157 research outputs found

    Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with Type 2 diabetes mellitus

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    Severe combined hyperlipidaemia has occasionally been associated with infiltration of tissues in addition to arteries and the skin. We report a woman with Type 2 diabetes mellitus (DM) and severe combined hyperlipidaemia who developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman with a 15-year history of Type 2 DM was admitted following a two-week history of progressive visual loss. Examination identified lipid infiltration into the retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL cholesterol and a broad beta band on lipoprotein electrophoresis, raising the possibility of familial dysbetalipoproteinaemia. However, gene sequencing analysis indicated that the patient was homozygous for the E3/E3 allele of the ApoE gene with no mutations detected in either the coding region or intron-exon boundaries. Her lipid profile improved following dietary therapy and gemfibrozil treatment, but this had little effect on either her fundal appearances or her visual acuity. Type 2 DM plays a vital role both in allowing expression of severe combined hyperlipoproteinaemia, in addition to serving as a risk factor for complications such as tissue infiltration

    The influence of membrane physical properties on microvesicle release in human erythrocytes

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    Exposure of human erythrocytes to elevated intracellular calcium causes fragments of the cell membrane to be shed as microvesicles. This study tested the hypothesis that microvesicle release depends on microscopic membrane physical properties such as lipid order, fluidity, and composition. Membrane properties were manipulated by varying the experimental temperature, membrane cholesterol content, and the activity of the trans-membrane phospholipid transporter, scramblase. Microvesicle release was enhanced by increasing the experimental temperature. Reduction in membrane cholesterol content by treatment with methyl-β-cyclodextrin also facilitated vesicle shedding. Inhibition of scramblase with R5421 impaired vesicle release. These data were interpreted in the context of membrane characteristics assessed previously by fluorescence spectroscopy with environment-sensitive probes such as laurdan, diphenylhexatriene, and merocyanine 540. The observations supported the following conclusions: 1) calcium-induced microvesicle shedding in erythrocytes relates more to membrane properties detected by diphenylhexatriene than by the other probes; 2) loss of trans-membrane phospholipid asymmetry is required for microvesicle release

    Real-world word learning: exploring children's developing semantic representations of a science term

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    Assessments of lexical acquisition are often limited to pre-school children on forced choice comprehension measures. This study assessed the understandings 30 school-age children (mean age = 6;7) acquired about the science term, eclipse following a naturalistic exposure to a solar eclipse. The knowledge children acquired about eclipses and a control term, comet was assessed at three points in time (baseline-test, two-week post-test and five-month post-test) using a range of assessment tasks (multiple-choice comprehension, picture-naming, drawing and a model of a solar system task). Children's knowledge was compared to 15 adult controls during the baseline-test and two-week post-test. Children acquired extensive knowledge about eclipses, but not comets; at the two-week post-test and five-month post-test, the majority of children named and drew eclipses and „made? an eclipse using models of the sun, moon and earth. Also, children's eclipse knowledge more closely approximated adult-level understandings at the two-week post-test than at the baseline-test. Implications for the study of lexical acquisition in later development are discussed

    A kpc-scale-resolved study of unobscured and obscured star formation activity in normal galaxies at z = 1.5 and 2.2 from ALMA and HiZELS

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    We present Atacama Large Millimeter/Submillimeter Array (ALMA) continuum observations of a sample of nine star-forming galaxies at redshifts 1.47 and 2.23 selected from the High-z Emission Line Survey (HiZELS). Four galaxies in our sample are detected at high significance by ALMA at a resolution of 0′′.25 at rest-frame 355 μm. Together with the previously observed H α emission, from adaptive optics-assisted integral-field-unit spectroscopy (∼0′′.15 resolution), and F606W and F140W imaging from the Hubble Space Telescope (∼0′′.2 resolution), we study the star formation activity, stellar and dust mass in these high-redshift galaxies at ∼kpc-scale resolution. We find that ALMA detection rates are higher for more massive galaxies (M* > 1010.5 M⊙) and higher [N II]/H α ratios (>0.25, a proxy for gas-phase metallicity). The dust extends out to a radius of 8 kpc, with a smooth structure, even for those galaxies presenting clumpy H α morphologies. The half-light radii (Rdust) derived for the detected galaxies are of the order ∼4.5 kpc, more than twice the size of submillimetre-selected galaxies at a similar redshift. Our global star formation rate estimates – from far-infrared and extinction-corrected H α luminosities – are in good agreement. However, the different morphologies of the different phases of the interstellar medium suggest complex extinction properties of the high-redshift normal galaxies

    EDF1 coordinates cellular responses to ribosome collisions

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    Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation

    Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients

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    Chronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution

    Halo masses for optically-selected and for radio-loud AGN from clustering and galaxy-galaxy lensing

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    We compute two-point correlation functions and measure the shear signal due to galaxy-galaxy lensing for 80,000 optically identified and 5,700 radio-loud AGN from Data Release 4 (DR4) of the Sloan Digital Sky Survey. Halo occupation models are used to estimate halo masses and satellite fractions for these two types of AGN. The large sample size allows us to separate AGN according to the stellar mass of their host galaxies. We study how the halo masses of optical and radio AGN differ from those of the parent population at fixed M*. Halo masses deduced from clustering and from lensing agree satisfactorily. Radio AGN are found in more massive halos than optical AGN: in our samples their mean halo masses are 1.6 x 10^{13} and 8 x 10^{11} M_{sun}/h, respectively. Optical AGN follow the same relation between stellar mass and halo mass as galaxies selected without regard to nuclear properties, but radio-loud AGN deviate significantly from this relation. The dark matter halos of radio-loud AGN are about twice as massive as those of control galaxies of the same stellar mass. This boost is independent of radio luminosity, and persists even when our analysis is restricted to field galaxies. The large-scale gaseous environment of the galaxy clearly plays a crucial role in producing observable radio emission. The dark matter halo masses that we derive for the AGN in our two samples are in good agreement with recent models in which feedback from radio AGN becomes dominant in halos where gas cools quasi-statically.Comment: 20 pages, 13 figures, submitted to MNRAS; version 2 includes minor changes in response to referee report, but no substantive changes in conclusion

    Cyclists in shared bus lanes: could there be unrecognised impacts on bus journey times?

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    This paper contributes to debates around improving the modelling of cycles, through an exploratory case study of bus–cycle interactions in London. This case study examines undocumented delays to buses caused by high volumes of cyclists in bus lanes. It has generally been assumed that cyclists do not noticeably delay buses in shared lanes. However, in many contexts where cyclists routinely share bus lanes, cyclist numbers have historically been low. In some such places, bus lanes are now seeing very high volumes of cyclists, far above those previously studied. This may have implications for bus – and cycle – journey times, but traditionally traffic modelling has not represented the effects of such interactions well. With some manipulation of parameters taken from models of other cities, the model described here demonstrates that cycles can cause significant delays to buses in shared lanes, at high cycling volumes. These delays are likely to become substantially larger if London's cycling demographic becomes more diverse, because cyclist speeds will decline. Hence bus journey time benefits may derive from separating cycles from buses, where cycle flows are high. The project also suggests that microsimulation modelling software, as typically used, remains problematic for representing cyclists
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