Diabetes is a systemic disease in which the body cannot regulate the amount of sugar, namely glucose, in the blood. High glucose toxicity has been implicated in the dysfunction of diabetic wound ...healing, following insufficient production (Type 1) or inadequate usage (Type 2) of insulin. Chronic non‐healing diabetic wounds are one of the major complications of both types of diabetes, which are serious concerns for public health and can impact the life quality of patients significantly. In general, diabetic wounds are characterized by deficient chemokine production, an unusual inflammatory response, lack of angiogenesis and epithelialization, and dysfunction of fibroblasts. Increasing scientific evidence from available experimental studies on animal and cell models strongly associates impaired wound healing in diabetes with dysregulated fibroblast differentiation to myofibroblasts, interrupted myofibroblast activity, and inadequate extracellular matrix production. Myofibroblasts play an important role in tissue repair by producing and organizing extracellular matrix and subsequently promoting wound contraction. Based on these studies, hyperglycaemic conditions can interfere with cytokine signalling pathways (such as growth factor‐β pathway) affecting fibroblast differentiation, alter fibroblast apoptosis, dysregulate dermal lipolysis, and enhance hypoxia damage, thus leading to damaged microenvironment for myofibroblast formation, inappropriate extracellular matrix modulation, and weakened wound contraction. In this review, we will focus on the current available studies on the impact of diabetes on fibroblast differentiation and myofibroblast function, as well as potential treatments related to the affected pathways.
Cometary nuclei consist mostly of dust and water ice. Previous observations have found nuclei to be low-density and highly porous bodies, but have only moderately constrained the range of allowed ...densities because of the measurement uncertainties. Here we report the precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov-Gerasimenko on the basis of its gravity field. The mass and gravity field are derived from measured spacecraft velocity perturbations at fly-by distances between 10 and 100 kilometres. The gravitational point mass is GM = 666.2 ± 0.2 cubic metres per second squared, giving a mass M = (9,982 ± 3) × 10(9) kilograms. Together with the current estimate of the volume of the nucleus, the average bulk density of the nucleus is 533 ± 6 kilograms per cubic metre. The nucleus appears to be a low-density, highly porous (72-74 per cent) dusty body, similar to that of comet 9P/Tempel 1. The most likely composition mix has approximately four times more dust than ice by mass and two times more dust than ice by volume. We conclude that the interior of the nucleus is homogeneous and constant in density on a global scale without large voids. The high porosity seems to be an inherent property of the nucleus material.
Context. During the period between 15 September 2014 and 4 February 2015, the Rosetta spacecraft accomplished the circular orbit phase around the nucleus of comet 67P/Churyumov-Gerasimenko (67P). The ...Grain Impact Analyzer and Dust Accumulator (GIADA) onboard Rosetta monitored the 67P coma dust environment for the entire period. Aims. We aim to describe the dust spatial distribution in the coma of comet 67P by means of in situ measurements. We determine dynamical and physical properties of cometary dust particles to support the study of the production process and dust environment modification. Methods. We analyzed GIADA data with respect to the observation geometry and heliocentric distance to describe the coma dust spatial distribution of 67P, to monitor its activity, and to retrieve information on active areas present on its nucleus. We combined GIADA detection information with calibration activity to distinguish different types of particles that populate the coma of 67P: compact particles and fluffy porous aggregates. By means of particle dynamical parameters measured by GIADA, we studied the dust acceleration region. Results. GIADA was able to distinguish different types of particles populating the coma of 67P: compact particles and fluffy porous aggregates. Most of the compact particle detections occurred at latitudes and longitudes where the spacecraft was in view of the comet’s neck region of the nucleus, the so-called Hapi region. This resulted in an oscillation of the compact particle abundance with respect to the spacecraft position and a global increase as the comet moved from 3.36 to 2.43 AU heliocentric distance. The speed of these particles, having masses from 10-10 to 10-7 kg, ranged from 0.3 to 12.2 m s-1. The variation of particle mass and speed distribution with respect to the distance from the nucleus gave indications of the dust acceleration region. The influence of solar radiation pressure on micron and submicron particles was studied. The integrated dust mass flux collected from the Sun direction, that is, particles reflected by solar radiation pressure, was three times higher than the flux coming directly from the comet nucleus. The awakening 67P comet shows a strong dust flux anisotropy, confirming what was suggested by on-ground dust coma observations performed in 2008.
Abstract
Dmc1 catalyzes homology search and strand exchange during meiotic recombination in budding yeast and many other organisms including humans. Here we reconstitute Dmc1 recombination in vitro ...using six purified proteins from budding yeast including Dmc1 and its accessory proteins RPA, Rad51, Rdh54/Tid1, Mei5-Sae3 and Hop2-Mnd1 to promote D-loop formation between ssDNA and dsDNA substrates. Each accessory protein contributed to Dmc1's activity, with the combination of all six proteins yielding optimal activity. The ssDNA binding protein RPA plays multiple roles in stimulating Dmc1's activity including by overcoming inhibitory effects of ssDNA secondary structure on D-loop reactions, and by elongating D-loops. In addition, we demonstrate that RPA limits inhibitory interactions of Hop2-Mnd1 and Rdh54/Tid1 that otherwise occur during assembly of Dmc1-ssDNA nucleoprotein filaments. Finally, we report interactions between the proteins employed in the biochemical reconstitution including a direct interaction between Rad51 and Dmc1 that is enhanced by Mei5-Sae3.
Context. Near-Earth asteroid (25143) Itokawa was visited by the Hayabusa spacecraft in 2005, resulting in a highly detailed shape and surface topography model. This model has led to several ...predictions for the expected radiative torques on this asteroid, suggesting that its spin rate should be decelerating. Aims. To detect changes in rotation rate that may be due to YORP-induced radiative torques, which in turn may be used to investigate the interior structure of the asteroid. Methods. Through an observational survey spanning 2001 to 2013 we obtained rotational lightcurve data at various times over the last five close Earth-approaches of the asteroid. We applied a polyhedron-shape-modelling technique to assess the spin-state of the asteroid and its long term evolution. We also applied a detailed thermophysical analysis to the shape model determined from the Hayabusa spacecraft. Results. We have successfully measured an acceleration in Itokawa’s spin rate of dω/dt = (3.54 ± 0.38) × 10-8 rad day-2, equivalent to a decrease of its rotation period of ~45 ms year-1. From the thermophysical analysis we find that the centre-of-mass for Itokawa must be shifted by ~21 m along the long-axis of the asteroid to reconcile the observed YORP strength with theory. Conclusions. This can be explained if Itokawa is composed of two separate bodies with very different bulk densities of 1750 ± 110 kg m-3 and 2850 ± 500 kg m-3, and was formed from the merger of two separate bodies, either in the aftermath of a catastrophic disruption of a larger differentiated body, or from the collapse of a binary system. We therefore demonstrate that an observational measurement of radiative torques, when combined with a detailed shape model, can provide insight into the interior structure of an asteroid. Futhermore, this is the first measurement of density inhomogeneity within an asteroidal body, that reveals significant internal structure variation. A specialised spacecraft is normally required for this.
The DIR2s RNA aptamer, a second-generation, in-vitro selected binder to dimethylindole red (DIR), activates the fluorescence of cyanine dyes, DIR and oxazole thiazole blue (OTB), allowing detection ...of two well-resolved emission colors. Using Fab BL3-6 and its cognate hairpin as a crystallization module, we solved the crystal structures of both the apo and OTB-SO
bound forms of DIR2s at 2.0 Å and 1.8 Å resolution, respectively. DIR2s adopts a compact, tuning fork-like architecture comprised of a helix and two short stem-loops oriented in parallel to create the ligand binding site through tertiary interactions. The OTB-SO
fluorophore binds in a planar conformation to a claw-like structure formed by a purine base-triple, which provides a stacking platform for OTB-SO
and an unpaired nucleotide, which partially caps the binding site from the top. The absence of a G-quartet or base tetrad makes the DIR2s aptamer unique among fluorogenic RNAs with known 3D structure.
The JAXA Hayabusa-2 mission was approved in 2010 and launched on December 3, 2014. The spacecraft will arrive at the near-Earth asteroid 162173 Ryugu (1999 JU3) in 2018 where it will perform a ...survey, land and obtainsurface material, then depart in December 2019 and return to Earth in December 2020. We observed Ryugu with the Herschel Space Observatory in April 2012 at far-infrared thermal wavelengths, supported by several ground-based observations to obtain optical lightcurves. We reanalysed previously published Subaru-COMICS and AKARI-IRC observations and merged them with a Spitzer-IRS data set. In addition, we used a large set of Spitzer-IRAC observations obtained in the period January to May, 2013. The data set includes two complete rotational lightcurves and a series of ten “point-and-shoot” observations, all at 3.6 and 4.5 μm. The almost spherical shape of the target together with the insufficient lightcurve quality forced us to combine radiometric and lightcurve inversion techniques in different ways to find the object’s spin-axis orientation, its shape and to improve the quality of the key physical and thermal parameters. Handling thermal data in inversion techniques remains challenging: thermal inertia, roughness or local structures influence the temperature distribution on the surface. The constraints for size, spin or thermal properties therefore heavily depend on the wavelengths of the observations. We find that the solution which best matches our data sets leads to this C class asteroid having a retrograde rotation with a spin-axis orientation of (λ = 310°−340°; β = −40° ± ~ 15°) in ecliptic coordinates, an effective diameter (of an equal-volume sphere) of 850 to 880 m, a geometric albedo of 0.044 to 0.050 and a thermal inertia in the range 150 to 300 J m-2 s-0.5 K-1. Based on estimated thermal conductivities of the top-layer surface in the range 0.1 to 0.6 W K-1 m-1, we calculated that the grain sizes are approximately equal to between 1 and 10 mm. The finely constrained values for this asteroid serve as a “design reference model”, which is currently used for various planning, operational and modelling purposes by the Hayabusa-2 team.
Abstract
The Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect is a small thermal-radiation torque experienced by small asteroids, and is considered to be crucial in their physical and dynamical ...evolution. It is important to understand this effect by providing measurements of YORP for a range of asteroid types to facilitate the development of a theoretical framework. We are conducting a long-term observational study on a selection of near-Earth asteroids to support this. We focus here on (68346) 2001 KZ66, for which we obtained both optical and radar observations spanning a decade. This allowed us to perform a comprehensive analysis of the asteroid’s rotational evolution. Furthermore, radar observations from the Arecibo Observatory enabled us to generate a detailed shape model. We determined that (68346) is a retrograde rotator with its pole near the southern ecliptic pole, within a 15○ radius of longitude 170○ and latitude −85○. By combining our radar-derived shape model with the optical light curves, we developed a refined solution to fit all available data, which required a YORP strength of $(8.43\pm 0.69)\times 10^{-8} \rm ~rad ~d^{-2}$. (68346) has a distinct bifurcated shape comprising a large ellipsoidal component joined by a sharp neckline to a smaller non-ellipsoidal component. This object likely formed either from the gentle merging of a binary system or from the deformation of a rubble pile due to YORP spin-up. The shape exists in a stable configuration close to its minimum in topographic variation, where regolith is unlikely to migrate from areas of higher potential.
We present an updated cumulative size distribution (CSD) for Jupiter Family comet (JFC) nuclei, including a rigorous assessment of the uncertainty on the slope of the CSD. The CSD is expressed as a ...power law, N(>r
N) ∝r
−q
N, where r
N is the radius of the nuclei and q is the slope. We include a large number of optical observations published by us and others since the comprehensive review in the Comets II book, and make use of an improved fitting method. We assess the uncertainty on the CSD due to all of the unknowns and uncertainties involved (photometric uncertainty, assumed phase function, albedo and shape of the nucleus) by means of Monte Carlo simulations. In order to do this we also briefly review the current measurements of these parameters for JFCs. Our final CSD has a slope q= 1.92 ± 0.20 for nuclei with radius r
N≥ 1.25 km.
PDF
