Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg2+-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal–entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308–9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 μM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2–10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency reduces the intensity and spatial extent of the IOS changes that accompany ictal synchronization in an in vitro slice preparation. This conclusion supports the view that repetitive stimulation may represent a potential therapeutic tool for controlling seizures in patients with pharmacoresistant epileptic disorders

The first solvent-free cyclotrimerization reaction of arylethynes catalyzed by rhodium porphyrins

Different rhodium(III) porphyrin chlorides have been used as catalysts for the cyclotrimerization of several arylethynes, giving in many cases high yields in substituted benzenes and selectivities based on the steric hindrance of the macrocycles and on the substitution of the substrates

The Planck-LFI flight model composite waveguides

The Low Frequency Instrument on board the PLANCK satellite is designed to give the most accurate map ever of the CMB anisotropy of the whole sky over a broad frequency band spanning 27 to 77 GHz. It is made of an array of 22 pseudo-correlation radiometers, composed of 11 actively cooled (20 K) Front End Modules (FEMs), and 11 Back End Modules (BEMs) at 300K. The connection between the two parts is made with rectangular Wave Guides. Considerations of different nature (thermal, electromagnetic and mechanical), imposed stringent requirements on the WGs characteristics and drove their design. From the thermal point of view, the WG should guarantee good insulation between the FEM and the BEM sections to avoid overloading the cryocooler. On the other hand it is essential that the signals do not undergo excessive attenuation through the WG. Finally, given the different positions of the FEM modules behind the focal surface and the mechanical constraints given by the surrounding structures, different mechanical designs were necessary. A composite configuration of Stainless Steel and Copper was selected to satisfy all the requirements. Given the complex shape and the considerable length (about 1.5-2 m), manufacturing and testing the WGs was a challenge. This work deals with the development of the LFI WGs, including the choice of the final configuration and of the fabrication process. It also describes the testing procedure adopted to fully characterize these components from the electromagnetic point of view and the space qualification process they underwent. Results obtained during the test campaign are reported and compared with the stringent requirements. The performance of the LFI WGs is in line with requirements, and the WGs were successfully space qualified.Comment: this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jins

Empathic and cognitive processing in people with schizophrenia: a study on an Italian sample

The aim of this study was to explore the relationships among empathy processes in terms of self-report empathy evaluation and recognition of emotional cues and Theory of Mind components. We used the Empathy Quotient – short form (EQ-s), the Pictures of Facial Affect (POFA) system, a (ToM) Irony appreciation task and the Wisconsin Card Sorting Test (WCST), respectively. The Positive and Negative Symptoms Scale (PANSS) and Global Assessment of Functioning (GAF) were also used to investigate the relationship with symptomatology and functioning. The sample consisted of 30 participants with diagnosis of schizophrenia. Our results found no significant correlations between EQ-s and other cognitive or clinical variables. PoFA total score and recognition of fear correlated with time spent to give a correct response to the ToM irony comprehension. Time spent to correctly respond to both ToM and physical vignettes correlated with negative symptoms. Positive, negative and cognitive clusters of the PANSS correlated with the GAF. The relationships we found among the considered constructs suggest that empathic processing acts on functionality improving the personal efficiency, in terms of readiness and rapidity, to cope with one’s environment, in the multifaceted social setting. Given that emotion perception in particular has been connected to social competence, independent living and community functioning, it is conceivable that emotion processing may be a potential catalyst within the mindreading process, which can have an impact both on symptomatology and social functioning

Planck-LFI radiometers' spectral response

The Low Frequency Instrument (LFI) is an array of pseudo-correlation radiometers on board the Planck satellite, the ESA mission dedicated to precision measurements of the Cosmic Microwave Background. The LFI covers three bands centred at 30, 44 and 70 GHz, with a goal bandwidth of 20% of the central frequency. The characterization of the broadband frequency response of each radiometer is necessary to understand and correct for systematic effects, particularly those related to foreground residuals and polarization measurements. In this paper we present the measured band shape of all the LFI channels and discuss the methods adopted for their estimation. The spectral characterization of each radiometer was obtained by combining the measured spectral response of individual units through a dedicated RF model of the LFI receiver scheme. As a consistency check, we also attempted end-to-end spectral measurements of the integrated radiometer chain in a cryogenic chamber. However, due to systematic effects in the measurement setup, only qualitative results were obtained from these tests. The measured LFI bandpasses exhibit a moderate level of ripple, compatible with the instrument scientific requirements.Comment: 16 pages, 9 figures, this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jins

Reduced GABA(B) receptor subunit expression and paired-pulse depression in a genetic model of absence seizures

Neocortical networks play a major role in the genesis of generalized spike-and-wave (SW) discharges associated with absence seizures in humans and in animal models, including genetically predisposed WAG/Rij rats. Here, we tested the hypothesis that alterations in GABAB receptors contribute to neocortical hyperexcitability in these animals. By using Real-Time PCR we found that mRNA levels for most GABAB(1) subunits are diminished in epileptic WAG/Rij neocortex as compared with age-matched non-epileptic controls (NEC), whereas GABAB(2) mRNA is unchanged. Next, we investigated the cellular distribution of GABAB(1) and GABAB(2) subunits by confocal microscopy and discovered that GABAB(1) subunits fail to localize in the distal dendrites of WAG/Rij neocortical pyramidal cells. Intracellular recordings from neocortical cells in an in vitro slice preparation demonstrated reduced paired-pulse depression of pharmacologically isolated excitatory and inhibitory responses in epileptic WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC slices was diminished by a GABAB receptor antagonist to a greater extent than in WAG/Rij rats further suggesting GABAB receptor dysfunction. In conclusion, our data identify changes in GABAB receptor subunit expression and distribution along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex. We propose that these alterations may contribute to neocorticalhyperexcitability and thus to SW generation in absence epilepsy

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1-/- mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1-/- mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1-/- mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

Erratic Jet Wobbling in the BL Lacertae Object OJ287 Revealed by Sixteen Years of 7mm VLBA Observations

We present the results from an ultra-high-resolution 7mm Very Long Baseline Array (VLBA) study of the relativistic jet in the BL Lacertae object OJ287 from 1995 to 2011 containing 136 total intensity images. Analysis of the image sequence reveals a sharp jet-position-angle swing by >100 deg. during [2004,2006], as viewed in the plane of the sky, that we interpret as the crossing of the jet from one side of the line of sight to the other during a softer and longer term swing of the inner jet. Modulating such long term swing, our images also show for the first time a prominent erratic wobbling behavior of the innermost ~0.4mas of the jet with fluctuations in position angle of up to ~40 deg. over time scales ~2yr. This is accompanied by highly superluminal motions along non-radial trajectories, which reflect the remarkable non-ballistic nature of the jet plasma on these scales. The erratic nature and short time scales of the observed behavior rules out scenarios such as binary black hole systems, accretion disk precession, and interaction with the ambient medium as possible origins of the phenomenon on the scales probed by our observations, although such processes may cause longer-term modulation of the jet direction. We propose that variable asymmetric injection of the jet flow; perhaps related to turbulence in the accretion disk; coupled with hydrodynamic instabilities, leads to the non-ballistic dynamics that cause the observed non-periodic changes in the direction of the inner jet.Comment: Accepted for Publication in The Astrophysical Journal. 11 pages, 6 figures, 4 tables. High resolution images on figure 1 and complete tables 1 and 2 may be provided on reques