Ocular Manifestations In COVID-19: Clinical Case Reports And A Literature (Review)

Coronavirus disease 2019 (COVID-19) has affected more than 130 million people as of April 2021. During the current pandemic, SARS-CoV-2 has been found to cause conjunctivitis with anecdotal evidence of a wide range of manifestations from scleritis to retinitis, occlusive vasculitis and optic neuritis. The purpose of this study is to raise awareness about possible COVID-19 related ocular manifestations, including papillophlebitis, anterior ischemic optic neuropathy, uveitis and neuroretinitis. Further detailed analyses will be needed to elucidate the link between SARS-CoV-2 and ocular pathology

Volume-limited radio survey of ultracool dwarfs

Aims. We aim to increase the sample of ultracool dwarfs studied in the radio domain to allow a more statistically significant understanding of the physical conditions associated with these magnetically active objects. Methods. We conducted a volume-limited survey at 4.9 GHz of 32 nearby ultracool dwarfs with spectral types covering the range M7–T8. A statistical analysis was performed on the combined data from the present survey and previous radio observations of ultracool dwarfs. Results. Whilst no radio emission was detected from any of the targets, significant upper limits were placed on the radio luminosities that are below the luminosities of previously detected ultracool dwarfs. Combining our results with those from the literature gives a detection rate for dwarfs in the spectral range M7–L3.5 of ~9%. In comparison, only one dwarf later than L3.5 is detected in 53 observations. We report the observed detection rate as a function of spectral type and the number distribution of the dwarfs as a function of spectral type and rotation velocity. Conclusions. The radio observations to date point to a drop in the detection rate toward the ultracool dwarfs. However, the emission levels of detected ultracool dwarfs are comparable to those of earlier type active M dwarfs, which may imply that a mildly relativistic electron beam or a strong magnetic field can exist in ultracool dwarfs. Fast rotation may be a sufficient condition to produce magnetic fields strengths of several hundred Gauss to several kilo Gauss, as suggested by the data for the active ultracool dwarfs with known rotation rates. A possible reason for the non-detection of radio emission from some dwarfs is that maybe the centrifugal acceleration mechanism in these dwarfs is weak (due to a low rotation rate) and thus cannot provide the necessary density and/or energy of accelerated electrons. An alternative explanation could be long-term variability, as is the case for several ultracool dwarfs whose radio emission varies considerably over long periods with emission levels dropping below the detection limit in some instances

Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production

Sertoli cells, can function as non-professional tolerogenic antigen-presenting cells, and sustain the blood-testis barrier formed by their tight junctions. The NOD-like receptor family members and the NALP3 inflammasome play a key role in pro-inflammatory innate immunity signalling pathways. Limited data exist on NOD1 and NOD2 expression in human and mouse Sertoli cells. Currently, there is no data on inflammasome expression or function in Sertoli cells. We found that in primary pre-pubertal Sertoli cells and in adult Sertoli line, TLR4\NOD1 and NOD2 crosstalk converged in NF?B activation and elicited a NALP3 activation, leading to de novo synthesis and inflammasome priming. This led to caspase-1 activation and IL-1? secretion. We demonstrated this process was controlled by mechanisms linked to autophagy. NOD1 promoted pro-IL-1? restriction and autophagosome maturation arrest, while NOD2 promoted caspase-1 activation, IL-1? secretion and autophagy maturation. NALP3 modulated NOD1 and pro-IL-1? expression, while NOD2 inversely promoted IL-1?. This study is proof of concept that Sertoli cells, upon specific stimulation, could participate in male infertility pathogenesis via inflammatory cytokine induction

Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer

Drugs that inhibit estrogen receptor-α (ER) activity have been highly successful in treating and reducing breast cancer progression in ER-positive disease. However, resistance to these therapies presents a major clinical problem. Recent genetic studies have shown that mutations in the ER gene are found in >20% of tumours that progress on endocrine therapies. Remarkably, the great majority of these mutations localize to just a few amino acids within or near the critical helix 12 region of the ER hormone binding domain, where they are likely to be single allele mutations. Understanding how these mutations impact on ER function is a prerequisite for identifying methods to treat breast cancer patients featuring such mutations. Towards this end, we used CRISPR-Cas9 genome editing to make a single allele knock-in of the most commonly mutated amino acid residue, tyrosine 537, in the estrogen-responsive MCF7 breast cancer cell line. Genomic analyses using RNA-seq and ER ChIP-seq demonstrated that the Y537S mutation promotes constitutive ER activity globally, resulting in estrogen-independent growth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen and fulvestrant. Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. These studies confirm the functional importance of ER mutations in endocrine resistance, demonstrate the utility of knock-in mutational models for investigating alternative therapeutic approaches and highlight CDK7 inhibition as a potential therapy for endocrine-resistant breast cancer mediated by ER mutations

Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples

This research was funded by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre. UKCTOCS was core funded by the Medical Research Council, Cancer Research UK, and the Department of Health with additional support from the Eve Appeal, Special Trustees of Bart’s and the London, and Special Trustees of UCLH. OB and JFT also received support from the Eve Appeal Gynaecological Cancer Research Trust and Cancer Research UK PRC Programme Grant A12677

MAGIC gamma-ray and multi-frequency observations of flat spectrum radio quasar PKS 1510-089 in early 2012

Aims. Amongst more than fifty blazars detected in very high energy (VHE, E> 100 GeV) γ rays, only three belong to the subclass of flat spectrum radio quasars (FSRQs). The detection of FSRQs in the VHE range is challenging, mainly because of their soft spectra in the GeV-TeV regime. MAGIC observed PKS 1510−089 (z = 0.36) starting 2012 February 3 until April 3 during a high activity state in the high energy (HE, E> 100 MeV) γ-ray band observed by AGILE and Fermi. MAGIC observations result in the detection of a source with significance of 6.0 standard deviations (σ). We study the multi-frequency behaviour of the source at the epoch of MAGIC observation, collecting quasi-simultaneous data at radio and optical (GASP-WEBT and F-Gamma collaborations, REM, Steward, Perkins, Liverpool, OVRO, and VLBA telescopes), X-ray (Swift satellite), and HE γ-ray frequencies. Methods. We study the VHE γ-ray emission, together with the multi-frequency light curves, 43 GHz radio maps, and spectral energy distribution (SED) of the source. The quasi-simultaneous multi-frequency SED from the millimetre radio band to VHE γ rays is modelled with a one-zone inverse Compton model. We study two different origins of the seed photons for the inverse Compton scattering, namely the infrared torus and a slow sheath surrounding the jet around the Very Long Baseline Array (VLBA) core. Results. We find that the VHE γ-ray emission detected from PKS 1510−089 in 2012 February-April agrees with the previous VHE observations of the source from 2009 March-April. We find no statistically significant variability during the MAGIC observations on daily, weekly, or monthly time scales, while the other two known VHE FSRQs (3C 279 and PKS 1222+216) have shown daily scale to sub-hour variability. The γ-ray SED combining AGILE, Fermi and MAGIC data joins smoothly and shows no hint of a break. The multi-frequency light curves suggest a common origin for the millimetre radio and HE γ-ray emission, and the HE γ-ray flaring starts when the new component is ejected from the 43 GHz VLBA core and the studied SED models fit the data well. However, the fast HE γ-ray variability requires that within the modelled large emitting region, more compact regions must exist. We suggest that these observed signatures would be most naturally explained by a turbulent plasma flowing at a relativistic speed down the jet and crossing a standing conical shock

Multiwavelength behaviour of the blazar OJ 248 from radio to γ -rays

© 2015 The Authors. We present an analysis of the multiwavelength behaviour of the blazar OJ 248 at z = 0.939 in the period 2006-2013. We use low-energy data (optical, near-infrared, and radio) obtained by 21 observatories participating in the Gamma-Ray Large Area Space Telescope (GLAST)-AGILE Support Program of the Whole Earth Blazar Telescope, as well as data from the Swift (optical-UV and X-rays) and Fermi (γ -rays) satellites, to study flux and spectral variability and correlations among emissions in different bands. We take into account the effect of absorption by the Damped Lyman α intervening system at z = 0.525. Two major outbursts were observed in 2006-2007 and in 2012-2013 at optical and near-IR wavelengths, while in the high-frequency radio light curves prominent radio outbursts are visible peaking at the end of 2010 and beginning of 2013, revealing a complex radio-optical correlation. Crosscorrelation analysis suggests a delay of the optical variations after the γ -ray ones of about a month, which is a peculiar behaviour in blazars. We also analyse optical polarimetric and spectroscopic data. The average polarization percentage P is less than 3 per cent, but it reaches~19 per cent during the early stage of the 2012-2013 outburst.Avague correlation of P with brightness is observed. There is no preferred electric vector polarization angle and during the outburst the linear polarization vector shows wide rotations in both directions, suggesting a complex behaviour/structure of the jet and possible turbulence. The analysis of 140 optical spectra acquired at the Steward Observatory reveals a strong Mg II broad emission line with an essentially stable flux of 6.2 × 10-15 erg cm-2 s-1 and a full width at half-maximum of 2053 km s-1

Multiwavelength behaviour of the blazar OJ 248 from radio to γ-rays

We present an analysis of the multiwavelength behaviour of the blazar OJ 248 at z = 0.939 in the period 2006-2013. We use low-energy data (optical, near-infrared, and radio) obtained by 21 observatories participating in the Gamma-Ray Large Area Space Telescope (GLAST)-AGILE Support Program of the Whole Earth Blazar Telescope, as well as data from the Swift (optical-UV and X-rays) and Fermi (γ-rays) satellites, to study flux and spectral variability and correlations among emissions in different bands. We take into account the effect of absorption by the Damped Lyman α intervening system at z = 0.525. Two major outbursts were observed in 2006-2007 and in 2012-2013 at optical and near-IR wavelengths, while in the high-frequency radio light curves prominent radio outbursts are visible peaking at the end of 2010 and beginning of 2013, revealing a complex radio-optical correlation. Cross-correlation analysis suggests a delay of the optical variations after the γ-ray ones of about a month, which is a peculiar behaviour in blazars. We also analyse optical polarimetric and spectroscopic data. The average polarization percentage P is less than 3 per cent, but it reaches ∼19 per cent during the early stage of the 2012-2013 outburst. A vague correlation of P with brightness is observed. There is no preferred electric vector polarization angle and during the outburst the linear polarization vector shows wide rotations in both directions, suggesting a complex behaviour/structure of the jet and possible turbulence. The analysis of 140 optical spectra acquired at the Steward Observatory reveals a strong Mg II broad emission line with an essentially stable flux of 6.2 × 10- 15 erg cm- 2 s- 1 and a full width at half-maximum of 2053 km s- 1