type I IFNs (alpha and beta) are well documented to cause bone marrow aplasia during viral infection. In models of infection and inflammation, IFNγ activates HSCs to differentiate and impairs their ability to self-renew, ultimately leading to HSC exhaustion. Recent evidence demonstrating that IFNγ also impacts the HSC microenvironment or niche, raises new questions regarding how IFNγ impairs HSC function in AA. Immune activation can also elicit type I interferons, which may exert effects both distinct from and overlapping with IFNγ on HSCs. IFNα/β increase HSC proliferation in models of sterile inflammation induced by polyinosinic:polycytidylic acid and lead to BM aplasia during viral infection. Moreover, patients being treated with IFNα exhibit cytopenias, in part due to BM suppression. Herein, we review the current understanding of how interferons contribute to the pathogenesis of acquired AA, and we explore additional potential mechanisms by which interferons directly and indirectly impair HSCs. A comprehensive understanding of how interferons impact hematopoiesis is necessary in order to identify novel therapeutic approaches for treating AA patients. PMID:27621733

  14. Distinctiveness of Ugandapithecus from Proconsul

    Gommery, D.

    2009-12-01

    Full Text Available The decision to create the genus Ugandapithecus by Senut et al., 2000 has been criticised, either directly and in detail by MacLatchy & Rossie (2005b who argued that it is a junior synonym of Proconsul, or indirectly without providing reasons, firstly by Harrison (2001 who wrote that he did not retain it as a genus distinct from Proconsul, and then by Suwa et al., (2007 who employed the name “Ugandapithecus” with inverted commas, implying some degree of doubt about its validity as a genus, but without providing details. More recently Harrison & Andrews (2009 have recognised the Meswa sample as a separate species but they argue that it should be maintained within Proconsul, despite the morphological differences that it has from other species of the genus. We here re-examine the question by comparing, on the one hand, the holotype maxilla of Proconsul africanus, the type species of the genus, with the upper dentition of Ugandapithecus major, and, on the other hand, the holotype mandible of Ugandapithecus major with the lower dentition and mandibles previously attributed to Proconsul africanus. We conclude that the differences between the known upper and lower dentitions of P. africanus and U. major are of such a degree that the two taxa warrant generic separation, and that the differences are not related to sexual dimorphism. Where Proconsul africanus differs from Ugandapithecus major, it approaches Proconsul nyanzae and Proconsul heseloni from Rusinga.Furthermore, the range of morphometric variation within the fossil samples previously attributed to Ugandapithecus major is so great that it far surpasses variation in any other hominoid, fossil or extant. Previously this great amount of variation was interpreted to mean that U. major was extremely dimorphic, with huge males and small females, but if this is true, then U. major would be unique among hominoids in having females in which the cheek teeth fall completely outside the range of

  15. Acquiring Control in Emerging Markets: Evidence from the Stock Market

    Anusha Chari; Paige P. Ouimet; Tesar, Linda L.

    2004-01-01

    When firms from developed markets acquire firms in emerging markets, market-capitalization-weighted monthly joint returns show a statistically significant increase of 1.8%. Panel data estimations suggest that the value gains from cross-border M&A transactions stem from the transfer of majority control from emerging-market targets to developed market acquirers' joint returns range from 5.8% to 7.8% when majority control is acquired. Announcement returns for acquirer and target firms estimate t...

  16. Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections

    Prabhakara, Ranjani; Foreman, Oded; De Pascalis, Roberto; Lee, Gloria M.; Plaut, Roger D.; Kim, Stanley Y.; Stibitz, Scott; Elkins, Karen L.; Merkel, Tod J.

    2013-01-01

    Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involv...

  17. Mucocutaneous manifestations of acquired hypoparathyroidism: An observational study

    Somenath Sarkar; Modhuchanda Mondal; Kapildev Das; Arpit Shrimal

    2012-01-01

    Hypoparathyroidism is a disorder of calcium and phosphorus metabolism due to decreased secretion of parathyroid hormone. Hypoparathyroidism can be hereditary and acquired. Acquired hypoparathyroidism usually occurs following neck surgery (thyroid surgery or parathyroid surgery). Along with systemic manifestations, hypoparathyroidism produces some skin manifestations. Lack of study regarding mucocutaneous manifestations of acquired hypoparathyroidism prompted us to undertake this study. To eva...

  18. 30 CFR 879.14 - Management of acquired land.

    2010-07-01

    ... ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.14 Management of acquired land. Land acquired under this part may be used for any lawful purpose that is... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Management of acquired land. 879.14 Section...

  19. Preschoolers Acquire General Knowledge by Sharing in Pretense

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  20. 24 CFR 1000.156 - Is affordable housing developed, acquired, or assisted under the IHBG program subject to...

    2010-04-01

    ..., acquired, or assisted under the IHBG program subject to limitations on cost or design standards? 1000.156... developed, acquired, or assisted under the IHBG program subject to limitations on cost or design standards... determination of moderate design applies to all housing assisted under an affordable housing activity,...

  1. Acquiring energy savings in manufactured housing

    In 1991, the Northwest utilities faced a complex situation. They needed new sources of electrical power to avoid future deficits. A significant block of energy savings was available in the manufactured housing sector in the form of energy savings from increased insulation to new manufactured homes. The manufacturers were interested in saving the electricity in the homes, but would only deal with the utility sector as a whole. Half of the homes targeted were sited in investor-owned utility (IOU) service territories, and half in the public sector made up of utilities that purchased some or all of their electricity from the Bonneville Power Administration. Utilities agreed to acquire energy from manufacturers In the form of thermal efficiency measures specified by the Bonneville Power Administration. The program that resulted from over one year of negotiations was called the Manufactured Housing Acquisition Program, or MAP. Manufacturers, the utilities, State Energy Offices, the Northwest Power Planning Council and Bonneville all worked closely and with tenacity to build the program that went into effect on April 1, 1992, and should save the region between 7 and 9 megawatts, enough energy to supply 11,000 homes in the Northwest

  2. Acquired Hemophilia A successfully treated with rituximab

    Giovanni D'Arena

    2015-02-01

    Full Text Available Acquired hemophilia A (AHA is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in  obtaining a long-term suppression of inhibitors of AHA,  besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with  a normalization of clotting  parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm. , but after stopping rituximab, an initial worsening of coagulation  parameters  induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days.  This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs remains to be established and warrants further investigation.

  3. Recent legal problems in acquiring nuclear fuel

    This paper surveys problems encountered by Southern California Edison Company in acquiring U concentrates to meet the needs of San Onofre Nuclear Generating Station Units 1, 2, and 3. References are made to San Onofre, Edison, and San Diego Gas and Electric Company in order to illustrate certain legal problems. The San Onofre Units are owned 80% by Edison and 20% by San Diego. Questions are posed about the traditional fuel procurement practices. A subsidiary of Edison, Mono Power Company, locates and delivers energy resources for Edison. Mono and Rocky Mountain Energy Company are jointing developing the Bear Creek urnaium mining and milling complex. The risk involved in converting a joint venture to a partnership is pointed out. The purchasing arrangement in the Palo Verde participants is discussed. Market value is used as a basis for pricing future U deliveries, but there is no really satisfactory method for determining future market value. It is concluded that the purchaser of nuclear fuel is faced with legal problems that transcend conventional problems of contracts and the commercial code

  4. Anticancer properties of distinct antimalarial drug classes.

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  5. The etiology of primary femoroacetabular impingement: genetics or acquired deformity?

    Packer, Jonathan D; Safran, Marc R

    2015-10-01

    The etiology of primary femoroacetabular impingement (FAI) remains controversial. Both genetic and acquired causes have been postulated and studied. While recent studies suggest that genetic factors may have a role in the development of FAI, there is no conclusive evidence that FAI is transmitted genetically. Currently, the most popular theory for the development of cam-type deformities is that a repetitive injury to the proximal femoral physis occurs during a critical period of development. There is a correlation between a high volume of impact activities during adolescence and the development of cam-type deformities. Multiple studies have found a high prevalence of FAI in elite football, ice hockey, basketball and soccer players. In this article, we review the current literature relating to the etiology of primary FAI. PMID:27011846

  6. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.

    Quddus, J; Johnson, K J; Gavalchin, J; Amento, E P; Chrisp, C E; Yung, R L; Richardson, B C

    1993-01-01

    Human antigen-specific CD4+ T cells become autoreactive after treatment with various DNA methylation inhibitors, including 5-azacytidine, procainamide, and hydralazine. This suggests a mechanism that could contribute to the development of some forms of autoimmunity. In this report we have asked whether T cells treated with DNA methylation inhibitors can induce autoimmunity. Murine CD4+ T cells were treated with 5-azacytidine or procainamide and were shown to respond to syngeneic antigen-presenting cells, similar to CD4+ human T cell clones treated with these drugs. Functional characterization demonstrated that cells treated with either drug spontaneously lysed syngeneic macrophages and secreted IL-4, IL-6, and IFN-gamma. Adoptive transfer of 5-azacytidine- or procainamide-treated cells into unirradiated syngeneic recipients induced an immune complex glomerulonephritis and IgG anti-DNA and antihistone antibodies. These experiments demonstrate that T cells treated with either of two distinct DNA methyltransferase inhibitors are sufficient to induce a lupus-like disease. It is possible that the lysis of macrophages, together with the release of cytokines promoting B cell differentiation, contributes to the autoantibody production and immune complex deposition. These results suggest that environmental agents that inhibit DNA methylation could interact with T cells in vivo to produce a lupus-like illness, a mechanism that could have relevance to drug-induced and idiopathic lupus. Images PMID:7686923

  7. Vestibular stimulation leads to distinct hemodynamic patterning

    Kerman, I. A.; Emanuel, B. A.; Yates, B. J.

    2000-01-01

    Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%). Relatively small changes (vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

  8. Three distinct reversing modes in the geodynamo

    Gallet, Y.; Pavlov, V. E.

    2016-03-01

    The data that describe the long-term reversing behavior of the geodynamo show strong and sudden changes in magnetic reversal frequency. This concerns both the onset and the end of superchrons and most probably the occurrence of episodes characterized by extreme geomagnetic reversal frequency (>10-15 rev./Myr). To account for the complexity observed in geomagnetic reversal frequency evolution, we propose a simple scenario in which the geodynamo operates in three distinct reversing modes: i—a "normal" reversing mode generating geomagnetic polarity reversals according to a stationary random process, with on average a reversal rate of ˜3 rev./Myr; ii—a non-reversing "superchron" mode characterizing long time intervals without reversal; iii—a hyper-active reversing mode characterized by an extreme geomagnetic reversal frequency. The transitions between the different reversing modes would be sudden, i.e., on the Myr time scale. Following previous studies, we suggest that in the past, the occurrence of these transitions has been modulated by thermal conditions at the core-mantle boundary governed by mantle dynamics. It might also be possible that they were more frequent during the Precambrian, before the nucleation of the inner core, because of a stronger influence on geodynamo activity of the thermal conditions at the core-mantle boundary.

  9. Life After Project Effort: Appying Values Acquired in a Responsibility-based Physical Activity Program. [Vida después del “Proyecto Esfuerzo”: Aplicación de los valores adquiridos en un programa de actividad física basado en la responsabilidad].

    Anthony Meléndez

    2015-07-01

    Full Text Available Among physical activity curricular models used in the youth development field, the Teaching Personal and Social Responsibility (TPSR model has been widely incorporated in many underserved youth community and school physical education programs around the United States and the world (Hellison, 2011. Project Effort is an extended day program that uses the TPSR model as a framework. Literature has shown that TPSR programs and Project Effort have had a positive impact on the life of the participants. The purpose of this study was to investigate what TPSR values former participants’ have acquired in Project Effort and through other sources, and how they have guided their lives. A multiple-case design was implemented to understand this phenomenon. The findings showed that former participants considered that four TPSR values (i.e. respect, effort, self-direction, helping others were really important to their lives. Participants reported that they learned the TPSR values of helping others and leadership in Project Effort. Also they mentioned that they acquired the TPSR life skills of being reflective, teamwork, and goal setting in Project Effort. The TPSR value of helping others, and the TPSR life skill of being reflective acquired in Project Effort were most useful to the participants. Participants learned the TPSR value of self-direction and the TPSR values of respect and caring. Resumen Entre los modelos curriculares de actividad física utilizados para el desarrollo de la juventud, la enseñanza personalizada y el modelo de Enseñanza de la Responsabilidad Personal y Social (TPSR han sido ampliamente incorporados en muchas comunidades los jóvenes marginados y en programas de educación física escolares en Estados Unidos y en el mundo (Hellison, 2011. El proyecto esfuerzo es un programa de día extendido que utiliza el modelo TPSR como fundamento. La literatura ha demostrado que los programas TPSR y el Proyecto Esfuerzo han tenido un impacto

  10. Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome

    GENG Shuang; YE Jun-jie; ZHAO Jia-liang; LI Tai-sheng; HAN Yang

    2011-01-01

    Background Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS.Methods It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4+ T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 μg) were performed in 4 eyes (2 patients).Results Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque.Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4+ T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6±25.3) ×106/L (range,(0-85) × 106/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed.Conclusions CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

  11. Regulator of G protein signaling 2 (RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1 in live cells.

    Sungho Ghil

    Full Text Available Protease-activated receptor 1 (PAR1 is a G-protein coupled receptor (GPCR that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins interact directly with certain GPCRs to modulate their signals, though cellular mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here, using bioluminescence resonance energy transfer (BRET, we tested whether RGS2 and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Gα-mediated signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in a G protein-dependent manner. Very little BRET activity is observed between PAR1-Venus (PAR1-Ven and either RGS2-Luciferase (RGS2-Luc or RGS4-Luc in the absence of Gα. However, in the presence of specific Gα subunits, BRET activity was markedly enhanced between PAR1-RGS2 by Gαq/11, and PAR1-RGS4 by Gαo, but not by other Gα subunits. Gαq/11-YFP/RGS2-Luc BRET activity is promoted by PAR1 and is markedly enhanced by agonist (TFLLR stimulation. However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A that eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1 binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4 inhibited PAR1/Gα-mediated calcium and MAPK/ERK signaling, respectively, but not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly with PAR1 in Gα-dependent manner to modulate PAR1/Gα-mediated signaling, and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

  12. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line - Pathways that are shared with and distinct from IL-10

    Lejeune, D; Dumoutier, L; Constantinescu, S; Kruijer, W; Schuringa, JJ; Renauld, JC

    2002-01-01

    IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called ZcytoR11/CRF2

  13. Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites

    Y. Han; Y. Noam; A.S. Lewis; J.J. Gallagher; W.J. Wadman; T.Z. Baram; D.M. Chetkovich

    2011-01-01

    Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly w

  14. CHARACTERIZATION OF HOSPITAL ACQUIRED METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS

    Preethi. B.M

    2012-12-01

    Full Text Available Methicillin Resistant Staphylococcus aureus (MRSA strains have emerged as one of the most important nosocomial pathogens. The MRSA can cause a wide range of diseases, which is associated with its production to large number of extracellular toxins and other virulence factors. The diseases are toxic shock syndrome, scalded skin syndrome and food poisoning. Hospital-acquired MRSA (HA-MRSA in persons who have had frequent or recent contact with hospitals or healthcare facilities within the previous year, has recently undergone an invasive medical procedure, or is immunocompromised. Mostly HA-MRSA are transmitted most frequently through direct skin-to-skin contact or contact with shared items or surfaces that have come into contact with someone else’s colonized or infected skin. Panton Valentine Leukocidin (PVL is a biocomponent toxin has been shown to induce lysis of host defence cells. The absence of the PVL gene confirms the MRSA as HA-MRSA. Slime layer plays a remarkable role in bacterial colonization of exterior surfaces by adhesion and production of slime factor plays an important role in antibiotic resistance. Beta lactamases render bacteria resistant to beta-lactam antibiotics by hydrolyzing the beta lactam ring of penicillin’s and cephalosporins.There is a linear correlation between beta-lactamase activity and the level of resistance of bacteria to penicillins. The phage groups II and III were present in hospital acquired MRSA which colonizes on the normal skin and enter the body through cut/wound or by fracture and cause osteomyelitis and bacterial arthritis. Bacteriophage typing of MRSA strains is an epidemiological marker and is a successful method in strain characterization.

  15. Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB

    Nef and Vpr are lentiviral accessory proteins that have been implicated in regulation of cellular gene expression. We noticed that Vpr can potentiate Nef-induced activation of nuclear factor of activated T cells (NFAT)-dependent transcription. Unlike Nef, which stimulated calcium signaling to activate NFAT, Vpr functioned farther downstream. Similar to the positive effects of Vpr on most of the transcriptional test systems that we used, potentiation of NFAT-directed gene expression was relatively modest in magnitude (two- to threefold) and depended on the cell cycle-arresting capacity of Vpr. By contrast, we found that Vpr could cause more than fivefold upregulation of cyclic AMP response element (CRE)-directed transcription via a mechanism that did not require Vpr-induced G2/M arrest. This effect, however, was only evident under suboptimal conditions known to lead to serine phosphorylation of the CRE binding factor (CREB) but not to CREB-dependent gene expression. This suggested that Vpr may act by stabilizing interactions with CREB and its transcriptional cofactor CREB binding protein (CBP). Indeed, this effect could be blocked by cotransfection of the adenoviral CBP inhibitor E1A. These results provide additional evidence for cell cycle-independent regulation of gene expression by Vpr and implicate CREB as a potentially important target for Vpr action in HIV-infected host cells

  16. Acquired pulmonary arteriovenous malformation secondary to hydatid cyst operation.

    Gezer, S; Turut, H; Oz, G; Demirag, F; Tastepe, I

    2007-10-01

    Pulmonary arteriovenous malformations are abnormal communications between pulmonary arteries and pulmonary veins. The majority of the cases are congenital in origin, and acquired pulmonary arteriovenous malformations are very rare. We present a case here, which - to the best of our knowledge - is the first acquired pulmonary arteriovenous malformation secondary to a hydatid cyst operation in the literature, and we discuss the etiology, clinical presentation, diagnostic modalities and treatment of acquired pulmonary arteriovenous malformations. PMID:17902072

  17. Distinct requirements for Wntless in habenular development.

    Kuan, Yung-Shu; Roberson, Sara; Akitake, Courtney M; Fortuno, Lea; Gamse, Joshua; Moens, Cecilia; Halpern, Marnie E

    2015-10-15

    Secreted Wnt proteins play pivotal roles in development, including regulation of cell proliferation, differentiation, progenitor maintenance and tissue patterning. The transmembrane protein Wntless (Wls) is necessary for secretion of most Wnts and essential for effective Wnt signaling. During a mutagenesis screen to identify genes important for development of the habenular nuclei in the dorsal forebrain, we isolated a mutation in the sole wls gene of zebrafish and confirmed its identity with a second, independent allele. Early embryonic development appears normal in homozygous wls mutants, but they later lack the ventral habenular nuclei, form smaller dorsal habenulae and otic vesicles, have truncated jaw and fin cartilages and lack swim bladders. Activation of a reporter for β-catenin-dependent transcription is decreased in wls mutants, indicative of impaired signaling by the canonical Wnt pathway, and expression of Wnt-responsive genes is reduced in the dorsal diencephalon. Wnt signaling was previously implicated in patterning of the zebrafish brain and in the generation of left-right (L-R) differences between the bilaterally paired dorsal habenular nuclei. Outside of the epithalamic region, development of the brain is largely normal in wls mutants and, despite their reduced size, the dorsal habenulae retain L-R asymmetry. We find that homozygous wls mutants show a reduction in two cell populations that contribute to the presumptive dorsal habenulae. The results support distinct temporal requirements for Wls in habenular development and reveal a new role for Wnt signaling in the regulation of dorsal habenular progenitors. PMID:26116173

  18. FnrP and NNR of Paracoccus denitrificans are both members of the FNR family of transcriptional activators but have distinct roles in respiratory adaptation in response to oxygen limitation.

    Van Spanning, R J; De Boer, A P; Reijnders, W N; Westerhoff, H V; Stouthamer, A H; Van Der Oost, J

    1997-03-01

    The Paracoccus denitrificans fnrP gene encoding a homologue of the Escherichia coli FNR protein was localized upstream of the gene cluster that encodes the high-affinity cbb3-type oxidase. FnrP harbours the invariant cysteine residues that are supposed to be the ligands of the redox-sensitive [4Fe-4S] cluster in FNR. NNR, another FNR-like transcriptional regulator in P. denitrificans, does not. Analysis of FnrP and NNR single and double mutants revealed that the two regulators each exert exclusive control on the expression of a discrete set of target genes. In FnrP mutants, the expression of cytochrome c peroxidase was blocked, that of membrane-bound nitrate reductase and the cbb3-type oxidase was significantly reduced, whilst the activity of the bb3-type quinol oxidase was increased. The amounts of the nitrite and nitric oxide reductases in these FnrP mutants were the same as in the wild type. NNR mutants, on the other hand, were disturbed exclusively in the concentrations of nitrite reductase and nitric oxide reductase. An FnrP.NNR double mutant combined the phenotypes of the single mutant strains. In all three mutants, the concentrations and/or activities of the aa3-type oxidase, cytochrome C550, cytochrome C552, and nitrous oxide reductase equalled those in the wild type. As the FNR boxes in front of the FnrP- and NNR-regulated genes are highly similar to or even identical to each other, the absence of cross-talk between the regulation by FnrP and NNR implies that as yet unidentified factors are important in the control. It is proposed that the redox state of an intracellular redox couple other than the oxygen/water couple is one of the factors that modulates the activity of FnrP. PMID:9076727

  19. Acquired facial lipoatrophy: pathogenesis and therapeutic options

    Szczerkowska-Dobosz, Aneta; Olszewska, Barbara; Lemańska, Małgorzata; Purzycka-Bohdan, Dorota; Nowicki, Roman

    2015-01-01

    Facial lipoatrophy refers to the loss of subcutaneous fat tissue presenting by flattening or indentation of convex contour of the face. Facial lipoatrophy is a feature of the normal ageing process. It may be also a manifestation of chronic diseases, most frequently it affects HIV-infected individuals treated with highly active antiretroviral therapy (HAART) and may constitute a complication of connective tissue diseases, like lupus erythematosus profundus or morphea. Early recognition and tre...

  20. Acquired Factor V Inhibitor: A Case Report

    Gaćina, Petar; Kušec, Rajko; Čaržavec, Dubravka; Raić, Biserka; Stančić, Vladimir

    2006-01-01

    A 19-year-old asymptomatic man who was admitted to our hospital for investigation of prolonged screening coagulation assays, prothrombin time and activated partial thromboplastin time is presented. Further evaluation revealed factor V deficiency and the presence of specific factor V inhibitors. The appearance of these inhibitors may be associated with administration of some antibiotics, topical bovine thrombin preparations containing bovine factor V during surgical or dental procedures, after...

  1. Acquiring Conceptual Knowledge about How Systems Behave

    Liem, Jochem; Bredeweg, Bert; Linnebank, Floris; Bühling, René; Wißner, Michael; Gracia del Río, Jorge; van Beek, W; Gómez-Pérez, A.

    2010-01-01

    There is a need for software that supports learners in actively dealing with theoretical concepts by having them create models and perform concept prediction and explanation (e.g. [3,4,5]). DynaLearn seeks to address this by developing a domain independent Interactive Learning Environment (ILE) based on Qualitative Reasoning (QR) [1]. The QR vocabulary fits the nature of conceptual knowledge, and the explicit representation of these notions in the software provides the handles to support an a...

  2. Acquired retinal folds in the cat.

    MacMillan, A D

    1976-06-01

    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  3. Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases

    Reiniger, Lilla; Mirabile, Ilaria; Lukic, Ana; Wadsworth, Jonathan DF; Linehan, Jacqueline M.; Groves, Michael; Lowe, Jessica; Druyeh, Ronald; Rudge, Peter; Collinge, John; Mead, Simon; Brandner, Sebastian

    2013-01-01

    Background Sporadic, inherited and acquired prion diseases show distinct histological patterns of abnormal prion protein (PrP) deposits. Many of the inherited prion diseases show striking histological patterns, which often associate with specific mutations. Most reports have focused on the pattern of PrP deposition in the cortical or cerebellar grey matter. Results We observed that the subcortical white matter in inherited prion diseases frequently contained filamentous depositions of abnorma...

  4. Distinct dopamine neurons mediate reward signals for short- and long-term memories

    Yamagata, N; T. Ichinose; Aso, Y; Placais, P.; Friedrich, A.; Sima, R.; Preat, T.; Rubin, G; Tanimoto, H.

    2014-01-01

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually dev...

  5. A role for tungsten in the biology of Campylobacter jejuni: tungstate stimulates formate dehydrogenase activity and is transported via an ultra-high affinity ABC system distinct from the molybdate transporter.

    Smart, Jonathan P; Cliff, Matthew J; Kelly, David J

    2009-11-01

    The food-borne pathogen Campylobacter jejuni possesses no known tungstoenzymes, yet encodes two ABC transporters (Cj0300-0303 and Cj1538-1540) homologous to bacterial molybdate (ModABC) uptake systems and the tungstate transporter (TupABC) of Eubacterium acidaminophilum respectively. The actual substrates and physiological role of these transporters were investigated. Tryptophan fluorescence spectroscopy and isothermal titration calorimetry of the purified periplasmic binding proteins of each system revealed that while Cj0303 is unable to discriminate between molybdate and tungstate (K(D) values for both ligands of 4-8 nM), Cj1540 binds tungstate with a K(D) of 1.0 +/- 0.2 pM; 50 000-fold more tightly than molybdate. Induction-coupled plasma mass spectroscopy of single and double mutants showed that this large difference in affinity is reflected in a lower cellular tungsten content in a cj1540 (tupA) mutant compared with a cj0303c (modA) mutant. Surprisingly, formate dehydrogenase (FDH) activity was decreased approximately 50% in the tupA strain, and supplementation of the growth medium with tungstate significantly increased FDH activity in the wild type, while inhibiting known molybdoenzymes. Our data suggest that C. jejuni possesses a specific, ultra-high affinity tungstate transporter that supplies tungsten for incorporation into FDH. Furthermore, possession of two MoeA paralogues may explain the formation of both molybdopterin and tungstopterin in this bacterium. PMID:19818021

  6. Cortisol modifies extinction learning of recently acquired fear in men.

    Merz, Christian Josef; Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

    2014-09-01

    Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS-) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS- than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS- differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear. PMID:23945999

  7. National symbols and distinctiveness: rhetorical strategies in creating distinct national identities.

    Finell, Eerika; Liebkind, Karmela

    2010-06-01

    The purpose of this study is to examine qualitatively how respondents create national distinctiveness using rhetorical identity strategies in the context of four Finnish national symbols. The data consist of 127 essays written by Finnish secondary school students. Analysis revealed five different strategies used to distinguish between the in-group and the out-group. These strategies differ on two dimensions: the level of polarization, and the extent to which the in-group-out-group relationship is depicted as being active versus passive. Furthermore, the analysis showed that the two dimensions of nationalism, particularism and universalism, have an important role in the differentiation processes and therefore highlighted the importance of taking into consideration ideological issues while studying social identities. The meaning of the contents of national identity in the differentiation processes is also discussed. PMID:19558753

  8. The case of Geely acquiring Volvo Car : A study on low brand equity acquiring high brand equity

    Zheng, Xiaoshu; Shi, Yuan

    2013-01-01

    Much previous research has studied high brand equity acquiring high brand equity or high brand equity acquiring low brand equity. However, very little research has been conducted to understand how that low brand equity acquiring high brand equity changes the low brand equity especially in China. This paper is on the case of Geely Group acquiring Volvo Car which was a typical acquisition of a high brand equity company by a low brand equity company. The aim of the paper is to verify whether thi...

  9. PATHOGENETIC MECHANISMS OF CHRONIC ACQUIRED TOXOPLASMOSIS

    Kotsyna S.S.

    2015-05-01

    Full Text Available Introduction. Toxoplasma gondii is an intracellular protozoan that infects approximately one-third of the world’s population. Infection in human generally occurs through consuming food or drink contaminated with oocysts and tissue cysts from undercooked meat. Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. Different conditions such as, number of parasite, virulence of the organism, genetic background, sex, and immunological status seem to affect the course of infection The demonstration that Toxoplasma infections can alter behavior, reproductive function in patients has led to a reconsideration of this assumption. During chronic acquired toxoplasmosis (САT identified the regularities of changes in the ratio of the immune system and the basal levels of sex hormones available informative methods, which made it possible to evaluate the severity of the flow chart and predict treatment outcome without resorting to complex research methods. Found that the host-parasite relationships and clinical manifestations of chronic toxoplasmosis depend largely on protective and adaptive responses and compensatory abilities of the human body. Material & methods. 112 patients attended in the 6 Department of Kharkiv Regional Infectious Diseases Hospital №22 (Department of Medical Parasitology and Tropical Diseases of Kharkiv Medical Academy of Postgraduate Education, in Kharkiv, Ukraine were enrolled in the study. Forty four patients (39,3±4,6% were male and sixty eight (60,7±4,6% were female. The age of the patients was 18 till 72 years. Results & discussion. All of 112 CAT patients had subjective clinical symptoms in various combinations: increased fatigue 99,1 ± 0,9%, headache and tiredness 95,5 ± 1,9%, pain in the liver 88,4 ± 3,1%, bitter taste in the mouth 93,8 ± 2,2%, muscle pain 81,3 ± 3,7% and joint pain

  10. Passport of global nuclear business. ASME code certificate acquirement and inspection practices

    There are possibilities of Japanese nuclear industries to participate in global business such as new and additional construction of nuclear power plants in US and also Asian and other developing countries in the world. It is requisite to acquire ASME code certificate for global business participation, just as passport. This article consists of five papers on present status of ASME code certificate acquirement and inspection practices of nuclear components vendors in the area of Japanese nuclear business. Activities of JSME Committee on Power Generation Facility Codes to make JSME codes corresponded to ASME nuclear codes and standards for their international deployment are also described. (T. Tanaka)

  11. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.472-7 Inventories of acquiring corporations....

  12. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.471-9 Inventories of acquiring corporations....

  13. 26 CFR 1.9002-6 - Acquiring corporation.

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5(d) of...

  14. Clinical aspects of acquired aphasia and dysarthria in childhood

    H.R. van Dongen (Hugo)

    1988-01-01

    textabstractFor the last decade, it has been a common clinical belief that the prognosis of acquired childhood aphasia is good. However, our own clinical experiences were rather conflicting on this point. As a consequence, we re-examined all the children (15) with an acquired aphasia who in a period

  15. Acquired Epiblepharon Treated by Lateral Orbital and fat Decompression

    Radwan Almousa; Gangadhara Sundar

    2011-01-01

    Conventional lid surgery of acquired epiblepharon secondary to increased orbital volume can be result of under correction of the epiblepharon, because the increased orbital volume remains unaddressed. In this case report, we present a case of acquired epiblepharon, secondary to increased orbital volume, treated with orbital decompression.

  16. Significance of acquired diverticular disease of the vermiform appendix

    Kallenbach, Klaus; Hjorth, Sofie Vetli; Engel, Ulla;

    2012-01-01

    To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms.......To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms....

  17. Hospital-acquired and Community-acquired Uropathogens; Modelling of Infection

    Aija ?ilevi?a

    2005-12-01

    Full Text Available Urinary tract infections are among the most common human infections. They may be community-acquired or nosocomial, and caused by a variety of microorganisms. In the present study, we analysed more than 4000 urine samples collected from in-patients and outpatients, and registered the differences in the etiological spectrum of agents. The most widespread uropathogens are gram-negative rods, from them E. coli, Klebsiella spp. and the non-fermentive genus Pseudomonas. Women are more intensively affected by E. coli. From gram-positive cocci, the leading agents are coagulase negative Staphylococci, followed by S. aureus. No differences were registered between the genders. Polyresistance among gram-negative uropathogens is high.

  18. Validity of Sensory Systems as Distinct Constructs

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  19. Acquired Class D β-Lactamases

    Nuno T. Antunes

    2014-08-01

    Full Text Available The Class D β-lactamases have emerged as a prominent resistance mechanism against β-lactam antibiotics that previously had efficacy against infections caused by pathogenic bacteria, especially by Acinetobacter baumannii and the Enterobacteriaceae. The phenotypic and structural characteristics of these enzymes correlate to activities that are classified either as a narrow spectrum, an extended spectrum, or a carbapenemase spectrum. We focus on Class D β-lactamases that are carried on plasmids and, thus, present particular clinical concern. Following a historical perspective, the susceptibility and kinetics patterns of the important plasmid-encoded Class D β-lactamases and the mechanisms for mobilization of the chromosomal Class D β-lactamases are discussed.

  20. Identification and functional characterisation of Complement Regulator Acquiring Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4

    Zipfel Peter F

    2010-02-01

    Full Text Available Abstract Background B. burgdorferi sensu lato (sl is the etiological agent of Lyme borreliosis in humans. Spirochetes have adapted themselves to the human immune system in many distinct ways. One important immune escape mechanism for evading complement activation is the binding of complement regulators Factor H (CFH or Factor H-like protein1 (FHL-1 to Complement Regulator-Acquiring Surface Proteins (CRASPs. Results We demonstrate that B. garinii OspA serotype 4 (ST4 PBi resist complement-mediated killing by binding of FHL-1. To identify the primary ligands of FHL-1 four CspA orthologs from B. garinii ST4 PBi were cloned and tested for binding to human CFH and FHL-1. Orthologs BGA66 and BGA71 were found to be able to bind both complement regulators but with different intensities. In addition, all CspA orthologs were tested for binding to mammalian and avian CFH. Distinct orthologs were able to bind to CFH of different animal origins. Conclusions B. garinii ST4 PBi is able to evade complement killing and it can bind FHL-1 to membrane expressed proteins. Recombinant proteins BGA66 can bind FHL-1 and human CFH, while BGA71 can bind only FHL-1. All recombinant CspA orthologs from B. garinii ST4 PBi can bind CFH from different animal origins. This partly explains the wide variety of animals that can be infected by B. garinii.

  1. Dynamic Linear Model Analysis of Optical Imaging Data Acquired from the Human Neocortex

    Lavine, Michael; Haglund, Michael M.; Hochman, Daryl W.

    2011-01-01

    The amount of light absorbed and scattered by neocortical tissue is altered by neuronal activity. Imaging of intrinsic optical signals (ImIOS), a technique for mapping these activity-evoked optical changes with an imaging detector, has the potential to be useful for both clinical and experimental investigations of the human neocortex. However, its usefulness for human studies is currently limited because intraoperatively acquired ImIOS data is noisy. To improve the reliability and usefulness ...

  2. Sociotopy in the temporoparietal cortex: common versus distinct processes

    Bahnemann, Markus; Dziobek, Isabel; Prehn, Kristin; Wolf, Ingo; Heekeren, Hauke R.

    2009-01-01

    A major controversy in the social cognitive neurosciences evolved around the question whether activity in the posterior superior temporal sulcus and adjacent temporoparietal junction (pSTS/TPJ-region) evoked by various tasks represents a common process or distinct processes. To investigate this question, we employed functional magnetic resonance imaging (fMRI) while participants performed Biological Motion (BM), Theory-of-Mind (ToM) and Moral Judgment (MJ) tasks. Importantly, for each task we...

  3. Two Distinct Dynamic Modes Subtend the Detection of Unexpected Sounds

    King, Jean-Rémi; Gramfort, Alexandre; Schurger, Aaron; Naccache, Lionel; Dehaene, Stanislas

    2014-01-01

    The brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stabl...

  4. Acquired Hemophagocytic Lymphohistiocytosis: A Case Report

    A Sobhani Araghi

    2006-07-01

    Full Text Available Background: Hemophagocytic lymphohistiocytosis (HLH is a rare and potentially fatal disease of normal but overactive histiocytes (macrophages that commonly appears in childhood. A fever, hepatosplenomegaly, pancytopenia, lymphadenopathy, and a rash often comprise the initial presentation. Cutaneous involvement occurs in up to 65% of patients. Although the signs of central nervous system (CNS involvement may be pronounced early, it usually develops later during the course of the disease. The pathological hallmark of this disease is the aggressive proliferation of activated macrophages and histiocytes, which phagocytose other cells, namely red blood cells, white blood cells, and platelets, leading to the clinical symptoms. Case Report: This paper presents a 4- years old girl that was admitted to the hospital because of abdominal distention .Her vital signs were normal. Physical examinations by her physician were revealed hepatosplenomegaly. She had pancytopenia, high erythrocyte sedimentation rate but tests for liver and kidney-functions were normal in primary laboratory data. The results of tests for viral hepatitis A, B, and C were negative. An abdominal ultrasonographic study confirmed the presence of hepatosplenomegaly, but no ascites was detected. Examination of a stained bone marrow aspirate (BMA revealed dyserythropoietic change. After 2 months, she presented with intermittent fever but three blood cultures yielded no growth at 48 hours. A liver biopsy was done and it showed a picture similar to chronic persistent hepatitis. Again, she has undergone bone marrow aspiration and showed the same findings with the past BMA (dyserythropoietic change .She was candidate for bone marrow biopsy and explorative laparotomy. During explorative laparotomy, specimens from liver (again, spleen, pancreas, and abdominal lymph nodes was obtained. There was evidence of hemophagocytosis in the spleen, marrow, lymph nodes specimens and the results of

  5. Acquired and innate immunity to polyaromatic hydrocarbons

    Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8+ T cells are effector cells in the response, whereas CD4+ T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents

  6. Acquirement of the observatory code of Langkawi National Observatory

    Loon, Chin Wei; Zainuddin, Mohd. Zambri; Ahmad, Nazhatulshima; Shukor, Muhammad Shamim; Tahar, Muhammad Redzuan

    2015-04-01

    Observatory code was assigned by The International Astronomical Union (IAU) Minor Planet Center (MPC) for a permanent observatory that intended to do astrometric CCD-observing program of minor planet or comets in solar system. The purpose of acquiring an observatory code is to document specific details about a particular observation site and the types of instruments used within the observatory. In addition, many astronomical centers and stations worldwide will know there is an active observatory at the particular location and international cooperation program in astronomy observation is possible. The Langkawi National Observatory has initiated an observation program to monitor minor planet, specifically those Near Earth Objects (NEOs) that may bring potentially hazardous to the Earth. In order to fulfil the requirement that stated by MPC for undertaking astrometric CCD-observing program, an observatory code was required. The instruments and methods that applied to obtain the observatory code will be discussed. The Langkawi National Observatory is now coded as O43 and listed in the MPC system, the single worldwide location for receipt and distribution of positional measurements of minor planets, comets and outer irregular natural satellites of major planets.

  7. Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity.

    Heinonen, Sini; Buzkova, Jana; Muniandy, Maheswary; Kaksonen, Risto; Ollikainen, Miina; Ismail, Khadeeja; Hakkarainen, Antti; Lundbom, Jesse; Lundbom, Nina; Vuolteenaho, Katriina; Moilanen, Eeva; Kaprio, Jaakko; Rissanen, Aila; Suomalainen, Anu; Pietiläinen, Kirsi H

    2015-09-01

    Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8-36.2 years of age, who were discordant (ΔBMI >3 kg/m(2), mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m(2), n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage. PMID:25972572

  8. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  9. Distinctiveness of Saudi Arabian EFL Learners

    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made.Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory 

  10. Diversity, Activity, and Evolution of CRISPR Loci in Streptococcus thermophilus▿ †

    Horvath, Philippe; Romero, Dennis A.; Coûté-Monvoisin, Anne-Claire; Richards, Melissa; Deveau, Hélène; Moineau, Sylvain; Boyaval, Patrick; Fremaux, Christophe; Barrangou, Rodolphe

    2007-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are hypervariable loci widely distributed in prokaryotes that provide acquired immunity against foreign genetic elements. Here, we characterize a novel Streptococcus thermophilus locus, CRISPR3, and experimentally demonstrate its ability to integrate novel spacers in response to bacteriophage. Also, we analyze CRISPR diversity and activity across three distinct CRISPR loci in several S. thermophilus strains. We show that both ...

  11. TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction.

    Si, Yu; Chen, Yu Bin; Chen, Sui Jun; Zheng, Yi Qing; Liu, Xiang; Liu, Yi; Jiang, Huai Li; Xu, Guo; Li, Zhuo Hao; Huang, Qiu Hong; Xiong, Hao; Zhang, Zhi Gang

    2015-01-01

    Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis. PMID:26639190

  12. The Scholarships of Teaching and Pedagogy: Time to Abandon the Distinction?

    Irons, Jessica G.; Buskist, William

    2008-01-01

    We surveyed the editorial board of "Teaching of Psychology" regarding their perspectives on the distinction between the scholarships of teaching and pedagogy. Respondents provided wide-ranging and divergent answers to our queries, suggesting that scholarship, its attendant activities, and distinctions among related terms are complex issues in need…

  13. Pilot study: Computer-based virtual anatomical interactivity for rehabilitation of individuals with chronic acquired brain injury

    C. Douglas Simmons, PhD, OTR/L, FAOTA; Sajay Arthanat, PhD, OTR/L, ATP; Vincent J. Macri, BA, MA

    2014-01-01

    Deficiencies in upper-limb motor function and executive functioning can compromise an affected individual’s ability to complete everyday activities. Impaired motor and executive functioning therefore pose a risk to increasing numbers of veterans who have been diagnosed with acquired brain injury. This article reports on changes in upper-limb motor function and executive functioning of 12 adult participants with chronic acquired brain injury using a novel, computer-based, motor and cognitive r...

  14. On Hobbes’s distinction of accidents

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  15. Distinctive Dynamic Capabilities for New Business Creation

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow and...... fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  16. Examination of the Accuracy of Coding Hospital-Acquired...

    U.S. Department of Health & Human Services — A new study, Examination of the Accuracy of Coding Hospital-Acquired Pressure Ulcer Stages, published in Volume 4, Issue 1 of the Medicare and Medicaid Research...

  17. A methodology for acquiring qualitative knowledge for probabilistic graphical models

    Kjærulff, Uffe Bro; Madsen, Anders L.

    2004-01-01

    We present a practical and general methodology that simplifies the task of acquiring and formulating qualitative knowledge for constructing probabilistic graphical models (PGMs). The methodology efficiently captures and communicates expert knowledge, and has significantly eased the model...

  18. The Impact of Hospital-Acquired Conditions on Medicare..

    U.S. Department of Health & Human Services — According to findings reported in The Impact of Hospital-Acquired Conditions on Medicare Program Payments, published in Volume 4, Issue 4 of the Medicare and...

  19. [Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia].

    Deĭkina, O N; Mishin, V Iu; Demikhova, O V

    2007-01-01

    The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%). PMID:17338353

  20. Empiric antibiotic choices for community-acquired biliary tract infections

    Kuo-Kuan Chang; Chin-Lu Chang; Fang-Ting Tai; Chun-Hsiang Wang; Ruey-Chang Lin

    2014-01-01

    Background: The study was conducted to reveal the most appropriate empiric antibiotics for the treatment of community-acquired biliary tract infections (CA-BTI) at a regional hospital in Taiwan. Methods: The study was performed between October 1, 2010 and October 31, 2012. All positive bile culture results of presumptive community-acquired origins were collected. The associated etiologic microorganisms and their antimicrobial susceptibilities were analyzed. The appropriateness of empiric t...

  1. Communicative Language Teaching enable students to acquire communicative competence

    2011-01-01

    English is the language of international affairs, cultures and economic systems. It is a language of wider communication. The main aim of the learners is to acquire the target language but it can be acquired easily only if the language is made use of in our daily affairs. In order to achieve that target communicative language teaching, it focuses on the language competency of the target language .Knowledge of the structure of the language is equally important in order to learn the language.

  2. Hospital acquired diarrhea in a burn center of Tehran

    Faranak Alinejad; Mitra Barati; Mahbobe Satarzadeh Tabrisi; Mohsen Saberi

    2016-01-01

    Background and Objectives: Incidence of hospital-acquired diarrhea has increased rapidly and burn patients are at high risk of getting it. Infection with C. difficile is the most common cause of antibiotic associated diarrhea. The aim of this study was to determine the baseline characteristics and clinical presentation of hospital-acquired diarrhea and compare C. difficile and non-C. difficile diarrhea in burn patients treated at a burn center.Materials and Methods: During a 1-year study all ...

  3. The Acquired Preparedness Model of Risk for Bulimic Symptom Development

    Combs, Jessica L.; Smith, Gregory T.; Flory, Kate; Simmons, Jean R.; Hill, Kelly K.

    2010-01-01

    The authors applied person-environment transaction theory to test the acquired preparedness model of eating disorder risk. The model holds that (a) middle school girls high in the trait of ineffectiveness are differentially prepared to acquire high risk expectancies for reinforcement from dieting/thinness; (b) those expectancies predict subsequent binge eating and purging; and (c) the influence of the disposition of ineffectiveness on binge eating and purging is mediated by dieting/thinness e...

  4. A Search/Crawl Framework for Automatically Acquiring Scientific Documents

    Gollapalli, Sujatha Das; Patel, Krutarth; Caragea, Cornelia

    2016-01-01

    Despite the advancements in search engine features, ranking methods, technologies, and the availability of programmable APIs, current-day open-access digital libraries still rely on crawl-based approaches for acquiring their underlying document collections. In this paper, we propose a novel search-driven framework for acquiring documents for scientific portals. Within our framework, publicly-available research paper titles and author names are used as queries to a Web search engine. Next, res...

  5. Two Distinct Pancreatic Amylase Genes Are Active in Ybr Mice

    Strahler, John R.; Meisler, Miriam,

    1982-01-01

    The genetic determinants of pancreatic amylase expression in YBR mice differ in two respects from those of other inbred strains. First, there are two nonallelic amylase isozymes present in YBR pancreas, while most mouse strains express a single pancreatic amylase protein. In addition, the in vivo rate of total pancreatic amylase synthesis is 50% of that in other strains. Both these traits are determined by genetic sites in the region of the Amy-2 locus on mouse chromosome 3. To determine the ...

  6. Acidosis láctica fatal en paciente con síndrome de inmunodeficiencia adquirido y tratamiento antiretroviral de alto grado de actividad: comunicación de un caso Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy: Report of one case

    Martín Lasso B; Jorge Pérez G; L. Miguel Noriega R; Rebeca Northland A

    2000-01-01

    Type B lactic acidosis occurs without any evidence of cellular hypoxia and is associated with the use of drugs or toxins. We report a 36 years old woman with acquired immunodeficiency syndrome that was admitted to the hospital with a severe lactic acidosis. She had been treated with didanosine, stavudine and efavirenz for four months prior to admission. Despite the use of high bicarbonate doses and vasoactive drugs, the patient had a catastrophic evolution and died in shock and multiple organ...

  7. Intensive care unit-acquired weakness in the burn population.

    Cubitt, Jonathan J; Davies, Menna; Lye, George; Evans, Janine; Combellack, Tom; Dickson, William; Nguyen, Dai Q

    2016-05-01

    Intensive care unit-acquired weakness is an evolving problem in the burn population. As patients are surviving injuries that previously would have been fatal, the focus of treatment is shifting from survival to long-term outcome. The rehabilitation of burn patients can be challenging; however, a certain subgroup of patients have worse outcomes than others. These patients may suffer from intensive care unit-acquired weakness, and their treatment, physiotherapy and expectations need to be adjusted accordingly. This study investigates the condition of intensive care unit-acquired weakness in our burn centre. We conducted a retrospective analysis of all the admissions to our burn centre between 2008 and 2012 and identified 22 patients who suffered from intensive care unit-acquired weakness. These patients were significantly younger with significantly larger burns than those without intensive care unit-acquired weakness. The known risk factors for intensive care unit-acquired weakness are commonplace in the burn population. The recovery of these patients is significantly affected by their weakness. PMID:26975787

  8. Motivational Spiral Models (MSM): common and distinct motivations in context.

    Fisher, Laurel J

    2013-01-01

    Motivational Spiral Models (MSM) show links over time among self concepts, feelings, strategies, skills and participation in everyday activities. In theory, MSM have many common features, with distinct features in particular contexts. This project examined children's motivation to participate in literacy (MSM-L), social (MSM-S) and physical activities (MSM-P). The participants in Study 1 (N = 32) were 9 to 11 years old, and in Study 2 (N = 73) were 4 to 12 year old children. Locations were close to the Australian national average in socio-economic indicators, and initial screening showed these were representative samples. Analyses used variable-oriented correlational models as well as person-oriented clusters that suggest the standard and alternative motivational pathways. The results of Study 1 suggested bi-directional links between children's self concepts and participation in activities. Study 2 identified the common features as: openness and stability over time; and self concepts that motivate and justify participation in activities. Distinct features of MSM-L show the few negative feelings that may limit reading. In MSM-S, self concepts support the positive feelings, and in MSM-P, positive feelings support the task strategies. In conclusion, findings support MSM theory with common features based on self concepts and distinct features of developing motivations in particular contexts. MSM provide a sound base for future research in the contexts of everyday activities for children. In addition, there are practical applications of the findings to prevention, monitoring and intervention programmes. PMID:24255859

  9. Dynamic Linear Model Analysis of Optical Imaging Data Acquired from the Human Neocortex

    Lavine, Michael; Haglund, Michael M.; Hochman, Daryl W.

    2011-01-01

    The amount of light absorbed and scattered by neocortical tissue is altered by neuronal activity. Imaging of intrinsic optical signals (ImIOS), a technique for mapping these activity-evoked optical changes with an imaging detector, has the potential to be useful for both clinical and experimental investigations of the human neocortex. However, its usefulness for human studies is currently limited because intraoperatively acquired ImIOS data is noisy. To improve the reliability and usefulness of ImIOS for human studies, it is desirable to find appropriate methods for the removal of noise artifacts and its statistical analysis. Here we develop a Bayesian, dynamic linear modeling approach that appears to address these problems. A dynamic linear model (DLM) was constructed that included cyclic components to model the heartbeat and respiration artifacts, and a local linear component to model the activity-evoked response. The robustness of the model was tested on a set of ImIOS data acquired from the exposed cortices of six human subjects illuminated with either 535 nm or 660 nm light. The DLM adequately reduced noise artifacts in these data while reliably preserving their activity-evoked optical responses. To demonstrate how these methods might be used for intraoperative neurosurgical mapping, optical data acquired from a single human subject during direct electrical stimulation of the cortex were quantitatively analyzed. This example showed that the DLM can be used to provide quantitative information about human ImIOS data that is not available through qualitative analysis alone. PMID:21640137

  10. Hydraulic fracturing with distinct element method

    Pruiksma, J.P.; Bezuijen, A.

    2002-01-01

    In this report, hydraulic fracturing is investigated using the distinct element code PFC2D from Itasca. Special routines were written to be able to model hydraulic fracturing. These include adding fluid flow to PFC2D and updating the fluid flow domains when fractures appear. A brief description of t

  11. HOW ROMANIAN FINANCIAL AND INTERNAL AUDITORS ACQUIRE ACCOUNTING INFORMATION SYSTEMS KNOWLEDGE AND COMPETENCES?

    Cardos Vasile - Daniel

    2011-07-01

    Full Text Available Research theme in this article we investigate how Romanian financial and internal auditors acquire accounting information systems knowledge and competences and how they use this knowledge to improve their activity in order to fulfill their mission as required by the professional standards. Objectives our main purpose is to establish through what type of courses Romanian financial and internal auditors acquiring accounting information systems knowledge and competences and how useful these courses are perceived by the auditors. Prior work audit professional organizations prescribed that auditors must acquire, maintain and develop their knowledge and competences. Information technology and information systems are considered to be a main knowledge component of professional development programs. The scientific literature indicates that auditors have to enhance their information systems knowledge in order to cope with the increasing complexity of the client's entities accounting information systems. We consider that our article embraces Curtis et al. (2009 call for research on how auditors obtain information systems knowledge. Methodology an electronic questionnaire was created and sent to Romanian financial and internal auditors, which were required to indicate the number of accounting information systems course they attended and how the knowledge gained improved their activity. Results We concluded that financial auditors acquire accounting information systems knowledge mainly by attending the courses organized by the Chamber of Financial Auditors of Romanian, while internal auditors by attending the course organized by the companies they are working with. Implications - The results of this study might be used by Romanian professional audit organizations in reconsidering their priorities regarding the accounting information systems knowledge and competence needs of their constituents. Originality/Contribution Our study is the first one to

  12. Role of distinct flavours of IOD events on Indian summer monsoon

    Anil, N.; RameshKumar, M.R.; Sajeev, R.; Saji, P.K.

    ) on the Indian monsoon activity is intriguing. The impacts of ENSO, IOD and Equatorial Indian Ocean Oscillation on monsoon are distinct. The ENSO (IOD) in general affects the monsoon negatively (positively). The present study aims to understand the role...

  13. Update on the emerging role of telavancin in hospital-acquired infections

    Nnedu ON

    2015-04-01

    Full Text Available Obinna N Nnedu,1 George A Pankey2 1Infectious Disease Department, Ochsner Clinic Foundation, New Orleans, LA, USA; 2Infectious Disease Research, Ochsner Clinic Foundation, New Orleans, LA, USA Abstract: Telavancin is a lipoglycopeptide that has activity against gram-positive aerobic and anaerobic bacteria. It has activity against methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus and non-Van-A strains of vancomycin-resistant enterococci. It has been approved by the US Food and Drug Administration (FDA for complicated skin and skin structure infections and hospital-acquired pneumonia. There is a need for more clinical studies to determine the role of telavancin in treating bacteremia and prosthetic device infections. In this review, we discuss the published data on the use of telavancin in treating hospital-acquired infections and provide an update on new research. Keywords: telavancin, vancomycin, linezolid, Staphylococcus aureus

  14. Knowledge transfer process of Brazilian multinationals: comparing acquired subsidiaries to the greenfield ones

    Natacha Bertoia Silva

    2012-07-01

    Full Text Available The main purpose of this study was to explore the knowledge transfer process between the subsidiaries and the headquarter of Brazilian multinationals, and to identify the most used mechanisms for transferring knowledge. This paper also aims to point out existing barriers in this process, comparing acquired subsidiaries to the greenfield ones. International studies have shown differences in the process of knowledge transfer due to the origin of foreign units (entry mode. We surveyed in 2006 and 2007 a sample of 66 Brazilian subsidiaries of multinationals with overseas activities. As a result, the knowledge transfer from the headquarter to the subsidiary has occurred through meetings with top executives and the reception of Brazilian executives in both types of units. The barriers to knowledge transfer are bland, being clearer in acquired subsidiaries. Cultural resistance is the most prominent. When we focus on the acquired units, the hierarchical structure is seen as a barrier, probably reflecting the centralized attitude by the headquarters. At the same time, the lack of incentives for sharing knowledge is more evident in greenfield units. Also, the syndrome of not invented here is a perceived barrier by acquired units.

  15. Spontaneous bleeding in a patient with malignant lymphoma: A case of acquired hemophilia

    Gesierich, Wolfgang; Munker, Reinhold; Geiersberger, U.; Pohlmann, H.; N. BRACK; Hartenstein, R.

    2000-01-01

    Background: Acquired hemophilia is a rare condition which can be associated with lymphoproliferative disease. Case Report: Eleven yea rs after the diagnosis of immunocytoma had been made, a 72-year-old man developed a high-titer factor VIII inhibitor. At this time, the lymphoma was without significant progress and there was no paraprotein in the serum. Partial thromboplastin time (PTT) was 83 a, factor-VIII clotting activity was

  16. Action observation and acquired motor skills: An fMRI study with expert dancers

    Calvo-Merino, B.; Glaser, D.E.; Grezes, J.; Passingham, R. E.; Haggard, P

    2005-01-01

    When we observe someone performing an action, do our brains simulate making that action? Acquired motor skills offer a unique way to test this question, since people differ widely in the actions they have learned to perform. We used functional magnetic resonance imaging to study differences in brain activity between watching an action that one has learned to do and an action that one has not, in order to assess whether the brain processes of action observation are modulated by the expertise a...

  17. Types of personality motivation structure of women who are acquiring higher education in psychology

    TETIANA PARTYKO

    2013-01-01

    The article deals with the results of empirical research on the types of personality motivation structure of women who are acquiring higher education in psychology. Two types have been singled out: expressive and impulsive. The expressive type comprises two components: ideal motivation aimed at life necessities, general activity and social utility, and real motivation aimed at comfort, social status and communication. In the structure of the impulsive type there are three components: real mot...

  18. Group techniques as a methodological strategy in acquiring teamwork abilities by college students

    César Torres Martín; María Julia Gámez Montalvo

    2013-01-01

    From the frame of the European Higher Education Space an adaptation of teaching-learning process is being promoted by means of the pedagogical renewal, introducing into the class a major number of active or participative methodologies in order to provide students with a major autonomy in said process. This requires taking into account the incorporation of basic skills within university curriculum, especially “teamwork”. By means of group techniques students can acquire interpersonal and cogni...

  19. Mucocutaneous manifestations of acquired hypoparathyroidism: An observational study

    Somenath Sarkar

    2012-01-01

    Full Text Available Hypoparathyroidism is a disorder of calcium and phosphorus metabolism due to decreased secretion of parathyroid hormone. Hypoparathyroidism can be hereditary and acquired. Acquired hypoparathyroidism usually occurs following neck surgery (thyroid surgery or parathyroid surgery. Along with systemic manifestations, hypoparathyroidism produces some skin manifestations. Lack of study regarding mucocutaneous manifestations of acquired hypoparathyroidism prompted us to undertake this study. To evaluate the mucocutaneous manifestations of acquired hypoparathyroidism. An observational study done in a tertiary care hospital of Kolkata by comprehensive history taking, through clinical examination and relevant laboratory investigations. Twenty-one patients were included in the study. The commonest form of acquired hypoparathyroidism was neck surgery (thyroidectomy and parathyroidectomy operation. Mucocutaneous manifestations were present in 76.19% of patients. The most frequent mucocutaneous manifestation was found in the hairs like the loss of axillary hair (61.9%, loss of pubic hair (52.38%, coarsening of body hair (47.62%, and alopecia areata (9.52%. The nail changes noted were brittle and ridged nail, followed by onycholysis, onychosezia, and onychomedesis. The most common skin features were xerotic skin in 11 patients (52.38%, followed by pellagra-like skin pigmentation, pustular psoriasis and acne form eruption, bullous impetigo, etc. Mucosa was normal in all the cases excepting the one which showed oral candidiasis.

  20. Acidosis láctica fatal en paciente con síndrome de inmunodeficiencia adquirido y tratamiento antiretroviral de alto grado de actividad: comunicación de un caso Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy: Report of one case

    Martín Lasso B

    2000-10-01

    Full Text Available Type B lactic acidosis occurs without any evidence of cellular hypoxia and is associated with the use of drugs or toxins. We report a 36 years old woman with acquired immunodeficiency syndrome that was admitted to the hospital with a severe lactic acidosis. She had been treated with didanosine, stavudine and efavirenz for four months prior to admission. Despite the use of high bicarbonate doses and vasoactive drugs, the patient had a catastrophic evolution and died in shock and multiple organ failure, 68 hours after admission. (Rev Méd Chile 2000; 128: 1139-43.

  1. Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming.

    Krijger, Peter Hugo Lodewijk; Di Stefano, Bruno; de Wit, Elzo; Limone, Francesco; van Oevelen, Chris; de Laat, Wouter; Graf, Thomas

    2016-05-01

    Forced expression of reprogramming factors can convert somatic cells into induced pluripotent stem cells (iPSCs). Here we studied genome topology dynamics during reprogramming of different somatic cell types with highly distinct genome conformations. We find large-scale topologically associated domain (TAD) repositioning and alterations of tissue-restricted genomic neighborhoods and chromatin loops, effectively erasing the somatic-cell-specific genome structures while establishing an embryonic stem-cell-like 3D genome. Yet, early passage iPSCs carry topological hallmarks that enable recognition of their cell of origin. These hallmarks are not remnants of somatic chromosome topologies. Instead, the distinguishing topological features are acquired during reprogramming, as we also find for cell-of-origin-dependent gene expression patterns. PMID:26971819

  2. Review of acquired cystic disease-associated renal cell carcinoma with focus on pathobiological aspects.

    Kuroda, Naoto; Ohe, Chisato; Mikami, Shuji; Hes, Ondrej; Michal, Michal; Brunelli, Matteo; Martignoni, Guido; Sato, Yasuharu; Yoshino, Tadashi; Kakehi, Yoshiyuki; Shuin, Taro; Lee, Gang-Hong

    2011-09-01

    Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently established entity. In this article, we introduce the general view of this new entity. Macroscopically, the disease exclusively occurs in ACD and may arise as a dominant mass or non-dominant masses. Histologically, the tumor is characterized by a microcystic pattern, neoplastic cells with an eosinophilic or oncocytic cytoplasm and frequent intratumoral oxalate crystal deposition. Prominent nucleoli of tumor cells are often observed. Immunohistochemically, neoplastic cells are generally positive for AMACR but negative for cytokeratin 7. Ultrastructurally, neoplastic cells contain abundant mitochondria in the cytoplasm. Genetically, the gain of chromosomes 3, 7, 17 and abnormality of the sex chromosome were frequently observed in several studies. In conclusion, ACD-associated RCC may be widely recognized as a distinct entity in the near future because this tumor is morphologically and genetically different from other renal tumor entities that have been previously established. PMID:21751153

  3. Distinct types of eigenvector localization in networks

    Pastor-Satorras, Romualdo

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of node's centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution $P(q) \\sim q^{-\\gamma}$, localization occurs on the largest hub if $\\gamma>5/2$; for $\\gamma<5/2$ a new type of localization arises on a mesoscopic subgraph associated to the shell with the largest index in the $K$-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  4. The influence of physical activity on body image in people with and without acquired mobility disability [Vliv pohybové aktivity na subjektivní vnímání těla u osob se získaným tělesným postižením a bez něj

    Ziya Koruç

    2011-12-01

    Full Text Available BACKGROUND: Body image in people with physical disability is important, but it has received little attention in the research literature. OBJECTIVE: The aim of the study was to determine whether differences exist between adolescents with acquired mobility disability (AMD and those without AMD regarding body image, and whether physical activity influences these differences. METHODS: Fifty-eight adolescents, aged 16 to 18 years, participated in this study. Half the participants had some form of AMD while the other half were healthy. Body image was evaluated with the Multidimensional Body-Self Relations Questionnaire (MBSRQ before and after 6 weeks of playing darts. A two-way ANOVA was used to analyse the results. RESULTS: At the end of the study, the healthy adolescents scored significantly higher than the AMD group on the subscales of fitness perception, orientation and overall health perception. No interaction was found between disability and exercise on any subscales of the MBSRQ. CONCLUSIONS: The results of this study demonstrate that people with AMD evaluate their health and fitness levels as being lower than healthy adolescents and that they are less concerned with fitness as compared with healthy adolescents. Six weeks of playing darts as a physical activity had no effect on improving the self-perceptions of the AMD group.[VÝCHODISKA: Subjektivní vnímání těla u lidí s tělesným postižením je důležitý aspekt, v odborné literatuře mu však nebylo věnováno příliš pozornosti. CÍLE: Cílem studie bylo stanovit, zda se vyskytují rozdíly mezi adolescenty se získaným tělesným postižením (AMD a adolescenty bez AMD, co se týče subjektivního vnímání těla, a zda tyto rozdíly ovlivňuje pohybová aktivita. METODIKA: Této studie se zúčastnilo padesát osm adolescentů ve věku mezi 16 a 18 lety. Polovina účastníků měla některou z forem AMD, zatímco druhá polovina byla zdravá. Subjektivní vnímání t

  5. Acceptance and Commitment Therapy: Distinctive Features

    Flaxman, Paul E.; Blackledge, J. T.; Bond, Frank W.

    2010-01-01

    What are the distinctive theoretical and practical features of acceptance and commitment therapy? Acceptance and commitment therapy (ACT) is a modern behaviour therapy that uses acceptance and mindfulness interventions alongside commitment and behaviour change strategies to enhance psychological flexibility. Psychological flexibility refers to the ability to contact the present moment and change or persist in behaviour that serves one’s personally chosen values. Divided into two secti...

  6. Hydraulic fracturing with distinct element method

    Pruiksma, J.P.; Bezuijen, A.

    2002-01-01

    In this report, hydraulic fracturing is investigated using the distinct element code PFC2D from Itasca. Special routines were written to be able to model hydraulic fracturing. These include adding fluid flow to PFC2D and updating the fluid flow domains when fractures appear. A brief description of this implementation and the modelling of the hydraulic fracturing is given. After the set-up of the hydraulic fracturing simulations has been discussed, with all the main input parameters, several m...

  7. Characterization of an antigenically distinct porcine rotavirus.

    Bridger, J C; Clarke, I. N.; McCrae, M A

    1982-01-01

    A porcine virus with rotavirus morphology, which was antigenically unrelated to previously described rotaviruses, is described. Particles with an outer capsid layer measured 75 nm and those lacking the outer layer were 63 nm in diameter. Particles which resembled cores were also identified. The virus was shown to be antigenically distinct from other rotaviruses as judged by immunofluorescence and immune electron microscopy, and it failed to protect piglets from challenge with porcine rotaviru...

  8. Create three distinct career paths for innovators.

    O'Connor, Gina Colarelli; Corbett, Andrew; Pierantozzi, Ron

    2009-12-01

    Large companies say they Create Three Distinct want to be Career Paths for Innovators innovative, but they fundamentally mismanage their talent. Expecting innovators to grow along with their projects-from discovery to incubation to acceleration--sets them up to fail. Most people excel at one of the phases, not all three. By allowing innovation employees to develop career paths suited to their strengths, companies will create a sustainable innovation function. PMID:19968059

  9. Mushrooms—Biologically Distinct and Nutritionally Unique

    Feeney, Mary Jo; Miller, Amy Myrdal; Roupas, Peter

    2014-01-01

    Mushrooms are fungi, biologically distinct from plant- and animal-derived foods (fruits, vegetables, grains, dairy, protein [meat, fish, poultry, legumes, nuts, and seeds]) that comprise the US Department of Agriculture food patterns operationalized by consumer-focused MyPlate messages. Although mushrooms provide nutrients found in these food groups, they also have a unique nutrient profile. Classified into food grouping systems by their use as a vegetable, mushrooms’ increasing use in main e...

  10. REVIEW OF A CASE OF CHILD WITH ACQUIRED APHASIA

    Silvana FILIPOVA

    2004-12-01

    Full Text Available Achieved children speech disabilities are manifested at certain level of development of speech from the age of 3 to 12 years. The speech disabilities with children from the age of one to three years have developmental and acquired characteristics. It is well-known when and why the disabilities occurr at acquired aphasia or disphasia.The child with acquired aphasia or disphasia has early brain impairements and a relative improvement happens with adequate treatment and prompt rehabilitation treatment. It is more obvious with children than with adults.This fast and complete rehabilitation happens due to the plastic character of child’s brain and the possibilities for intro-hemisphere and inter-hemisphere reorganization of speech functions in childhood.

  11. Tuberculosis and the acquired immune deficiency syndrome in South Brazil

    Tuberculosis and the acquired immune deficiency syndrome in South Brazil. The authors studied the incidence of tuberculosis in South Brazilian patients with acquired immune deficiency syndrome from January 1985 to June 1988. During this period, tuberculosis occurred in 10.3% of acquired immune deficiency syndrome patients. The socioeconomic conditions and the incidence of disease in the population were not confirmed as a potential risk for tuberculosis infection. Chest radiographs revealed pulmonary infiltrates in six patients, hilar and/or mediastinal adenopathy in three, and pleural effusion in two. The two remaining patients had pulmonary consolidation associated with other features. None of these patients presented pulmonary cavitation or radiographic findings of typical reactivation of pulmonary tuberculosis. (author)

  12. Acquired night blindness due to bad eating patterns.

    Parafita-Fernández, A; Escalona-Fermín, M M; Sampil, M; Moraña, N; Viso, E; Fernández-Vila, P C

    2015-06-01

    We report a case of acquired night blindness in a developed country (Spain) without risk factors for nutritional deficiency disease or family history of hereditary retinal disease. A 76-year-old woman presented with acquired night blindness of 6-month progression. After a thorough inquiry about eating patterns she becomes suspicious of vitamin A low dietary intake, which is analytically confirmed and successfully treated. Despite being very uncommon in our environment and even more in patients without digestive problems, in a patient reporting acquired night blindness vitamin A deficiency should not be discarded until eating patterns have been investigated. It might be especially relevant in certain socioeconomic situations and eating disorders such as bulimia or anorexia nervosa. PMID:25804276

  13. Free Auricular Composite Graft for Acquired Nasal Stenosis

    Riley, Charles A.; Lawlor, Claire M.; Gray, Mingyang Liu; Graham, H. Devon

    2016-01-01

    Background: Acquired nasal stenosis poses a reconstructive challenge for the facial plastic surgeon. Many surgical options are available, ranging from primary closure to skin grafts to free flap reconstruction for complex defects. The free auricular composite graft is a single-stage procedure that can be used to repair nasal vestibular stenosis causing nasal obstruction. Case Report: We present the case of a patient with acquired nasal stenosis as a result of prolonged nasal tampon placement secondary to severe epistaxis and subsequent nasal vestibular infection. Repair via auricular composite graft was successful, and we provide a thorough explanation of graft design and operative technique. Conclusion: Free auricular composite grafts can produce desirable functional and aesthetic outcomes and should be considered in patients presenting with acquired nasal stenosis. PMID:27303225

  14. Development of individually distinct recognition cues.

    Mateo, Jill M

    2006-11-01

    Despite extensive research on the functions of kin recognition, little is known about ontogenetic changes in the cues mediating such recognition. In Belding's ground squirrels, Spermophilus beldingi, secretions from oral glands are both individually distinct and kin distinct, and function in social recognition across many contexts. Behavioral studies of recognition and kin preferences suggest that these cues may change across development, particularly around the time of weaning and emergence from natal burrows (around 25 days of age). I used an habituation-discrimination task with captive S. beldingi, presenting subjects with odors collected from a pair of pups at several ages across early development. I found that at 21 days of age, but not at 7 or 14, young produce detectable odors. Odors are not individually distinct, however, until 28 days of age, after young have emerged from their burrows and begun foraging. In addition, an individual's odor continues to develop after emergence: odors produced by an individual at 20 and 40 days of age are perceived as dissimilar, yet odors produced at 28 and 40 days are treated as similar. Developmental changes in odors provide a proximate explanation for why S. beldingi littermate preferences are not consolidated until after natal emergence, and demonstrate that conspecifics must update their recognition templates as young develop. PMID:17016836

  15. Acquired pathology of the pediatric spine and spinal cord

    Pediatric spine pathology poses a diagnostic challenge for radiologists. Acquired spine pathology often yields nonspecific signs and symptoms in children, especially in the younger age groups, and diagnostic delay can carry significant morbidity. This review is focused on some of the more common diagnostic dilemmas we face when attempting to evaluate and diagnose acquired pediatric spine anomalies in daily practice. An understanding of some of the key differentiating features of these disease processes in conjunction with pertinent history, physical exam, and advanced imaging techniques can indicate the correct diagnosis. (orig.)

  16. ACQUIRE: A data acquisition system for CAMAC on SUN workstation

    The data acquisition software package ACQUIRE been used for many years by the Princeton University Cyclotron Laboratory for nuclear physics research applications. This code has been ported to the SUN Sparc workstation and is fully functional, including block data transfers using an in crate Event Handler. A SCSI interface to CAMAC is utilized, and the device handling software has been developed in such a way that little modification was needed in the ACQUIRE code for the SUN implementation. The Higz X windows graphics package from CERN is used for data display

  17. Acquired pathology of the pediatric spine and spinal cord

    Palasis, Susan; Hayes, Laura L. [Children' s Healthcare of Atlanta, Department of Radiology at Scottish Rite, Atlanta, GA (United States)

    2015-09-15

    Pediatric spine pathology poses a diagnostic challenge for radiologists. Acquired spine pathology often yields nonspecific signs and symptoms in children, especially in the younger age groups, and diagnostic delay can carry significant morbidity. This review is focused on some of the more common diagnostic dilemmas we face when attempting to evaluate and diagnose acquired pediatric spine anomalies in daily practice. An understanding of some of the key differentiating features of these disease processes in conjunction with pertinent history, physical exam, and advanced imaging techniques can indicate the correct diagnosis. (orig.)

  18. [Features of morbidity community-acquired pneumonia among young recruits].

    Serdukov, D U; Gordienko, A V; Kozlov, M S; Mikhailov, A A; Davydov, P A

    2015-10-01

    Were examined 3338 military personnel of the combined training center. 183 of them diagnosed community-acquired pneumonia, in 3155 focal and infiltrative changes in lung tissue were not identified. The analisys of prevalence been made among young recruits of the acute respiratory illness before arriving in part and at the assembly point, foci of chronic infection, smoking, low body weight. 511 military personnel arrived at the training center in the disease state with symptoms of acute respiratory illness. Examined the relationship these risk factor to the development of community-acquired pneumonia in this category of servicemen. PMID:26827502

  19. Microsoft Acquired Nokia in Unipolar Operating System Market

    Netra Pal Singh

    2014-01-01

    The recent big tickets include Microsoft acquiring part of Nokia for US$ 7.2 billion, Verizon buy 45% stake in Vodafone for US$130 billion, Google acquiring Motorola for 12.5 billion. These buyouts are analyzed and commented by experts of the industry. This research paper attempted to collate their view in the context of Microsoft and Nokia deal on six parameters. These parameters are (i) reasons for the downfall of the Nokia market share, (ii) general comments of the experts, (iii) similarit...

  20. Multivariate neural biomarkers of emotional states are categorically distinct.

    Kragel, Philip A; LaBar, Kevin S

    2015-11-01

    Understanding how emotions are represented neurally is a central aim of affective neuroscience. Despite decades of neuroimaging efforts addressing this question, it remains unclear whether emotions are represented as distinct entities, as predicted by categorical theories, or are constructed from a smaller set of underlying factors, as predicted by dimensional accounts. Here, we capitalize on multivariate statistical approaches and computational modeling to directly evaluate these theoretical perspectives. We elicited discrete emotional states using music and films during functional magnetic resonance imaging scanning. Distinct patterns of neural activation predicted the emotion category of stimuli and tracked subjective experience. Bayesian model comparison revealed that combining dimensional and categorical models of emotion best characterized the information content of activation patterns. Surprisingly, categorical and dimensional aspects of emotion experience captured unique and opposing sources of neural information. These results indicate that diverse emotional states are poorly differentiated by simple models of valence and arousal, and that activity within separable neural systems can be mapped to unique emotion categories. PMID:25813790

  1. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab.

    Wheeler, Deric L; Iida, Mari; Kruser, Tim J; Nechrebecki, Meghan M; Dunn, Emily F; Armstrong, Eric A; Huang, Shyhmin; Harari, Paul M

    2009-04-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a major role in oncogenesis. Cetuximab is an EGFR-blocking antibody that is FDA approved for use in patients with metastatic colorectal cancer (mCRC) and head and neck squamous cell carcinoma (HNSCC). Although cetuximab has shown strong clinical benefit for a subset of cancer patients, most become refractory to cetuximab therapy. We reported that cetuximab-resistant NSCLC line NCI-H226 cells have increased steady-state expression and activity of EGFR secondary to altered trafficking/degradation and this increase in EGFR expression and activity lead to hyper-activation of HER3 and down stream signals to survival. We now present data that Src family kinases (SFKs) are highly activated in cetuximab-resistant cells and enhance EGFR activation of HER3 and PI(3)K/Akt. Studies using the Src kinase inhibitor dasatinib decreased HER3 and PI(3)K/Akt activity. In addition, cetuximab-resistant cells were resensitized to cetuximab when treated with dasatinib. These results indicate that SFKs and EGFR cooperate in acquired resistance to cetuximab and suggest a rationale for clinical strategies that investigate combinatorial therapy directed at both the EGFR and SFKs in patients with acquired resistance to cetuximab. PMID:19276677

  2. A Few Observations on the Distinctive Features of the Greek Culture

    Robert A. Sucharski

    2015-01-01

    A Few Observations on the Distinctive Features of the Greek CultureThe article is devoted to one of the most interesting features of the Greek culture in antiquity, namely for an almost total insensitivity of the Hellenes to sounds and colours of any other language. It is no coincidence that the once-non-pejorative word βάρβαρος over time acquired its current meaning of ‘barbaric/barbarian’, shared by probably all modern languages which take inspiration from classical antiquity. The Greeks, h...

  3. Toll-like receptors 2, 3 and 4 (TLR-2, TLR-3 and TLR-4) are expressed in the microenvironment of human acquired cholesteatoma.

    Szczepański, Mirosław; Szyfter, Witold; Jenek, Renata; Wróbel, Maciej; Lisewska, Iwona Mozer; Zeromski, Jan

    2006-07-01

    Human toll-like receptors (TLR 1-10) are crucial in the induction and activation of innate immunity in the course of an infection. They are expressed mainly on the cells of the immune system, and also on some epithelia and endothelia. Their ligands so called pathogen associated molecular patterns are abundant on invading microbes. TLR-ligand binding results in cell signal transduction and subsequent production of various proinflammatory cytokines such as IL-1 and TNF-alpha. Acquired cholesteatoma is formed during chronic otitis media in the proportion of cases. It has adverse effects on ear structures, resulting in osteolysis and bone resorption. Its formation and pathogenesis are not fully understood. The current study attempted to search the possible role of TLRs in this somewhat awkward pathological condition. Surgical specimens of human acquired cholesteatoma (n=15) and normal external auditory canal skin (n=5, control tissues) were tested by immunohistochemistry for the presence of TLRs. Three TLRs were examined: TLR-2, TLR-3 and TLR-4. All TLRs tested were demonstrated in matrix (layer of keratinizing epithelium) and perimatrix (granulation tissue) of this inflammatory tumour. Expression of particular TLRs within the keratinizing epithelium was distinct and uneven. In the perimatrix, numerous T (CD3+) cells were seen and relatively few macrophages (CD11c+, HLA-DR+). There was a weak expression of all TLRs on normal (non-inflammatory) skin. Expression of TLR-3 both on the epithelium and some cells within the perimatrix and the presence of T cells may suggest that apart from innate immune responses, mechanisms of adaptive immunity also operate in cholesteatoma. Weak expression of these receptors on normal skin may also suggest the important role of TLRs in the etiopathogenesis of cholesteatoma. PMID:16538507

  4. Pathology of the thoracic wall: congenital and acquired

    Garcia-Pena, Pilar; Barber, Ignasi [Hospital Materno-Infantil, Pediatric Radiology, Barcelona (Spain)

    2010-06-15

    This review aims to cover the main congenital and acquired lesions that arise in the thoracic wall of infants and children. Imaging often plays an essential role in the evaluation of symptomatic and asymptomatic thoracic wall abnormalities. The use of appropriate imaging modalities for each condition will be addressed, as well as the range of benign and malignant conditions that can occur. (orig.)

  5. School Reentry for Children with Acquired Central Nervous Systems Injuries

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  6. The pilot workshop TOR and the experience acquired in reprocessing

    This report reviews the experience acquired by the Group CEA in the reprocessing and the fast reactor fuels. TOR Treatment of Fast Oxide is the present stage in the development of reprocessing installations; TOR is a pre-industrial installation and will allow to develop the main technical choices

  7. Purpura fulminans due to acquired protein C deficiency

    Devdeep Mukherjee

    2015-01-01

    Full Text Available Purpura fulminans (PF may be the presenting symptom in a patient with protein C (PC deficiency. It is a hematological emergency and presents with extensive areas of hemorrhagic necrosis of the skin. PC deficiency is usually genetically inherited. However, we report a 1 year and 4 months boy, who presented with acquired PC deficiency possibly of postinfectious etiology and developed PF.

  8. Cognitive Rehabilitation for Children with Acquired Brain Injury

    Slomine, Beth; Locascio, Gianna

    2009-01-01

    Cognitive deficits are frequent consequences of acquired brain injury (ABI) and often require intervention. We review the theoretical and empirical literature on cognitive rehabilitation in a variety of treatment domains including attention, memory, unilateral neglect, speech and language, executive functioning, and family involvement/education.…

  9. Practitioner Review: Cognitive Rehabilitation for Children with Acquired Brain Injury

    Limond, Jenny; Leeke, Rachel

    2005-01-01

    Background: The need to address acquired cognitive impairments is increasing in child populations seen across a range of settings. However, current clinical practice following brain injury in children does not necessarily incorporate the use of cognitive rehabilitation models or techniques. The aim of this paper is to review the literature in this…

  10. Unexpected postpartum hemorrhage due to an acquired factor VIII inhibitor.

    Paidas, Michael J; Hossain, Nazli

    2014-09-01

    Unexplained postpartum hemorrhage (PPH) refractory to standard hemostatic measures should trigger a heightened clinical suspicion of an acquired bleeding disorder. When hemostatic medical interventions and surgical procedures fail to control the bleeding, then significant postoperative blood loss, debilitating morbidity, loss of fertility, and death may occur. In the setting of an autoantibody inhibitor to factor VIII (FVIII), control of life-threatening PPH and avoidance of subsequent bleeding episodes depends on a timely and accurate diagnosis, prompt hemostatic treatment and eradication of FVIII inhibitors, and appropriate long-term patient care and management. Acquired postpartum hemophilia due to a FVIII inhibitor is a rare cause of PPH; however, delayed treatment can lead to increased maternal morbidity and mortality. Acquired FVIII inhibitors also pose an emerging bleeding threat to the neonate as a result of possible transplacental transfer of FVIII autoantibodies to the fetus during the last trimester of pregnancy. The purpose of this review is to increase awareness among hematologists and obstetricians/gynecologists regarding the occurrence of FVIII neutralizing autoantibodies as a cause of PPH, and emphasize the importance of collaboration between obstetrician/gynecologists and hematology specialists to optimize the diagnostic evaluation, treatment, and long-term management of women who experience PPH due to an acquired FVIII inhibitor. PMID:24338123

  11. Acquired TTP: ADAMTS13 meets the immune system

    N. Sorvillo

    2013-01-01

    Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers, initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura (TTP). At present it is not clear why previously healthy individuals develop anti-ADAMTS13 antibodies. The studies de

  12. Grief and Needs of Adults with Acquired Visual Impairments

    Murray, Shirley A.; McKay, Robert C.; Nieuwoudt, Johan M.

    2010-01-01

    This report aims to illuminate the complex phenomenon of grief and the needs experienced throughout the time course of their impairments by adults with acquired visual impairments. The study applied a phenomenological research strategy using 10 case studies of South African adults, visually impaired within and beyond six years. Qualitative…

  13. Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults

    Postma, Douwe F.; Van Werkhoven, Cornelis H.; Van Elden, Leontine J R; Thijsen, Steven F T; Hoepelman, Andy I M; Kluytmans, Jan A J W; Boersma, Wim G.; Compaijen, Clara J.; Van Der Wall, Eva; Prins, Jan M.; Oosterheert, Jan J.; Bonten, Marc J M

    2015-01-01

    BACKGROUND The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We compared strategies of empirical treatment (al

  14. A case of acquired Gitelman syndrome presenting as hypokalemic paralysis

    Kulkarni, M.; Kadri, P.; Pinto, R.

    2015-01-01

    We report a case of a young female patient who presented with weakness of upper and lower limbs. On evaluation, she had hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. Anti-Ro (SSA) antibody was positive. She had an acquired Gitelman syndrome due to primary Sjögren's syndrome (SS). SS presenting with features of Gitelman syndrome is very rare.

  15. A case of acquired Gitelman syndrome presenting as hypokalemic paralysis.

    Kulkarni, M; Kadri, P; Pinto, R

    2015-01-01

    We report a case of a young female patient who presented with weakness of upper and lower limbs. On evaluation, she had hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. Anti-Ro (SSA) antibody was positive. She had an acquired Gitelman syndrome due to primary Sjögren's syndrome (SS). SS presenting with features of Gitelman syndrome is very rare. PMID:26199478

  16. Learning through Business Games: Acquiring Competences within Virtual Realities

    Fortmuller, Richard

    2009-01-01

    The didactic function of business games is often seen only in the development of sociocommunicative competences and general problem-solving strategies. An equally important aspect of business games lies in the acquirement of technical and problem-oriented knowledge, which is the focus of this article. Moreover, this knowledge dimension is further…

  17. Heat Stress Screening of Peanut Seedlings for Acquired Thermotolerance

    The objective of this research was to develop a user-friendly and medium throughput laboratory protocol using acquired thermotolerance (ATT) in peanut seedlings as a measure of one mechanism of heat stress tolerance. Sixteen genotypes, including selected accessions of the U.S. peanut min...

  18. [Acquired agammaglobulinaemia with predominantly intestinal symptoms (author's transl)].

    Goldach, R; Wittwer, J

    1977-11-01

    In a 45-year-old female patient primary acquired agammaglobulinaemia was diagnosed. Intestinal symptoms predominated. The disease was characterized by a B-cell defect. Substitution with gamma-globulin (Beriglobin) practically cured the symptoms. The pathogenesis of the disease remains unexplained. PMID:72639

  19. Acquiring Software Design Schemas: A Machine Learning Perspective

    Harandi, Mehdi T.; Lee, Hing-Yan

    1991-01-01

    In this paper, we describe an approach based on machine learning that acquires software design schemas from design cases of existing applications. An overview of the technique, design representation, and acquisition system are presented. the paper also addresses issues associated with generalizing common features such as biases. The generalization process is illustrated using an example.

  20. Bleomycin Containing Chemotherapeutic Regimen Induced Acquired Partial Lipodystrophy

    Tandon, Vishal R; Gupte, Novy; Mahajan, Vivek; Sharma, Rahul; Langer, Cheena; Khajuria, Vijay; Mahajan, Annil

    2016-01-01

    Bleomycin toxicity predominantly affects the skin and lungs. Cutaneous toxicity classically known to present with bleomycin are flagellate erythema and drug rash. We hereby report an isolated case of (bleomyicn)-induced acquired partial (lipodytrophy) having potential cosmetic implications in a young women prescribed postoperatively following a case of germ cell carcinoma of ovary (endodermal sinus tumor). PMID:26955139

  1. Hemorrhagic abscess in a patient with the acquired immunodeficiency syndrome

    Cerebral toxoplasmosis is frequent among patients with the acquired immunodeficiency syndrome. The common computed tomography appearance of this complication is multiple low density area with ring enhancement. We describe a very rare picture of cerebral toxoplasmosis, this is multiple hemorrhagic toxoplasmic abscess. (orig.)

  2. A Corpus-Based Comparative Study of "Learn" and "Acquire"

    Yang, Bei

    2016-01-01

    As an important yet intricate linguistic feature in English language, synonymy poses a great challenge for second language learners. Using the 100 million-word British National Corpus (BNC) as data and the software Sketch Engine (SkE) as an analyzing tool, this article compares the usage of "learn" and "acquire" used in natural…

  3. On the difficulties of acquiring mathematical experience: Case rural education

    Booss-Bavnbek, Bernhelm

    2014-01-01

    Based on a variety of philosophical approaches and my own work for decades in pure and applied mathematics teaching and research, I explain my view upon the basic difficulties of acquiring the “Mathematical Experience” (in the sense of P.J. Davis and R. Hersh 1981) and submit a list of claims how...

  4. Acquired Dysarthria in Conversation: Identifying Sources of Understandability Problems

    Bloch, Steven; Wilkinson, Ray

    2009-01-01

    Background: Acquired progressive dysarthria is traditionally assessed, rated, and researched using measures of speech perception and intelligibility. The focus is commonly on the individual with dysarthria and how speech deviates from a normative range. A complementary approach is to consider the features and consequences of dysarthric speech as…

  5. Ethnicity Knowledge and Attitudes toward Acquired Immune Deficiency Syndrome.

    Goh, David S.

    This study examined the effects of race/ethnicity and degree of acculturation on knowledge and attitudes about human immunodeficiency virus/Acquired Immune Deficiency Syndrome (HIV/AIDS). Subjects were 274 college students from 5 racial/ethnic groups (Whites, Blacks, Hispanics, Asian Americans, U.S. born, having an Asian origin with families that…

  6. Spoken Persuasive Discourse Abilities of Adolescents with Acquired Brain Injury

    Moran, Catherine; Kirk, Cecilia; Powell, Emma

    2012-01-01

    Purpose: The aim of this study was to examine the performance of adolescents with acquired brain injury (ABI) during a spoken persuasive discourse task. Persuasive discourse is frequently used in social and academic settings and is of importance in the study of adolescent language. Method: Participants included 8 adolescents with ABI and 8 peers…

  7. Pharmacotherapy and the risk for community-acquired pneumonia

    Mody Lona

    2010-07-01

    Full Text Available Abstract Background Some forms of pharmacotherapy are shown to increase the risk of community-acquired pneumonia (CAP. The purpose of this study is to investigate whether pharmacotherapy with proton pump inhibitors (PPI, inhaled corticosteroids, and atypical antipsychotics was associated with the increased risk for CAP in hospitalized older adults with the adjustment of known risk factors (such as smoking status and serum albumin levels. Methods A retrospective case-control study of adults aged 65 years or older at a rural community hospital during 2004 and 2006 was conducted. Cases (N = 194 were those with radiographic evidence of pneumonia on admission. The controls were patients without the discharge diagnosis of pneumonia or acute exacerbation of chronic obstructive pulmonary disease (COPD (N = 952. Patients with gastric tube feeding, ventilator support, requiring hemodialysis, metastatic diseases or active lung cancers were excluded. Results Multiple logistic regression analysis revealed that the current use of inhaled corticosteroids (adjusted odds ratio [AOR] = 2.89, 95% confidence interval [CI] = 1.56-5.35 and atypical antipsychotics (AOR = 2.26, 95% CI = 1.23-4.15 was an independent risk factor for CAP after adjusting for confounders, including age, serum albumin levels, sex, smoking status, a history of congestive heart failure, coronary artery disease, and COPD, the current use of PPI, β2 agonist and anticholinergic bronchodilators, antibiotic(s, iron supplement, narcotics, and non-steroidal anti-inflammatory drugs. The crude OR and the AOR of PPI use for CAP was 1.41 [95% CI = 1.03 - 1.93] and 1.18 [95% CI = 0.80 - 1.74] after adjusting for the above confounders, respectively. Lower serum albumin levels independently increased the risk of CAP 1.89- fold by decreasing a gram per deciliter (AOR = 2.89, 95% CI = 2.01 - 4.16. Conclusion Our study reaffirmed that the use of inhaled corticosteroids and atypical antipsychotics was both

  8. A Neural Basis for the Acquired Capability for Suicide

    Deshpande, Gopikrishna; Baxi, Madhura; Witte, Tracy; Robinson, Jennifer L.

    2016-01-01

    The high rate of fatal suicidal behavior (SB) in men is an urgent issue as highlighted in the public eye via news sources and media outlets. In this study, we have attempted to address this issue and understand the neural substrates underlying the gender differences in the rate of fatal SB. The Interpersonal–Psychological Theory of Suicide has proposed an explanation for the seemingly paradoxical relationship between gender and SB, i.e., greater non-fatal suicide attempts by women but higher number of deaths by suicide in men. This theory states that possessing suicidal desire (due to conditions such as depression) alone is not sufficient for a lethal suicide attempt. It is imperative for an individual to have the acquired capability for suicide (ACS) along with suicidal desire in order to die by suicide. Therefore, higher levels of ACS in men may explain why men are more likely to die by suicide than women, despite being less likely to experience suicidal ideation or depression. In this study, we used activation likelihood estimation meta-analysis to investigate a potential ACS network that involves neural substrates underlying emotional stoicism, sensation-seeking, pain tolerance, and fearlessness of death, along with a potential depression network that involves neural substrates that underlie clinical depression. Brain regions commonly found in ACS and depression networks for males and females were further used as seeds to obtain regions functionally and structurally connected to them. We found that the male-specific networks were more widespread and diverse than the female-specific ones. Also, while the former involved motor regions, such as the premotor cortex and cerebellum, the latter was dominated by limbic regions. This may support the fact that suicidal desire generally leads to fatal/decisive action in males, while, in females, it manifests as depression, ideation, and generally non-fatal actions. The proposed model is a first attempt to characterize

  9. Removing movement artifacts from equine ECG recordings acquired with textile electrodes.

    Lanata, Antonio; Guidi, Andrea; Baragli, Paolo; Paradiso, Rita; Valenza, Gaetano; Scilingo, Enzo Pasquale

    2015-08-01

    This study reports on the implementation of a novel system to detect and reduce movement artifact (MA) contribution in electrocardiogram (ECG) recordings acquired from horses in free movement conditions. The system comprises both integrated textile electrodes for ECG acquisition and one triaxial accelerometer for movement monitoring. Here, ECG and physical activity are continuously acquired from seven horses through the wearable system and a model that integrates cardiovascular and movement information to estimate the MA contribution is implemented. Moreover, in this study we propose a new algorithm where the Stationary Wavelet Transform (SWT) decomposition algorithm is employed to identify and remove movement artifacts from ECG recodigns. Achieved results showed a reduction of MA percentage greater than 40% between before- and after- the application of the proposed algorithm to seven hours of recordings. PMID:26736667

  10. Experimental Space Shuttle Orbiter Studies to Acquire Data for Code and Flight Heating Model Validation

    Wadhams, T. P.; Holden, M. S.; MacLean, M. G.; Campbell, Charles

    2010-01-01

    In an experimental study to obtain detailed heating data over the Space Shuttle Orbiter, CUBRC has completed an extensive matrix of experiments using three distinct models and two unique hypervelocity wind tunnel facilities. This detailed data will be employed to assess heating augmentation due to boundary layer transition on the Orbiter wing leading edge and wind side acreage with comparisons to computational methods and flight data obtained during the Orbiter Entry Boundary Layer Flight Experiment and HYTHIRM during STS-119 reentry. These comparisons will facilitate critical updates to be made to the engineering tools employed to make assessments about natural and tripped boundary layer transition during Orbiter reentry. To achieve the goals of this study data was obtained over a range of Mach numbers from 10 to 18, with flight scaled Reynolds numbers and model attitudes representing key points on the Orbiter reentry trajectory. The first of these studies were performed as an integral part of Return to Flight activities following the accident that occurred during the reentry of the Space Shuttle Columbia (STS-107) in February of 2003. This accident was caused by debris, which originated from the foam covering the external tank bipod fitting ramps, striking and damaging critical wing leading edge heating tiles that reside in the Orbiter bow shock/wing interaction region. During investigation of the accident aeroheating team members discovered that only a limited amount of experimental wing leading edge data existed in this critical peak heating area and a need arose to acquire a detailed dataset of heating in this region. This new dataset was acquired in three phases consisting of a risk mitigation phase employing a 1.8% scale Orbiter model with special temperature sensitive paint covering the wing leading edge, a 0.9% scale Orbiter model with high resolution thin-film instrumentation in the span direction, and the primary 1.8% scale Orbiter model with detailed

  11. A new sieve for distinct coordinate counting

    2010-01-01

    We present a new sieve for the distinct coordinate counting problem.This significantly improves the classical inclusion-exclusion sieve for this problem,in the sense that the number of terms is reduced from 2(k 2) to k!,and reduced further to p(k) in the symmetric case,where p(k) denotes the number of partitions of k.As an illustration of applications,we give an in-depth study of a basic example arising from coding theory and graph theory.

  12. How distinctive is philosophers’ intuition talk?

    Andow, James

    2015-01-01

    The word “intuition” is one frequently used in philosophy. It is often assumed that the way in which philosophers use the word, and others like it, is very distinctive. This claim has been subjected to little empirical scrutiny, however. This article presents the first steps in a qualitative analysis of the use of intuition talk in the academy. It presents the findings of two preliminary empirical studies. The first study examines the use of intuition talk in spoken academic English. The seco...

  13. Hospital acquired diarrhea in a burn center of Tehran

    Faranak Alinejad

    2016-01-01

    Full Text Available Background and Objectives: Incidence of hospital-acquired diarrhea has increased rapidly and burn patients are at high risk of getting it. Infection with C. difficile is the most common cause of antibiotic associated diarrhea. The aim of this study was to determine the baseline characteristics and clinical presentation of hospital-acquired diarrhea and compare C. difficile and non-C. difficile diarrhea in burn patients treated at a burn center.Materials and Methods: During a 1-year study all patients with hospital-acquired diarrhea at Motahari Burn Hospital, Teh- ran, Iran enrolled in this study. We compared patients with a stool sample positive for C. difficile toxin or tracing the antigen in patients who were negative for detection of toxin in their stool sample specimens.Results: Diarrhea developed in 37 patients out of 3200 admitted patients with a mean burn size of 34.8 ±20.1%. Among them, 8 patients had a positive result for C. difficile. The mean time between antibiotic therapy and occurrence of diarrhea was 9.5 ± 6.2 days. Nine (23.7% patients died in the 7.8± 4.2 days, mostly due to co-morbidities. The mean duration of di- arrhea was 3.6 ± 2 days. Twenty two (57.9% patients were treated with oral metronidazol and eleven (28.9% patients were treated with combination of metronidazole and vancomycin, higher rate of combination therapy was seen in Clostridium difficile CDI.Conclusion: Overall, the prevalence of hospital-acquired diarrhea was 120/10,000  and 21% of them caused by infection with C. difficile. Presence of peripheral leukocytosis and colitis were the alarm sign for diagnosis of C. difficile infection. Keywords: Hospital-acquired diarrhea (HAD, Burn, Clostridium difficile infection (CDI

  14. Left Ventricular Noncompaction: A Distinct Genetic Cardiomyopathy?

    Arbustini, Eloisa; Favalli, Valentina; Narula, Nupoor; Serio, Alessandra; Grasso, Maurizia

    2016-08-30

    Left ventricular noncompaction (LVNC) describes a ventricular wall anatomy characterized by prominent left ventricular (LV) trabeculae, a thin compacted layer, and deep intertrabecular recesses. Individual variability is extreme, and trabeculae represent a sort of individual "cardioprinting." By itself, the diagnosis of LVNC does not coincide with that of a "cardiomyopathy" because it can be observed in healthy subjects with normal LV size and function, and it can be acquired and is reversible. Rarely, LVNC is intrinsically part of a cardiomyopathy; the paradigmatic examples are infantile tafazzinopathies. When associated with LV dilation and dysfunction, hypertrophy, or congenital heart disease, the genetic cause may overlap. The prevalence of LVNC in healthy athletes, its possible reversibility, and increasing diagnosis in healthy subjects suggests cautious use of the term LVNC cardiomyopathy, which describes the morphology but not the functional profile of the cardiomyopathy. PMID:27561770

  15. Natural Microbial Assemblages Reflect Distinct Organismal and Functional Partitioning

    Wilmes, P.; Andersson, A.; Kalnejais, L. H.; Verberkmoes, N. C.; Lefsrud, M. G.; Wexler, M.; Singer, S. W.; Shah, M.; Bond, P. L.; Thelen, M. P.; Hettich, R. L.; Banfield, J. F.

    2007-12-01

    The ability to link microbial community structure to function has long been a primary focus of environmental microbiology. With the advent of community genomic and proteomic techniques, along with advances in microscopic imaging techniques, it is now possible to gain insights into the organismal and functional makeup of microbial communities. Biofilms growing within highly acidic solutions inside the Richmond Mine (Iron Mountain, Redding, California) exhibit distinct macro- and microscopic morphologies. They are composed of microorganisms belonging to the three domains of life, including archaea, bacteria and eukarya. The proportion of each organismal type depends on sampling location and developmental stage. For example, mature biofilms floating on top of acid mine drainage (AMD) pools exhibit layers consisting of a densely packed bottom layer of the chemoautolithotroph Leptospirillum group II, a less dense top layer composed mainly of archaea, and fungal filaments spanning across the entire biofilm. The expression of cytochrome 579 (the most highly abundant protein in the biofilm, believed to be central to iron oxidation and encoded by Leptospirillum group II) is localized at the interface of the biofilm with the AMD solution, highlighting that biofilm architecture is reflected at the functional gene expression level. Distinct functional partitioning is also apparent in a biological wastewater treatment system that selects for distinct polyphosphate accumulating organisms. Community genomic data from " Candidatus Accumulibacter phosphatis" dominated activated sludge has enabled high mass-accuracy shotgun proteomics for identification of key metabolic pathways. Comprehensive genome-wide alignment of orthologous proteins suggests distinct partitioning of protein variants involved in both core-metabolism and specific metabolic pathways among the dominant population and closely related species. In addition, strain- resolved proteogenomic analysis of the AMD biofilms

  16. Timing the generation of distinct retinal cells by homeobox proteins.

    Sarah Decembrini

    2006-09-01

    Full Text Available The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR, we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.

  17. Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease

    Fernando G. Romeiro

    2011-06-01

    Full Text Available Acquired hepatocerebral degeneration (AHD and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE can be even more complicated. We describe three cases of AHD (two having HE with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

  18. Oxytocin and vasopressin: distinct receptors in myometrium

    The binding characteristics of [3H]oxytocin [( 3H]OT) and [3H]lysine vasopressin [( 3H]LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas [3H]OT was found to bind to a single class of sites with high affinity [Kd, 1.5 +/- 0.4 (+/- SEM) nM] and low capacity [maximum binding (Bmax), 34 +/- 6 fmol/mg protein], [3H]LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for [3H]OT and [3H]LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for [3H]LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin

  19. Distinct types of eigenvector localization in networks

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  20. The Distinctive Challenges of Protecting Radioactive Sources

    The physical protection of nuclear material and nuclear facilities is a highly mature field, dating virtually from the inception of the nuclear age, with longstanding international requirements and guidance. While the international community, including both the IAEA and Member States, has achieved much progress within the decade since approval of the Code of Conduct, the security of radioactive sources remains a new field. This relative novelty is generally well recognized. Much less discussed, however, is the central proposition of this paper: that the security of radioactive sources is not just new, it also poses challenges that are distinct from the security of nuclear material and nuclear facilities. As a result, the apparent assumption on the part of much of the international community that the security of radioactive sources is essentially a lighter version of nuclear security needs to be seriously examined and the corresponding approaches to radioactive source security programmes need to be more fully adapted to these distinct challenges. The result will be a more practical, straightforward approach that is more readily understood by users and regulators, and thus that is more likely to be applied and institutionalized, and in the end more effective and sustainable. (author)