569 research outputs found
Methylglyoxal-dependent glycative stress and deregulation of SIRT1 functional network in the ovary of PCOS mice
Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1 alpha), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response
The magnetar emission in the IR band: the role of magnetospheric currents
There is a general consensus about the fact that the magnetar scenario
provides a convincing explanation for several of the observed properties of the
Anomalous X-ray Pulsars and the Soft Gamma Repeaters. However, the origin of
the emission observed at low energies is still an open issue. We present a
quantitative model for the emission in the optical/infrared band produced by
curvature radiation from magnetospheric charges, and compare results with
current magnetars observations.Comment: 6 Pages, 2 Figures. Astrophysics and Space Science, in press.
Proceedings of the ICREA Workshop on The High-Energy Emission from Pulsars
and their Systems, Sant Cugat, April 12-16 201
The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial
BACKGROUND:
Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency.
OBJECTIVE:
To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD.
METHODS:
BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo.
RESULTS:
Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group.
CONCLUSIONS:
Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effect
A variable absorption feature in the X-ray spectrum of a magnetar
Soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are slowly
rotating, isolated neutron stars that sporadically undergo episodes of
long-term flux enhancement (outbursts) generally accompanied by the emission of
short bursts of hard X-rays. This behaviour can be understood in the magnetar
model, according to which these sources are mainly powered by their own
magnetic energy. This is supported by the fact that the magnetic fields
inferred from several observed properties of AXPs and SGRs are greater than -
or at the high end of the range of - those of radio pulsars. In the peculiar
case of SGR 0418+5729, a weak dipole magnetic moment is derived from its timing
parameters, whereas a strong field has been proposed to reside in the stellar
interior and in multipole components on the surface. Here we show that the
X-ray spectrum of SGR 0418+5729 has an absorption line, the properties of which
depend strongly on the star's rotational phase. This line is interpreted as a
proton cyclotron feature and its energy implies a magnetic field ranging from
2E14 gauss to more than 1E15 gauss.Comment: Nature, 500, 312 (including Supplementary Information
Development of Predictive Models of the Kinetics of a Hydrogen Abstraction Reaction Combining Quantum-Mechanical Calculations and Experimental Data
The importance of developing accurate modeling tools for the prediction of reaction kinetics is well recognized. In this work, a thorough investigation of the suitability of quantum mechanical (QM) calculations to predict the effect of temperature on the rate constant of the reaction between ethane and the hydroxyl radical is presented. Further, hybrid models that combine a limited number of QM calculations and experimental data are developed in order to increase their reliability. The activation energy barrier of the reaction is computed using various computational methods, such as B3LYP, M05-2X, M06-2X, MP2 and PMP2, CBS-QB3, and W1BD, with a selection of basis sets. A broad range of values is obtained, including negative barriers for all of the calculations with B3LYP. The rate constants are also obtained for each method, using conventional transition state theory, and are compared with available experimental values at 298 K. The best agreement is achieved with the M05-2X functional with cc-pV5Z basis set. Rate constants calculated at this level of theory are also found to be in good agreement with experimental values at different temperatures, resulting in a mean absolute error of the logarithm (MAEln) of the calculated values of 0.213 over a temperature range of 200–1250 K and 0.108 over a temperature range of 300–499 K. Tunnelling and vibrational anharmonicities are identified as important sources of discrepancies at low and high temperatures, respectively. Hybrid models are proposed and found to provide good correlated rate-constant values and to be competitive with conventional kinetic models, i.e., the Arrhenius and the three-parameter Arrhenius models. The combination of QM-calculated and experimental data sources proves particularly beneficial when fitting to scarce experimental data. The parameters of the model built on the hybrid strategy have a significantly reduced uncertainty (reflected in the much narrower 95% confidence intervals) compared with the conventional kinetic models while also capturing well the experimental reaction rates with a MAEln of the rate constant of 0.118. This provides a useful strategy for kinetic model development
Killer immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Aged Subjects: Observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST)
BACKGROUND: Natural Killer Cells (NK) play an important role in detection and elimination of virus-infected, damaged or cancer cells. NK cell function is guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with altered HLA self-antigens, damaged by viruses or tumours. We have previously described increased numbers of NK and NK-related subsets in association with sIL-2R cytokine serum levels in BELFAST octo/nonagenarians. We hypothesised that changes in KIR A and B haplotype gene frequencies could explain the increased cytokine profiles and NK compartments previously described in Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) octo/nonagenarians, who show evidence of ageing well. RESULTS: In the BELFAST study, 24% of octo/nonagenarians carried the KIR A haplotype and 76% KIR B haplotype with no differences for KIR A haplogroup frequency between male or female subjects (23% v 24%; p=0.88) or for KIR B haplogroup (77% v 76%; p=0.99). Octo/nonagenarian KIR A haplotype carriers showed increased NK numbers and percentage compared to Group B KIR subjects (p=0.003; p=0.016 respectively). There were no KIR A/ B haplogroup-associated changes for related CD57+CD8 ((high or low)) subsets. Using logistic regression, KIR B carriers were predicted to have higher IL-12 cytokine levels compared to KIR A carriers by about 3% (OR 1.03, confidence limits CI 0.99–1.09; p=0.027) and 14% higher levels for TGF-β (active), a cytokine with an anti-inflammatory role, (OR 1.14, confidence limits CI 0.99–1.09; p=0.002). CONCLUSION: In this observational study, BELFAST octo/nonagenarians carrying KIR A haplotype showed higher NK cell numbers and percentage compared to KIR B carriers. Conversely, KIR B haplotype carriers, with genes encoding for activating KIRs, showed a tendency for higher serum pro-inflammatory cytokines compared to KIR A carriers. While the findings in this study should be considered exploratory they may serve to stimulate debate about the immune signatures of those who appear to age slowly and who represent a model for good quality survivor-hood
Strongly magnetized pulsars: explosive events and evolution
Well before the radio discovery of pulsars offered the first observational
confirmation for their existence (Hewish et al., 1968), it had been suggested
that neutron stars might be endowed with very strong magnetic fields of
-G (Hoyle et al., 1964; Pacini, 1967). It is because of their
magnetic fields that these otherwise small ed inert, cooling dead stars emit
radio pulses and shine in various part of the electromagnetic spectrum. But the
presence of a strong magnetic field has more subtle and sometimes dramatic
consequences: In the last decades of observations indeed, evidence mounted that
it is likely the magnetic field that makes of an isolated neutron star what it
is among the different observational manifestations in which they come. The
contribution of the magnetic field to the energy budget of the neutron star can
be comparable or even exceed the available kinetic energy. The most magnetised
neutron stars in particular, the magnetars, exhibit an amazing assortment of
explosive events, underlining the importance of their magnetic field in their
lives. In this chapter we review the recent observational and theoretical
achievements, which not only confirmed the importance of the magnetic field in
the evolution of neutron stars, but also provide a promising unification scheme
for the different observational manifestations in which they appear. We focus
on the role of their magnetic field as an energy source behind their persistent
emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of
"NewCompStar" European COST Action MP1304, 43 pages, 8 figure
Activated Magnetospheres of Magnetars
Like the solar corona, the external magnetic field of magnetars is twisted by
surface motions of the star. The twist energy is dissipated over time. We
discuss the theory of this activity and its observational status. (1) Theory
predicts that the magnetosphere tends to untwist in a peculiar way: a bundle of
electric currents (the "j-bundle") is formed with a sharp boundary, which
shrinks toward the magnetic dipole axis. Recent observations of shrinking hot
spots on magnetars are consistent with this behavior. (2) Continual discharge
fills the j-bundle with electron-positron plasma, maintaining a nonthermal
corona around the neutron star. The corona outside a few stellar radii strongly
interacts with the stellar radiation and forms a "radiatively locked" outflow
with a high e+- multiplicity. The locked plasma annihilates near the apexes of
the closed magnetic field lines. (3) New radiative-transfer simulations suggest
a simple mechanism that shapes the observed X-ray spectrum from 0.1 keV to 1
MeV: part of the thermal X-rays emitted by the neutron star are reflected from
the outer corona and then upscattered by the inner relativistic outflow in the
j-bundle, producing a beam of hard X-rays.Comment: 23 pages, 7 figures; review chapter in the proceedings of ICREA
Workshop on the High-Energy Emission from Pulsars and Their Systems, Sant
Cugat, Spain, April 201
Swings between rotation and accretion power in a millisecond binary pulsar
It is thought that neutron stars in low-mass binary systems can accrete
matter and angular momentum from the companion star and be spun-up to
millisecond rotational periods. During the accretion stage, the system is
called a low-mass X-ray binary, and bright X-ray emission is observed. When the
rate of mass transfer decreases in the later evolutionary stages, these
binaries host a radio millisecond pulsar whose emission is powered by the
neutron star's rotating magnetic field. This evolutionary model is supported by
the detection of millisecond X-ray pulsations from several accreting neutron
stars and also by the evidence for a past accretion disc in a rotation-powered
millisecond pulsar. It has been proposed that a rotation-powered pulsar may
temporarily switch on during periods of low mass inflow in some such systems.
Only indirect evidence for this transition has hitherto been observed. Here we
report observations of accretion-powered, millisecond X-ray pulsations from a
neutron star previously seen as a rotation-powered radio pulsar. Within a few
days after a month-long X-ray outburst, radio pulses were again detected. This
not only shows the evolutionary link between accretion and rotation-powered
millisecond pulsars, but also that some systems can swing between the two
states on very short timescales.Comment: 43 pages, 9 figures, 4 table. Published by Nature on 26 Sep 2013.
Includes Supplementary information. Minor differences with published version
may exis
X-ray emission from isolated neutron stars
X-ray emission is a common feature of all varieties of isolated neutron stars
(INS) and, thanks to the advent of sensitive instruments with good
spectroscopic, timing, and imaging capabilities, X-ray observations have become
an essential tool in the study of these objects. Non-thermal X-rays from young,
energetic radio pulsars have been detected since the beginning of X-ray
astronomy, and the long-sought thermal emission from cooling neutron star's
surfaces can now be studied in detail in many pulsars spanning different ages,
magnetic fields, and, possibly, surface compositions. In addition, other
different manifestations of INS have been discovered with X-ray observations.
These new classes of high-energy sources, comprising the nearby X-ray Dim
Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the
Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to
several tens of confirmed members, plus many candidates, and allow us to study
a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant
Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from
pulsars and their systems", held in April, 201
- …