28 research outputs found
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia.
Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemiainduced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance
Effect of planting density on green ear yield of maize cultivars bred in different periods
Australia's National Bowel Cancer Screening Program: does it work for Indigenous Australians?
<p>Abstract</p> <p>Background</p> <p>Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP) using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population.</p> <p>This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups.</p> <p>Methods</p> <p>A search was undertaken of peer-reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions.</p> <p>Results</p> <p>The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening.</p> <p>Conclusions</p> <p>Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating the already widening disparities in cancer outcomes that exist among Indigenous Australians. Modifications to the program are recommended to facilitate access and participation by Indigenous and other minority populations. Further research is also needed to understand the needs and social and cultural sensitivities of these groups around cancer screening and inform alternative approaches to bowel cancer screening.</p
Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry
OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc).
METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers.
RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group.
CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies
Use of fractal models to define the scaling behavior of the aquifers’ parameters at the mesoscale
Biotechnological Means for Genetic Improvement in Castor Bean as a Crop of the Future
Not AvailableProfitable cultivation of castor bean is beset
with problems of vulnerability of cultivars and
hybrids to a multitude of insect pests and
diseases. The presence of the toxic proteins
ricin and hyperallergenic Ricinus communis
agglutinin (RCA) in the endosperm restricts
the use of deoiled seed cake as cattle feed.
Due to this crop’s low genetic diversity,
genetic engineering can be an efficient
approach to introduce resistance to biotic
and abiotic stresses as well as seed quality
traits. Recently, castor oil gained attention as a
sustainable second-generation feedstock for
biojet fuel that would reduce carbon dioxide
emissions. Because of a growing interest in
castor oil as a biofuel and the presence of the
powerful toxin ricin in its seed, metabolic
pathways and regulatory genes involved in
both oil and ricin production have been
analyzed and characterized. Genetic engineering
of castor bean offers new possibilities to
increase oil yield and oxidative stability,
confers stress tolerance, and improves other
agronomics traits, such as reduced plant
height to facilitate mechanical harvesting.
However, difficulties in tissue culture-based
regeneration and poor reproducibility of results are major bottlenecks for genetic
transformation of castor bean. Despite
advances in tissue culture research over the
past four decades, direct or callus-mediated
adventitious shoot regeneration systems that
are genotype-independent remain a much
sought-after goal in castor bean. Genetic
transformation attempts to develop insect resistant
and ricin-free transgenic castor bean
lines have been based on shoot proliferation
from meristematic tissues. This chapter
describes new transformation methods under
development and the progress achieved so far
in genetic engineering of castor bean for
agronomically desirable attributes.Not Availabl