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1.
J Chem Phys ; 154(18): 184301, 2021 May 14.
Article in English | MEDLINE | ID: mdl-34241001

ABSTRACT

Propionitrile (CH3CH2CN, PN) is a molecule relevant for interstellar chemistry. There is credible evidence that anions, molecules, and radicals that may originate from PN could also be involved in the formation of more complex organic compounds. In the present investigation, dissociative electron attachment to CH3CH2CN has been studied in a crossed electron-molecular beam experiment in the electron energy range of about 0-15 eV. In the experiment, seven anionic species were detected: C3H4N-, C3H3N-, C3H2N-, C2H2N-, C2HN-, C2N-, and CN-. The anion formation is most efficient for CN- and anions originating from the dehydrogenation of the parent molecule. A discussion of possible reaction channels for all measured negative ions is provided. The experimental results are compared with calculations of thermochemical thresholds of the detected anions.

2.
Mol Psychiatry ; 23(5): 1303-1319, 2018 05.
Article in English | MEDLINE | ID: mdl-28397836

ABSTRACT

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with ß-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.


Subject(s)
Alcoholism/genetics , Anxiety/genetics , Calcium-Binding Proteins/genetics , Adolescent , Adult , Alcohol Drinking/genetics , Animals , Anxiety Disorders/genetics , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Polymorphism, Single Nucleotide , Risk-Taking , Xenopus laevis
3.
Acta Psychiatr Scand ; 136(1): 96-107, 2017 07.
Article in English | MEDLINE | ID: mdl-28383757

ABSTRACT

OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.


Subject(s)
Alcoholism/blood , Alcoholism/physiopathology , Androgens/metabolism , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Substance Withdrawal Syndrome/blood , Substance Withdrawal Syndrome/physiopathology , Adult , Alcohol Drinking/epidemiology , Alcoholism/epidemiology , Alcoholism/metabolism , Cross-Sectional Studies , Denmark/epidemiology , Dihydrotestosterone/blood , Female , Fingers/anatomy & histology , Humans , Longitudinal Studies , Male , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Sex Factors , Smoking/epidemiology , Stress, Psychological/epidemiology , Testosterone/blood
4.
J Chem Phys ; 144(22): 224309, 2016 Jun 14.
Article in English | MEDLINE | ID: mdl-27306009

ABSTRACT

Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its radiosensitizing capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO(-), water, and the amidogen (NH2) radical. The second and third most dominant dissociation channels are associated with formation of NCNH(-) and NHCONH2 (-), respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH2 (-)/O(-), OH(-), CN(-), HNOH(-), NCONH2 (-), and ONHCONH2 (-).


Subject(s)
Hydroxyurea/chemistry , Radiation-Sensitizing Agents/chemistry , Electrons , Free Radicals/chemistry , Mass Spectrometry , Models, Chemical , Quantum Theory
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