The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be ...described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA. Many studies have investigated whether val158met genotype moderates the effects of dopaminergic drugs on PFC-dependent cognitive functions. A review of 25 such studies suggests evidence for this pharmacogenetic effect is mixed for stimulants and COMT inhibitors, which have greater effects on D1 receptors, and strong for antipsychotics, which have greater effects on D2 receptors. Overall, COMT val158met genotype represents an enticing target for identifying individuals who are more likely to respond positively to dopaminergic drugs.
ABSTRACT
A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may ...attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate‐based meta‐analytic method, to analyze the brain areas activated by alcohol‐related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue‐elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue‐elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region‐of‐interest analyses that interrogated only limbic regions. These findings support long‐standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue‐elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue‐elicited activation of these areas.
The world continues experiencing a steady decrease in the availability of conventional light or even medium crude oils, and hence, refineries inevitably face the challenge of processing increasing ...amounts of (extra) heavy crude oils while preserving their economic targets. This requires changes/improvements in existing refining technologies for converting heavy crude oil, which may be conveniently preceded by an improvement in its flowing properties in the underground reservoir itself. In this context, this research focuses on the use of liquid catalysts containing Cu, Fe, Ni, or Zr for upgrading in situ a heavy crude oil stream (12.6 °API) in a bench-scale batch-stirred reactor operated at 380 °C and 10.8 MPa for 1 h, in the presence of high-purity hydrogen. Upon reaction, the heavy crude oil properties improve while catalysts undergo in situ transformations identifying from the analysis of residual solid recovered from the bottom of the reactor, the formation of some metallic sulfides and oxides (by X-ray diffraction (XRD)), which exhibit Bronsted and/or Lewis-type acidity (via Fourier transform infrared (FT-IR) spectroscopy). While converting ca. 43% of the heavy crude oil residue fraction (>524 °C), the Zr-containing catalyst, which exhibits relatively strong Bronsted and Lewis acid sites thus increasing the cracking rate, decreases the kinematic viscosity (1444–24 cSt, at 37.5 °C) as well as the amount of asphaltenes (28–13 wt %) and sulfur (5.14–2.8 wt %), and increases the content of light and middle distillates (18.9–34.1 wt %) along with the API gravity (12.6–21°). The results indicate that the use of liquid catalyst appears as a promising option on the way to development of an “inside-reservoir technology” for heavy crude oil processing.
Marijuana craving in the brain Filbey, Francesca M; Schacht, Joseph P; Myers, Ursula S ...
Proceedings of the National Academy of Sciences - PNAS,
08/2009, Letnik:
106, Številka:
31
Journal Article
Recenzirano
Odprti dostop
Craving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying ...neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue. These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis dependence.
As previous work has highlighted the significance of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes with respect to cannabis dependence (CD), this study sought to ...characterize the neural mechanisms that underlie these genetic effects. To this end, we collected DNA samples and fMRI data using a cue-elicited craving paradigm in thirty-seven 3-day-abstinent regular marijuana users. The participants were grouped according to their genotype on two single-nucleotide polymorphisms (SNPs) earlier associated with CD phenotypes: rs2023239 in CNR1 and rs324420 in FAAH. Between-group comparisons showed that carriers of the CNR1 rs2023239 G allele had significantly greater activity in reward-related areas of the brain, such as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate gyrus (ACG), during exposure to marijuana cues, as compared with those with the A/A genotype for this SNP. The FAAH group contrasts showed that FAAH rs324420 C homozygotes also had greater activation in widespread areas within the reward circuit, specifically in the OFC, ACG, and nucleus accumbens (NAc), as compared with the FAAH A-allele carriers. Moreover, there was a positive correlation between neural response in OFC and NAc and the total number of risk alleles (cluster-corrected p<0.05). These findings are in accord with earlier reported associations between CNR1 and FAAH and CD intermediate phenotypes, and suggest that the underlying mechanism of these genetic effects may be enhanced neural response in reward areas of the brain in carriers of the CNR1 G allele and FAAH C/C genotype in response to marijuana cues.
Heavy crude oil enhanced into a lighter oil by hydrocracking process with nickel nanoparticles (Ni NPs) as catalysts. Ni NPs were synthesized by colloidal method (chemical reduction of metal salts). ...The reduction of nickel nitrate hexahydrate ((Ni(NO
3
)
2
·6H
2
O) was done using sodium borohydride (NaBH
4
) as a reducing agent in presence of polyvinylpyrrolidone which worked as a protective and stabilizing agent; ethanol was used as a solvent. The properties of the nanoparticles were investigated by FT-IR, TEM, XRD, and HRTEM. These techniques confirmed the formation of Ni NPs with an average size of 10 nm and a tetragonal structure. The experiments were carried out in a batch reactor at 45 Kg
f
cm
−2
(initial H
2
pressure), 380 °C, stirring speed of 500 rpm and reaction time of 1 h. In all cases, the increase in the concentration of Ni nanoparticles improved the physical and chemical properties of heavy crude oil, even in limited hydrogen conditions; these properties were measured in terms of viscosity, SARA analysis, sulfur and nitrogen removal, and chromatographic analysis of gaseous products. The asphaltenes conversion was of 26.31% and moderate sulfur removal was achieved, these results are promising for EOR application.
Graphic Abstract
Autosomal recessive microcephaly and chorioretinopathy‐1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin‐Gamma Complex Associated Protein 6 ...(TUBGCP6, MIM#610053). Clinical features of this disorder include microcephaly, cognitive impairment, dysmorphic features, and variable ophthalmological anomalies including chorioretinopathy. Microcephaly can be recognized prenatally and visual impairment becomes evident during the first year of life. The clinical presentation resembles the findings in some acquired conditions such as congenital toxoplasmosis and cytomegalovirus infections; thus, it is important to recognize and diagnose this syndrome in view of its impact on patient health management and familial reproductive plans. To date, only seven molecularly confirmed patients from five unrelated families have been reported. We report an additional four unrelated patients with TUBGCP6 variants including one prenatal diagnosis and review the clinical phenotypes and genotypes of all the known cases. This report expands the molecular and phenotypic spectrum of TUBGCP6 and includes additional prenatal findings associated with MCCRP1.
•A liquid catalyst for hydrocracking reactions of heavy hydrocarbons was developed.•Catalyst’s acidic and metallic functions promote cracking and hydrogenation reactions.•Heavy hydrocarbons were ...converted into lighter hydrocarbons up to 65wt%.•Pollutants such as sulfur and nitrogen were substantially eliminated.
The heterogeneous catalytic hydrocracking process of residues convert heavy hydrocarbons, including asphaltenes into light distillates, removes sulfur and nitrogen, saturates aromatics and olefins and retains heavy metals (Ni, V, Fe, Cu, etc.). One of the greatest problems of the hydrocracking process is the high catalyst consumption due to its fast deactivation, the logistic of the supply of fresh catalyst and disposal of wasted catalyst may become very complicated because of the environmental regulations. In order to overcome this problem it has been proposed the use of more active poisoning resistant, however, this has only solved partially the problem. As an alternative, we propose the use of a liquid catalyst which has a strong acid function for cracking heavy hydrocarbons and a hydrogenation function to promote sulfur and nitrogen removal. This catalyst can be recovered and reactivated to be used again in the process with the additional advantage of being cheaper than solid catalysts. Experimental results show that by hydrocracking heavy oil using this liquid catalyst, more than 60wt% of asphaltenes and heavy molecules were transformed into lighter hydrocarbons in the boiling range of gasoline, diesel and gasoil. Likewise, sulfur and nitrogen were removed by 60 and 30wt% respectively. In this work the experimental results are presented and discussed.
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