CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease

Disturbed circadian rhythms with sleep problems and disrupted diurnal activity are often seen in patients suffering from Alzheimer disease (AD). Both endogenous CLOCK genes and external Zeitgeber are responsible for the maintenance of circadian rhythmicity in humans. Therefore, modifications of the internal CLOCK system and its interactions with exogenous factors might constitute the neurobiological basis for clinically observed disruptions in rhythmicity, which often have grave consequences for the quality of life of patients and their caregivers. Presently, more and more data are emerging demonstrating how alterations of the CLOCK gene system might contribute to the pathophysiology of AD and other forms of dementia. At the same time, the impact of neuropsychiatric medication on CLOCK gene expression is under investigation

Defining the origins of multiple emission/excitation in rhenium-bisthiazole complexes

The underlying mechanism of the unusual emissive behavior of [Re(CO) 3 -1,1-bis-4-thiazole-(1,4)-diaminobutane)] bromide (4-BT) has been investigated. Synthesis and spectroscopic characterization of structurally similar isomers ([Re(CO) 3 -1,1-bis-2-thiazole-(1,4)-diaminobutane)] bromide (2-BT)) and the location of triplet states, solid state and low temperature spectroscopic measurements, and DFT calculations show that the photophysical properties are not due to photoisomerization as previously hypothesized. The results show that the unusual emissive behavior is not observed in structural isomers, is specific to the previously reported complex, 4-BT, and may arise from vibrational energy relaxation and vibrational cooling. Translation of the unusual emissive behavior to the solid state offers an interesting platform allowing this complex to be potentially utilized as a probe, sensor or photonic device

Deciphering the Activity and Quiescence of High-redshift Cluster Environments : ALMA Observations of Cl J1449+0856 at z=2

We present Atacama Large Millimeter/submillimeter Array observations of the 870 mu m continuum and CO(4-3) line emission in the core of the galaxy cluster Cl J1449+0856 at z = 2, a near-IR-selected, X-ray-detected system in the mass range of typical progenitors of today's massive clusters. The 870 mu m map reveals six F-870 mu m > 0.5 mJy sources spread over an area of 0.07 arcmin(2), giving an overdensity of a factor of similar to 10 (6) with respect to blank-field counts down to F-870 mu m > 1 mJy (> 0.5 mJy). On the other hand, deep CO(4-3) follow-up confirms membership of three of these sources but suggests that the remaining three, including the brightest 870 mu m sources in the field (F-870 mu m greater than or similar to 2 mJy), are likely interlopers. The measurement of 870 mu m continuum and CO(4-3) line fluxes at the positions of previously known cluster members provides a deep probe of dusty star formation occurring in the core of this high-redshift structure, adding up to a total star formation rate of similar to 700 +/- 100 M-circle dot yr(-1) and yielding an integrated star formation rate density of similar to 10(4) M-circle dot yr(-1) Mpc(-3), five orders of magnitude larger than in the field at the same epoch, due to the concentration of star-forming galaxies in the small volume of the dense cluster core. The combination of these observations with previously available Hubble Space Telescope imaging highlights the presence in this same volume of a population of galaxies with already suppressed star formation. This diverse composition of galaxy populations in Cl J1449+0856 is especially highlighted at the very cluster center, where a complex assembly of quiescent and star-forming sources is likely forming the future brightest cluster galaxy.Peer reviewe

Rotation Curves in z ∼ 1–2 Star-forming Disks: Evidence for Cored Dark Matter Distributions

We report high quality, Halpha or CO rotation curves (RCs) to several Re for 41 large, massive, star-forming disk galaxies (SFGs), across the peak of cosmic galaxy evolution (z~0.67-2.45), taken with the ESO-VLT, the LBT and IRAM-NOEMA. Most RC41 SFGs have reflection symmetric RCs plausibly described by equilibrium dynamics. We fit the major axis position-velocity cuts with beam-convolved, forward modeling with a bulge, a turbulent rotating disk, and a dark matter (DM) halo. We include priors for stellar and molecular gas masses, optical light effective radii and inclinations, and DM masses from abundance matching scaling relations. Two-thirds or more of the z>1.2 SFGs are baryon dominated within a few Re of typically 5.5 kpc, and have DM fractions less than maximal disks (=0.12). At lower redshift (z<1.2) that fraction is less than one-third. DM fractions correlate inversely with the baryonic angular momentum parameter, baryonic surface density and bulge mass. Inferred low DM fractions cannot apply to the entire disk & halo but more plausibly reflect a flattened, or cored, inner DM density distribution. The typical central 'DM deficit' in these cores relative to NFW distributions is ~30% of the bulge mass. The observations are consistent with rapid radial transport of baryons in the first generation massive gas rich halos forming globally gravitationally unstable disks, and leading to efficient build-up of massive bulges and central black holes. A combination of heating due to dynamical friction and AGN feedback may drive DM out of the initial cusps.Comment: 15 figures, 4 tables, accepted for publication in Ap

Rotation Curves in z ∼ 1–2 Star-forming Disks: Comparison of Dark Matter Fractions and Disk Properties for Different Fitting Methods

We present a follow-up analysis examining the dynamics and structures of 41 massive, large star-forming galaxies at z~0.67-2.45 using both ionized and molecular gas kinematics. We fit the galaxy dynamics with models consisting of a bulge, a thick, turbulent disk, and a NFW dark matter halo, using code that fully forward models the kinematics, including all observational and instrumental effects. We explore the parameter space using Markov Chain Monte Carlo (MCMC) sampling, including priors based on stellar and gas masses and disk sizes. We fit the full sample using extracted 1D kinematic profiles. For a subset of 14 well-resolved galaxies, we also fit the 2D kinematics. The MCMC approach robustly confirms the results from least-squares fitting presented in Paper I (Genzel et al. 2020): the sample galaxies tend to be baryon-rich on galactic scales (within one effective radius). The 1D and 2D MCMC results are also in good agreement for the subset, demonstrating that much of the galaxy dynamical information is captured along the major axis. The 2D kinematics are more affected by the presence of non-circular motions, which we illustrate by constructing a toy model with constant inflow for one galaxy that exhibits residual signatures consistent with radial motions. This analysis, together with results from Paper I and other studies, strengthens the finding that massive, star-forming galaxies at z~1-2 are baryon-dominated on galactic scales, with lower dark matter fractions towards higher baryonic surface densities. Finally, we present details of the kinematic fitting code used in this analysis.Comment: Accepted for publication in ApJ (23 pages, 8 figures, 5 tables

Use of antidepressant medications in relation to the incidence of breast cancer

Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case–control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N=2904) and five controls were selected for each case (N=14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio=1.06, 95% CI 0.94–1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR=0.98, 95% CI 0.80–1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants

A systematic review of correlates of sedentary behaviour in adults aged 18–65 years: a socio-ecological approach

Background: Recent research shows that sedentary behaviour is associated with adverse cardio-metabolic consequences even among those considered sufficiently physically active. In order to successfully develop interventions to address this unhealthy behaviour, factors that influence sedentariness need to be identified and fully understood. The aim of this review is to identify individual, social, environmental, and policy-related determinants or correlates of sedentary behaviours among adults aged 18-65 years. Methods: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between January 2000 and September 2015. The search strategy was based on four key elements and their synonyms: (a) sedentary behaviour (b) correlates (c) types of sedentary behaviours (d) types of correlates. Articles were included if information relating to sedentary behaviour in adults (18-65 years) was reported. Studies on samples selected by disease were excluded. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42014009823). Results: 74 original studies were identified out of 4041: 71 observational, two qualitative and one experimental study. Sedentary behaviour was primarily measured as self-reported screen leisure time and total sitting time. In 15 studies, objectively measured total sedentary time was reported: accelerometry (n = 14) and heart rate (n = 1). Individual level factors such as age, physical activity levels, body mass index, socio-economic status and mood were all significantly correlated with sedentariness. A trend towards increased amounts of leisure screen time was identified in those married or cohabiting while having children resulted in less total sitting time. Several environmental correlates were identified including proximity of green space, neighbourhood walkability and safety and weather. Conclusions: Results provide further evidence relating to several already recognised individual level factors and preliminary evidence relating to social and environmental factors that should be further investigated. Most studies relied upon cross-sectional design limiting causal inference and the heterogeneity of the sedentary measures prevented direct comparison of findings. Future research necessitates longitudinal study designs, exploration of policy-related factors, further exploration of environmental factors, analysis of inter-relationships between identified factors and better classification of sedentary behaviour domains

Non-state space: The strategic ejection of dangerous and high maintenance urban space

Some commentators have characterised so-called ‘no-go’ areas as sites in which the exercise of authority is prevented. Here we suggest that many such spaces are produced by state, policing and citizen repertoires that aim to minimise the costs and risks of engaging, supporting and servicing such spaces and their populations. In this article we locate strategies of public spending, policing and political action that offer a governing logic in which neighbourhoods are essentially subtracted from the constitution of the city. During such designations the assurances of citizenship, vitality of civic institutions and presence of policing may be partially or wholly suspended. We present a framework for the identification of such strategies in which these forms of social, political and spatial exiting are described as being autotomic in nature – spaces that are ejected in order to avoid losses or further damage to the body politic of the city in ways akin to the response of certain animals that protect themselves from predation by shedding a limb or body part. This term adds force and depth to assessments of the ways in which both temporary and more sustained exits by policing, management and state servicing are designed in order to avoid responsibility over, or engagement with, spaces that are deemed a threat in order to maintain the integrity of the remaining, included city