Observed flux density enhancement at submillimeter wavelengths during an X-class flare

We analyse the 30 October, 2004, X1.2/SF solar event that occurred in AR 10691 (N13 W18) at around 11:44 UT. Observations at 212 and 405 GHz of the Solar Submillimeter Telescope (SST), with high time resolution (5 ms), show an intense impulsive burst followed by a long-lasting thermal phase. EUV images from the Extreme Ultraviolet Imaging Telescope (SOHO/EIT) are used to identify the possible emitting sources. Data from the Radio Solar Telescope Network (RSTN) complement our spectral observations below 15 GHz. During the impulsive phase the turnover frequency is above 15.4 GHz. The long-lasting phase is analysed in terms of thermal emission and compared with GOES observations. From the ratio between the two GOES soft X-ray bands, we derive the temperature and emission measure, which is used to estimate the free-free submillimeter flux density. Good temporal agreement is found between the estimated and observed profiles, however the former is larger than the latter.Comment: 13 pages, 7 figure

Comparison of 30 THz impulsive burst time development to microwaves, H-alpha, EUV, and GOES soft X-rays

The recent discovery of impulsive solar burst emission in the 30 THz band is raising new interpretation challenges. One event associated with a GOES M2 class flare has been observed simultaneously in microwaves, H-alpha, EUV, and soft X-ray bands. Although these new observations confirm some features found in the two prior known events, they exhibit time profile structure discrepancies between 30 THz, microwaves, and hard X-rays (as inferred from the Neupert effect). These results suggest a more complex relationship between 30 THz emission and radiation produced at other wavelength ranges. The multiple frequency emissions in the impulsive phase are likely to be produced at a common flaring site lower in the chromosphere. The 30 THz burst emission may be either part of a nonthermal radiation mechanism or due to the rapid thermal response to a beam of high-energy particles bombarding the dense solar atmosphere.Comment: accepted to Astronomy and Astrophysic

O055. Headache and psychopathological aspects in Gilles de la Tourette Sindrome:a comparison between paediatric and adult patients

Only few studies have analyzed the occurrence of headache in patients with Gilles de la Tourette syndrome (GTS) [1–3]. The aim of this study was to compare the prevalence and characteristics of headache in paediatric and adult patients with GTS and the relationship of headache with tic severity, psychiatric comorbidities and quality of life

Cas9/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery

P23H is the most common mutation in the RHODOPSIN (RHO) gene leading to a dominant form of retinitis pigmentosa (RP), a rod photoreceptor degeneration that invariably causes vision loss. Specific disruption of the disease P23H RHO mutant while preserving the wild-type (WT) functional allele would be an invaluable therapy for this disease. However, various technologies tested in the past failed to achieve effective changes and consequently therapeutic benefits. We validated a CRISPR/Cas9 strategy to specifi

Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress

It is known that long-term treatment with antipsychotic drugs (APDs) produces neuroadaptive changes through the modulation of different proteins that, by enhancing neuronal plasticity and cellular resiliency, may improve core disease symptoms. The aim of this study was to investigate the ability of chronic treatment with the novel antipsychotic lurasidone to modulate BDNF expression in hippocampus and prefrontal cortex, under basal conditions or in response to an acute stress, a major precipitating element in psychiatric disorders. By means of real-time PCR, we found that (1) chronic lurasidone treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus; (2) the modulation of BDNF mRNA levels in response to acute swim stress in lurasidone-treated rats was markedly potentiated in hippocampus, and to less extent in prefrontal cortex, through the selective regulation of different neurotrophin isoforms. The increase of BDNF mRNA levels in prefrontal cortex was paralleled by an enhancement of mature BDNF protein levels. In conclusion, repeated exposure to lurasidone regulates BDNF expression, through a finely tuned modulation of its transcripts. This effect may contribute to the amelioration of functions, such as cognition, closely associated with neuronal plasticity, which are deteriorated in schizophrenia patients

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells

The structural bases for agonist diversity in an Arabidopsis thaliana glutamate receptor-like channel

Arabidopsis thaliana glutamate receptor-like (GLR) channels are amino acid-gated ion channels involved in physiological processes including wound signaling, stomatal regulation, and pollen tube growth. Here, fluorescence microscopy and genetics were used to confirm the central role of GLR3.3 in the amino acid-elicited cytosolic Ca2+ increase in Arabidopsis seedling roots. To elucidate the binding properties of the receptor, we biochemically reconstituted the GLR3.3 ligand-binding domain (LBD) and analyzed its selectivity profile; our binding experiments revealed the LBD preference for L-Glu but also for sulfur-containing amino acids. Furthermore, we solved the crystal structures of the GLR3.3 LBD in complex with 4 different amino acid ligands, providing a rationale for how the LBD binding site evolved to accommodate diverse amino acids, thus laying the grounds for rational mutagenesis. Last, we inspected the structures of LBDs from nonplant species and generated homology models for other GLR isoforms. Our results establish that GLR3.3 is a receptor endowed with a unique amino acid ligand profile and provide a structural framework for engineering this and other GLR isoforms to investigate their physiology

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy