The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients

Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two auxiliary β-subunits, several of which have been well studied in epileptic conditions. However, despite the β4-subunits’ role having been reported in some neurological conditions, there is little research investigating its potential significance in epilepsy. Therefore, the purpose of this work was to assess the role of SCN4β in epilepsy by using a combination of molecular and bioinformatics approaches. We first demonstrated that there was a reduction in the relative expression of SCN4B in the drug-resistant TLE patients compared to non-epileptic control specimens, both at the mRNA and protein levels. By analyzing a co-expression network in the neighborhood of SCN4B we then discovered a linkage between the expression of this gene and K+ channels activated by Ca2+, or K+ two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of SCN4B. These observations support the hypothesis that SCN4B is a key factor in AED-resistant TLE, which could help direct both the drug selection of TLE treatments and the development of future AED

Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus

Several neurotransmitters, including GABA acting at presynaptic GABAB receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABAB receptor-mediated heterosynaptic depression among populations of mossy fibers. This was accompanied by a decrease in the sensitivity of mossy fiber transmission to the exogenous GABAB receptor agonist baclofen. Autoradiography revealed a reduction in GABAB receptor binding in the stratum lucidum after status epilepticus. Failure of GABAB receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus

First crystal-structure determination of chromites from an acapulcoite and ordinary chondrites

We report the first crystal structure determinations of chromites from an acapulcoite and from ordinary chondrites. Cell edges range from 8.3212 (3) to 8.3501 (1) \uc5, while the oxygen positional parameters are in the range 0.2624 (3) to 0.26298 (9). Their compositions show they are very close to the chromite end-member FeCr2O4 with limited Al and Mg content. Titanium oxide content exceeds 1%, whereas the amount of Fe3+ is negligible. Extraterrestrial chromite is readily distinguished from terrestrial analogues on the basis of cell edge and oxygen positional parameter. These distinctions will facilitate ongoing attempts to reconstruct the paleoflux of meteorites to Earth from resistant extraterrestrial spinel grains recovered from ancient sediments

Quantitative expression and localization of GABAB receptor protein subunits in hippocampi from patients with refractory temporal lobe epilepsy

This study investigates GABAB protein expression and mRNA levels in three types of specimens. Two types of specimens from patients with temporal lobe epilepsy (TLE), secondary to hippocampal sclerosis, sclerotic hippocampal samples (TLE-HS), and tissue from the structurally preserved non-spiking ipsilateral superior temporal gyrus (TLE-STG) removed from the same patient during epilepsy surgery; and third specimen is hippocampal tissue from individuals with no history of epilepsy (post-mortem controls, PMC). mRNA expression of GABAB subunits was quantified in TLE-HS, TLE-STG and PMC specimens by qRT-PCR. Qualitative and quantitative Western blot (WB) and immunohistochemistry techniques were employed to quantify and localize GABAB proteins subunits. qRT-PCR data demonstrated an overall decrease of both GABAB1 isoforms in TLE-HS compared to TLE-STG. These results were mirrored by the WB findings. GABAB2 mRNA and protein were significantly reduced in TLE-HS samples compared to TLE-STG; however they appeared to be upregulated in TLE-HS compared to the PMC samples. Immunohistochemistry (IHC) showed that GABAB proteins were widely distributed in PMC and TLE-HS hippocampal sections with regional differences in the intensity of the signal. The higher expression of mature GABAB protein in TLE-HS than PMC is in agreement with previous studies. However, these findings could be due to post-mortem changes in PMC specimens. The TLE-STG samples examined here represent a better 'control' tissue compared to TLE-HS samples characterized by lower than expected GABAB expression. This interpretation provides a better explanation for previous functional studies suggesting reduced inhibition in TLE-HS tissue due to attenuated GABAB currents. [Abstract copyright: Copyright © 2017. Published by Elsevier Ltd.

IL CONTRATTO NELLA FAMIGLIA E NELLA CONVIVENZA: RIFLESSIONI E PROSPETTIVE A SEGUITO DELL'APPROVAZIONE DELLA LEGGE 20 MAGGIO 2016, N. 76

Dopo decenni di attesa, il legislatore italiano affronta il tema della convivenza, approvando la legge 20 maggio 2016, n.76. Tale legge fa idealmente seguito al lavoro della dottrina e della giurisprudenza, che per molti anni si sono confrontate con le questioni attinenti alla libera convivenza tra persone, enucleando regole e principi divenuti diritto vivente, in relazione a singoli aspetti della più ampia questione, in attesa che il legislatore varasse una norma generale ed astratta. L'intervento legislativo, giunto al termine di un esasperato confronto pubblico, è tutt'altro che esente da critiche e riflessioni: la fretta con la quale il legislatore ha confezionato la norma lo ha portato a commettere parecchi errori tecnici, dei quali si cerca di dare una lettura sistematica atta a superarli. In particolare, il legislatore ha ritenuto di trattare la convivenza in maniera differente a seconda dell'orientamento sessuale dei conviventi, prevedendo per i conviventi omosessuali un istituto peculiare(unione civile), che vorrebbe essere, per il legislatore, una sorta di matrimonio omossesuale, ma che tale non è. Ai conviventi eterosessuali è data una legislazione scarsa e lacunosa: il legislatore si limita ad istituzionalizzare, non senza imprecisioni, il diritto giurisprudenziale creatosi sulla convivenza, ed innova la materia tipizzando il contratto tra conviventi. Tale contratto, diffusosi oltre i confini nazionali, ma già noto alla prassi notarile, è tuttavia marginalizzato dalla norma: ciò sia dal punto di vista privatistico che pubblicistico. Dal primo punti di vista, poiché se ne disciplinano superficialmente sia il ridotto oggetto tipico, sia la causa, e si consente alle parti il recesso ad nutum. Dal punto di vista pubblicistico, il contratto non segna la nascita della convivenza, come invece prevede la legge francese sul PACS, ma è un mero regolamento di aspetti patrimoniali, al punto che esso potrebbe anche non esistere, senza perciò pregiudicare l'esistenza del rapporto. Inoltre, il legislatore dimentica di considerare le convivenze diverse da quelle contratte more uxorio, le cc.dd. unioni di mutuo aiuto, che hanno invece risalto in altri ordinamenti europei. Tali scelte del legislatore inducono a considerare con prudenza anche l'impiego del contratto all'interno della famiglia tradizionale, con particolare riferimento ai cc.dd. "prenuptial agreements", il cui principio ispiratore, il cd. principio di autodeterminazione, deve ancora necessariamente contemperarsi con le norme, ancora vigenti, che si ispirano all'opposto principio della cd. solidarietà postconiugale, e ciò almeno fino a che quest'ultimo principio non sarà superato, o, come è preferibile, riformato in senso differente da quello attualmente attribuitogli

Estudio sedimentológico preliminar y análisis de minerales pesados en la cueva Pocala

[Abstract] In 1999 two borings were performedin the area of Pocala Cave, one outside the cave and the other inside in the cave. In particular four samples of the first boring were studied.It seems that mineralogy is strictly connected with sedimentology where quartz and plagioclase are present. It could be a consequence of a periodical floods of flysch sediments during interglacial perio

Botánica del caos: tra catalogazione ed entropia

La microficción de Ana María Shua ofrece ejemplos extraordinarios de metatextualidad y metaliterariedad. La intertextualidad de los relatos sitúa a l lector en un universo en el que el acto de la escritura y el de la lectura pertenecen al proceso de la vida tanto como el del arte. El lector es convocado por Shua como parte activa de la narración no solo por sus competencias que permiten el funcionamiento dle mecanismo elíptico y humorístico del microcuento, sino también como agente del acto de lectura, que se convierte en parte constitutiva del texto violando las fronteras entre el mundo textual y el extratextual

Pressure stability field of Mg-perovskite under deep mantle conditions: A topological approach based on Bader's analysis coupled with catastrophe theory

The pressure stability field of the Mg-perovskite phase was investigated by characterizing the evolution of the electron arrangement in the crystal. Ab initio calculations of the perovskite structures in the range 0\u2013185 GPa were performed at the HF/DFT (Hartree-Fock/Density Functional Theory) exchange\u2013correlation terms level. The electron densities, calculated throughout the ab-initio wave functions, were analysed by means of the Bader's theory, coupled with Thom's catastrophe theory. To the best of our knowledge the approach is used for the first time. The topological results show the occurrence of two topological anomalies at P~20 GPa and P~110 GPa which delineate the pressure range where Mg-perovskite is stable. The paper accomplishes the twofold objectives of providing a contribution in shading light into the behaviour of the dominant component of the Earth's lower mantle across the D\u2019\u2019 layer and of proposing a novel approach in predicting the stability of a compound at extreme conditions

GABAB Receptors in Neurodegeneration

GABA is the main inhibitory neurotransmitter in the mammalian central nervous system (CNS) and acts via metabotropic GABAB receptors. Neurodegenerative diseases are a major burden and affect an ever increasing number of humans. The actual therapeutic drugs available are partially effective to slow down the progression of the diseases, but there is a clear need to improve pharmacological treatment thus find alternative drug targets and develop newer pharmaco-treatments. This chapter is dedicated to reviewing the latest evidence about GABAB receptors and their inhibitory mechanisms and pathways involved in the neurodegenerative pathologies

Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Background: In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease. Methods: The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated. Results: The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model. Conclusions: Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity