513 research outputs found
LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.
The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low
Happiness matters : exploring the linkages between personality, personal happiness, and work-related psychological health among priests and sisters in Italy
This study responds to the challenge posed by Rossetti’s work to explore the antecedents and consequences of individual differences in happiness among priests and religious sisters. The Oxford Happiness Questionnaire was completed together with measures of personality and work-related psychological health by 95 priests and 61 religious sisters. Overall the data demonstrated high levels of personal happiness among priests and religious sisters, but also significant signs of vulnerability. Personality provided significant prediction of individual differences in both personal happiness and work-related psychological health. However, personal happiness provided additional protection against work-related emotional exhaustion and additional enhancement of work-related satisfaction. These findings suggest that acknowledging and affirming personal happiness may enhance the work-related psychological health of Catholic priests and religious sisters
Sustainable Land Use: Methodology and Application
The chapters in this volume are edited versions of papers presented at the NATO Ad- vanced Research Workshop on Environmental Change Adaptation and Security held in Budapest, Hungary, from October 16 - 18, 1997. As is evident in this volume, the papers ranged from descriptions of environmental and health issues in Russia and Eastern Europe to models of sustainable land use. This diversity of perspectives on environ- ment and security is indicative of both the breadth of this new area of research as well as the varied background of the researchers involved. The discussions at the NATO workshop were remarkably animated and exciting, not surprising given the interest in the topic. I think this vitality is reflected in the papers in this volume as well. The main purpose of the NATO ARW is to foster research links among researchers from NATO countries and Central and Eastern European States, Russia, and the Newly Independent States. In editing this volume, a decision was made to keep to the spirit of this purpose and-if at all possible-include all papers prepared for the workshop. This required extensive editing and rewriting of some of the papers (and consequent delays in production).
A determination was made early in the process by the workshop steering committee that the value of publishing the entire collection of articles out- weighed the advantages of accepting only a limited number
Mink Farms Predict Aleutian Disease Exposure in Wild American Mink
BACKGROUND: Infectious diseases can often be of conservation importance for wildlife. Spillover, when infectious disease is transmitted from a reservoir population to sympatric wildlife, is a particular threat. American mink (Neovison vison) populations across Canada appear to be declining, but factors thus far explored have not fully explained this population trend. Recent research has shown, however, that domestic mink are escaping from mink farms and hybridizing with wild mink. Domestic mink may also be spreading Aleutian disease (AD), a highly pathogenic parvovirus prevalent in mink farms, to wild mink populations. AD could reduce fitness in wild mink by reducing both the productivity of adult females and survivorship of juveniles and adults. METHODS: To assess the seroprevalence and geographic distribution of AD infection in free-ranging mink in relation to the presence of mink farms, we conducted both a large-scale serological survey, across the province of Ontario, and a smaller-scale survey, at the interface between a mink farm and wild mink. CONCLUSIONS/SIGNIFICANCE: Antibodies to AD were detected in 29% of mink (60 of 208 mink sampled); however, seroprevalence was significantly higher in areas closer to mink farms than in areas farther from farms, at both large and small spatial scales. Our results indicate that mink farms act as sources of AD transmission to the wild. As such, it is likely that wild mink across North America may be experiencing increased exposure to AD, via disease transmission from mink farms, which may be affecting wild mink demographics across their range. In light of declining mink populations, high AD seroprevalence within some mink farms, and the large number of mink farms situated across North America, improved biosecurity measures on farms are warranted to prevent continued disease transmission at the interface between mink farms and wild mink populations
Compositional controls on oceanic plates : geophysical evidence from the MELT area
Author Posting. © The Authors, 2005. This is the author's version of the work. It is
posted here by permission of Nature Publishing Group for personal use, not for redistribution. The
definitive version was published in Nature 437 (2005): 249-252, doi:10.1038/nature04014.Magnetotelluric (MT) and seismic data, collected during the MELT
experiment at the Southern East Pacific Rise (SEPR) constrain the distribution
of melt beneath this mid-ocean-ridge spreading center and also the evolution of the
oceanic lithosphere during its early cooling history. In this paper, we focus on
structure imaged at distances ~100 to 350 km east of the ridge crest, corresponding
to seafloor ages of ~1.3 to 4.5 Ma, where the seismic and electrical conductivity
structure is nearly constant, independent of age. Beginning at a depth of about 60
km, there is a large increase in electrical conductivity and a change from isotropic
to transversely anisotropic electrical structure with higher conductivity in the
direction of fast propagation for seismic waves. Because conductive cooling
models predict structure that increases in depth with age, extending to about 30
km at 4.5 Ma, we infer that the structure of young oceanic plates is instead
controlled by a decrease in water content above 60 km induced by the melting
process beneath the spreading center.US participation in the MELT experiment and subsequent analysis was funded by NSF grants through the Marine Geology and Geophysics Program, Ocean Sciences Division
Activating mutation in MET oncogene in familial colorectal cancer
<p>Abstract</p> <p>Background</p> <p>In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The <it>MET </it>proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.</p> <p>Methods</p> <p><it>MET </it>exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C <b>></b>T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors.</p> <p>Results</p> <p>Here we report a germline non-synonymous change in the <it>MET </it>proto-oncogene at amino acid position T992I (also reported as <it>MET </it>p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in <1% in the general population. The threonine at amino acid position 992 lies in the tyrosine kinase domain of MET and a change to isoleucine at this position has been shown to promote metastatic behavior in cell-based models. The average age of CRC diagnosis in patients in this study is 63 years in mutation carriers, which is 8 years earlier than the general population average for CRC.</p> <p>Conclusions</p> <p>Although the <it>MET </it>p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this <it>MET </it>genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will be an important extension of this work to define the clinical significance.</p
Asteroseismology and Interferometry
Asteroseismology provides us with a unique opportunity to improve our
understanding of stellar structure and evolution. Recent developments,
including the first systematic studies of solar-like pulsators, have boosted
the impact of this field of research within Astrophysics and have led to a
significant increase in the size of the research community. In the present
paper we start by reviewing the basic observational and theoretical properties
of classical and solar-like pulsators and present results from some of the most
recent and outstanding studies of these stars. We centre our review on those
classes of pulsators for which interferometric studies are expected to provide
a significant input. We discuss current limitations to asteroseismic studies,
including difficulties in mode identification and in the accurate determination
of global parameters of pulsating stars, and, after a brief review of those
aspects of interferometry that are most relevant in this context, anticipate
how interferometric observations may contribute to overcome these limitations.
Moreover, we present results of recent pilot studies of pulsating stars
involving both asteroseismic and interferometric constraints and look into the
future, summarizing ongoing efforts concerning the development of future
instruments and satellite missions which are expected to have an impact in this
field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume
14, Issue 3-4, pp. 217-36
The Pioneer Anomaly
Radio-metric Doppler tracking data received from the Pioneer 10 and 11
spacecraft from heliocentric distances of 20-70 AU has consistently indicated
the presence of a small, anomalous, blue-shifted frequency drift uniformly
changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was
interpreted as a constant sunward deceleration of each particular spacecraft at
the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of
the Newton's gravitational inverse-square law has become known as the Pioneer
anomaly; the nature of this anomaly remains unexplained. In this review, we
summarize the current knowledge of the physical properties of the anomaly and
the conditions that led to its detection and characterization. We review
various mechanisms proposed to explain the anomaly and discuss the current
state of efforts to determine its nature. A comprehensive new investigation of
the anomalous behavior of the two Pioneers has begun recently. The new efforts
rely on the much-extended set of radio-metric Doppler data for both spacecraft
in conjunction with the newly available complete record of their telemetry
files and a large archive of original project documentation. As the new study
is yet to report its findings, this review provides the necessary background
for the new results to appear in the near future. In particular, we provide a
significant amount of information on the design, operations and behavior of the
two Pioneers during their entire missions, including descriptions of various
data formats and techniques used for their navigation and radio-science data
analysis. As most of this information was recovered relatively recently, it was
not used in the previous studies of the Pioneer anomaly, but it is critical for
the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living
Reviews in Relativit
Reviewing evidence of marine ecosystem change off South Africa
Recent changes have been observed in South African marine ecosystems. The main pressures on these
ecosystems are fishing, climate change, pollution, ocean acidification and mining. The best long-term datasets are
for trends in fishing pressures but there are many gaps, especially for non-commercial species. Fishing pressures
have varied over time, depending on the species being caught. Little information exists for trends in other
anthropogenic pressures. Field observations of environmental variables are limited in time and space. Remotely
sensed satellite data have improved spatial and temporal coverage but the time-series are still too short to
distinguish long-term trends from interannual and decadal variability. There are indications of recent cooling on the
West and South coasts and warming on the East Coast over a period of 20 - 30 years. Oxygen concentrations on the
West Coast have decreased over this period. Observed changes in offshore marine communities include southward
and eastward changes in species distributions, changes in abundance of species, and probable alterations in
foodweb dynamics. Causes of observed changes are difficult to attribute. Full understanding of marine ecosystem
change requires ongoing and effective data collection, management and archiving, and coordination in carrying out
ecosystem research.DHE
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