We report the discovery and analysis of a massive, compact, hierarchical triple system (TIC 470710327) initially identified by citizen scientists in data obtained by NASA's Transiting Exoplanet ...Survey Satellite (TESS). Spectroscopic follow-up observations obtained with the HERMES spectrograph, combined with eclipse timing variations (ETVs), confirm that the system is comprised of three OB stars, with a compact 1.10 d eclipsing binary and a non-eclipsing tertiary on a 52.04 d orbit. Dynamical modelling of the system (from radial velocity and ETVs) reveal a rare configuration wherein the tertiary star (O9.5-B0.5V; 14-17 M\(_{\odot}\)) is more massive than the combined mass of the inner binary (10.9-13.2 M\(_{\odot}\)). Given the high mass of the tertiary, we predict that this system will undergo multiple phases of mass transfer in the future, and likely end up as a double neutron star gravitational wave progenitor or an exotic Thorne-Zytkow object. Further observational characterisation of this system promises constraints on both formation scenarios of massive stars as well as their exotic evolutionary end-products.
Lightcurves of many classical novae deviate from the canonical "fast rise - smooth decline" pattern and display complex variability behavior. We present the first TESS-space-photometry-based ...investigation of this phenomenon. We use TESS Sector 41 full-frame images to extract a lightcurve of the slow Galactic nova V606 Vul that erupted nine days prior to the start of the TESS observations. The lightcurve covers the first of two major peaks of V606 Vul that was reached 19 days after the start of the eruption. The nova reached its brightest visual magnitude V=9.9 in its second peak 64 days after the eruption onset, following the completion of Sector 41 observations. To increase the confidence level of the extracted lightcurve, we performed the analysis using four different codes implementing the aperture photometry (Lightkurve, VaST) and image subtraction (TESSreduce, tequila_shots) and find good agreement between them. We performed ground-based photometric and spectroscopic monitoring to complement the TESS data. The TESS lightcurve reveals two features: periodic variations (0.12771d, 0.01mag average peak-to-peak amplitude) that disappeared when the source was within 1mag of peak optical brightness and a series of isolated mini-flares (with peak-to-peak amplitudes of up to 0.5mag) appearing at seemingly random times. We interpret the periodic variations as the result of azimuthal asymmetry of the photosphere engulfing the nova-hosting binary that was distorted by and rotating with the binary. Whereas we use spectra to associate the two major peaks in the nova lightcurve with distinct episodes of mass ejection, the origin of mini-flares remains elusive.
We report on the discovery and validation of a two-planet system around a bright (V = 8.85 mag) early G dwarf (1.43 \(R_{\odot}\), 1.15 \(M_{\odot}\), TOI 2319) using data from NASA's Transiting ...Exoplanet Survey Satellite (TESS). Three transit events from two planets were detected by citizen scientists in the month-long TESS light curve (sector 25), as part of the Planet Hunters TESS project. Modelling of the transits yields an orbital period of \Pb\ and radius of \(3.41 _{ - 0.12 } ^ { + 0.14 }\) \(R_{\oplus}\) for the inner planet, and a period in the range 19.26-35 days and a radius of \(5.83 _{ - 0.14 } ^ { + 0.14 }\) \(R_{\oplus}\) for the outer planet, which was only seen to transit once. Each signal was independently statistically validated, taking into consideration the TESS light curve as well as the ground-based spectroscopic follow-up observations. Radial velocities from HARPS-N and EXPRES yield a tentative detection of planet b, whose mass we estimate to be \(11.56 _{ - 6.14 } ^ { + 6.58 }\) \(M_{\oplus}\), and allow us to place an upper limit of \(27.5\) \(M_{\oplus}\) (99 per cent confidence) on the mass of planet c. Due to the brightness of the host star and the strong likelihood of an extended H/He atmosphere on both planets, this system offers excellent prospects for atmospheric characterisation and comparative planetology.
In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts ...called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.
Hendra and Nipah viruses (genus Henipavirus, family Paramyxoviridae) are highly pathogenic bat-borne viruses. The need for high biocontainment when studying henipaviruses has hindered the development ...of therapeutics and knowledge of the viral infection cycle. We have performed a genome-wide siRNA screen at biosafety level 4 that identified 585 human proteins required for henipavirus infection. The host protein with the largest impact was fibrillarin, a nucleolar methyltransferase that was also required by measles, mumps and respiratory syncytial viruses for infection. While not required for cell entry, henipavirus RNA and protein syntheses were greatly impaired in cells lacking fibrillarin, indicating a crucial role in the RNA replication phase of infection. During infection, the Hendra virus matrix protein co-localized with fibrillarin in cell nucleoli, and co-associated as a complex in pulldown studies, while its nuclear import was unaffected in fibrillarin-depleted cells. Mutagenesis studies showed that the methyltransferase activity of fibrillarin was required for henipavirus infection, suggesting that this enzyme could be targeted therapeutically to combat henipavirus infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zoonotic viruses that emerge from wildlife and domesticated animals pose a serious threat to human and animal health. In many instances, mouse models have improved our understanding of the human ...immune response to infection; however, when dealing with emerging zoonotic diseases, they may be of limited use. This is particularly the case when the model fails to reproduce the disease status that is seen in the natural reservoir, transmission species or human host. In this Review, we discuss how researchers are placing more emphasis on the study of the immune response to zoonotic infections in the natural reservoir hosts and spillover species. Such studies will not only lead to a greater understanding of how these infections induce variable disease and immune responses in distinct species but also offer important insights into the evolution of mammalian immune systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of ...host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection. miR-181 also promoted Nipah virus infection, but did not affect infection by paramyxoviruses from other genera, indicating specificity in the virus-host interaction. Infection promotion was primarily mediated via the ability of miR-181 to significantly enhance henipavirus-induced membrane fusion. Cell signalling receptors of ephrins, namely EphA5 and EphA7, were identified as novel negative regulators of henipavirus fusion. The expression of these receptors, as well as EphB4, were suppressed by miR-181 overexpression, suggesting that simultaneous inhibition of several Ephs by the miRNA contributes to enhanced infection and fusion. Immune-responsive miR-181 levels was also up-regulated in the biofluids of ferrets and horses infected with Hendra virus, suggesting that the host innate immune response may promote henipavirus spread and exacerbate disease severity. This study is the first genome-wide screen of miRNAs influencing infection by a clinically significant mononegavirus and nominates select miRNAs as targets for future anti-viral therapy development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so ...understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here, we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.
The human protein-coding gene
(inflammation and lipid regulator with UBA-like and NBR1-like domains; previously C6orf106) was identified as a proviral factor for Hendra virus infection and was ...recently characterized to function as an inhibitor of type I interferon expression. Here, we have utilized transcriptome sequencing (RNA-seq) to define cellular pathways regulated by ILRUN in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of Caco-2 cells. We find that inhibition of ILRUN expression by RNA interference alters transcription profiles of numerous cellular pathways, including upregulation of the SARS-CoV-2 entry receptor
and several other members of the renin-angiotensin aldosterone system. In addition, transcripts of the SARS-CoV-2 coreceptors
and
were also upregulated. Inhibition of ILRUN also resulted in increased SARS-CoV-2 replication, while overexpression of ILRUN had the opposite effect, identifying ILRUN as a novel antiviral factor for SARS-CoV-2 replication. This represents, to our knowledge, the first report of ILRUN as a regulator of the renin-angiotensin-aldosterone system (RAAS).
There is no doubt that the current rapid global spread of COVID-19 has had significant and far-reaching impacts on our health and economy and will continue to do so. Research in emerging infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is growing rapidly, with new breakthroughs in the understanding of host-virus interactions to assist with the development of innovative and exciting therapeutic strategies. Here, we present the first evidence that modulation of the human protein-coding gene
functions as an antiviral factor for SARS-CoV-2 infection, likely through its newly identified role in regulating the expression of SARS-CoV-2 entry receptors ACE2, TMPRSS2, and CTSL. These data improve our understanding of biological pathways that regulate host factors critical to SARS-CoV-2 infection, contributing to the development of antiviral strategies to deal with the current SARS-CoV-2 pandemic.
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