200 research outputs found
Effects of insulin on intracellular GLUT4 vesicles in adipocytes: Evidence for a secretory mode of regulation
The facilitative glucose transporter, GLUT4 undergoes insulin-dependent movement to the cell surface in adipocytes, The magnitude of the insulin effect is much greater for CLUT4 than other recycling proteins such as the CD-MPR, In the present study we have studied the colocalisation of these proteins in adipocytes in an effort to explain this selective insulin-dependent recruitment of CLUT4, Using immunofluorescence microscopy or immuno-EM on 3T3-L1 adipocytes we find that there is considerable colocalisation between these proteins particularly within the area of the TGN, However, the distribution of CD-MPR was not significantly effected by insulin. The insulin-dependent recruitment of GLUT4 was concomitant with a selective decrease in GLUT4 labelling of cytoplasmic vesicles whereas the amount of CLUT4 in the TGN region (approx. 50% of total GLUT4) was relatively unaffected. To explore the possibility that the cytoplasmic GLUT4(+) vesicles represent an intracellular insulin-responsive storage compartment we performed quantitative immuno-EM on whole mounts of intracellular vesicles isolated from basal and insulin-stimulated adipocytes. These studies revealed that: (1) GLUT4 and CD-MPR were concentrated in small (30-200 nm) vesicles at a labelling density of 1-20+ gold particles/vesicle; (2) there was significant overlap between both proteins in that 70% of the total GLUT4 pool colocalised with CD-MPR; (3) a significant amount of GLUT4 (approx, 50% of total) was found in a subpopulation of vesicles that contained as little as 5% of the total CD-MPR pool; (4) the GLUT4(+)/CD-MPR(-) vesicles were highly insulin-responsive, and (5) the total number of GLUT4(+) vesicles, but not CD-MPR(+) vesicles, decreased by approx. 30% in response to insulin treatment. These data are consistent with a model in which GLUT4 is selectively sorted into a vesicular compartment in adipocytes that is recruited to the plasma membrane by insulin stimulation
Effects of microRNAs on angiogenesis in diabetic wounds
Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis
PBjam: A Python package for automating asteroseismology of solar-like oscillators
Asteroseismology is an exceptional tool for studying stars by using the
properties of observed modes of oscillation. So far the process of performing
an asteroseismic analysis of a star has remained somewhat esoteric and
inaccessible to non-experts. In this software paper we describe PBjam, an
open-source Python package for analyzing the frequency spectra of solar-like
oscillators in a simple but principled and automated way. The aim of PBjam is
to provide a set of easy-to-use tools to extract information about the radial
and quadrupole oscillations in stars that oscillate like the Sun, which may
then be used to infer bulk properties such as stellar mass, radius and age or
even structure. Asteroseismology and its data analysis methods are becoming
increasingly important as space-based photometric observatories are producing a
wealth of new data, allowing asteroseismology to be applied in a wide range of
contexts such as exoplanet, stellar structure and evolution, and Galactic
population studies.Comment: 12 Pages, 4 figures. Accepted for publication in AJ. Associated
software available at https://doi.org/10.5281/zenodo.430007
External validation of the Scandinavian guidelines for management of minimal, mild and moderate head injuries in children
© 2018 The Author(s). Background: Clinical decision rules (CDRs) aid in the management of children with traumatic brain injury (TBI). Recently, the Scandinavian Neurotrauma Committee (SNC) has published practical, evidence-based guidelines for children with Glasgow Coma Scale (GCS) scores of 9-15. This study aims to validate these guidelines and to compare them with other CDRs. Methods: A large prospective cohort of children (< 18 years) with TBI of all severities, from ten Australian and New Zealand hospitals, was used to assess the SNC guidelines. Firstly, a validation study was performed according to the inclusion and exclusion criteria of the SNC guideline. Secondly, we compared the accuracy of SNC, CATCH, CHALICE and PECARN CDRs in patients with GCS 13-15 only. Diagnostic accuracy was calculated for outcome measures of need for neurosurgery, clinically important TBI (ciTBI) and brain injury on CT. Results: The SNC guideline could be applied to 19,007/20,137 of patients (94.4%) in the validation process. The frequency of ciTBI decreased significantly with stratification by decreasing risk according to the SNC guideline. Sensitivities for the detection of neurosurgery, ciTBI and brain injury on CT were 100.0% (95% CI 89.1-100.0; 32/32), 97.8% (94.5-99.4; 179/183) and 95% (95% CI 91.6-97.2; 262/276), respectively, with a CT/admission rate of 42% (mandatory CT rate of 5%, 18% CT or admission and 19% only admission). Four patients with ciTBI were missed; none needed specific intervention. In the homogenous comparison cohort of 18,913 children, the SNC guideline performed similar to the PECARN CDR, when compared with the other CDRs. Conclusion: The SNC guideline showed a high accuracy in a large external validation cohort and compares well with published CDRs for the management of paediatric TBI
The Star Formation Reference Survey. I. Survey Description and Basic Data
Star formation is arguably the most important physical process in the cosmos.
It is a fundamental driver of galaxy evolution and the ultimate source of most
of the energy emitted by galaxies. A correct interpretation of star formation
rate (SFR) measures is therefore essential to our understanding of galaxy
formation and evolution. Unfortunately, however, no single SFR estimator is
universally available or even applicable in all circumstances: the numerous
galaxies found in deep surveys are often too faint (or too distant) to yield
significant detections with most standard SFR measures, and until now there
have been no global, multi-band observations of nearby galaxies that span all
the conditions under which star-formation is taking place. To address this need
in a systematic way, we have undertaken a multi-band survey of all types of
star-forming galaxies in the local Universe. This project, the Star Formation
Reference Survey (SFRS), is based on a statistically valid sample of 369 nearby
galaxies that span all existing combinations of dust temperature, SFR, and
specific SFR. Furthermore, because the SFRS is blind with respect to AGN
fraction and environment it serves as a means to assess the influence of these
factors on SFR. Our panchromatic global flux measurements (including GALEX
FUV+NUV, SDSS ugriz, 2MASS JHKs, Spitzer 3-8{\mu}m, and others) furnish uniform
SFR measures and the context in which their reliability can be assessed. This
paper describes the SFRS survey strategy, defines the sample, and presents the
multi-band photometry collected to date.Comment: 48 pages, 12 figures, 10 tables. Accepted by PASP. This version
edited to correct references and typographical error
Queer Youth and the Culture Wars: From Classroom to Courtroom in Australia, Canada and the United States
This article builds on Lugg\u27s (2006) discussion of surveillance in public schools and how queer youth are resisting schools\u27 current efforts to regulate sexual orientation and gender expression in the U.S. and internationally. Legal complaints initiated by queer youth against their schools for harassment and access to extra-curricular activities are discussed. The number of cases in the past five years has increased significantly and the courts are siding with the youth and their allies, demonstrating that queer youth are significantly impacting the dismantling of heteronormative regulatory regimes and improving the school experiences for themselves and queer adults
INSGFP/w human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells
AIMS/HYPOTHESIS: We aimed to generate human embryonic stem cell (hESC) reporter lines that would facilitate the characterisation of insulin-producing (INS⁺) cells derived in vitro. METHODS: Homologous recombination was used to insert sequences encoding green fluorescent protein (GFP) into the INS locus, to create reporter cell lines enabling the prospective isolation of viable INS⁺ cells. RESULTS: Differentiation of INS(GFP/w) hESCs using published protocols demonstrated that all GFP⁺ cells co-produced insulin, confirming the fidelity of the reporter gene. INS-GFP⁺ cells often co-produced glucagon and somatostatin, confirming conclusions from previous studies that early hESC-derived insulin-producing cells were polyhormonal. INS(GFP/w) hESCs were used to develop a 96-well format spin embryoid body (EB) differentiation protocol that used the recombinant protein-based, fully defined medium, APEL. Like INS-GFP⁺ cells generated with other methods, those derived using the spin EB protocol expressed a suite of pancreatic-related transcription factor genes including ISL1, PAX6 and NKX2.2. However, in contrast with previous methods, the spin EB protocol yielded INS-GFP⁺ cells that also co-expressed the beta cell transcription factor gene, NKX6.1, and comprised a substantial proportion of monohormonal INS⁺ cells. CONCLUSIONS/INTERPRETATION: INS(GFP/w) hESCs are a valuable tool for investigating the nature of early INS⁺ progenitors in beta cell ontogeny and will facilitate the development of novel protocols for generating INS⁺ cells from differentiating hESCs
A Novel Sperm-Delivered Toxin Causes Late-Stage Embryo Lethality and Transmission Ratio Distortion in C. elegans
The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it
Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study
BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management
- …