951 resultados para MAP KINASES


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Hi-fi mapping: Multiplexing fluorescent sensors that simultaneously target proton concentration and polarity move to micellar nanospaces, self-regulate their positions, and report their pKa values and wavelengths, which are controlled by their local environments. Such sensory functions enable maps of proton gradients near micellar membranes to be drawn.

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Since 1994, Irish cattle have been exposed to greater risks of acquiring Mycobacterium avium subspecies paratuberculosis (MAP) infection as a consequence of the importation of over 70,000 animals from continental Europe. In recent years, there has been an increase in the number of reported clinical cases of paratuberculosis in Ireland. This study examines the prevalence of factors that promote the introduction and within-herd transmission of Mycobacterium avium subspecies paratuberculosis (MAP) on selected Irish dairy farms in the Cork region, and the association between these factors and the results of MAP screening tests on milk sock filter residue (MFR). A total of 59 dairy farms, selected using non-random methods but apparently free of endemic paratuberculosis, were enrolled into the study. A questionnaire was used to collect data about risk factors for MAP introduction and transmission. The MFR was assessed on six occasions over 24 months for the presence of MAP, using culture and immunomagnetic separation prior to polymerase chain reaction (IMS-PCR). Furthermore, blood samples from all entire male and female animals over one year of age in 20 herds were tested by ELISA. Eighteen (31%) farms had operated as closed herds since 1994, 28 (47%) had purchased from multiple sources and 14 (24%) had either direct or indirect (progeny) contact with imported animals. Milk and colostrum were mixed on 51% of farms, while 88% of farms fed pooled milk. Thirty (51%) herds tested negative to MFR culture and IMS-PCR, 12 (20%) were MFR culture positive, 26 (44%) were IMS-PCR positive and seven (12%) were both culture and IMS-PCR positive. The probability of a positive MFR culture was significantly associated with reduced attendance at calving, and with increased use of individual calf pens and increased (but not significantly) if multiple suckling was practised. There was poor agreement between MFR culture and MFR IMS-PCR results, but moderate agreement between MFR culture and ELISA test results. This study highlights a lack of awareness among Irish dairy farmers about the effect of inadequate biosecurity on MAP introduction. Furthermore, within-herd transmission will be facilitated by traditional calf rearing and waste management practices. The findings of viable MAP in the presence of known transmission factors in non-clinically affected herds could be a prelude to long-term problems for the Irish cattle and agri-business generally.

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Tissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells. We investigated mechanisms regulating Mtb-induced collagenolytic activity in fibroblasts in vitro and in patients. Lung fibroblasts were stimulated with conditioned media from Mtb-infected monocytes (CoMTb). CoMTb induced sustained increased MMP-1 (74 versus 16 ng/ml) and decreased tissue inhibitor of metalloproteinase (TIMP)-1 (8.6 versus 22.3 ng/ml) protein secretion. CoMTb induced a 2.7-fold increase in MMP-1 promoter activation and a 2.5-fold reduction in TIMP-1 promoter activation at 24 hours (P = 0.01). Consistent with this, TIMP-1 did not co-localize with fibroblasts in patient granulomas. MMP-1 up-regulation and TIMP-1 down-regulation were p38 (but not extracellular signal–regulated kinase or c-Jun N-terminal kinase) mitogen-activated protein kinase–dependent. STAT3 phosphorylation was detected in fibroblasts in vitro and in tuberculous granulomas.STAT3 inhibition reduced fibroblast MMP-1 secretion by 60% (P = 0.046). Deletion of the MMP-1 promoter NF-B–binding site abrogated promoter induction in response to CoMTb. TNF-, IL-1ß, or Oncostatin M inhibition in CoMTb decreased MMP-1 secretion by 65, 63, and 25%, respectively. This cytokine cocktail activated the same signaling pathways in fibroblasts and induced MMP-1 secretion similar to that induced by CoMTb. This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-B, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients.

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This paper describes an investigation of various shroud bleed slot configurations of a centrifugal compressor using CFD with a manual multi-block structured grid generation method. The compressor under investigation is used in a turbocharger application for a heavy duty diesel engine of approximately 400 hp. The baseline numerical model has been developed and validated against experimental performance measurements. The influence of the bleed slot flow field on a range of operating conditions between surge and choke has been analysed in detail.
The impact of the returning bleed flow on the incidence at the impeller blade leading edge due to its mixing with the main through-flow has also been studied. From the baseline geometry, a number of modifications to the bleed slot width have been proposed, and a detailed comparison of the flow characteristics performed. The impact of slot variations on the inlet incidence angle has been investigated, highlighting the improvement in surge and choked flow capability. Along with this, the influence of the bleed slot on stabilising the blade passage flow by the suction of the tip and over-tip vortex flow by the slot has been considered near surge.

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Billions of songbirds migrate several thousand kilometers from breeding to wintering grounds and are challenged with crossing ecological barriers and facing displacement by winds along the route. A satisfactory explanation of long-distance animal navigation is still lacking, partly because of limitations on field-based study. The navigational tasks faced by adults and juveniles differ fundamentally, because only adults migrate toward wintering grounds known from the previous year. Here, we show by radio tracking from small aircraft that only adult, and not juvenile, long-distance migrating white-crowned sparrows rapidly recognize and correct for a continent-wide displacement of 3,700 km from the west coast of North America to previously unvisited areas on the east coast. These results show that the learned navigational map used by adult long-distance migratory songbirds extends at least on a continental scale. The juveniles with less experience rely on their innate program to find their distant wintering areas and continue to migrate in the innate direction without correcting for displacement.

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The question of whether homing pigeons use visual landmarks for orientation from distant, familiar sites is an unresolved issue in the field of avian navigation. Where evidence has been found, the question still remains as to whether the landmarks are used independent of the map and compass mechanism for orientation that is so important to birds. Recent research has challenged the extent to which experiments that do not directly manipulate the visual sense can be used as evidence for compass-independent orientation. However, it is proposed that extending a new technique for research on vision in homing to include manipulation of the compasses used by birds might be able to resolve this issue. The effect of the structure of the visual sense of the homing pigeon on its use of visual landmarks is also considered.

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In previous experiments suggesting that previewing visual landscapes speeds homing from familiar release sites, restricted access to olfactory cues may have artefactually encouraged homing pigeons, Calumba livia, to resort to visual landmark orientation. Since evidence for the role of visual landmarks in wide-ranging avian orientation is still equivocal, Braithwaite & Guilford's (1991, Proc. R. Sec. Lond. Ser. B, 245, 183-186) 'previewing' experiments were replicated: birds were allowed or denied visual access to a familiar site prior to release, but allowed ample access to olfactory cues. In experiment 1, allowing birds to preview familiar sites for 5 min prior to release enhanced homing speeds by about 12%. In experiment 2, modified to reduce between-day effects on variation, previewing enhanced homing speeds by about 16%. These experiments support the conclusion that visual landmarks remote from sight of the loft are an important component of the familiar area map, although the nature of the landmarks and how they are encoded remain to be determined. (C) 1997 The Association for the Study of Animal Behaviour.