Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P &lt; .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P &lt; .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P &lt; .01) or delta VF (r = 0.51; P &lt; .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF

Maximum likelihood models and algorithms for gene tree evolution with duplications and losses

<p>Abstract</p> <p>Background</p> <p>The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes.</p> <p>Results</p> <p>We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data.</p> <p>Conclusions</p> <p>In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.</p

Transmission Spectroscopy of the Habitable Zone Exoplanet LHS 1140 b with JWST/NIRISS

LHS 1140 b is the second-closest temperate transiting planet to Earth with an equilibrium temperature low enough to support surface liquid water. At 1.730 ± 0.025 R ⊕, LHS 1140 b falls within the radius valley separating H2-rich mini-Neptunes from rocky super-Earths. Recent mass and radius revisions indicate a bulk density significantly lower than expected for an Earth-like rocky interior, suggesting that LHS 1140 b could be either a mini-Neptune with a small envelope of hydrogen (∼0.1% by mass) or a water world (9%–19% water by mass). Atmospheric characterization through transmission spectroscopy can readily discern between these two scenarios. Here we present two JWST/NIRISS transit observations of LHS 1140 b, one of which captures a serendipitous transit of LHS 1140 c. The combined transmission spectrum of LHS 1140 b shows a telltale spectral signature of unocculted faculae (5.8σ), covering ∼20% of the visible stellar surface. Besides faculae, our spectral retrieval analysis reveals tentative evidence of residual spectral features, best fit by Rayleigh scattering from a N2-dominated atmosphere (2.3σ), irrespective of the consideration of atmospheric hazes. We also show through Global Climate Models (GCMs) that H2-rich atmospheres of various compositions (100×, 300×, 1000× solar metallicity) are ruled out to >10σ. The GCM calculations predict that water clouds form below the transit photosphere, limiting their impact on transmission data. Our observations suggest that LHS 1140 b is either airless or, more likely, surrounded by an atmosphere with a high mean molecular weight. Our tentative evidence of a N2-rich atmosphere provides strong motivation for future transmission spectroscopy observations of LHS 1140 b

Star Formation in Galaxy Mergers with Realistic Models of Stellar Feedback & the Interstellar Medium

We use simulations with realistic models for stellar feedback to study galaxy mergers. These high resolution (1 pc) simulations follow formation and destruction of individual GMCs and star clusters. The final starburst is dominated by in situ star formation, fueled by gas which flows inwards due to global torques. The resulting high gas density results in rapid star formation. The gas is self gravitating, and forms massive (~10^10 M_sun) GMCs and subsequent super-starclusters (masses up to 10^8 M_sun). However, in contrast to some recent simulations, the bulk of new stars which eventually form the central bulge are not born in superclusters which then sink to the center of the galaxy, because feedback efficiently disperses GMCs after they turn several percent of their mass into stars. Most of the mass that reaches the nucleus does so in the form of gas. The Kennicutt-Schmidt law emerges naturally as a consequence of feedback balancing gravitational collapse, independent of the small-scale star formation microphysics. The same mechanisms that drive this relation in isolated galaxies, in particular radiation pressure from IR photons, extend over seven decades in SFR to regulate star formation in the most extreme starbursts (densities >10^4 M_sun/pc^2). Feedback also drives super-winds with large mass loss rates; but a significant fraction of the wind material falls back onto the disks at later times, leading to higher post-starburst SFRs in the presence of stellar feedback. Strong AGN feedback is required to explain sharp cutoffs in star formation rate. We compare the predicted relic structure, mass profile, morphology, and efficiency of disk survival to simulations which do not explicitly resolve GMCs or feedback. Global galaxy properties are similar, but sub-galactic properties and star formation rates can differ significantly.Comment: 17 pages, 13 figures (+appendices), MNRAS accepted (matches published). Movies of the simulations are available at http://www.tapir.caltech.edu/~phopkins/Site/Movies_sbw_mgr.htm

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells

The MYST-Containing Protein Chameau Is Required for Proper Sensory Organ Specification during Drosophila Thorax Morphogenesis

The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern of mechanosensory bristles called macrochaetes. Here, we report that the MYST containing protein Chameau (Chm) contributes to the establishment of this pattern in the most dorsal part of the thorax. Chm mutant pupae present extra-dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the other macrochaetes. We provide evidences that chm restricts the singling out of sensory organ precursors from proneural clusters and genetically interacts with transcriptional regulators involved in the regulation of achaete and scute in the DC and SC proneural cluster. This function of chm likely relies on chromatin structure regulation since a protein with a mutation in the conserved catalytic site fails to rescue the formation of supernumerary DC and SC bristles in chm mutant flies. This is further supported by the finding that mutations in genes encoding chromatin modifiers and remodeling factors, including Polycomb group (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of chm extra bristle phenotype. These data support a critical role for chromatin structure modulation in the establishment of the stereotyped sensory bristle pattern in the fly thorax

New Mass and Radius Constraints on the LHS 1140 Planets -- LHS 1140 b is Either a Temperate Mini-Neptune or a Water World

The two-planet transiting system LHS 1140 has been extensively observed since its discovery in 2017, notably with $Spitzer$, HST, TESS, and ESPRESSO, placing strong constraints on the parameters of the M4.5 host star and its small temperate exoplanets, LHS 1140 b and c. Here, we reanalyse the ESPRESSO observations of LHS 1140 with the novel line-by-line framework designed to fully exploit the radial velocity content of a stellar spectrum while being resilient to outlier measurements. The improved radial velocities, combined with updated stellar parameters, consolidate our knowledge on the mass of LHS 1140 b (5.60$\pm$0.19 M$_{\oplus}$) and LHS 1140 c (1.91$\pm$0.06 M$_{\oplus}$) with unprecedented precision of 3%. Transits from $Spitzer$, HST, and TESS are jointly analysed for the first time, allowing us to refine the planetary radii of b (1.730$\pm$0.025 R$_{\oplus}$) and c (1.272$\pm$0.026 R$_{\oplus}$). Stellar abundance measurements of refractory elements (Fe, Mg and Si) obtained with NIRPS are used to constrain the internal structure of LHS 1140 b. This planet is unlikely to be a rocky super-Earth as previously reported, but rather a mini-Neptune with a $\sim$0.1% H/He envelope by mass or a water world with a water-mass fraction between 9 and 19% depending on the atmospheric composition and relative abundance of Fe and Mg. While the mini-Neptune case would not be habitable, a water-abundant LHS 1140 b potentially has habitable surface conditions according to 3D global climate models, suggesting liquid water at the substellar point for atmospheres with relatively low CO$_2$ concentration, from Earth-like to a few bars.Comment: 31 pages, 18 figures, accepted for publication in ApJ

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons’ activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders