157 research outputs found
Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.
Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1ÎČ, to activate a systemic APR in recipient naĂŻve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naĂŻve animals. EVs derived from brain endothelial cell cultures treated with IL-1ÎČ also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses
Naturalness Bounds on Dipole Moments from New Physics
Assuming naturalness that the quantum corrections to the mass should not
exceed the order of the observed mass, we derive and apply model-independent
bounds on the anomalous magnetic moments and electric dipole moments of leptons
and quarks due to new physics.Comment: 4 pages, 2 figure
The WEBT Campaign on the Blazar 3C279 in 2006
The quasar 3C279 was the target of an extensive multiwavelength monitoring
campaign from January through April 2006, including an optical-IR-radio
monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration.
In this paper we focus on the results of the WEBT campaign. The source
exhibited substantial variability of optical flux and spectral shape, with a
characteristic time scale of a few days. The variability patterns throughout
the optical BVRI bands were very closely correlated with each other. In
intriguing contrast to other (in particular, BL Lac type) blazars, we find a
lag of shorter- behind longer-wavelength variability throughout the RVB ranges,
with a time delay increasing with increasing frequency. Spectral hardening
during flares appears delayed with respect to a rising optical flux. This, in
combination with the very steep IR-optical continuum spectral index of ~ 1.5 -
2.0, may indicate a highly oblique magnetic field configuration near the base
of the jet. An alternative explanation through a slow (time scale of several
days) acceleration mechanism would require an unusually low magnetic field of <
0.2 G, about an order of magnitude lower than inferred from previous analyses
of simultaneous SEDs of 3C279 and other FSRQs with similar properties.Comment: Accepted for publication in Ap
The unprecedented optical outburst of the quasar 3C 454.3. The WEBT campaign of 2004-2005
The radio quasar 3C 454.3 underwent an exceptional optical outburst lasting
more than 1 year and culminating in spring 2005. The maximum brightness
detected was R = 12.0, which represents the most luminous quasar state thus far
observed (M_B ~ -31.4). In order to follow the emission behaviour of the source
in detail, a large multiwavelength campaign was organized by the Whole Earth
Blazar Telescope (WEBT). Continuous optical, near-IR and radio monitoring was
performed in several bands. ToO pointings by the Chandra and INTEGRAL
satellites provided additional information at high energies in May 2005. The
historical radio and optical light curves show different behaviours. Until
about 2001.0 only moderate variability was present in the optical regime, while
prominent and long-lasting radio outbursts were visible at the various radio
frequencies, with higher-frequency variations preceding the lower-frequency
ones. After that date, the optical activity increased and the radio flux is
less variable. This suggests that the optical and radio emissions come from two
separate and misaligned jet regions, with the inner optical one acquiring a
smaller viewing angle during the 2004-2005 outburst. Moreover, the colour-index
behaviour (generally redder-when-brighter) during the outburst suggests the
presence of a luminous accretion disc. A huge mm outburst followed the optical
one, peaking in June-July 2005. The high-frequency (37-43 GHz) radio flux
started to increase in early 2005 and reached a maximum at the end of our
observing period (end of September 2005). VLBA observations at 43 GHz during
the summer confirm theComment: 7 pages, 4 figures, to be published in A&
The radio delay of the exceptional 3C 454.3 outburst. Follow-up WEBT observations in 2005-2006
In spring 2005 the blazar 3C 454.3 was observed in an unprecedented bright
state from the near-IR to the hard X-ray frequencies. A mm outburst peaked in
June-July 2005, and it was followed by a flux increase at high radio
frequencies. In this paper we report on multifrequency monitoring by the WEBT
aimed at following the further evolution of the outburst in detail. In
particular, we investigate the expected correlation and time delays between the
optical and radio emissions in order to derive information on the variability
mechanisms and jet structure. A comparison among the light curves at different
frequencies is performed by means of visual inspection and discrete correlation
function, and the results are interpreted with a simple model taking into
account Doppler factor variations of geometric origin. The high-frequency radio
light curves show a huge outburst starting during the dimming phase of the
optical one and lasting more than 1 year. The first phase is characterized by a
slow flux increase, while in early 2006 a major flare is observed. The
lower-frequency radio light curves show a progressively delayed and fainter
event, which disappears below 8 GHz. We suggest that the radio major peak is
not physically connected with the spring 2005 optical one, but it is actually
correlated with a minor optical flare observed in October-November 2005. This
interpretation involves both an intrinsic and a geometric mechanism. The former
is represented by disturbances travelling down the emitting jet, the latter
being due to the curved-jet motion, with the consequent differential changes of
viewing angles of the different emitting regions.Comment: 5 pages, 3 figures, to be published in A&A (Letters
Inhibition of Dehydration-Induced Water Intake by Glucocorticoids Is Associated with Activation of Hypothalamic Natriuretic Peptide Receptor-A in Rat
Atrial natriuretic peptide (ANP) provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP) content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR) mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of water intake and revealed that the glucocorticoids can act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume
Orexin-1 Receptor Co-Localizes with Pancreatic Hormones in Islet Cells and Modulates the Outcome of Streptozotocin-Induced Diabetes Mellitus
Recent studies have shown that orexins play a critical role in the regulation of sleep/wake states, feeding behaviour, and reward processes. The exocrine and endocrine pancreas are involved in the regulation of food metabolism and energy balance. This function is deranged in diabetes mellitus. This study examined the pattern of distribution of orexin-1 receptor (OX1R) in the endocrine cells of the pancreas of normal and diabetic Wistar (a model of type 1 diabetes), Goto-Kakizaki (GK, a model of type 2 diabetes) rats and in orexin-deficient (OXâ/â) and wild type mice. Diabetes mellitus (DM) was induced in Wistar rats and mice by streptozotocin (STZ). At different time points (12 h, 24 h, 4 weeks, 8 months and 15 months) after the induction of DM, pancreatic fragments of normal and diabetic rats were processed for immunohistochemistry and Western blotting. OX1R-immunoreactive nerves were observed in the pancreas of normal and diabetic Wistar rats. OX1R was also discernible in the pancreatic islets of normal and diabetic Wistar and GK rats, and wild type mice. OX1R co-localized with insulin (INS) and glucagon (GLU) in the pancreas of Wistar and GK rats. The number of OX1R-positive cells in the islets increased markedly (p<0.0001) after the onset of DM. The increase in the number of OX1R-positive cells is associated with a high degree of co-localization with GLU. The number of GLU- positive cells expressing OX1R was significantly (p<0.0001) higher after the onset of DM. The tissue level of OX1R protein increased with the duration of DM especially in type 1 diabetes where it co-localized with cleaved caspase 3 in islet cells. In comparison to STZ-treated wild type mice, STZ-treated OXâ/â animals exhibited reduced hyperglycemia and handled glucose more efficiently in glucose tolerance test. The findings suggest an important role for the OX-OX1R pathway in STZ-induced experimental diabetes
The WEBT campaign on the blazar 3C 279 in 2006
The quasar 3C279 was the target of an extensive multiwavelength monitoring
campaign from January through April 2006, including an optical-IR-radio
monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration.
In this paper we focus on the results of the WEBT campaign. The source
exhibited substantial variability of optical flux and spectral shape, with a
characteristic time scale of a few days. The variability patterns throughout
the optical BVRI bands were very closely correlated with each other. In
intriguing contrast to other (in particular, BL Lac type) blazars, we find a
lag of shorter- behind longer-wavelength variability throughout the RVB ranges,
with a time delay increasing with increasing frequency. Spectral hardening
during flares appears delayed with respect to a rising optical flux. This, in
combination with the very steep IR-optical continuum spectral index of ~ 1.5 -
2.0, may indicate a highly oblique magnetic field configuration near the base
of the jet. An alternative explanation through a slow (time scale of several
days) acceleration mechanism would require an unusually low magnetic field of <
0.2 G, about an order of magnitude lower than inferred from previous analyses
of simultaneous SEDs of 3C279 and other FSRQs with similar properties
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