169 research outputs found
Aestivation: Signaling and hypometabolism
Aestivation is a survival strategy used by many vertebrates and invertebrates to endure arid environmental conditions. Key features of aestivation include strong metabolic rate suppression, strategies to retain body water, conservation of energy and body fuel reserves, altered nitrogen metabolism, and mechanisms to preserve and stabilize organs, cells and macromolecules over many weeks or months of dormancy. Cell signaling is crucial to achieving both a hypometabolic state and reorganizing multiple metabolic pathways to optimize long-term viability during aestivation. This commentary examines the current knowledge about cell signaling pathways that participate in regulating aestivation, including signaling cascades mediated by the AMPactivated kina
Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease
Copyright Ā© 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD
Pesticide toxicity
Pesticides are known for their high persistence and pervasiveness in the environment, and along with products of
their biotransformation, they may remain in and interact with the environment and living organisms in multiple
ways, according to their nature and chemical structure, dose and targets. In this review, the classifications of pesticides
based on their nature, use, physical state, pathophysiological effects, and sources are discussed. The effects
of these xenobiotics on the environment, their biotransformation in terms of bioaccumulation are highlighted
with special focus on the molecular mechanisms deciphered to date. Basing on targeted organisms, most pesticides
are classified as herbicides, fungicides, and insecticides. Herbicides are known as growth regulators,
seedling growth inhibitors, photosynthesis inhibitors, inhibitors of amino acid and lipid biosynthesis, cell membrane
disrupters, and pigment biosynthesis inhibitors, whereas fungicides include inhibitors of ergosterol biosynthesis,
protein biosynthesis, and mitochondrial respiration. Insecticides mainly affect nerves and muscle, growth
and development, and energy production. Studying the impact of pesticides and other related chemicals is of
great interest to animal and human health risk assessment processes since potentially everyone can be exposed to
these compounds which may cause many diseases, including metabolic syndrome, malnutrition, atherosclerosis,
inflammation, pathogen invasion, nerve injury, and susceptibility to infectious diseases. Future studies should be
directed to investigate influence of long term effects of low pesticide doses and to minimize or eliminate influence
of pesticides on non-target living organisms, produce more specific pesticides and using modern technologies
to decrease contamination of food and other goods by pesticides
Optimising patient recall of adverse events over prolonged time periods
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Alzheimer's disease-like paired helical filament assembly from truncated tau protein is independent of disulphide cross-linking
Abstract Alzheimer's disease is characterised by the self-assembly of tau and amyloid ĆĀ² proteins into oligomers and fibrils. Tau protein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observed in neuronal cell bodies in individuals with Alzheimer's disease. The mechanism of initiation of tau assembly into {PHFs} is not well understood. Here we report that a truncated 95-amino acid tau fragment (corresponding to residues 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other additives to initiate or template the process. Using electron microscopy, circular dichroism and X-ray fibre diffraction, we have characterised the structure of the fibrils formed from truncated tau for the first time. To explore the contribution of disulphide formation to fibril formation, we have compared the assembly of tau(297-391) under reduced and non-reducing conditions and for truncated tau carrying a {C322A} substitution. We show that disulphide bond formation inhibits assembly and that the {C322A} variant rapidly forms long and highly ordered PHFs
Spitzer IRS Observations of the Galactic Center: Shocked Gas in the Radio Arc Bubble
We present Spitzer IRS spectra (R ~600, 10 - 38 micron) of 38 positions in
the Galactic Center (GC), all at the same Galactic longitude and spanning
plus/minus 0.3 degrees in latitude. Our positions include the Arches Cluster,
the Arched Filaments, regions near the Quintuplet Cluster, the ``Bubble'' lying
along the same line-of-sight as the molecular cloud G0.11-0.11, and the diffuse
interstellar gas along the line-of-sight at higher Galactic latitudes. From
measurements of the [O IV], [Ne II], [Ne III], [Si II], [S III], [S IV], [Fe
II], [Fe III], and H_2 S(0), S(1), and S(2) lines we determine the gas
excitation and ionic abundance ratios. The Ne/H and S/H abundance ratios are ~
1.6 times that of the Orion Nebula. The main source of excitation is
photoionization, with the Arches Cluster ionizing the Arched Filaments and the
Quintuplet Cluster ionizing the gas nearby and at lower Galactic latitudes
including the far side of the Bubble. In addition, strong shocks ionize gas to
O^{+3} and destroy dust grains, releasing iron into the gas phase (Fe/H ~ 1.3
times 10^{-6} in the Arched Filaments and Fe/H ~ 8.8 times 10^{-6} in the
Bubble). The shock effects are particularly noticeable in the center of the
Bubble, but O is present in all positions. We suggest that the shocks
are due to the winds from the Quintuplet Cluster Wolf-Rayet stars. On the other
hand, the H_2 line ratios can be explained with multi-component models of warm
molecular gas in photodissociation regions without the need for H_2 production
in shocks.Comment: 51 pages, 17 figures To be published in the Astrophysical Journa
A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases Ī±-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy
The authors acknowledge Heide Lueck for excellent technical assistance and for maintenance of animals. AMS Biotechnology generated monoclonal antibodies from recombinant Ī±-Syn prepared by JR.Peer reviewedPublisher PD
Tau (297ā391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimerās disease brain
The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimerās disease (AD) and other tauopathies. Fullālength tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297ā391 known as ādGAEā, spontaneously forms crossāĪ²ācontaining PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation
Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse tauopathy models
Acknowledgements The authors acknowledge the contributions of Bettina Seelhorst (histological analysis), Anna Thoma (animal care), Marlene Arthur (animal dosing) and Pierre-Henri Moreau (experimental discussions). This work was supported by TauRx Therapeutics Ltd., Singapore.Peer reviewedPublisher PD
Training of Instrumentalists and Development of New Technologies on SOFIA
This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal
Survey (Astro2010)1 Committee on the State of the Profession to emphasize the
potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to
contribute to the training of instrumentalists and observers, and to related
technology developments. This potential goes beyond the primary mission of
SOFIA, which is to carry out unique, high priority astronomical research.
SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable
astronomical observations anywhere, any time, and at most wavelengths between
0.3 microns and 1.6 mm not accessible from ground-based observatories. These
attributes, accruing from the mobility and flight altitude of SOFIA, guarantee
a wealth of scientific return. Its instrument teams (nine in the first
generation) and guest investigators will do suborbital astronomy in a
shirt-sleeve environment. The project will invest $10M per year in science
instrument development over a lifetime of 20 years. This, frequent flight
opportunities, and operation that enables rapid changes of science instruments
and hands-on in-flight access to the instruments, assure a unique and extensive
potential - both for training young instrumentalists and for encouraging and
deploying nascent technologies. Novel instruments covering optical, infrared,
and submillimeter bands can be developed for and tested on SOFIA by their
developers (including apprentices) for their own observations and for those of
guest observers, to validate technologies and maximize observational
effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on
State of the Professio
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