122 research outputs found
The product of the split ends gene is required for the maintenance of positional information during Drosophila development
BACKGROUND: The Drosophila split ends (spen) gene encodes a large nuclear protein containing three RNP-type RNA binding motifs, and a conserved transcriptional co-repressor-interacting domain at the C-terminus. Genetic analyses indicate that spen interacts with pathways that regulate the function of Hox proteins, the response to various signaling cascades and cell cycle control. Although spen mutants affect only a small subset of morphological structures in embryos, it has been difficult to find a common theme in spen mutant structural alterations, or in the interactions of spen with known signaling pathways. RESULTS: By generating clones of spen mutant cells in wing imaginal discs, we show that spen function is required for the correct formation and positioning of veins and mechanosensory bristles both on the anterior wing margin and on the notum, and for the maintenance of planar polarity. Wing vein phenotypic alterations are enhanced by mutations in the crinkled (ck) gene, encoding a non-conventional myosin, and correlate with an abnormal spatial expression of Delta, an early marker of vein formation in third instar wing imaginal discs. Positioning defects were also evident in the organization of the embryonic peripheral nervous system, accompanied by abnormal E-Cadherin expression in the epidermis. CONCLUSIONS: The data presented indicate that the role of spen is necessary to maintain the correct positioning of cells within a pre-specified domain throughout development. Its requirement for epithelial planar polarity, its interaction with ck, and the abnormal E-Cadherin expression associated with spen mutations suggest that spen exerts its function by interacting with basic cellular mechanisms required to maintain multicellular organization in metazoans. This role for spen may explain why mutations in this gene interact with the outcome of multiple signaling pathways
Status and challenges of electrical stimulation use in chronic wound healing:Reviewing chronic wound bioelectricity principles
High-resolution near-IR Spectral mapping with H and [Fe II] lines of Multiple Outflows around LkH 234
We present a high-resolution, near-IR spectroscopic study of multiple
outflows in the LkH 234 star formation region using the Immersion
GRating INfrared Spectrometer (IGRINS). Spectral mapping over the blueshifted
emission of HH 167 allowed us to distinguish at least three separate, spatially
overlapped, outflows in H and [Fe II] emission. We show that the H
emission represents not a single jet, but complex multiple outflows driven by
three known embedded sources: MM1, VLA 2, and VLA 3. There is a redshifted
H outflow at a low velocity, \VLSR 50 {\kms}, with respect to
the systemic velocity of \VLSR 11.5 {\kms}, that coincides with the
HO masers seen in earlier radio observations two arcseconds southwest of
VLA 2. We found that the previously detected [Fe II] jet with \VLSR
100 {\kms} driven by VLA 3B is also detected in H emission, and confirm
that this jet has a position angle about 240. Spectra of the
redshifted knots at 14\arcsec65\arcsec northeast of LkH 234 are
presented for the first time. These spectra also provide clues to the existence
of multiple outflows. We detected high-velocity (50120 {\kms}) H gas
in the multiple outflows around LkH 234. Since these gases move at
speeds well over the dissociation velocity ( 40 {\kms}), the emission must
originate from the jet itself rather than H gas in the ambient medium.
Also, position-velocity diagrams and excitation diagram indicate that emission
from knot C in HH 167 come from two different phenomena, shocks and
photodissociation.Comment: 32 pages, 12 figures, 2 tables, Accepted for publication in the
Astrophysical Journa
Effective Temperatures of Low-Mass Stars from High-Resolution H-band Spectroscopy
High-resolution, near-infrared spectra will be the primary tool for finding
and characterizing Earth-like planets around low-mass stars. Yet, the
properties of exoplanets can not be precisely determined without accurate and
precise measurements of the host star. Spectra obtained with the Immersion
GRating INfrared Spectrometer (IGRINS) simultaneously provide diagnostics for
most stellar parameters, but the first step in any analysis is the
determination of the effective temperature. Here we report the calibration of
high-resolution H-band spectra to accurately determine effective temperature
for stars between 4000-3000 K (K8--M5) using absorption line depths of Fe
I, OH, and Al I. The field star sample used here contains 254 K and M stars
with temperatures derived using BT-Settl synthetic spectra. We use 106 stars
with precise temperatures in the literature to calibrate our method with
typical errors of about 140 K, and systematic uncertainties less than 120
K. For the broadest applicability, we present T--line-depth-ratio
relationships, which we test on 12 members of the TW Hydrae Association and at
spectral resolving powers between 10,000--120,000. These ratios offer a
simple but accurate measure of effective temperature in cool stars that is
distance and reddening independent.Comment: 19 pages, 11 figures and 3 tables. Accepted in Ap
Tissue iron promotes wound repair via M2 macrophage polarisation and the chemokines CCL17 and CCL22
Macrophages are important for effective iron recycling and erythropoiesis, but they also play a crucial role in wound healing, orchestrating tissue repair. Recently, we demonstrated a significant accumulation of iron in healing wounds and a requirement of iron for effective repair. Herein, we sought to determine the influence of iron on macrophage function in the context of wound healing. Interestingly, wound macrophages extensively sequestered iron throughout healing, associated with a prohealing M2 phenotype. In delayed healing diabetic mouse wounds, both macrophage polarization and iron sequestration were impaired. In vitro studies revealed that iron promotes differentiation, while skewing macrophages toward a hypersecretory M2-like polarization state. These macrophages produced high levels of chemokine (C-C motif) ligands 17 and 22, promoting wound reepithelialization and extracellular matrix deposition in a human ex vivo wound healing model. Together, these findings reveal a novel, unappreciated role for iron in modulating macrophage behavior to promote subsequent wound repair. These findings support therapeutic evaluation of iron use to promote wound healing in the clinic
Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.
AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130
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