28,870 research outputs found
Recent developments in the application of risk analysis to waste technologies.
The European waste sector is undergoing a period of unprecedented change driven
by business consolidation, new legislation and heightened public and government
scrutiny. One feature is the transition of the sector towards a process industry
with increased pre-treatment of wastes prior to the disposal of residues and the
co-location of technologies at single sites, often also for resource recovery
and residuals management. Waste technologies such as in-vessel composting, the
thermal treatment of clinical waste, the stabilisation of hazardous wastes,
biomass gasification, sludge combustion and the use of wastes as fuel, present
operators and regulators with new challenges as to their safe and
environmentally responsible operation. A second feature of recent change is an
increased regulatory emphasis on public and ecosystem health and the need for
assessments of risk to and from waste installations. Public confidence in waste
management, secured in part through enforcement of the planning and permitting
regimes and sound operational performance, is central to establishing the
infrastructure of new waste technologies. Well-informed risk management plays a
critical role. We discuss recent developments in risk analysis within the sector
and the future needs of risk analysis that are required to respond to the new
waste and resource management agenda
A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons
Mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved in the
biogenesis and activity of several types of RNAs, and its role in the pathogenesis of ALS may involve both direct effects of
disease-associated mutations through gain- and loss-of-function mechanisms and indirect effects due to the cross talk between
different classes of FUS-dependent RNAs. To explore how FUS mutations impinge on motor neuron-specific RNA-based
circuitries, we performed transcriptome profiling of small and long RNAs of motor neurons (MNs) derived from mouse
embryonic stem cells carrying a FUS-P517L knock-in mutation, which is equivalent to human FUS-P525L, associated with a
severe and juvenile-onset form of ALS. Combining ontological, predictive and molecular analyses, we found an inverse correlation
between several classes of deregulated miRNAs and their corresponding mRNA targets in both homozygous and heterozygous
P517L MNs. We validated a circuitry in which the upregulation of miR-409-3p and miR-495-3p, belonging to a brainspecific
miRNA subcluster implicated in several neurodevelopmental disorders, produced the downregulation of Gria2, a subunit
of the glutamate αâaminoâ3âhydroxyâ5âmethyl-4-isoxazole propionic acid (AMPA) receptor with a significant role in excitatory
neurotransmission. Moreover, we found that FUS was involved in mediating such miRNA repression. Gria2 alteration has been
proposed to be implicated in MN degeneration, through disturbance of Ca2+ homeostasis, which triggers a cascade of damaging
âexcitotoxicâ events. The molecular cross talk identified highlights a role for FUS in excitotoxicity and in miRNA-dependent
regulation of Gria2. This circuitry also proved to be deregulated in heterozygosity, which matches the human condition perfectly
An Outlook on the Localisation and Structure-Function Relationships of R Proteins in Solanum
The co-evolution of plants and plant-pathogens shaped a multi-layered defence system in plants, in which Resistance proteins (R proteins) play a significant role. A fundamental understanding of the functioning of these R proteins and their position in the broader defence system of the plant is essential. Sub-project 3 of the BIOEXPLOIT programme studies how R proteins are activated upon effector recognition and how recognition is conveyed in resistance signalling pathways, using the solanaceous R proteins Rx1 (from S. tuberosum spp. andigena; conferring extreme resistance against Potato Virus X), I-2 (from S. lycopersicon; mediating resistance to Fusarium oxysporum) and Mi-1.2 (from S. lycopersicon; conferring resistance to Meloidogyne incognita) as model systems. The results obtained in this project will serve as a model for other R proteins and will be translated to potential applications or alternative strategies for disease resistance. These include the modification of the recognition specificity of R proteins with the aim to obtain broad spectrum resistance to major pathogens in potato
The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster
Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance.
Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly.
Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways.
Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress
Focal Spot, Winter 2005/2006
https://digitalcommons.wustl.edu/focal_spot_archives/1101/thumbnail.jp
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