Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Humans are not fooled by size illusions in attractiveness judgements

Could signallers use size contrast illusions to dishonestly exaggerate their attractiveness to potential mates? Using composite photographs of women from three body mass index (BMI) categories designed to simulate small groups, we show that target women of medium size are judged as thinner when surrounded by larger women than when surrounded by thinner women. However, attractiveness judgements of the same target women were unaffected by this illusory change in BMI, despite small true differences in the BMIs of the target women themselves producing strong effects on attractiveness. Thus, in the context of mate choice decisions, the honesty of female body size as a signal of mate quality appears to have been maintained by the evolution of assessment strategies that are immune to size contrast illusions. Our results suggest that receiver psychology is more flexible than previously assumed, and that illusions are unlikely to drive the evolution of exploitative neighbour choice in human sexual displays. © 2014 The Authors

Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways

Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intake, is most prevalent in young adults and is a risk factor for excessive alcohol consumption and alcohol dependence. Although the alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking in the dark (DID) as a model of binge alcohol drinking to assess its effects on spike timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch-clamp recordings with calcium imaging and optogenetics. After 2 weeks of daily alcohol binges, synaptic plasticity was profoundly altered. STDP in MSNs expressing dopamine D1 receptors shifted from spike-timing-dependent long-term depression (tLTD), the predominant form of plasticity in naive male mice, to spike-timing-dependent long-term potentiation (tLTP) in DID mice, an effect that was totally reversed in the presence of 4 mum SCH23390, a dopamine D1 receptor antagonist. In MSNs presumably expressing dopamine D2 receptors, tLTP, the main form of plasticity in naive mice, was inhibited in DID mice. Interestingly, 1 mum sulpiride, a D2 receptor antagonist, restored tLTP. Although we observed no alterations of AMPA and NMDA receptor properties, we found that the AMPA/NMDA ratio increased at cortical and amygdaloid inputs but not at hippocampal inputs. Also, DID effects on STDP were accompanied by lower dendritic calcium transients. These data suggest that the role of dopamine in mediating the effects of binge alcohol drinking on synaptic plasticity of NAc MSNs differs markedly whether these neurons belong to the direct or indirect pathways. SIGNIFICANCE STATEMENT We examined the relationship between binge alcohol drinking and spike timing-dependent plasticity in nucleus accumbens (NAc) neurons. We found that repeated drinking bouts modulate differently synaptic plasticity in medium spiny neurons of the accumbens direct and indirect pathways. While timing-dependent long-term depression switches to long-term potentiation (LTP) in the former, timing-dependent LTP is inhibited in the latter. These effects are not accompanied by changes in AMPA and NMDA receptor properties at cortical, amygdaloid, and hippocampal synapses. Interestingly, dopamine D1 and D2 receptor antagonists have opposite effects on plasticity. Our data show that whether core NAc medium spiny neurons belong to the direct or indirect pathways determines the form of spike timing-dependent plasticity (STDP), the manner by which STDP responds to binge alcohol drinking, and its sensitivity to dopamine receptor antagonists

HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry

<p>Abstract</p> <p>Background</p> <p>Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists <it>in vitro </it>is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists <it>in vitro </it>including MVC, vicriviroc and AD101.</p> <p>Findings</p> <p>Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists.</p> <p>Conclusions</p> <p>Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists <it>in vitro</it>. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.</p

Choreography, controversy and child sex abuse: Theoretical reflections on a cultural criminological analysis of dance in a pop music video

This article was inspired by the controversy over claims of ‘pedophilia!!!!’ undertones and the ‘triggering’ of memories of childhood sexual abuse in some viewers by the dance performance featured in the music video for Sia’s ‘Elastic Heart’ (2015). The case is presented for acknowledging the hidden and/or overlooked presence of dance in social scientific theory and cultural studies and how these can enhance and advance cultural criminological research. Examples of how these insights have been used within other disciplinary frameworks to analyse and address child sex crime and sexual trauma are provided, and the argument is made that popular cultural texts such as dance in pop music videos should be regarded as significant in analysing and tracing public perceptions and epistemologies of crimes such as child sex abuse