The ubiquitin-like modifier FAT10 inhibits retinal PDE6 activity and mediates its proteasomal degradation

The retina-specific chaperone aryl hydrocarbon interacting protein-like 1 (AIPL1) is essential for the correct assembly of phosphodiesterase 6 (PDE6), which is a pivotal effector enzyme for phototransduction and vision because it hydrolyzes cGMP. AIPL1 interacts with the cytokine-inducible ubiquitin-like modifier FAT10, which gets covalently conjugated to hundreds of proteins and targets its conjugation substrates for proteasomal degradation, but whether FAT10 affects PDE6 function or turnover is unknown. Here, we show that FAT10 mRNA is expressed in human retina and identify rod PDE6 as a retina-specific substrate of FAT10 conjugation. We found that AIPL1 stabilizes the FAT10 monomer and the PDE6-FAT10 conjugate. Additionally, we elucidated the functional consequences of PDE6 FAT10ylation. On the one hand, we demonstrate that FAT10 targets PDE6 for proteasomal degradation by formation of a covalent isopeptide linkage. On the other hand, FAT10 inhibits PDE6 cGMP hydrolyzing activity by noncovalently interacting with the PDE6 GAFa and catalytic domains. Therefore, FAT10 may contribute to loss of PDE6 and, as a consequence, degeneration of retinal cells in eye diseases linked to inflammation and inherited blindness-causing mutations in AIPL1

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study

<p>Abstract</p> <p>Background</p> <p>Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.</p> <p>Methods/Design</p> <p>In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.</p> <p>Discussion</p> <p>Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN16211826.</p

Rotation and X-ray emission from protostars

The ASCA satellite has recently detected variable hard X-ray emission from two Class I protostars in the rho Oph cloud, YLW15 (IRS43) and WL6, with a characteristic time scale ~20h. In YLW15, the X-ray emission is in the form of quasi-periodic energetic flares, which we explain in terms of strong magnetic shearing and reconnection between the central star and the accretion disk. In WL6, X-ray flaring is rotationally modulated, and appears to be more like the solar-type magnetic activity ubiquitous on T Tauri stars. We find that YLW15 is a fast rotator (near break-up), while WL6 rotates with a significantly longer period. We derive a mass M_\star ~ 2 M_\odot and \simlt 0.4 M_\odot for the central stars of YLW15 and WL6 respectively. On the long term, the interactions between the star and the disk results in magnetic braking and angular momentum loss of the star. On time scales t_{br} ~ a few 10^5 yrs, i.e., of the same order as the estimated duration of the Class~I protostar stage. Close to the birthline there must be a mass-rotation relation, t_{br} \simpropto M_\star, such that stars with M_\star \simgt 1-2 M_\odot are fast rotators, while their lower-mass counterparts have had the time to spin down. The rapid rotation and strong star-disk magnetic interactions of YLW15 also naturally explain the observation of X-ray ``superflares''. In the case of YLW15, and perhaps also of other protostars, a hot coronal wind (T~10^6 K) may be responsible for the VLA thermal radio emission. This paper thus proposes the first clues to the rotation status and evolution of protostars.Comment: 13 pages with 6 figures. To be published in ApJ (April 10, 2000 Part 1 issue

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals

Abundance anomalies in pre-main-sequence stars: Stellar evolution models with mass loss

The effects of atomic diffusion on internal and surface abundances of A and F pre-main-sequence stars with mass loss are studied in order to determine at what age the effects materialize, as well as to further understand the processes at play in HAeBe and young ApBp stars. Self-consistent stellar evolution models of 1.5 to 2.8Msun with atomic diffusion (including radiative accelerations) for all species within the OPAL opacity database were computed and compared to observations of HAeBe stars. Atomic diffusion in the presence of weak mass loss can explain the observed abundance anomalies of pre-main-sequence stars, as well as the presence of binary systems with metal rich primaries and chemically normal secondaries such as V380 Ori and HD72106. This is in contrast to turbulence models which do not allow for abundance anomalies to develop on the pre-main-sequence. The age at which anomalies can appear depends on stellar mass. For A and F stars, the effects of atomic diffusion can modify both the internal and surface abundances before the onset of the MS. The appearance of important surface abundance anomalies on the pre-main-sequence does not require mass loss, though the mass loss rate affects their amplitude. Observational tests are suggested to decipher the effects of mass loss from those of turbulent mixing. If abundance anomalies are confirmed in pre-main-sequence stars they would severely limit the role of turbulence in these stars.Comment: 9 pages, 6 figures, accepeted for publicatio

Tropospheric Products from High-Level GNSS Processing in Latin America

ARTÍCULO PUBLICADO EN REVISTA EXTERNA. The present geodetic reference frame in Latin America and the Caribbean is given by a network of about 400 continuously operating GNSS stations. These stations are routinely processed by ten Analysis Centres following the guidelines and standards set up by the International Earth Rotation and Reference Systems Service (IERS) and International GNSS Service (IGS). The Analysis Centres estimate daily and weekly station positions and station zenith tropospheric path delays (ZTD) with an hourly sampling rate. This contribution presents some attempts aiming at combining the individual ZTD estimations to generate consistent troposphere solutions over the entire region and to provide reliable time series of troposphere parameters, to be used as a reference. The study covers ZTD and IWV series for a time-span of 5 years (2014–2018). In addition to the combination of the individual solutions, some advances based on the precise point positioning technique using BNC software (BKG NTRIP Client) and Bernese GNSS Software V.5.2 are presented. Results are validated using the IGS ZTD products and radiosonde IWV data. The agreement was evaluated in terms of mean bias and rms of the ZTD differences w.r.t IGS products (mean bias 1.5 mm and mean rms 6.8 mm) and w.r.t ZTD from radiosonde data (mean bias 2 mm and mean rms 7.5 mm). IWV differences w.r.t radiosonde IWV data (mean bias 0.41 kg/m2 and mean rms 3.5 kg/m2).Sitio de la revista: https://link.springer.com/chapter/10.1007/1345_2020_12

Carry-over of aflatoxin B1-feed into aflatoxin M1-milk in dairy cows treated with natural sources of aflatoxin and bentonite

High occurrence of aflatoxin contamination in feed stuffs implicates for a long time experience of aflatoxin B1 (AFB1) exposure to dairy cattle in Indonesia. A latin square 4X4 research design was adopted to study the characteristic of AFB1 carry-over rate (COR) of Indonesian crossbred Friesian Holstein (PFH) as effects of inclusions of AFB1-naturally contaminated feed and bentonite in the diet. Results showed a rapid aflatoxin M1 (AFM1) excretion in the milk, detected in the first milking sample or 10 hours after AFB1 ingestion. The steady state of AFM1 concentration observed since the first day of treatment period and AFM1 contamination was still detected until 5 days after AFB1 removed from the diet. The COR in this study was observed 0.1%. AFM1 concentration was highly significantly (P0.05) of levels of AFB1 and bentonite inclusions on the COR, nutrients intake, milk production, and milk composition. IIt is concluded that AFM1 concentration was influenced by AFB1 intake and that transfer of AFB1-feed into AFM1-milk (COR) in PFH cow was lower compare to reported COR value for dairy cow in sub tropical region

Solar models and solar neutrino oscillations

We provide a summary of the current knowledge, theoretical and experimental, of solar neutrino fluxes and of the masses and mixing angles that characterize solar neutrino oscillations. We also summarize the principal reasons for doing new solar neutrino experiments and what we think may be learned from the future measurements.Comment: Submitted to the Neutrino Focus Issue of New Journal of Physics at http://www.njp.or

Detection of an inner gaseous component in a Herbig Be star accretion disk: Near- and mid-infrared spectro-interferometry and radiative transfer modeling of MWC 147

We study the geometry and the physical conditions in the inner (AU-scale) circumstellar region around the young Herbig Be star MWC 147 using long-baseline spectro-interferometry in the near-infrared (NIR K-band, VLTI/AMBER observations and PTI archive data) as well as the mid-infrared (MIR N-band, VLTI/MIDIobservations). The emission from MWC 147 is clearly resolved and has a characteristic physical size of approx. 1.3 AU and 9 AU at 2.2 micron and 11 micron respectively (Gaussian diameter). The spectrally dispersed AMBER and MIDI interferograms both show a strong increase in the characteristic size towards longer wavelengths, much steeper than predicted by analytic disk models assuming power-law radial temperature distributions. We model the interferometric data and the spectral energy distribution of MWC 147 with 2-D, frequency-dependent radiation transfer simulations. This analysis shows that models of spherical envelopes or passive irradiated Keplerian disks (with vertical or curved puffed-up inner rim) can easily fit the SED, but predict much lower visibilities than observed; the angular size predicted by such models is 2 to 4 times larger than the size derived from the interferometric data, so these models can clearly be ruled out. Models of a Keplerian disk with optically thick gas emission from an active gaseous disk (inside the dust sublimation zone), however, yield a good fit of the SED and simultaneously reproduce the absolute level and the spectral dependence of the NIR and MIR visibilities. We conclude that the NIR continuum emission from MWC 147 is dominated by accretion luminosity emerging from an optically thick inner gaseous disk, while the MIR emission also contains contributions from the outer, irradiated dust disk.Comment: 44 pages, 15 figures, accepted for publication in The Astrophysical Journal. The quality of the figures was slightly reduced in order to comply with the astro-ph file-size restrictions. You can find a high-quality version of the paper at http://www.mpifr-bonn.mpg.de/staff/skraus/papers/mwc147.pd