A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinkingFil: Bocarsly, Miriam E.. National Institutes of Health; Estados UnidosFil: da Silva e Silva, Daniel. National Institutes of Health; Estados UnidosFil: Kolb, Vanessa. National Institutes of Health; Estados UnidosFil: Luderman, Kathryn D.. National Institutes of Health; Estados UnidosFil: Shashikiran, Sannidhi. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sibley, David R.. National Institutes of Health; Estados UnidosFil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados UnidosFil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unido

Optimising infection prevention and control practice using behavior change: a systematic review

Despite significant investment in infection prevention and control (IPC), there has been little consideration of the effectiveness of behaviour change interventions or the application of behavioural theory (BT) or social marketing (SM) to influence healthcare workers' (HCWs) behaviour and to reduce healthcare associated infection

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

Long-term culture captures injury-repair cycles of colonic stem cells

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hop

Identification of \u3ci\u3eBrucella\u3c/i\u3e spp. in feral swine (\u3ci\u3eSus scrofa\u3c/i\u3e) at abattoirs in Texas, USA

Various tissues, nasal swabs, urine and blood samples were collected from 376 feral swine at two federally inspected abattoirs in Texas during six separate sampling periods in 2015. Samples were tested for Brucella spp. by culture and serology. Brucella spp. were cultured from 13.0% of feral swine, and antibodies were detected in 9.8%. Only 32.7% of culture-positive feral swine were also antibody positive, and 43.2% of antibody-positive feral swine were culture positive. Approximately, the same number of males (14.0%) and females (12.1%) were culture positive, and slightly more males (10.5%) than females (8.7%) were antibody positive. Our results indicate that serology likely underestimates the prevalence of feral swine infected, and that those who come in contact with feral swine should be aware of the symptoms of infection with Brucella spp. to ensure prompt treatment

Studies of the dynamics of nuclear clustering in human syncytiotrophoblast

Syncytial nuclear aggregates (SNAs), clusters of nuclei in the syncytiotrophoblast of the human placenta, are increased as gestation advances and in pregnancy pathologies. The origins of increased SNAs are unclear; however, a better appreciation of the mechanism may give insight into placental ageing and factors underpinning dysfunction. We developed three models to investigate whether SNA formation results from a dynamic process of nuclear movement and to generate alternative hypotheses. SNA count and size were measured in placental explants cultured over 16 days and particles released into culture medium were quantified. Primary trophoblasts were cultured for 6 days. Explants and trophoblasts were cultured with and without cytoskeletal inhibitors. An in silico model was developed to examine the effects of modulating nuclear behaviour on clustering. In explants, neither median SNA number (108 SNA/mm(2) villous area) nor size (283 μm(2)) changed over time. Subcellular particles from conditioned culture medium showed a wide range of sizes that overlapped with those of SNAs. Nuclei in primary trophoblasts did not change position relative to other nuclei; apparent movement was associated with positional changes of the syncytial cell membrane. In both models, SNAs and nuclear clusters were stable despite pharmacological disruption of cytoskeletal activity. In silico, increased nuclear movement, adhesiveness and sites of cytotrophoblast fusion were related to nuclear clustering. The prominence of SNAs in pregnancy disorders may not result from an active process involving cytoskeleton-mediated rearrangement of syncytial nuclei. Further insights into the mechanism(s) of SNA formation will aid understanding of their increased presence in pregnancy pathologies

Nonequilibrium molecular dynamics simulations of nanoconfined fluids at solidliquid interfaces

We investigate the hydrodynamic properties of a Lennard-Jones fluid confined to a nanochannel using molecular dynamics simulations. For channels of different widths and hydrophilic-hydrophobic surface wetting properties, profiles of the fluid density, stress, and viscosity across the channel are obtained and analysed. In particular, we propose a linear relationship between the density and viscosity in confined and strongly inhomogeneous nanofluidic flows. The range of validity of this relationship is explored in the context of coarse grained models such as dynamic density functional-theory