165 research outputs found
Deep Impact Mission to Tempel 1 Favours New Explosive Cosmogony of Comets
The assumption that short-period (SP) comets are fragments of massive icy
envelopes of Ganymede-like bodies saturated by products of ice electrolysis
that underwent global explosions provides a plausible explanation of all known
manifestations of comets, including the jet character of outflows, the presence
of ions in the vicinity of the nucleus, the bursts and splitting of cometary
nuclei, etc., with solar radiation initiating burning of the products of
electrolysis in the nucleus. As shown persuasively by numerical simulation
carried out in hydrodynamic approximation, the shock wave initiated by the Deep
Impact (DI) impactor in the cometary ice saturated originally by the
electrolysis products 2H2 + O2 is capable of activating under certain
conditions exothermal reactions (of the type O2 + H2 + organics = H2O + CO +
HCN + other products of incomplete burning of organics including its light and
heavy pyrolyzed compounds, soot, etc.), which will slow down shock wave damping
(forced detonation) and increase many times the energy release. As a result,
the measured energetics of ejections and outflows from the crater have to
exceed the DI energetics. Analysis of different clusters of the DI experiment
data confirms these conclusions and expectations and thus it favours the
planetary origin of comets.Comment: 21 pages incluging 3 figure
Vascular cognitive impairment linked to brain endothelium inflammation in early stages of heart failure in mice
Background
Although advanced heart failure (
HF
) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of
HF
are equivocal. Here, we characterize vascular cognitive impairment in the early stages of
HF
development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved.
Methods and Results
Tgαq*44 mice with slowly developing isolated
HF
triggered by cardiomyocyteâspecific overexpression of Gâαq*44 protein were studied before the endâstage
HF
, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6â to 10âmonthâold but not in 3âmonthâold Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised bloodâbrain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased Eâselectin immunoreactivity, which was accompanied by increased amyloidâÎČ
1â42
accumulation in piriform cortex and increased cortical oxidative stress (8â
OH
dG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo
NO
âdependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3â to 10âmonthâold Tgαq*44 mice, but it was not associated with increased plateletâdependent thrombogenicity.
Conclusions
We report for the first time that vascular cognitive impairment is already present in the early stage of
HF
development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation.
</jats:sec
Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias
The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events
Đ ĐĐĐŹ ĐĐĐĐĐ RLM Đ AVRLM Đ Đ ĐĐĐĐĐĐĐŠĐĐ ĐĄĐĐĐŠĐĐ€ĐЧĐĐĄĐĐĐ ĐŁĐĄĐąĐĐЧĐĐĐХйРРЀĐĐĐĐĐŁ ĐŁ Đ ĐĐĐĄĐ
As part of the study, DNA markers for local races L. maculans were identified and found that the AvrLm4-7 sequence in the selected fungus population is specifically recognized by the resistance Rlm4 and Rlm7 genes. The SCAR marker BN204 was identified, which allows us to identify homozygous and heterozygous plants carrying the Rlm4 gene. The work collection, including 22 varieties and 39 hybrids of rape, was analyzed using the DNA marker BN204. PCR results allowed us to establish that the number of individual plants with the resistance Rlm4 gene was higher than the number of stable forms characterized by the infection of leaf explants with pathogen races carrying the AvrLm4-7 sequence. It is supposed that these individual plants contain the Rlm4 gene, but they lack the Rlm7 gene.Đ Ń
ĐŸĐŽĐ” ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ ĐČŃŃĐČĐ»Đ”ĐœŃ ĐĐĐ-ĐŒĐ°ŃĐșĐ”ŃŃ Đș ĐŒĐ”ŃŃĐœŃĐŒ ŃĐ°ŃĐ°ĐŒ L. maculans Đž ŃŃŃĐ°ĐœĐŸĐČĐ»Đ”ĐœĐŸ, ŃŃĐŸ ĐČ ĐżĐŸĐżŃĐ»ŃŃОО ĐŸŃĐŸĐ±ŃĐ°ĐœĐœĐŸĐłĐŸ ĐłŃОба ĐżŃĐžŃŃŃŃŃĐČŃĐ”Ń ĐżĐŸŃĐ»Đ”ĐŽĐŸĐČĐ°ŃДлŃĐœĐŸŃŃŃ AvrLm4-7, ĐșĐŸŃĐŸŃĐ°Ń ŃпДŃĐžŃĐžŃĐœĐŸ ŃĐ°ŃĐżĐŸĐ·ĐœĐ°Đ”ŃŃŃ ĐłĐ”ĐœĐ°ĐŒĐž ŃŃŃĐŸĐčŃĐžĐČĐŸŃŃĐž Rlm4 Đž Rlm7. ĐŃŃĐČĐ»Đ”Đœ SCAR-ĐŒĐ°ŃĐșĐ”Ń BN204, ĐżĐŸĐ·ĐČĐŸĐ»ŃŃŃĐžĐč ĐžĐŽĐ”ĐœŃĐžŃĐžŃĐžŃĐŸĐČĐ°ŃŃ ĐłĐŸĐŒĐŸĐ·ĐžĐłĐŸŃĐœŃĐ” Đž гДŃĐ”ŃĐŸĐ·ĐžĐłĐŸŃĐœŃĐ” ŃĐ°ŃŃĐ”ĐœĐžŃ, ĐœĐ”ŃŃŃОД ĐłĐ”Đœ Rlm4. ĐĄ ĐžŃĐżĐŸĐ»ŃĐ·ĐŸĐČĐ°ĐœĐžĐ”ĐŒ ĐĐĐ-ĐŒĐ°ŃĐșĐ”ŃĐ° BN204 бŃла ĐżŃĐŸĐ°ĐœĐ°Đ»ĐžĐ·ĐžŃĐŸĐČĐ°ĐœĐ° ŃĐ°Đ±ĐŸŃĐ°Ń ĐșĐŸĐ»Đ»Đ”ĐșŃĐžŃ, ĐČĐșĐ»ŃŃĐ°ŃŃĐ°Ń 22 ŃĐŸŃŃĐ° Đž 39 ŃĐŸŃŃĐŸĐŸĐ±ŃĐ°Đ·ŃĐŸĐČ ŃĐ°ĐżŃĐ°. РДзŃĐ»ŃŃĐ°ŃŃ ĐĐŠĐ ĐżĐŸĐ·ĐČĐŸĐ»ĐžĐ»Đž ŃŃŃĐ°ĐœĐŸĐČĐžŃŃ, ŃŃĐŸ ĐșĐŸĐ»ĐžŃĐ”ŃŃĐČĐŸ ĐžĐœĐŽĐžĐČОЎŃĐ°Đ»ŃĐœŃŃ
ŃĐ°ŃŃĐ”ĐœĐžĐč Ń ĐłĐ”ĐœĐŸĐŒ ŃŃŃĐŸĐčŃĐžĐČĐŸŃŃĐž Rlm4 бŃĐ»ĐŸ ĐČŃŃĐ”, ŃĐ”ĐŒ ĐșĐŸĐ»ĐžŃĐ”ŃŃĐČĐŸ ŃŃŃĐŸĐčŃĐžĐČŃŃ
ŃĐŸŃĐŒ, ĐŸŃ
Đ°ŃĐ°ĐșŃĐ”ŃĐžĐ·ĐŸĐČĐ°ĐœĐœŃŃ
ĐżŃŃĐ”ĐŒ Đ·Đ°ŃĐ°Đ¶Đ”ĐœĐžŃ Đ»ĐžŃŃĐŸĐČŃŃ
ŃĐșŃĐżĐ»Đ°ĐœŃĐŸĐČ ŃĐ°ŃĐ°ĐŒĐž паŃĐŸĐłĐ”ĐœĐ°, ĐœĐ”ŃŃŃĐžĐŒĐž ĐżĐŸŃĐ»Đ”ĐŽĐŸĐČĐ°ŃДлŃĐœĐŸŃŃŃ AvrLm4-7. ĐŃĐ”ĐŽĐżĐŸĐ»Đ°ĐłĐ°Đ”ŃŃŃ, ŃŃĐŸ ĐŽĐ°ĐœĐœŃĐ” ĐžĐœĐŽĐžĐČОЎŃĐ°Đ»ŃĐœŃĐ” ŃĐ°ŃŃĐ”ĐœĐžŃ ŃĐŸĐŽĐ”ŃĐ¶Đ°Ń ĐłĐ”Đœ Rlm4, ĐŸĐŽĐœĐ°ĐșĐŸ Ń ĐœĐžŃ
ĐŸŃŃŃŃŃŃĐČŃĐ”Ń ĐłĐ”Đœ Rlm7.
A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification
Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the
cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate
specifcity and exhibits a diferent catalytic mechanism when compared to other members of the family. Here, the role of a
key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the frst time
a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to
oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic
cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent
interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate
for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells
Identification and structural analysis of C-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases
<p>Abstract</p> <p>Background</p> <p>Prion diseases are fatal neurodegenerative disorders that accompany an accumulation of the disease-associated form(s) of prion protein (PrP<sup>Sc</sup>) in the central nervous system. The neuropathological changes in the brain begin with focal deposits of PrP<sup>Sc</sup>, followed by pathomorphological abnormalities of axon terminal degeneration, synaptic loss, atrophy of dendritic trees, and eventual neuronal cell death in the lesions. However, the underlying molecular basis for these neuropathogenic abnormalities is not fully understood.</p> <p>Results</p> <p>In a proteomic analysis of soluble proteins in the brains of mice challenged intracerebrally with scrapie prion (Obihiro I strain), we found that the amount of the full-length form of collapsin response mediator protein-2 (CRMP-2; 61 kDa) decreased in the late stages of the disease, while the amount of its truncated form (56 kDa) increased to comparable levels observed for the full-length form. Detailed analysis by liquid chromatography-electrospray ionization-tandem mass spectrometry showed that the 56-kDa form (named CRMP-2-ÎC) lacked the sequence from serine<sup>518 </sup>to the C-terminus, including the C-terminal phosphorylation sites important for the regulation of axonal growth and axon-dendrite specification in developing neurons. The invariable size of the mRNA transcript in Northern blot analysis suggested that the truncation was due to post-translational proteolysis. By overexpression of CRMP-2-ÎC in primary cultured neurons, we observed the augmentation of the development of neurite branch tips to the same levels as for CRMP-2<sup>T514A/T555A</sup>, a non-phosphorylated mimic of the full-length protein. This suggests that the increased level of CRMP-2-ÎC in the brain modulates the integrity of neurons, and may be involved in the pathogenesis of the neuronal abnormalities observed in the late stages of the disease.</p> <p>Conclusions</p> <p>We identified the presence of CRMP-2-ÎC in the brain of a murine model of prion disease. Of note, C-terminal truncations of CRMP-2 have been recently observed in models for neurodegenerative disorders such as ischemia, traumatic brain injury, and Wallerian degeneration. While the structural identity of CRMP-2-ÎC in those models remains unknown, the present study should provide clues to the molecular pathology of degenerating neurons in prion diseases in connection with other neurodegenerative disorders.</p
Not gods but animals : human dignity and vulnerable subjecthood
Drawing on earlier work on the conceptual structure of dignity, this paper will suggest a particular type of connectedness between vulnerability and human dignity; namely, that the ââorganizing ideaââ of human dignity is the idea of a particular sort of ethical response to universal human vulnerability. It is common ground among many, if not all, approaches to ethics that vulnerability requires us to respond ethically. Here, I argue that human dignity is distinctive among ethical values in that it values us because of, rather than in spite of, or regardless of, our universal vulnerability. The term ââdignityââ is used synonymously with ââhuman dignityââ here, since an investigation of the dignity of non-human entities forms no part of the present examination
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
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