55 research outputs found

    A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse

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    Asthma and mouse models of allergic respiratory inflammation are invariably associated with a pulmonary eosinophilia; however, this association has remained correlative. In this report, a causative relationship between eosinophils and allergen-provoked pathologies was established using eosinophil adoptive transfer. Eosinophils were transferred directly into the lungs of either naive or OVA-treated IL-5-/- mice. This strategy resulted in a pulmonary eosinophilia equivalent to that observed in OVA-treated wild-type animals. A concomitant consequence of this eosinophil transfer was an increase in Th2 bronchoalveolar lavage cytokine levels and the restoration of intracellular epithelial mucus in OVA-treated IL-5-/- mice equivalent to OVA-treated wild-type levels. Moreover, the transfer also resulted in the development of airway hyperresponsiveness. These pulmonary changes did not occur when eosinophils were transferred into naive IL-5-/- mice, eliminating nonspecific consequences of the eosinophil transfer as a possible explanation. Significantly, administration of OVA-treated IL-5-/- mice with GK1.5 (anti-CD4) Abs abolished the increases in mucus accumulation and airway hyperresponsiveness following adoptive transfer of eosinophils. Thus, CD4+ T cell-mediated inflammatory signals as well as signals derived from eosinophils are each necessary, yet alone insufficient, for the development of allergic pulmonary pathology. These data support an expanded view of T cell and eosinophil activities and suggest that eosinophil effector functions impinge directly on lung function

    Limb development genes underlie variation in human fingerprint patterns

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    Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized “pattern-block” correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning

    Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study

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    Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence to inform treatment of relapsed or refractory severe aplastic anemia for pediatric patients is also limited. The clinical features and outcomes for 314 children treated from 2002 to 2014 with immunosuppressive therapy for acquired severe aplastic anemia were analyzed retrospectively from 25 institutions in the North American Pediatric Aplastic Anemia Consortium. The majority of subjects (n=264) received horse anti-thymocyte globulin (hATG) plus cyclosporine (CyA) with a median 61 months follow up. Following hATG/CyA, 71.2% (95%CI: 65.3,76.6) achieved an objective response. In contrast to adult studies, the quality of response achieved in pediatric patients was high, with 59.8% (95%CI: 53.7,65.8) complete response and 68.2% (95%CI: 62.2,73.8) achieving at least a very good partial response with a platelet count ≥50×109L. At five years post-hATG/CyA, overall survival was 93% (95%CI: 89,96), but event-free survival without subsequent treatment was only 64% (95%CI: 57,69) without a plateau. Twelve of 171 evaluable patients (7%) acquired clonal abnormalities after diagnosis after a median 25.2 months (range: 4.3-71 months) post treatment. Myelodysplastic syndrome or leukemia developed in 6 of 314 (1.9%). For relapsed/refractory disease, treatment with a hematopoietic stem cell transplant had a superior event-free survival compared to second immunosuppressive therapy treatment in a multivariate analysis (HR=0.19, 95%CI: 0.08,0.47; P=0.0003). This study highlights the need for improved therapies to achieve sustained high-quality remission for children with severe aplastic anemia

    On the typology and the worship status of sacred trees with a special reference to the Middle East

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    This article contains the reasons for the establishment of sacred trees in Israel based on a field study. It includes 97 interviews with Muslim and Druze informants. While Muslims (Arabs and Bedouins) consider sacred trees especially as an abode of righteous figures' (Wellis') souls or as having a connection to their graves, the Druze relate sacred trees especially to the events or deeds in the lives of prophets and religious leaders. A literary review shows the existence of 24 known reasons for the establishment of sacred trees worldwide, 11 of which are known in Israel one of these is reported here for the first time. We found different trends in monotheistic and polytheistic religions concerning their current worship of sacred trees

    Edmund Husserl's Phenomenology

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    All of the major themes of Edmund Husserl's phenomenology, from the Logical lnvestigations to The Crisis of the European Sciences,are investigated from a critical point of view by James M. Edie. The philosophy of logic is considered insofar as it relates to the phenomenological and transcendental foundation of logic itself. Transcendental logic is studied with reference to both the formal logic of Aristotle and Leibniz and the dialectical logic of Hegel. Edie considers Husserl's theories of meaning and reference, intentionality, the distinction between perceptual and eidetic intuition, the notion of the ideality of meaning, the laws of objectivity in general, and formal and material ontology, as well as Husserl's reinterpretation of the apriori. Concerned throughout with the study of language and its place in phenomenology, Edie pays special attention to Husserl's conception of pure apriori grammar in its relationship to contemporary linguistic structuralism. The book culminates in an exploration of the more dramatic elements in Husserl's phenomenology, which are frequently misinterpreted by the existentialists and neglected by the stricter logicians, such as the theory of freedom, the relationship of phenomenology to existentialism, and the various correlative levels of meaning and being within a phenomenological analysis of our experiencing-in-the-world

    Was Merleau-Ponty a Structuralist?

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    Phenomenology in America, 1984

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    Speaking and meaning: The phenomenology of language

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    xiii, 271 hal; 20,5 c

    Contrasting responses of functional diversity to major losses in taxonomic diversity

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    Taxonomic diversity of benthic marine invertebrate shelf species declines at present by nearly an order of magnitude from the tropics to the poles in each hemisphere along the latitudinal diversity gradient (LDG), most steeply along the western Pacific where shallow-sea diversity is at its tropical maximum. In the Bivalvia, a model system for macroevolution and macroecology, this taxonomic trend is accompanied by a decline in the number of functional groups and an increase in the evenness of taxa distributed among those groups, with maximum functional evenness (FE) in polar waters of both hemispheres. In contrast, analyses of this model system across the two era-defining events of the Phanerozoic, the Permian-Triassic and Cretaceous-Paleogene mass extinctions, show only minor declines in functional richness despite high extinction intensities, resulting in a rise in FE owing to the persistence of functional groups. We hypothesize that the spatial decline of taxonomic diversity and increase in FE along the present-day LDG primarily reflect diversity-dependent factors, whereas retention of almost all functional groups through the two mass extinctions suggests the operation of diversity-independent factors. Comparative analyses of different aspects of biodiversity thus reveal strongly contrasting biological consequences of similarly severe declines in taxonomic diversity and can help predict the consequences for functional diversity among different drivers of past, present, and future biodiversity loss
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