479 research outputs found
Collapse-and-revival dynamics of strongly laser-driven electrons
The relativistic quantum dynamics of an electron in an intense single-mode
quantized electromagnetic field is investigated with special emphasis on the
spin degree of freedom. In addition to fast spin oscillations at the laser
frequency, a second time scale is identified due to the intensity dependent
emissions and absorptions of field quanta. In analogy to the well-known
phenomenon in atoms at moderate laser intensity, we put forward the conditions
of collapses and revivals for the spin evolution in laser-driven electrons
starting at feasible W/cm.Comment: 18 pages, 4 figure
Enhanced inverse bremsstrahlung heating rates in a strong laser field
Test particle studies of electron scattering on ions, in an oscillatory
electromagnetic field have shown that standard theoretical assumptions of small
angle collisions and phase independent orbits are incorrect for electron
trajectories with drift velocities smaller than quiver velocity amplitude. This
leads to significant enhancement of the electron energy gain and the inverse
bremsstrahlung heating rate in strong laser fields. Nonlinear processes such as
Coulomb focusing and correlated collisions of electrons being brought back to
the same ion by the oscillatory field are responsible for large angle, head-on
scattering processes. The statistical importance of these trajectories has been
examined for mono-energetic beam-like, Maxwellian and highly anisotropic
electron distribution functions. A new scaling of the inverse bremsstrahlung
heating rate with drift velocity and laser intensity is discussed.Comment: 12 pages, 12 figure
CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.
Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases
N-Acetylcholinesterase-Induced Apoptosis in Alzheimer's Disease
Background: Alzheimer’s disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended ‘‘synaptic’ ’ acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena. Methodology and Principal Findings: In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation. Rapid internalization of fluorescently labeled fasciculin-2 to N-AChE-S transfected cells indicated membranal localization. In cultured cell lines, N-AChE-S transfection activated the Tau kinase GSK3, induced Tau hyper-phosphorylation and caused apoptosis. N-AChE-S-induced cell death was suppressible by inhibiting GSK3 or caspases, by enforced overexpression of the anti-apoptotic Bcl2 proteins, or by AChE inhibition or silencing. Moreover, inherent N-AChE-S was upregulated by stressors inducing protein misfolding and calcium imbalances, both characteristic of AD; and in cortical tissues from AD patients, N-AChE-S overexpression coincides with Tau hyper-phosphorylation. Conclusions: Together, these findings attribute an apoptogenic role to N-AChE-S and outline a potential value to ACh
The morphology of human rod ERGs obtained by silent substitution stimulation
YesPurpose To record transient ERGs from the lightadapted
human retina using silent substitution stimuli
which selectively reflect the activity of rod photoreceptors.
We aim to describe the morphology of these
waveforms and examine how they are affected by the
use of less selective stimuli and by retinal pathology.
Methods Rod-isolating stimuli with square-wave
temporal profiles (250/250 ms onset/offset) were
presented using a 4 primary LED ganzfeld stimulator.
Experiment 1: ERGs were recorded using a rodisolating
stimulus (63 ph Td, rod contrast,
Crod = 0.25) from a group (n = 20) of normal
trichromatic observers. Experiment 2: Rod ERGs
were recorded from a group (n = 5) using a rodisolating
stimulus (Crod = 0.25) which varied in
retinal illuminance from 40 to 10,000 ph Td. Experiment
3: ERGs were elicited using 2 kinds of nonisolating
stimuli; (1) broadband and (2) rod-isolating
stimuli which contained varying degrees of L- and
M-cone excitation. Experiment 4: Rod ERGs were
recorded from two patient groups with rod monochromacy
(n = 3) and CSNB (type 1; n = 2).
Results The rod-isolated ERGs elicited from normal
subjects had a waveform with a positive onset
component followed by a negative offset. Response
amplitude was maximal at retinal illuminances\100
ph Td and was virtually abolished at 400 ph Td. The
use of non-selective stimuli altered the ERG waveform
eliciting more photopic-like ERG responses. Rod
ERGs recorded from rod monochromats had similar
features to those recorded from normal trichromats, in
contrast to those recorded from participants with
CSNB which had an electronegative appearance.
Conclusions Our results demonstrate that ERGs
elicited by silent substitution stimuli can selectively
reflect the operation of rod photoreceptors in the
normal, light-adapted human retina.Deutsche Forschungsgemeinschaft (DFG) (KR1317/13-1) and Bundesministerium für Bildung und Forschung (BMBF) (01DN14009) provided financial support for JK
Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa
Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa
Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study
BACKGROUND: Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs. METHODS: To test this hypothesis, we studied the postoperative pulmonary leak index (PLI) for (67)Ga-transferrin and (transpulmonary) extravascular lung water (EVLW) in consecutive patients undergoing on-pump (n = 31) and off-pump (n = 8) cardiac surgery. We also studied transfusion history, radiographs, ventilatory and gas exchange variables. RESULTS: The postoperative PLI and EVLW were elevated above normal in 42 and 29% after on-pump surgery and 63 and 37% after off-pump surgery, respectively (ns). Transfusion of red blood cell (RBC) concentrates, PLI, EVLW, occurrence of atelectasis, ventilatory variables and duration of mechanical ventilation did not differ between groups, whereas patients with atelectasis had higher venous admixture and airway pressures than patients without atelectasis (P = 0.037 and 0.049). The PLI related to number of RBC concentrates infused (P = 0.025). CONCLUSION: The lung vascular injury in about half of patients after cardiac surgery is not caused by CPB perfusion but by trauma necessitating RBC transfusion, so that off-pump surgery may not afford a benefit in this respect. However, atelectasis rather than lung vascular injury is a major determinant of postoperative pulmonary dysfunction, irrespective of CPB perfusion
The rise and fall of methanotrophy following a deepwater oil-well blowout
The blowout of the Macondo oil well in the Gulf of Mexico in April 2010 injected up to 500,000 tonnes of natural gas, mainly methane, into the deep sea1. Most of the methane released was thought to have been consumed by marine microbes between July and August 20102, 3. Here, we report spatially extensive measurements of methane concentrations and oxidation rates in the nine months following the spill. We show that although gas-rich deepwater plumes were a short-lived feature, water column concentrations of methane remained above background levels throughout the rest of the year. Rates of microbial methane oxidation peaked in the deepwater plumes in May and early June, coincident with a rapid rise in the abundance of known and new methane-oxidizing microbes. At this time, rates of methane oxidation reached up to 5,900 nmol l−1 d−1—the highest rates documented in the global pelagic ocean before the blowout4. Rates of methane oxidation fell to less than 50 nmol l−1 d−1 in late June, and continued to decline throughout the remainder of the year. We suggest the precipitous drop in methane consumption in late June, despite the persistence of methane in the water column, underscores the important role that physiological and environmental factors play in constraining the activity of methane-oxidizing bacteria in the Gulf of Mexico
A radioimmunoassay for quantifying carbonic anhydrase isozymes in crude lysates
A radioimmunoassay was developed for quantifying each of the two genetically distinct forms of primate carbonic anhydrase, carbonic anhydrases I and II, in unpurified lysates. Under the given experimental conditions, the assay is capable of detecting a minimum of 0.025 μg of carbonic anhydrase I and 0.005 μg of carbonic anhydrase II. There is approximately 98% reproducibility upon repeated assays of a given hemolysate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44165/1/10528_2004_Article_BF00485779.pd
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