Invited commentary on Stewart and Davis " 'Big data' in mental health research-current status and emerging possibilities"

No abstract available

Cholinergic Modulation of Locomotion and Striatal Dopamine Release Is Mediated by α6α4* Nicotinic Acetylcholine Receptors

Dopamine (DA) release in striatum is governed by firing rates of midbrain DA neurons, striatal cholinergic tone, and nicotinic ACh receptors (nAChRs) on DA presynaptic terminals. DA neurons selectively express α6* nAChRs, which show high ACh and nicotine sensitivity. To help identify nAChR subtypes that control DA transmission, we studied transgenic mice expressing hypersensitive α6^(L9’S*) receptors. α6^(L9’S) mice are hyperactive, travel greater distance, exhibit increased ambulatory behaviors such as walking, turning, and rearing, and show decreased pausing, hanging, drinking, and grooming. These effects were mediated by α6 α4* pentamers, as α6^(L9’S) mice lacking α4 subunits displayed essentially normal behavior. In α6^(L9’S) mice, receptor numbers are normal, but loss of α4 subunits leads to fewer and less sensitive α6* receptors. Gain-of-function nicotine-stimulated DA release from striatal synaptosomes requires α4 subunits, implicating α6α4β2* nAChRs in α6^(L9’S) mouse behaviors. In brain slices, we applied electrochemical measurements to study control of DA release by α6^(L9’S) nAChRs. Burst stimulation of DA fibers elicited increased DA release relative to single action potentials selectively in α6^(L9’S), but not WT or α4KO/ α6^(L9’S), mice. Thus, increased nAChR activity, like decreased activity, leads to enhanced extracellular DA release during phasic firing. Bursts may directly enhance DA release from α6^(L9’S) presynaptic terminals, as there was no difference in striatal DA receptor numbers or DA transporter levels or function in vitro. These results implicate α6α4β2* nAChRs in cholinergic control of DA transmission, and strongly suggest that these receptors are candidate drug targets for disorders involving the DA system

A new population of recently quenched elliptical galaxies in the SDSS

We use the Sloan Digital Sky Survey to investigate the properties of massive elliptical galaxies in the local Universe (z\leq0.08) that have unusually blue optical colors. Through careful inspection, we distinguish elliptical from non-elliptical morphologies among a large sample of similarly blue galaxies with high central light concentrations (c_r\geq2.6). These blue ellipticals comprise 3.7 per cent of all c_r\geq2.6 galaxies with stellar masses between 10^10 and 10^11 h^{-2} {\rm M}_{\sun}. Using published fiber spectra diagnostics, we identify a unique subset of 172 non-star-forming ellipticals with distinctly blue urz colors and young (< 3 Gyr) light-weighted stellar ages. These recently quenched ellipticals (RQEs) have a number density of 2.7-4.7\times 10^{-5}\,h^3\,{\rm Mpc}^{-3} and sufficient numbers above 2.5\times10^{10} h^{-2} {\rm M}_{\sun} to account for more than half of the expected quiescent growth at late cosmic time assuming this phase lasts 0.5 Gyr. RQEs have properties that are consistent with a recent merger origin (i.e., they are strong `first-generation' elliptical candidates), yet few involved a starburst strong enough to produce an E+A signature. The preferred environment of RQEs (90 per cent reside at the centers of < 3\times 10^{12}\,h^{-1}{\rm M}_{\sun} groups) agrees well with the `small group scale' predicted for maximally efficient spiral merging onto their halo center and rules out satellite-specific quenching processes. The high incidence of Seyfert and LINER activity in RQEs and their plausible descendents may heat the atmospheres of small host halos sufficiently to maintain quenching.Comment: 26 pages, 9 figures. Revised version; accepted for publication in MNRA

Alzheimer disease genetic risk factor APOE e4, and cognitive abilities in 111,739 UK Biobank participants

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment