The Detection of a Red Sequence of Massive Field Galaxies at z~2.3 and its Evolution to z~0

The existence of massive galaxies with strongly suppressed star formation at z~2.3, identified in a previous paper, suggests that a red sequence may already be in place beyond z=2. In order to test this hypothesis, we study the rest-frame U-B color distribution of massive galaxies at 2<z<3. The sample is drawn from our near-infrared spectroscopic survey for massive galaxies. The color distribution shows a statistically significant (>3 sigma) red sequence, which hosts ~60% of the stellar mass at the high-mass end. The red-sequence galaxies have little or no ongoing star formation, as inferred from both emission-line diagnostics and stellar continuum shapes. Their strong Balmer breaks and their location in the rest-frame U-B, B-V plane indicate that they are in a post-starburst phase, with typical ages of ~0.5-1.0 Gyr. In order to study the evolution of the red sequence, we compare our sample with spectroscopic massive galaxy samples at 0.02<z<0.045 and 0.6<z<1.0. The rest-frame U-B color reddens by ~0.25 mag from z~2.3 to the present at a given mass. Over the same redshift interval, the number and stellar mass density on the high-mass end (>10^11 Msol) of the red sequence grow by factors of ~8 and ~6, respectively. We explore simple models to explain the observed evolution. Passive evolution models predict too strong d(U-B), and produce z~0 galaxies that are too red. More complicated models that include aging, galaxy transformations, and red mergers can explain both the number density and color evolution of the massive end of the red sequence between z~2.3 and the present.Comment: Accepted for publication in the Astrophysical Journa

A Compact Early-type Galaxy at z = 0.6 Under a Magnifying Lens: Evidence For Inside-out Growth

We use Keck laser guide star adaptive optics imaging and exploit the magnifying effects of strong gravitational lensing (the effective resolution is FWHM ~ 200 pc) to investigate the sub-kpc scale of an intermediate-redshift (z = 0.63) massive early-type galaxy being lensed by a foreground early-type galaxy; we dub this class of strong gravitational lens systems EELs, e.g., early-type/early-type lenses. We find that the background source is massive (M* = 10^{10.9} M_sun) and compact (r_e = 1.1 kpc), and a two-component fit is required to model accurately the surface brightness distribution, including an extended low-surface-brightness component. This extended component may arise from the evolution of higher-redshift `red nuggets' or may already be in place at z ~ 2 but is unobservable due to cosmological surface brightness dimming.Comment: 5 pages, 4 figures; accepted to MNRA

Preferences and beliefs of Dutch orthopaedic surgeons and patients reduce the implementation of "Choosing Wisely" recommendations in degenerative knee disease

Purpose: The purpose of this study was to assess which factors were associated with the implementation of “Choosing Wisely” recommendations to refrain from routine MRI and arthroscopy use in degenerative knee disease. Methods: Cross-sectional surveys were sent to 123 patients (response rate 95%) and 413 orthopaedic surgeons (response rate 62%) fulfilling the inclusion criteria. Univariate and multivariate logistic regression analyses were used to identify factors associated with implementation of “Choosing Wisely” recommendations. Results: Factors reducing implementation of the MRI recommendation among patients included explanation of added value by an orthopaedic surgeon [OR 0.18 (95% CI 0.07–0.47)] and patient preference for MRI [OR 0.27 (95% CI 0.08–0.92)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own MRI experience than existing evidence [OR 0.41 (95% CI 0.19–0.88)] and higher estimated patients’ knowledge to participate in shared decision-making [OR 0.38 (95% CI 0.17–0.88)]. Factors reducing implementation of the arthroscopy recommendation among patients were orthopaedic surgeons’ preferences for an arthroscopy [OR 0.03 (95% CI 0.00–0.22)] and positive experiences with arthroscopy of friends/family [OR 0.03 (95% CI 0.00–0.39)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own arthroscopy experience than existing evidence [OR 0.17 (95% CI 0.07–0.46)] and belief in the added value [OR 0.28 (95% CI 0.10–0.81)]. Conclusions: Implementation of “Choosing Wisely” recommendations in degenerative knee disease can be improved by strategies to change clinician beliefs about the added value of MRIs and arthroscopies, and by patient-directed strategies addressing patient preferences and underlying beliefs for added value of MRI and arthroscopies resulting from experiences of people in their environment. Level of evidence: IV

Inhibition of diacylglycerol lipase beta modulates lipid and endocannabinoid levels in the ex vivo human placenta

IntroductionLipids and fatty acids are key components in metabolic processes of the human placenta, thereby contributing to the development of the fetus. Placental dyslipidemia and aberrant activity of lipases have been linked to diverse pregnancy associated complications, such as preeclampsia and preterm birth. The serine hydrolases, diacylglycerol lipase alpha and beta (DAGL alpha, DAGL beta) catalyze the degradation of diacylglycerols, leading to the formation of monoacylglycerols (MAG), including one main endocannabinoid 2-arachidonoylglycerol (2-AG). The major role of DAGL in the biosynthesis of 2-AG is evident from various studies in mice but has not been investigated in the human placenta. Here, we report the use of the small molecule inhibitor DH376, in combination with the ex vivo placental perfusion system, activity-based protein profiling (ABPP) and lipidomics, to determine the impact of acute DAGL inhibition on placental lipid networks. MethodsDAGL alpha and DAGL beta mRNA expression was detected by RT-qPCR and in situ hybridization in term placentas. Immunohistochemistry staining for CK7, CD163 and VWF was applied to localize DAGL beta transcripts to different cell types of the placenta. DAGL beta activity was determined by in- gel and MS-based activity-based protein profiling (ABPP) and validated by addition of the enzyme inhibitors LEI-105 and DH376. Enzyme kinetics were measured by EnzChek (TM) lipase substrate assay. Ex vivo placental perfusion experiments were performed +/- DH376 [1 mu M] and changes in tissue lipid and fatty acid profiles were measured by LC-MS. Additionally, free fatty acid levels of the maternal and fetal circulations were determined. ResultsWe demonstrate that mRNA expression of DAGL beta prevails in placental tissue, compared to DAGL alpha (p <= 0.0001) and that DAGL beta is mainly located to CK7 positive trophoblasts (p <= 0.0001). Although few DAGL alpha transcripts were identified, no active enzyme was detected applying in-gel or MS-based ABPP, which underlined that DAGL beta is the principal DAGL in the placenta. DAGL beta dependent substrate hydrolysis in placental membrane lysates was determined by the application of LEI-105 and DH376. Ex vivo pharmacological inhibition of DAGL beta by DH376 led to reduced MAG tissue levels (p <= 0.01), including 2-AG (p <= 0.0001). We further provide an activity landscape of serine hydrolases, showing a broad spectrum of metabolically active enzymes in the human placenta. DiscussionOur results emphasize the role of DAGL beta activity in the human placenta by determining the biosynthesis of 2-AG. Thus, this study highlights the special importance of intra-cellular lipases in lipid network regulation. Together, the activity of these specific enzymes may contribute to the lipid signaling at the maternal-fetal interface, with implications for function of the placenta in normal and compromised pregnancies.Molecular Physiolog

The size evolution of galaxies since z~3: combining SDSS, GEMS and FIRES

We present the evolution of the luminosity-size and stellar mass-size relations of luminous (L_V>3.4x10^10h_70^-2L_sun) and of massive (M_*>3x10^10h_70^-2M_sun) galaxies in the last ~11 Gyr. We use very deep near-infrared images of the Hubble Deep Field-South and the MS1054-03 field in the J_s, H and K_s bands from FIRES to retrieve the sizes in the optical rest-frame for galaxies with z>1. We combine our results with those from GEMS at 0.2<z<1 and SDSS at z~0.1 to achieve a comprehensive picture of the optical rest-frame size evolution from z=0 to z=3. Galaxies are differentiated according to their light concentration using the Sersic index n. For less concentrated objects, the galaxies at a given luminosity were typically ~3+-0.5 (+-2 sigma) times smaller at z~2.5 than those we see today. The stellar mass-size relation has evolved less: the mean size at a given stellar mass was \~2+-0.5 times smaller at z~2.5, evolving proportional to (1+z)^{-0.40+-0.06}. Simple scaling relations between dark matter halos and baryons in a hierarchical cosmogony predict a stronger (although consistent within the error bars) than observed evolution of the stellar mass-size relation. The observed luminosity-size evolution out to z~2.5 matches well recent infall model predictions for Milky-Way type objects. For low-n galaxies, the evolution of the stellar mass-size relation would follow naturally if the individual galaxies grow inside-out. For highly concentrated objects, the situation is as follows: at a given luminosity, these galaxies were ~2.7+-1.1 times smaller at z~2.5 (or put differently, were typically ~2.2+-0.7 mag brighter at a given size than they are today), and at a given stellar mass the size has evolved proportional to (1+z)^{-0.45+-0.10}.Comment: Accepted for publication in ApJ. The new version includes several improvements: much accurate size estimations and a better completeness and robustness analysis. Tables of data are included. 29 pages and 14 figures (one low resolution

Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified alpha-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the alpha-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs

Fetal and post-natal outcomes in offspring after intrauterine metformin exposure:A systematic review and meta-analysis of animal experiments

Aims: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. Methods: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. Results: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. Conclusion: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.</p

Morphologies of z~0.7 AGN host galaxies in CANDELS : no trend of merger incidence with AGN luminosity

PS would like to acknowledge funding through grant ASI I/005/11/0. DKoo would like to acknowledge funding through grant NSF AST-0808133. SJ acknowledges financial support from the EC through an ERC grant StG-257720.The processes that trigger active galactic nuclei (AGN) remain poorly understood. While lower luminosity AGN may be triggered by minor disturbances to the host galaxy, stronger disturbances are likely required to trigger luminous AGN. Major wet mergers of galaxies are ideal environments for AGN triggering since they provide large gas supplies and galaxy scale torques. There is however little observational evidence for a strong connection between AGN and major mergers. We analyse the morphological properties of AGN host galaxies as a function of AGN and host galaxy luminosity and compare them to a carefully matched sample of control galaxies. AGN are X-ray selected in the redshift range 0.5 < z < 0.8 and have luminosities 41 ≲ log (LX [erg s−1]) ≲ 44.5. ‘Fake AGN’ are simulated in the control galaxies by adding point sources with the magnitude of the matched AGN. We find that AGN host and control galaxies have comparable asymmetries, Sérsic indices and ellipticities at rest frame ∼950 nm. AGN host galaxies show neither higher average asymmetries nor higher fractions of very disturbed objects. There is no increase in the prevalence of merger signatures with AGN luminosity. At 95 per cent confidence we find that major mergers are responsible for <6 per cent of all AGN in our sample as well as <40 per cent of the highest luminosity AGN (log  (LX [erg s−1]) ∼ 43.5). Major mergers therefore either play only a very minor role in the triggering of AGN in the luminosity range studied or time delays are too long for merger features to remain visible.PostprintPeer reviewe

Discovery of a Ringlike Dark Matter Structure in the Core of the Galaxy Cluster Cl 0024+17

We present a comprehensive mass reconstruction of the rich galaxy cluster Cl 0024+17 at z~0.4 from ACS data, unifying both strong- and weak-lensing constraints. The weak-lensing signal from a dense distribution of background galaxies (~120 per square arcmin) across the cluster enables the derivation of a high-resolution parameter-free mass map. The strongly-lensed objects tightly constrain the mass structure of the cluster inner region on an absolute scale, breaking the mass-sheet degeneracy. The mass reconstruction of Cl 0024+17 obtained in such a way is remarkable. It reveals a ringlike dark matter substructure at r~75" surrounding a soft, dense core at r~50". We interpret this peculiar sub-structure as the result of a high-speed line-of-sight collision of two massive clusters 1-2 Gyr ago. Such an event is also indicated by the cluster velocity distribution. Our numerical simulation with purely collisionless particles demonstrates that such density ripples can arise by radially expanding, decelerating particles that originally comprised the pre-collision cores. Cl 0024+17 can be likened to the bullet cluster 1E0657-56, but viewed $along$ the collision axis at a much later epoch. In addition, we show that the long-standing mass discrepancy for Cl 0024+17 between X-ray and lensing can be resolved by treating the cluster X-ray emission as coming from a superposition of two X-ray systems. The cluster's unusual X-ray surface brightness profile that requires a two isothermal sphere description supports this hypothesis.Comment: To appear in the June 1 issue of The Astrophysical Journa