Ubiquitin carboxyl-terminal hydrolases are required for period maintenance of the circadian clock at high temperature in Arabidopsis

Protein ubiquitylation participates in a number of essential cellular processes including signal transduction and transcription, often by initiating the degradation of specific substrates through the 26S proteasome. Within the ubiquitin-proteasome system, deubiquitylating enzymes (DUBs) not only help generate and maintain the supply of free ubiquitin monomers, they also directly control functions and activities of specific target proteins by modulating the pool of ubiquitylated species. Ubiquitin carboxyl-terminal hydrolases (UCHs) belong to an enzymatic subclass of DUBs, and are represented by three members in Arabidopsis, UCH1, UCH2 and UCH3. UCH1 and UCH2 influence auxin-dependent developmental pathways in Arabidopsis through their deubiquitylation activities, whereas biological and enzymatic functions of UCH3 remain unclear. Here, we demonstrate that Arabidopsis UCH3 acts to maintain the period of the circadian clock at high temperatures redundantly with UCH1 and UCH2. Whereas single uch1, uch2 and uch3 mutants have weak circadian phenotypes, the triple uch mutant displays a drastic lengthening of period at high temperatures that is more extreme than the uch1 uch2 double mutant. UCH3 also possesses a broad deubiquitylation activity against a range of substrates that link ubiquitin via peptide and isopeptide linkages. While the protein target(s) of UCH1-3 are not yet known, we propose that these DUBs act on one or more factors that control period length of the circadian clock through removal of their bound ubiquitin moieties, thus ensuring that the clock oscillates with a proper period even at elevated temperature

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Measuring impact of vaccination among wildlife: The case of bait vaccine campaigns for classical swine fever epidemic among wild boar in Japan

Understanding the impact of vaccination in a host population is essential to control infectious diseases. However, the impact of bait vaccination against wildlife diseases is difficult to evaluate. The vaccination history of host animals is generally not observable in wildlife, and it is difficult to distinguish immunity by vaccination from that caused by disease infection. For these reasons, the impact of bait vaccination against classical swine fever (CSF) in wild boar inhabiting Japan has not been evaluated accurately. In this study, we aimed to estimate the impact of the bait vaccination campaign by modelling the dynamics of CSF and the vaccination process among a Japanese wild boar population. The model was designed to estimate the impact of bait vaccination despite lack of data regarding the demography and movement of wild boar. Using our model, we solved the theoretical relationship between the impact of vaccination, the time-series change in the proportion of infected wild boar, and that of immunised wild boar. Using this derived relationship, the increase in antibody prevalence against CSF because of vaccine campaigns in 2019 was estimated to be 12.1 percentage points (95% confidence interval: 7.8-16.5). Referring to previous reports on the basic reproduction number (R-0) of CSF in wild boar living outside Japan, the amount of vaccine distribution required for CSF elimination by reducing the effective reproduction number under unity was also estimated. An approximate 1.6 (when R-0 = 1.5, target vaccination coverage is 33.3% of total population) to 2.9 (when R-0 = 2.5, target vaccination coverage is 60.0% of total population) times larger amount of vaccine distribution would be required than the total amount of vaccine distribution in four vaccination campaigns in 2019

Estimation of the Lethality Rate, Recovery Rate, and Case Fatality Ratio of Classical Swine Fever in Japanese Wild Boar: An Analysis of the Epidemics From September 2018 to March 2019

Understanding the morbidity and lethality of diseases is necessary to evaluate the effectiveness of countermeasure against the epidemics (e.g., vaccination). To estimate them, detailed data on host population dynamics are required; however, estimating the population size for wildlife is often difficult. We aimed to elucidate the morbidity and lethality of classical swine fever (CSF) currently highly prevalent in the wild boar population in Japan. To this end, we estimated lethality rate, recovery rate, and case fatality ratio (CFR) of CSF without detailed data on the population estimates of wild boar. A mathematical model was constructed to describe the CSF dynamics and population dynamics of wild boar. We fitted the model to the (i) results of the reverse transcription polymerase chain reaction (RT-PCR) test for the CSFV gene and the (ii) results of the enzyme-linked immunosorbent assay (ELISA) test for the antibody against CSFV in sampled wild boar. In the 280 wild boar sampled from September 2018 to March 2019 in the major CSF-affected area in Japan, the lethality rate and recovery rate of CSF per week were estimated as 0.165 (95% confidence interval: 0.081-0.250) and 0.004 (0-0.009), respectively. While the estimate of lethality rate of CSF was similar with the estimates in previous studies, the recovery rate was lower than those reported previously. CFR was estimated as 0.959 (0.904-0.981) using our estimate of recovery rate. This study is the first to estimate lethality rate of CSF from the dynamics of CSF epidemics in the wild boar population. Since the value of CFR is sensitive to the value of recovery rate, the accuracy in the estimate of recovery rate is a key for the accurate estimation of CFR. A long-term transmission experiment of moderately virulent strains may lead to more accurate estimation of the recovery rate and CFR of CSF

Phosphorylation of CONSTANS and its COP1-dependent degradation during photoperiodic flowering of Arabidopsis

Seasonal flowering involves responses to changes in day length. In Arabidopsis thaliana, the CONSTANS (CO) transcription factor promotes flowering in the long days of spring and summer. Late flowering in short days is due to instability of CO, which is efficiently ubiquitinated in the dark by the CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase complex. Here we show that CO is also phosphorylated. Phosphorylated and unphosphorylated forms are detected throughout the diurnal cycle but their ratio varies, with the relative abundance of the phosphorylated form being higher in the light and lower in the dark. These changes in relative abundance require COP1, because in the cop1 mutant the phosphorylated form is always more abundant. Inactivation of the PHYTOCHROME A (PHYA), CRYPTOCHROME 1 (CRY1) and CRYPTOCHROME 2 (CRY2) photoreceptors in the phyA cry1 cry2 triple mutant most strongly reduces the amount of the phosphorylated form so that unphosphorylated CO is more abundant. This effect is caused by increased COP1 activity, as it is overcome by introduction of the cop1 mutation in the cop1 phyA cry1 cry2 quadruple mutant. Degradation of CO is also triggered in red light, and as in darkness this increases the relative abundance of unphosphorylated CO. Finally, a fusion protein containing truncated CO protein including only the carboxy-terminal region was phosphorylated in transgenic plants, locating at least one site of phosphorylation in this region. We propose that CO phosphorylation contributes to the photoperiodic flowering response by enhancing the rate of CO turnover via activity of the COP1 ubiquitin ligase.Peer reviewe