No abstract

The plant circadian clock is proposed to be a network of several interconnected feedback loops, and loss of any component leads to changes in oscillator speed. We previously reported that Arabidopsis thaliana EARLY FLOWERING4 (ELF4) is required to sustain this oscillator and that the elf4 mutant is arrhythmic. This phenotype is shared with both elf3 and lux. Here, we show that overexpression of either ELF3 or LUX ARRHYTHMO (LUX) complements the elf4 mutant phenotype. Furthermore, ELF4 causes ELF3 to form foci in the nucleus. We used expression data to direct a mathematical position of ELF3 in the clock network. This revealed direct effects on the morning clock gene PRR9, and we determined association of ELF3 to a conserved region of the PRR9 promoter. A cis-element in this region was suggestive of ELF3 recruitment by the transcription factor LUX, consistent with both ELF3 and LUX acting genetically downstream of ELF4. Taken together, using integrated approaches, we identified ELF4/ELF3 together with LUX to be pivotal for sustenance of plant circadian rhythms.

Transcriptional feedback loops are a feature of circadian clocks in both animals and plants. We show that the plant circadian clock also incorporates the cytosolic signaling molecule cyclic adenosine diphosphate ribose (cADPR). cADPR modulates the circadian oscillator's transcriptional feedback loops and drives circadian oscillations of Ca2+ release. The effects of antagonists of cADPR signaling, manipulation of cADPR synthesis, and mathematical simulation of the interaction of cADPR with the circadian clock indicate that cADPR forms a feedback loop within the plant circadian clock.

We screened the electronic records of 2,799 patients admitted in Tongji Hospital from January 10th to February 18th, 2020. There were 375 discharged patients including 201 survivors. We built a prognostic prediction model based on XGBoost machine learning algorithm and then tested 29 patients (included 3 patients from other hospital) who were cleared after February 19th. Results:The mean age of the 375 patients was 58.83 years old with 58.7% of males. Fever was the most common initial symptom (49.9%), followed by cough (13.9%), fatigue (3.7%), and dyspnea (2.1%). Our model identified three key clinical features, i.e., lactic dehydrogenase (LDH), lymphocyte and High-sensitivity C-reactive protein (hs-CRP), from a pool of more than 300 features. The clinical route is simple to check and can precisely and quickly assess the risk of death. Therefore, it is of great clinical significance. : medRxiv preprint Conclusion:The three indices-based prognostic prediction model we built is able to predict the mortality risk, and present a clinical route to the recognition of critical cases from severe cases. It can help doctors with early identification and intervention, thus potentially reducing mortality.