Continuous stellate ganglion block in delayed cerebral ischemia: A possible supplementary approach to traditional therapy?

Delayed Cerebral Ischemia (DCI) is a major contributor to morbidity and mortality after SAH. Currently the prevention of vasospasm and DCI relies on nimodipine administration and on maintaining an adequate cerebral perfusion pressure. We report a patient with initial DCI after SAH in which stellate ganglion block (SGB) was performed after nimodipine administration. Firstly the procedure was characterized by a iv and intra-arterial nimodipine administration which did not result into a normal perfusion pattern. Therefore a single-shot stellate ganglion block was performed, as suggested in literature. Because of the not sufficient but promising perfusion improvement, we decided to deliver a continuous ganglion block (cSGB) for 5 days. Consequently a further improvement of the cerebral perfusion on CTPerfusion and Real Time Angiographic Perfusion Assessment was registered. In order to treat cerebral vasospasm, SGB is known to be a further valuable treatment, despite its temporary effect. However the continuous use of SGB during initial DCI has never been described before

Bump Hunting in Latent Space

Unsupervised anomaly detection could be crucial in future analyses searching for rare phenomena in large datasets, as for example collected at the LHC. To this end, we introduce a physics inspired variational autoencoder (VAE) architecture which performs competitively and robustly on the LHC Olympics Machine Learning Challenge datasets. We demonstrate how embedding some physical observables directly into the VAE latent space, while at the same time keeping the classifier manifestly agnostic to them, can help to identify and characterise features in measured spectra as caused by the presence of anomalies in a dataset.Comment: 5 pages, 4 figure

Maladaptive defensive behaviours in monoamine oxidase A-deficient mice

Rich evidence indicates that monoamine oxidase (MAO) A, the major enzyme catalysing the degradation of monoamine neurotransmitters, plays a key role in emotional regulation. Although MAOA deficiency is associated with reactive aggression in humans and mice, the involvement of this enzyme in defensive behaviour remains controversial and poorly understood. To address this issue, we tested MAOA knockout (KO) mice in a spectrum of paradigms and settings associated with variable degrees of threat. The presentation of novel inanimate objects induced a significant reduction in exploratory approaches and increase in defensive behaviours, such as tail-rattling, biting and digging. These neophobic responses were context-dependent and particularly marked in the home cage. In the elevated plus-and T-mazes, MAOA KO mice and wild-type (WT) littermates displayed equivalent locomotor activity and time in closed and open arms; however, MAOA KO mice featured significant reductions in risk assessment, as well as unconditioned avoidance and escape. No differences between genotypes were observed in the defensive withdrawal and emergence test. Conversely, MAOA KO mice exhibited a dramatic reduction of defensive and fear-related behaviours in the presence of predator-related cues, such as predator urine or an anaesthetized rat, in comparison with those observed in their WT littermates. The behavioural abnormalities in MAOA KO mice were not paralleled by overt alterations in sensory and microvibrissal functions. Collectively, these results suggest that MAOA deficiency leads to a general inability to appropriately assess contextual risk and attune defensive and emotional responses to environmental cues

Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity

This is the published version. Copyright 2014 Oxford University PressCatechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous single-nucleotide polymorphism (SNP) that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood post-translational mechanisms. One post-translational modification is methionine sulfoxide, which can be reduced by the methionine sulfoxide reductase (Msr) A and B enzymes. We used recombinant COMT proteins (Val/Met108) and mice (wild-type (WT) and MsrA knockout) to determine the effect of methionine oxidation on COMT activity and COMT interaction with Msr, through a combination of enzymatic activity and Western blot assays. Recombinant COMT activity is positively regulated by MsrA, especially under oxidative conditions, whereas brains of MsrA knockout mice exhibited lower COMT activity (as compared with their WT counterparts). These results suggest that COMT activity may be reduced by methionine oxidation, and point to Msr as a key molecular determinant for the modulation of COMT activity in the brain. The role of Msr in modulating cognitive functions in healthy individuals and schizophrenia patients is yet to be determined

Acute stress impairs sensorimotor gating via the neurosteroid allopregnanolone in the prefrontal cortex

Ample evidence indicates that environmental stress impairs information processing, yet the underlying mechanisms remain partially elusive. We showed that, in several rodent models of psychopathology, the neurosteroid allopregnanolone (AP) reduces the prepulse inhibition (PPI) of the startle, a well-validated index of sensorimotor gating. Since this GABAA receptor activator is synthesized in response to acute stress, we hypothesized its participation in stress-induced PPI deficits. Systemic AP administration reduced PPI in C57BL/6J mice and Long-Evans, but not Sprague-Dawley rats. These effects were reversed by isoallopregnanolone (isoAP), an endogenous AP antagonist, and the GABAA receptor antagonist bicuculline and mimicked by AP infusions in the medial prefrontal cortex (mPFC). Building on these findings, we tested AP's implication in the PPI deficits produced by several complementary regimens of acute and short-term stress (footshock, restraint, predator exposure, and sleep deprivation). PPI was reduced by acute footshock, sleep deprivation as well as the combination of restraint and predator exposure in a time- and intensity-dependent fashion. Acute stress increased AP concentrations in the mPFC, and its detrimental effects on PPI were countered by systemic and intra-mPFC administration of isoAP. These results collectively indicate that acute stress impairs PPI by increasing AP content in the mPFC. The confirmation of these mechanisms across distinct animal models and several acute stressors strongly supports the translational value of these findings and warrants future research on the role of AP in information processing

Photo-induced curing of thymine-based bioinspired polymers. A chemometric analysis

The curing process of new materials based on styrene monomers functionalized with thymine and charged ionic groups was studied using UV-vis spectroscopy in combination with chemomet-ric models. The effect of the copolymer molecular weight on the immobilization point was analyzed. The evolution of the curing process of the copolymer (4-vinylbenzyl) thymine (VBT) -vinylbenzyl triethyl ammonium chloride (VBA) involved three species, which absorb in the spectral region analyzed. The contributions of each species to the total signal at each irradiation time were determined, and the ki-netic constant of the crosslinking reaction was esti-mated. The study allowed evaluating the consistency of the chemometric decomposition, obtaining a rea-sonable correlation between the frequency spectra and the time evolution calculated with the algorithm. The chemometric analysis showed to be a powerful tool to provide complementary information on photo-induced immobilization of VBT-VBA films, which is crucial for developing new environmentally benign materials and new energy-saving methods.Fil: Bortolato, Santiago Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Investigación para la Industria Química (i); ArgentinaFil: Barbarini, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Investigación para la Industria Química (i); ArgentinaFil: Benitez, R. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Investigación para la Industria Química (i); ArgentinaFil: Martino, Debora Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Investigación para la Industria Química (i); ArgentinaFil: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Salta. Instituto de Investigación para la Industria Química (i); Argentin

Performance of the Fully Digital FPGA-based Front-End Electronics for the GALILEO Array

In this work we present the architecture and results of a fully digital Front End Electronics (FEE) read out system developed for the GALILEO array. The FEE system, developed in collaboration with the Advanced Gamma Tracking Array (AGATA) collaboration, is composed of three main blocks: preamplifiers, digitizers and preprocessing electronics. The slow control system contains a custom Linux driver, a dynamic library and a server implementing network services. The digital processing of the data from the GALILEO germanium detectors has demonstrated the capability to achieve an energy resolution of 1.53 per mil at an energy of 1.33 MeV.Comment: 5 pages, 6 figures, preprint version of IEEE Transactions on Nuclear Science paper submitted for the 19th IEEE Real Time Conferenc

The enzymatic activities of brain COMT and methionine sulfoxide reductase are correlated in a COMT Val/Met allele-dependent fashion

This is the peer reviewed version of the following article: J. Moskovitz, C. Walss-Bass, D. A. Cruz, P. M. Thompson, J. Hairston and M. Bortolato (2015) Neuropathology and Applied Neurobiology The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion, which has been published in final form at http://doi.org/10.1111/nan.12219. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.AIMS: The enzyme catechol-O-methyl transferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best-characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulfoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. METHODS: COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects, by using catechol and dabsyl-Met sulfoxide as substrates, respectively. Allelic discrimination of COMT Val108/185Met SNP was performed using the Taqman 5’nuclease assay. RESULTS: Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR were significantly correlated throughout all tested brain regions. DISCUSSION: These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulfoxidation, and point to MSR as a key molecular determinant for the modulation of COMT activity

Population-specific call order in chimpanzee greeting vocal sequences

This study was funded by the Max Planck Society and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program awarded to C.C. (grant agreement no. 679787) and ERC (Prilang GA283871) and by Leverhulme Trust Research Leadership Award. Core funding for the Taï Chimpanzee Project has been provided by the Max Planck Society since 1997 and for Budongo Conservation Field station by the Royal Zoological Society of Scotland.Primates rarely learn new vocalisations, but they can learn to use their vocalizations in different contexts. Such ‘vocal usage learning’, particularly in vocal sequences, is a hallmark of human language, but remains understudied in non-human primates. We assess usage learning in four wild chimpanzee communities of Taï and Budongo Forests by investigating population differences in call ordering of a greeting vocal sequence. Whilst in all groups, these sequences consisted of pant-hoots (long-distance contact call) and pant-grunts (short-distance submissive call), the order of the two calls differed across populations. Taï chimpanzees consistently commenced greetings with pant-hoots whereas Budongo chimpanzees started with pant-grunts. We discuss different hypotheses to explain this pattern and conclude that higher intra-group aggression in Budongo may have led to a local pattern of individuals signalling submission first. This highlights how within-species variation in social dynamics may lead to flexibility in call order production, possibly acquired via usage learning.Publisher PDFPeer reviewe