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

Chimpanzees produce diverse vocal sequences with ordered and recombinatorial properties

The origins of human language remains a major question in evolutionary science. Unique to human language is the capacity to flexibly recombine a limited sound set into words and hierarchical sequences, generating endlessly new sentences. In contrast, sequence production of other animals appears limited, stunting meaning generation potential. However, studies have rarely quantified flexibility and structure of vocal sequence production across the whole repertoire. Here, we used such an approach to examine the structure of vocal sequences in chimpanzees, known to combine calls used singly into longer sequences. Focusing on the structure of vocal sequences, we analysed 4826 recordings of 46 wild adult chimpanzees from Taï National Park. Chimpanzees produced 390 unique vocal sequences. Most vocal units emitted singly were also emitted in two-unit sequences (bigrams), which in turn were embedded into three-unit sequences (trigrams). Bigrams showed positional and transitional regularities within trigrams with certain bigrams predictably occurring in either head or tail positions in trigrams, and predictably co-occurring with specific other units. From a purely structural perspective, the capacity to organize single units into structured sequences offers a versatile system potentially suitable for expansive meaning generation. Further research must show to what extent these structural sequences signal predictable meanings

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

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

Sex-Dimorphic Interactions of MAOA Genotype and Child Maltreatment Predispose College Students to Polysubstance Use

This work is licensed under a Creative Commons Attribution 4.0 International License.Polysubstance use (PSU) is highly prevalent among college students. Recent evidence indicates that PSU is based on gene x environment (G×E) interactions, yet the specific biosocial factors underlying this problem remain elusive. We recently reported that lifetime use of tobacco and cannabis in college students is influenced by the interaction of the X-linked MAOA (monoamine oxidase A) gene and child maltreatment. Building on these premises, here we evaluated whether the same G×E interaction may also predict PSU in this population. Students of a large Midwestern university (n = 470; 50.9% females) took part in a computer survey for substance use, as well as childhood trauma exposure, using the Child Trauma Questionnaire (CTQ). DNA was extracted from their saliva samples and genotyped for MAOA variable-number of tandem repeat (VNTR) variants. Findings indicated that the highest number of substances were used by male students harboring low-activity MAOA alleles with a history of childhood emotional abuse. In contrast, female homozygous high-activity MAOA carriers with a history of emotional and physical abuse reported consumption of the greatest number of substances. Our results indicate that PSU among college students is influenced by the interaction of MAOA and child maltreatment in a sex-specific fashion. Further studies are warranted to understand the mechanisms of sex differences in the biosocial interplays underlying PSU in this at-risk group

Making Structural Sense of Dimerization Interfaces of Delta Opioid Receptor Homodimers†

ABSTRACT: Opioid receptors, like other members of theG protein-coupled receptor (GPCR) family, have been shown to associate to form dimers and/or oligomers at the plasma membrane. Whether this association is stable or transient is not known. Recent compelling evidence suggests that at least some GPCRs rapidly associate and dissociate. We have recently calculated binding affinities from free energy estimates to predict transient association between mouse delta opioid receptor (DOR) protomers at a symmetric interface involving the fourth transmembrane (TM4) helix (herein termed “4 ” dimer). Here we present disulfide cross-linking experiments with DOR constructs with cysteines substituted at the extracellular ends of TM4 or TM5 that confirm the formation of DOR complexes involving these helices. Our results are consistent with the involvement of TM4 and/or TM5 at the DOR homodimer interface, but possibly with differing association propensities. Coarse-grained (CG) well-tempered metadynamics simulations of two different dimeric arrangements of DOR involving TM4 alone or with TM5 (herein termed “4/5 ” dimer) in an explicit lipid-water environment confirmed the presence of two structurally and energetically similar configurations of the 4 dimer, as previously assessed by umbrella sampling calculations, and revealed a single energetic minimum of the 4/5 dimer. Additional CG umbrella sampling simulations of the 4/5 dimer indicated that the strength of association between DOR protomers varies depending on the protein region at the interface, wit

Naphthochromenones: Organic Bimodal Photocatalysts Engaging in Both Oxidative and Reductive Quenching Processes

Twelve naphthochromenone photocatalysts (PCs) were synthesized on gram scale.They absorb across theUV/Vis range and feature an extremely wide redox window (up to 3.22 eV) that is accessible using simple visible light irradiation sources (CFL or LED). Their excited-state redox potentials, PC*/PCC (up to 1.65 V) and PCC+/PC* (up to 1.77 V vs. SCE), are such that these novel PCs can engage in both oxidative and reductive quenching mechanisms with strong thermodynamic requirements. The potential of these bimodal PCs was benchmarked in synthetically relevant photocatalytic processes with extreme thermodynamic requirements. Their ability to efficiently catalyze mechanistically opposite oxidative/reductive photoreactions is a unique feature of these organic photocatalysts, thus representing a decisive advance towards generality, sustainability, and cost efficiency in photocatalysis

Naphthochromenones: Organic Bimodal Photocatalysts Engaging in Both Oxidative and Reductive Quenching Processes

Twelve naphthochromenone photocatalysts (PCs) were synthesized on gram scale.They absorb across theUV/Vis range and feature an extremely wide redox window (up to 3.22 eV) that is accessible using simple visible light irradiation sources (CFL or LED). Their excited-state redox potentials, PC*/PCC (up to 1.65 V) and PCC+/PC* (up to 1.77 V vs. SCE), are such that these novel PCs can engage in both oxidative and reductive quenching mechanisms with strong thermodynamic requirements. The potential of these bimodal PCs was benchmarked in synthetically relevant photocatalytic processes with extreme thermodynamic requirements. Their ability to efficiently catalyze mechanistically opposite oxidative/reductive photoreactions is a unique feature of these organic photocatalysts, thus representing a decisive advance towards generality, sustainability, and cost efficiency in photocatalysis

Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin

This is the publisher's version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8920271&fileId=S1461145712000909Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate. In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioural functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioural organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviours in the tail-suspension and forced swim tests. The agent induced no significant behavioural changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gatin