Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent ...studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. To better understand MIF's activity in growth control, we generated and characterized a strain of MIF-knockout (MIF-KO) mice in the inbred, C57BL/6 background. Embryonic fibroblasts from MIF-KO mice exhibit p53-dependent growth alterations, increased p53 transcriptional activity, and resistance to ras-mediated transformation. Concurrent deletion of the p53 gene in vivo reversed the observed phenotype of cells deficient in MIF. In vivo studies showed that fibrosarcomas induced by the carcinogen benzoαpyrene are smaller in size and have a lower mitotic index in MIF-KO mice relative to their WT counterparts. The data provide direct genetic evidence for a functional link between MIF and the p53 tumor suppressor and indicate an important and previously unappreciated role for MIF in carcinogenesis.
Clostridium difficile infection (CDI) is the most important infective cause of healthcare-associated diarrhoea in high income countries and one of the most important healthcare-associated pathogens ...in both Europe and the United States. It is associated with high morbidity and mortality resulting in both societal and financial burden. A significant proportion of this burden is potentially preventable by a combination of targeted infection prevention and control measures and antimicrobial stewardship. The aim of this guidance document is to provide an update on recommendations for prevention of CDI in acute care settings to provide guidance to those responsible for institutional infection prevention and control programmes.
An expert group was set up by the European society of clinical microbiology and infectious diseases (ESCMID) Study Group for C. difficile (ESGCD), which performed a systematic review of the literature on prevention of CDI in adults hospitalized in acute care settings and derived respective recommendations according to the GRADE approach. Recommendations are stratified for both outbreak and endemic settings.
This guidance document provides thirty-six statements on strategies to prevent CDI in acute care settings, including 18 strong recommendations. No recommendation was provided for three questions.
The Triassic-Jurassic transition marks an important change in the basin configuration of the Greater Barents Sea. A contiguous basin with km-thick sedimentary successions changed into a partitioned ...basin with uplift in the west and foreland basins in the east with significant implication for the basin infill history. Our study employs a range of different high-resolution datasets from a distal part of the basin which unravels the complex pattern of differential uplift and erosion in the basin during this period.
We record for the first time distinct angular unconformities between Upper Triassic strata and overlying Lower Jurassic strata within the basin, showing that large parts of it formed topographic highs. Our study links these angular unconformities to compression induced by the Novaya Zemlya Fold and Thrust Belt. A heterolithic basement below a thick sedimentary succession where the fold belt developed created a complex uplift pattern in the basin, at the same time similar to but different from typical forebulge areas. Compression caused inversion of older basement rooted faults defining platforms and graben systems throughout western parts of the Barents Sea basin, in addition to salt remobilization that resulted in differential uplift and erosion. These local zones of uplift controlled the sediment distribution pattern to the basin at a time when the most important reservoir units in the basin were deposited. This new understanding of the basin development explains hitherto enigmatic sequence boundaries that has inspired complex paleogeographic models in the past.
•Compression-induced uplift of sedimentary basin•Tectonic control on distribution of reservoir rocks•Impact of Novaya Zemlya Fold and Thrust Belt•Northward continuation and late stage evolution of the Uralide orogeny•Remobilization of salt
The rotational states of the members in the dwarf planet-satellite systems in the trans-Neptunian region are determined by formation conditions and the tidal interaction between the components. These ...rotational characteristics serve as prime tracers of their evolution. A number of authors have claimed a very broad range of values for the rotation period for the dwarf planet Eris, ranging from a few hours to a rotation that is (nearly) synchronous with the orbital period (15.8 d) of its satellite, Dysnomia. In this Letter, we present new light curve data for Eris, taken with ∼1–2 m-class ground based telescopes and with the TESS and
Gaia
space telescopes. The TESS data did not provide a well-defined light curve period, but it could be used to constrain light curve variations to a maximum possible light curve amplitude of Δ
m
≤ 0.03 mag (1-
σ
) for
P
≤ 24 h periods. Both the combined ground-based data and
Gaia
measurements unambiguously point to a light curve period equal to the orbital period of Dysnomia,
P
= 15.8 d, with a light curve amplitude of Δ
m
≈ 0.03 mag, indicating that the rotation of Eris is tidally locked. Assuming that Dysnomia has a collisional origin, calculations with a simple tidal evolution model show that Dysnomia must be relatively massive (mass ratio of
q
= 0.01–0.03) and large (radius of
R
s
≥ 300 km) to have the potential to slow Eris down to a synchronised rotation. These simulations also indicate that (assuming tidal parameters usually considered for trans-Neptunian objects) the density of Dysnomia should be 1.8–2.4 g cm
−3
. This is an exceptionally high value among similarly sized trans-Neptunian objects, setting important constraints on their formation conditions.
Non-resolved thermal infrared observations enable studies of thermal and physical properties of asteroids via thermo-physical models provided the shape and rotational properties of the target are ...well determined. We used calibration-programme
Herschel
PACS data (70, 100, 160
μ
m) and state-of-the-art shape models derived from adaptive-optics observations and/or optical light curves to constrain for the first time the thermal inertia of twelve large main-belt asteroids. We also modelled previously well-characterised targets such as (1) Ceres or (4) Vesta as they constitute important benchmarks. Using the scale as a free parameter, most targets required a re-scaling ~5% consistent with what would be expected given the absolute calibration error bars. This constitutes a good cross-validation of the scaled shape models, although some targets required larger re-scaling to reproduce the IR data. We obtained low thermal inertias typical of large main belt asteroids studied before, which continues to give support to the notion that these surfaces are covered by fine-grained insulating regolith. Although the wavelengths at which PACS observed are longwards of the emission peak for main-belt asteroids, they proved to be extremely valuable to constrain size and thermal inertia and not too sensitive to surface roughness. Finally, we also propose a graphical approach to help examine how different values of the exponent used for scaling the thermal inertia as a function of heliocentric distance (i.e. temperature) affect our interpretation of the results.
Objective
White matter (WM) alterations have been reported in children and adults with autism spectrum disorder (ASD). In particular, impaired connectivity of limbic structures may be related to ...social deficits. Heterogeneous findings could be explained in terms of differences in sample characteristics and methodology. In this context, non‐syndromic forms might differ substantially in WM structure from secondary ASD forms.
Method
In an attempt to recruit a homogeneous study sample, we included adults with high‐functioning ASD and an IQ > 100 to decrease the influence of syndromic forms being often associated with cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30 participants with ASD and 30 pairwise‐matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were calculated.
Results
We found a significant FA decrease in the ASD group in the genu and body of the corpus callosum (CC). Increased MD was detected in the subgenual anterior cingulate cortex (sACC).
Conclusion
The finding of decreased WM integrity in the genu of the CC is in line with earlier studies reporting a decreased number of interhemispheric fibers in the frontal lobe of ASD. Alterations in the sACC might be associated with ‘Theory of mind’ deficits.
Considerable progress has been made in identifying the molecular composition of complex signaling networks controlling cell proliferation, differentiation, and survival. However, to discover general ...building principles and predict the dynamic behavior of signaling networks, it is necessary to develop quantitative models based on experimental observations. Here we report a mathematical model of the core module of the Janus family of kinases (JAK)-signal transducer and activator of transcription (STAT) signaling pathway based on time-resolved measurements of receptor and STAT5 phosphorylation. Applying the fitted model, we can determine the quantitative behavior of STAT5 populations not accessible to experimental measurement. By in silico investigations, we identify the parameters of nuclear shuttling as the most sensitive to perturbations and verify experimentally the model prediction that inhibition of nuclear export results in a reduced transcriptional yield. The model reveals that STAT5 undergoes rapid nucleocytoplasmic cycles, continuously coupling receptor activation and target gene transcription, thereby forming a remote sensor between nucleus and receptor. Thus, dynamic modeling of signaling pathways can promote functional understanding at the systems level.
Context. Physical characterization of trans-Neptunian objects, a primitive population of the outer solar system, may provide constraints on their formation and evolution. Aims. The goal of this work ...is to characterize a set of 15 scattered disk (SDOs) and detached objects, in terms of their size, albedo, and thermal properties. Methods. Thermal flux measurements obtained with the Herschel-PACS instrument at 70, 100 and 160 mu m, and whenever applicable, with Spitzer-MIPS at 24 and 70 mu m, are modeled with radiometric techniques, in order to derive the objects' individual size, albedo and when possible beaming factor. Error bars are obtained from a Monte-Carlo approach. We look for correlations between these and other physical and orbital parameters. Results. Diameters obtained for our sample range from 100 to 2400 km, and the geometric albedos (in V band) vary from 3.8% to 84.5%. The unweighted mean V geometric albedo for the whole sample is 11.2% (excluding Eris); 6.9% for the SDOs, and 17.0% for the detached objects (excluding Eris). We obtain new bulk densities for three binary systems: Ceto/Phorcys, Typhon/Echidna and Eris/Dysnomia. Apart from correlations clearly due to observational bias, we find significant correlations between albedo and diameter (more reflective objects being bigger), and between albedo, diameter and perihelion distance (brighter and bigger objects having larger perihelia). We discuss possible explanations for these correlations.
The goal of this work is to determine the physical characteristics of resonant, detached and scattered disk objects in the trans-Neptunian region, observed mainly in the framework of the “TNOs are ...Cool”
Herschel
open time key programme. Based on thermal emission measurements with the
Herschel
/PACS and
Spitzer
/MIPS instruments, we determine size, albedo, and surface thermal properties for 23 objects using radiometric modeling techniques. This is the first analysis in which the physical properties of objects in the outer resonances are determined for a notable sample. In addition to the results for individual objects, we compared these characteristics with the bulk properties of other populations of the trans-Neptunian region. The newly analyzed objects show a large variety of beaming factors, indicating a diversity of thermal properties, and in general they follow the albedo-color clustering identified earlier for Kuiper belt objects and Centaurs, further strengthening the evidence for a compositional discontinuity in the young Solar System.
The goal of this work is to characterize the ensemble thermal properties of the Centaurs / trans-Neptunian population. Thermal flux measurements obtained with Herschel/PACS and Spitzer/MIPS provide ...size, albedo, and beaming factors for 85 objects (13 of which are presented here for the first time) by means of standard radiometric techniques. The measured beaming factors are influenced by the combination of surface roughness and thermal inertia effects. Our results suggest highly porous surfaces, in which the heat transfer is affected by radiative conductivity within pores and increases with depth in the subsurface.
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