Summary
Cultured human myoblasts fail to immortalize following the introduction of telomerase. The availability of an immortalization protocol for normal human myoblasts would allow one to isolate ...cellular models from various neuromuscular diseases, thus opening the possibility to develop and test novel therapeutic strategies. The parameters limiting the efficacy of myoblast transfer therapy (MTT) could be assessed in such models. Finally, the presence of an unlimited number of cell divisions, and thus the ability to clone cells after experimental manipulations, reduces the risks of insertional mutagenesis by many orders of magnitude. This opportunity for genetic modification provides an approach for creating a universal donor that has been altered to be more therapeutically useful than its normal counterpart. It can be engineered to function under conditions of chronic damage (which are very different than the massive regeneration conditions that recapitulate normal development), and to overcome the biological problems such as cell death and failure to proliferate and migrate that limit current MTT strategies. We describe here the production and characterization of a human myogenic cell line, LHCN‐M2, that has overcome replicative aging due to the expression of telomerase and cyclin‐dependent kinase 4. We demonstrate that it functions as well as young myoblasts in xenotransplant experiments in immunocompromized mice under conditions of regeneration following muscle damage.
Abstract We present a JWST imaging survey of I Zw 18, the archetypal extremely metal-poor, star-forming (SF), blue compact dwarf galaxy. With an oxygen abundance of only ∼3% Z ⊙ , it is among the ...lowest-metallicity systems known in the local Universe, and is, therefore, an excellent accessible analog for the galactic building blocks which existed at early epochs of ionization and star formation. These JWST data provide a comprehensive infrared (IR) view of I Zw 18 with eight filters utilizing both Near Infrared Camera (F115W, F200W, F356W, and F444W) and Mid-Infrared Instrument (F770W, F1000W, F1500W, and F1800W) photometry, which we have used to identify key stellar populations that are bright in the near- and mid-IR. These data allow for a better understanding of the origins of dust and dust-production mechanisms in metal-poor environments by characterizing the population of massive, evolved stars in the red supergiant (RSG) and asymptotic giant branch (AGB) phases. In addition, it enables the identification of the brightest dust-enshrouded young stellar objects (YSOs), which provide insight into the formation of massive stars at extremely low metallicities typical of the very early Universe. This paper provides an overview of the observational strategy and data processing, and presents first science results, including identifications of dusty AGB, RSG, and bright YSO candidates. These first results assess the scientific quality of JWST data and provide a guide for obtaining and interpreting future observations of the dusty and evolved stars inhabiting compact dwarf SF galaxies in the local Universe.
Context
. The Medium Resolution integral field Spectrometer (MRS) of the Mid-Infrared Instrument (MIRI) on board the
James Webb
Space Telescope (JWST) performs spectroscopy between 5 and 28 µm, with ...a field of view varying from ~13 to ~56 sq. arcsec. The optics of the MRS introduce substantial distortion and this needs to be rectified in order to reconstruct the observed astrophysical scenario.
Aims
. We aim to use data from the JWST/MIRI commissioning and cycle 1 calibration phase to derive the MRS geometric distortion and astrometric solution, a critical step in the calibration of MRS data. These solutions come in the form of transform matrices that map the detector pixels to spatial coordinates of a local MRS coordinate system called
α
/
β
, to the global JWST observatory coordinates
V
2 and
V
3 (
V
2+
V
3).
Methods
. For every MRS spectral band and each slice dispersed on the detector, we fit the transform of detector pixels to
α
/
β
by a two-dimensional (2D) polynomial, using a raster of point source observations. The dispersed trace of the point source on the detector was initially estimated by fitting a one-dimensional (1D) empirical function and then iterating on the first distortion solution using forward modelling of the point spread function model based on the
webbpsf python
package. A polynomial transform was used to map the coordinates from α/
β
to
V
2+
V
3.
Results
. We calibrated the distortion of all 198 discrete slices of the MIRI/MRS integral field units and derived an updated field of view (FoV) for each MRS spectral band. The precision of the distortion solution is estimated to be better than one-tenth of a spatial resolution element, with a root mean square (rms) of 10 milli-arc-second (mas) at 5 µm, to 23 mas at 27 µm. Finally, we found that the wheel positioning repeatability causes an additional astrometric rms error of 30 mas.
Conclusions
. We demonstrate the application of the MRS astrometric calibration strategy and analysis for all four integral field units and all spectral bands of the MRS that enable the calibration of MRS spectra. This is a critical step in the data pipeline of every MRS observation. The distortion calibration was folded into the JWST pipeline in the Calibration Reference Data System (CRDS) context (jwst_1094.pmap), meeting the pre-launch requirement, with an estimated total astrometric uncertainty of 50 mas.
The James Webb space telescope GARDNER, Jonathan P; MATHER, John C; LUNINE, Jonathan I ...
Space science reviews,
01/2006, Letnik:
123, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Issue Title: The James Webb Space Telescope The James Webb Space Telescope (JWST) is a large (6.6 m), cold (<50 K), infrared (IR)-optimized space observatory that will be launched early in the next ...decade into orbit around the second Earth-Sun Lagrange point. The observatory will have four instruments: a near-IR camera, a near-IR multiobject spectrograph, and a tunable filter imager will cover the wavelength range, 0.6 < ; < 5.0 μ m, while the mid-IR instrument will do both imaging and spectroscopy from 5.0 < ; < 29 μ m. The JWST science goals are divided into four themes. The key objective of The End of the Dark Ages: First Light and Reionization theme is to identify the first luminous sources to form and to determine the ionization history of the early universe. The key objective of The Assembly of Galaxies theme is to determine how galaxies and the dark matter, gas, stars, metals, morphological structures, and active nuclei within them evolved from the epoch of reionization to the present day. The key objective of The Birth of Stars and Protoplanetary Systems theme is to unravel the birth and early evolution of stars, from infall on to dust-enshrouded protostars to the genesis of planetary systems. The key objective of the Planetary Systems and the Origins of Life theme is to determine the physical and chemical properties of planetary systems including our own, and investigate the potential for the origins of life in those systems. Within these themes and objectives, we have derived representative astronomical observations. To enable these observations, JWST consists of a telescope, an instrument package, a spacecraft, and a sunshield. The telescope consists of 18 beryllium segments, some of which are deployed. The segments will be brought into optical alignment on-orbit through a process of periodic wavefront sensing and control. The instrument package contains the four science instruments and a fine guidance sensor. The spacecraft provides pointing, orbit maintenance, and communications. The sunshield provides passive thermal control. The JWST operations plan is based on that used for previous space observatories, and the majority of JWST observing time will be allocated to the international astronomical community through annual peer-reviewed proposal opportunities.PUBLICATION ABSTRACT
Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that ...neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV.
Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better ...understanding of genetic and environmental influences on methylation.
We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM.
The correlation in GWAM for twin pairs was ∼0.8 at birth, decreased with age during adolescence and was constant at ∼0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 95% confidence interval (CI): 0.05-0.30 to 0.28 (95% CI: 0.08-0.48), except for middle-aged siblings (0.01, 95% CI: -0.10-0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95% CI: 0.3-0.43) to 0.31 (95% CI: 0.05-0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90% (95% CI: 74-95%) at birth, decreased in early life and plateaued at 28% (95% CI: 17-39%) in middle age and beyond. There was a cohabitation-related environmental component of variance.
GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.
Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFβ and perhaps additional mechanisms. ...Proepithelin (PEPI), an epithelial growth factor, can be converted to epithelins (EPIs) in vivo by unknown mechanisms with unknown consequences. We found that PEPI and EPIs exert opposing activities. EPIs inhibit the growth of epithelial cells but induce them to secrete the neutrophil attractant IL-8, while PEPI blocks neutrophil activation by tumor necrosis factor, preventing release of oxidants and proteases. SLPI and PEPI form complexes, preventing elastase from converting PEPI to EPIs. Supplying PEPI corrects the wound-healing defect in SLPI null mice. Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface between innate immunity and wound healing.
On 24th March, the world commemorates the day in 1882 when Dr Robert Koch announced his discovery of
Mycobacterium tuberculosis (MTB). Over 130 years later, tuberculosis (TB) continues to affect ...individuals, communities, and entire health systems and economies. Koch unsuccessfully tried to 'cure' TB, and despite major advances in other areas of medicine, control of TB remains elusive- in 2016 TB was the leading infectious cause of death. The STOP TB partnership and World Health Organization (WHO) have announced their theme for World TB Day 2018 "Wanted: Leaders for a TB-Free World. You can make history. End TB." This theme recognizes that TB is much larger than any one person, institute or discipline of research, and provides an opportunity for us to reflect on the major challenges and consider how we, as a scientific community, can work together and take the lead to address the global crisis of drug-resistant TB (DR-TB).
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