Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake

The Tully-Fisher relation at intermediate redshift

Using the Very Large Telescope in Multi Object Spectroscopy mode, we have observed a sample of 113 field spiral galaxies in the FORS Deep Field (FDF) with redshifts in the range 0.1<z<1.0. The galaxies were selected upon apparent brightness (R<23) and encompass all late spectrophotometric types from Sa to Sdm/Im. Spatially resolved rotation curves have been extracted for 77 galaxies and fitted with synthetic velocity fields taking into account all observational effects from inclination and slit misalignment to seeing and slit width. We also compared different shapes for the intrinsic rotation curve. To gain robust values of V_max, our analysis is focussed on galaxies with rotation curves which extend well into the region of constant rotation velocity at large radii. If the slope of the local Tully-Fisher relation (TFR) is held fixed, we find evidence for a mass-dependent luminosity evolution which is as large as up to 2 mag for the lowest-mass galaxies, but is small or even negligible for the highest-mass systems in our sample. In effect, the TFR slope is shallower at z~0.5 in comparison to the local sample. We argue for a mass-dependent evolution of the mass-to-light ratio. An additional population of blue, low-mass spirals does not seem a very appealing explanation. The flatter tilt we find for the distant TFR is in contradiction to the predictions of recent semi-analytic simulations.Comment: 18 pages, 14 figures, A&A, in press. Section on sample completeness added. Please note that the entire analysis is based on undisturbed, high quality rotation curves! Potential effects of tidal interactions are also discusse

Density profiles of dark matter haloes on Galactic and Cluster scales

In the present paper, we improve the "Extended Secondary Infall Model" (ESIM) of Williams et al. (2004) to obtain further insights on the cusp/core problem. The model takes into account the effect of ordered and random angular momentum, dynamical friction and baryon adiabatic contraction in order to obtain a secondary infall model more close to the collapse reality. The model is applied to structures on galactic scales (normal and dwarf spiral galaxies) and on cluster of galaxies scales. The results obtained suggest that angular momentum and dynamical friction are able, on galactic scales, to overcome the competing effect of adiabatic contraction eliminating the cusp. The NFW profile can be reobtained, in our model only if the system is constituted just by dark matter and the magnitude of angular momentum and dynamical friction are reduced with respect to the values predicted by the model itself. The rotation curves of four LSB galaxies from de Blok & Bosma (2002) are compared to the rotation curves obtained by the model in the present paper obtaining a good fit to the observational data. On scales smaller than $\simeq 10^{11} h^{-1} M_{\odot}$ the slope $\alpha \simeq 0$ and on cluster scales we observe a similar evolution of the dark matter density profile but in this case the density profile slope flattens to $\alpha \simeq 0.6$ for a cluster of $\simeq 10^{14} h^{-1} M_{\odot}$. The total mass profile, differently from that of dark matter, shows a central cusp well fitted by a NFW model.Comment: 26 pages; 4 figures A&A Accepte

Colour Evolution of Disk Galaxy Models from z=4 to z=0

We calculate synthetic UBVRIJHKLM images, integrated spectra and colours for the disk galaxy formation models of Samland & Gerhard (2002), from redshift z=4 to z=0. Two models are considered, an accretion model based on LambdaCDM structure formation simulations, and a classical collapse model in a dark matter halo. Both models provide the star formation history and dynamics of the baryonic component within a three-dimensional chemo-dynamical description. To convert to spectra and colours, we use the latest, metallicity-calibrated spectral library of Westera et al. (2002), including internal absorption. As a first application, we compare the derived colours with Hubble Deep Field North bulge colours and find good agreement. With our model, we disentangle metallicity effects and absorption effects on the integrated colours, and find that absorption effects are dominant for redshift z < 1.5. Furthermore, we confirm the quality of m_K as a mass tracer, and find indications for a correlation between (J-K) and metallicity gradients.Comment: 29 pages, LaTeX, 17 figures, revised version, submitted to A&A, a high resolution version can be found at http://www.astro.unibas.ch/leute/ms.shtm

Targeted 'Next-Generation' sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations

<p>Abstract</p> <p>Background</p> <p>Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M.</p> <p>Methods</p> <p>We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing.</p> <p>Results</p> <p>We verified three mutations - c.542delC in S<it>OX2</it>, resulting in p.Pro181Argfs*22, p.Glu105X in <it>OTX2 </it>and p.Cys240X in <it>FOXE3</it>. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in <it>CRYBA4</it>, p.Val201Met in <it>FOXE3 </it>and p.Asp291Asn in <it>VSX2</it>. Our analysis methodology gave one false positive result comprising a mutation in <it>PAX6 </it>(c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in <it>SOX2</it>.</p> <p>Conclusions</p> <p>Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.</p

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Unassisted solar lignin valorisation using a compartmented photo-electro-biochemical cell

Lignin is a major component of lignocellulosic biomass. Although it is highly recalcitrant to break down, it is a very abundant natural source of valuable aromatic carbons. Thus, the effective valorisation of lignin is crucial for realising a sustainable biorefinery chain. Here, we report a compartmented photo-electro-biochemical system for unassisted, selective, and stable lignin valorisation, in which a TiO2 photocatalyst, an atomically dispersed Co-based electrocatalyst, and a biocatalyst (lignin peroxidase isozyme H8, horseradish peroxidase) are integrated, such that each system is separated using Nafion and cellulose membranes. This cell design enables lignin valorisation upon irradiation with sunlight without the need for any additional bias or sacrificial agent and allows the protection of the biocatalyst from enzymedamaging elements, such as reactive radicals, gas bubbles, and light. The photo-electrobiochemical system is able to catalyse lignin depolymerisation with a 98.7% selectivity and polymerisation with a 73.3% yield using coniferyl alcohol, a lignin monomer

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND: Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN: Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION: The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.</p> <p>Methods</p> <p>NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.</p> <p>Results</p> <p>We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.</p> <p>Conclusion</p> <p>Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.</p

The Dramatic Size and Kinematic Evolution of Massive Early-type Galaxies

We aim to provide a holistic view on the typical size and kinematic evolution of massive early-type galaxies (ETGs) that encompasses their high-z star-forming progenitors, their high-z quiescent counterparts, and their configurations in the local Universe. Our investigation covers the main processes playing a relevant role in the cosmic evolution of ETGs. Specifically, their early fast evolution comprises biased collapse of the low angular momentum gaseous baryons located in the inner regions of the host dark matter halo; cooling, fragmentation, and infall of the gas down to the radius set by the centrifugal barrier; further rapid compaction via clump/gas migration toward the galaxy center, where strong heavily dust-enshrouded star formation takes place and most of the stellar mass is accumulated; and ejection of substantial gas amount from the inner regions by feedback processes, which causes a dramatic puffing-up of the stellar component. In the late slow evolution, passive aging of stellar populations and mass additions by dry merger events occur. We describe these processes relying on prescriptions inspired by basic physical arguments and by numerical simulations to derive new analytical estimates of the relevant sizes, timescales, and kinematic properties for individual galaxies along their evolution. Then we obtain quantitative results as a function of galaxy mass and redshift, and compare them to recent observational constraints on half-light size Re, on the ratio v/\u3c3 between rotation velocity and velocity dispersion (for gas and stars) and on the specific angular momentum j 17of the stellar component; we find good consistency with the available multiband data in average values and dispersion, both for local ETGs and for their z 3c 1-2 star-forming and quiescent progenitors. The outcomes of our analysis can provide hints to gauge sub-grid recipes implemented in simulations, to tune numerical experiments focused on specific processes, and to plan future multiband, high-resolution observations on high-redshift star-forming and quiescent galaxies with next-generation facilities