The kangaroo endogenous retrovirus (KERV) was previously reported to have undergone a rapid copy number increase in the red-necked wallaby; however, the mode of amplification was left to be ...clarified. The present study revealed that the long terminal repeat (LTR) (0.6 kb) and internal region (2.0 kb) of a provirus are repeated alternately, forming megasatellite DNA which we named kervRep. This repetition pattern was the same as that observed for walbRep, megasatellite DNA originating from another endogenous retrovirus. Their formation process can be explained using a simple model: pairing slippage followed by homologous recombination. This model features that the initial step is triggered by the presence of two identical sequences within a short distance; the possession of LTRs by endogenous retroviruses fulfills this condition. The discovery of two cases suggests that formation of this type of satellite DNA is one of non-negligible effects of endogenous retroviruses on their host genomes.
•Megasatellite DNA originating from an endogenous retrovirus.•Tandem duplications of a provirus sequence.•Expansion in the centromere regions of chromosomes.•Simple formation model based on the structure of endogenous retrovirus.
High-cadence transient surveys are able to capture supernovae closer to their first light than ever before. Applying analytical models to such early emission, we can constrain the progenitor stars' ...properties. In this paper, we present observations of SN 2018fif (ZTF 18abokyfk). The supernova was discovered close to first light and monitored by the Zwicky Transient Facility (ZTF) and the Neil Gehrels Swift Observatory. Early spectroscopic observations suggest that the progenitor of SN 2018fif was surrounded by relatively small amounts of circumstellar material compared to all previous cases. This particularity, coupled with the high-cadence multiple-band coverage, makes it a good candidate to investigate using shock-cooling models. We employ the SOPRANOS code, an implementation of the model by Sapir & Waxman and its extension to early times by Morag et al. Compared with previous implementations, SOPRANOS has the advantage of including a careful account of the limited temporal validity domain of the shock-cooling model as well as allowing usage of the entirety of the early UV data. We find that the progenitor of SN 2018fif was a large red supergiant with a radius of and an ejected mass of . Our model also gives information on the explosion epoch, the progenitor's inner structure, the shock velocity, and the extinction. The distribution of radii is double-peaked, with smaller radii corresponding to lower values of the extinction, earlier recombination times, and a better match to the early UV data. If these correlations persist in future objects, denser spectroscopic monitoring constraining the time of recombination, as well as accurate UV observations (e.g., with ULTRASAT), will help break the extinction/radius degeneracy and independently determine both.
We present a survey of the early evolution of 12 Type IIn supernovae (SNe IIn) at ultraviolet and visible light wavelengths. We use this survey to constrain the geometry of the circumstellar material ...(CSM) surrounding SN IIn explosions, which may shed light on their progenitor diversity. In order to distinguish between aspherical and spherical CSM, we estimate the blackbody radius temporal evolution of the SNe IIn of our sample, following the method introduced by Soumagnac et al. We find that higher-luminosity objects tend to show evidence for aspherical CSM. Depending on whether this correlation is due to physical reasons or to some selection bias, we derive a lower limit between 35% and 66% for the fraction of SNe IIn showing evidence for aspherical CSM. This result suggests that asphericity of the CSM surrounding SNe IIn is common-consistent with data from resolved images of stars undergoing considerable mass loss. It should be taken into account for more realistic modeling of these events.
Two theories have been proposed to explain the evolution of introns within eukaryotic genes. The introns early theory, or ``exon theory of genes,'' proposes that introns are ancient and that ...recombination within introns provided new exon structure, and thus new genes. The introns late theory, or ``insertional theory of introns,'' proposes that ancient genes existed as uninterrupted exons and that introns have been introduced during the course of evolution. There is still controversy as to how intron-exon structure evolved and whether the majority of introns are ancient or novel. Although there is extensive evidence in support of the introns early theory, phylogenetic comparisons of several genes indicate recent gain and loss of introns within these genes. However, no example has been shown of a protein coding gene, intronless in its ancestral form, which has acquired an intron in a derived form. The mammalian sex determining gene, SRY, is intronless in all mammals studied to date, as is the gene from which it recently evolved. However, we report here comparisons of genomic and cDNA sequences that now provide evidence of a de novo insertion of an intron into the SRY gene of dasyurid marsupials. This recently (approximately 45 million years ago) inserted sequence is not homologous with known transposable elements. Our data demonstrate that introns may be inserted as spliced units within a developmentally crucial gene without disrupting its function.
Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular ...coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation. The mechanism of release involves type I IFN-induced caspase-11 which promotes macrophage pyroptosis. Here we find that F3 is a type I IFN-stimulated gene. Furthermore, F3 induction by lipopolysaccharide (LPS) is inhibited by the anti-inflammatory agents dimethyl fumarate (DMF) and 4-octyl itaconate (4-OI). Mechanistically, inhibition of F3 by DMF and 4-OI involves suppression of Ifnb1 expression. Additionally, they block type I IFN- and caspase-11-mediated macrophage pyroptosis, and subsequent TF release. Thereby, DMF and 4-OI inhibit TF-dependent thrombin generation. In vivo, DMF and 4-OI suppress TF-dependent thrombin generation, pulmonary thromboinflammation, and lethality induced by LPS, E. coli, and S. aureus, with 4-OI additionally attenuating inflammation-associated coagulation in a model of SARS-CoV-2 infection. Our results identify the clinically approved drug DMF and the pre-clinical tool compound 4-OI as anticoagulants that inhibit TF-mediated coagulopathy via inhibition of the macrophage type I IFN-TF axis.
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and ...interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H
export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.
We aimed to determine the effect of a Mediterranean-style diet, tailored to meet dietary recommendations for older adults, on blood pressure and arterial stiffness. In 12 months, randomized ...controlled trial (NU-AGE New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe), blood pressure was measured in 1294 healthy participants, aged 65 to 79 years, recruited from 5 European centers, and arterial stiffness in a subset of 225 participants. The intervention group received individually tailored standardized dietary advice and commercially available foods to increase adherence to a Mediterranean diet. The control group continued on their habitual diet and was provided with current national dietary guidance. In the 1142 participants who completed the trial (88.2%), after 1 year the intervention resulted in a significant reduction in systolic blood pressure (−5.5 mm Hg; 95% CI, −10.7 to −0.4; P=0.03), which was evident in males (−9.2 mm Hg, P=0.02) but not females (−3.1 mm Hg, P=0.37). The −1.7 mm Hg (95% CI, −4.3 to 0.9) decrease in diastolic pressure after intervention did not reach statistical significance. In a subset (n=225), augmentation index, a measure of arterial stiffness, was improved following intervention (−12.4; 95% CI, −24.4 to −0.5; P=0.04) with no change in pulse wave velocity. The intervention also resulted in an increase in 24-hour urinary potassium (8.8 mmol/L; 95% CI, 0.7–16.9; P=0.03) and in male participants (52%) a reduction in pulse pressure (−6.1 mm Hg; 95% CI, −12.0 to −0.2; P=0.04) and 24-hour urinary sodium (−27.1 mmol/L; 95% CI, −53.3 to −1.0; P=0.04). In conclusion, a Mediterranean-style diet is effective in improving cardiovascular health with clinically relevant reductions in blood pressure and arterial stiffness.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicialtrials.gov. Unique identifierNCT01754012.
High cadence transient surveys are able to capture supernovae closer to their first light than before. Applying analytical models to such early emission, we can constrain the progenitor stars ...properties. In this paper, we present observations of SN2018fif (ZTF18abokyfk). The supernova was discovered close to first light and monitored by the Zwicky Transient Facility (ZTF) and the Neil Gehrels Swift Observatory. Early spectroscopic observations suggest that the progenitor of SN2018fif was surrounded by relatively small amounts of circumstellar material (CSM) compared to all previous cases. This particularity, coupled with the high cadence multiple-band coverage, makes it a good candidate to investigate using shock-cooling models. We employ the SOPRANOS code, an implementation of the model by Sapir & Waxman and its extension to early times by Morag, Sapir & Waxman. Compared with previous implementations, SOPRANOS has the advantage of including a careful account of the limited temporal validity domain of the shock-cooling model as well as allowing usage of the entirety of the early UV data. We find that the progenitor of SN2018fif was a large red supergiant, with a radius of R=744.0_{-128.0}^{+183.0} solar radii and an ejected mass of Mej=9.3_{-5.8}^{+0.4} solar masses. Our model also gives information on the explosion epoch, the progenitor inner structure, the shock velocity and the extinction. The distribution of radii is double-peaked, with lower radii corresponding to lower values of the extinction, earlier recombination times and better match to the early UV data. If these correlations persist in future objects, denser spectroscopic monitoring constraining the time of recombination, as well as accurate UV observations (e.g. with ULTRASAT), will help break the radius-extinction degeneracy and independently determine both.
Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, ...cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery.
We present a survey of the early evolution of 12 Type IIn supernovae (SNe IIn) in the Ultra-Violet (UV) and visible light. We use this survey to constrain the geometry of the circumstellar material ...(CSM) surrounding SN IIn explosions, which may shed light on their progenitor diversity. In order to distinguish between aspherical and spherical circumstellar material (CSM), we estimate the blackbody radius temporal evolution of the SNe IIn of our sample, following the method introduced by Soumagnac et al. We find that higher luminosity objects tend to show evidence for aspherical CSM. Depending on whether this correlation is due to physical reasons or to some selection bias, we derive a lower limit between 35% and 66% on the fraction of SNe IIn showing evidence for aspherical CSM. This result suggests that asphericity of the CSM surrounding SNe IIn is common - consistent with data from resolved images of stars undergoing considerable mass loss. It should be taken into account for more realistic modelling of these events.
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