Circadian clocks regulate growth and development in plants and animals, but the role of circadian regulation in crop production is poorly understood. Rice (
) grain yield is largely determined by ...tillering, which is mediated by physiological and genetic factors. Here we report a regulatory loop that involves the circadian clock, sugar, and strigolactone (SL) pathway to regulate rice tiller-bud and panicle development. Rice
(
) positively regulates expression of
(
, also known as
),
(
), and
(
, also known as
) to repress tiller-bud outgrowth. Downregulating and overexpressing
increases and reduces tiller numbers, respectively, whereas manipulating
(
) expression results in the opposite effects.
also regulates
expression to mediate panicle and grain development. Genetic analyses using double mutants and overexpression in the mutants show that
,
, and
act downstream of
Sugars repress
expression in roots and tiller buds to promote tiller-bud outgrowth. The circadian clock integrates sugar responses and the SL pathway to regulate tiller and panicle development, providing insights into improving plant architecture and yield in rice and other cereal crops.
Hybridization and backcrossing are commonly used in animal and plant breeding to induce heritable variation including epigenetic changes such as paramutation. However, the molecular basis for ...hybrid-induced epigenetic memory remains elusive.
Here, we report that hybridization between the inbred parents B73 and Mo17 induces trans-acting hypermethylation and hypomethylation at thousands of loci; several hundreds (~ 3%) are transmitted through six backcrossing and three selfing generations. Notably, many transgenerational methylation patterns resemble epialleles of the nonrecurrent parent, despite > 99% of overall genomic loci are converted to the recurrent parent. These epialleles depend on 24-nt siRNAs, which are eliminated in the isogenic hybrid Mo17xB73:mop1-1 that is defective in siRNA biogenesis. This phenomenon resembles paramutation-like events and occurs in both intraspecific (Mo17xB73) and interspecific (W22xTeosinte) hybrid maize populations. Moreover, siRNA abundance and methylation levels of these epialleles can affect expression of their associated epigenes, many of which are related to stress responses.
Divergent siRNAs between the hybridizing parents can induce trans-acting epialleles in the hybrids, while the induced epigenetic status is maintained for transgenerational inheritance during backcross and hybrid breeding, which alters epigene expression to enhance growth and adaptation. These genetic and epigenetic principles may apply broadly from plants to animals.
As sessile organisms, plants must respond constantly to ever-changing environments to complete their life cycle; this includes the transition from vegetative growth to reproductive development. This ...process is mediated by photoperiodic response to sensing the length of night or day through circadian regulation of light-signaling molecules, such as phytochromes, to measure the length of night to initiate flowering. Flowering time is the most important trait to optimize crop performance in adaptive regions. In this review, we focus on interplays between circadian and light signaling pathways that allow plants to optimize timing for flowering and seed production in Arabidopsis, rice, soybean, and cotton. Many crops are polyploids and domesticated under natural selection and breeding. In response to adaptation and polyploidization, circadian and flowering pathway genes are epigenetically reprogrammed. Understanding the genetic and epigenetic bases for photoperiodic flowering will help improve crop yield and resilience in response to climate change.
N-terminal acetylation is one of the most common protein modifications in eukaryotes, and approximately 40% of human and plant proteomes are acetylated by ribosome-associated N-terminal ...acetyltransferase A (NatA) in a co-translational manner. However, the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear. Here, we identify Huntingtin Yeast partner K (HYPK), an evolutionarily conserved chaperone-like protein, as a positive regulator of NatA activity in rice. We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses, attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover. Furthermore, we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation, probably through the Ac/N-degron pathway, which could be induced by abiotic stresses. Taken together, our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover, which are essential for maintaining adaptive phenotypic plasticity in rice.
N-terminal acetyltransferase A (NatA) acetylates approximately 40% of human and plant proteomes. This study reveals that OsHYPK acts as both a positive regulator and a substrate of NatA to coordinate plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover, thereby promoting adaptive phenotypic plasticity in rice.
Inbreeding depression is linked to persistent epigenetic and gene expression changes, which are reversible by random mating.
Inbreeding depression is widespread across plant and animal kingdoms and ...may arise from the exposure of deleterious alleles and/or loss of overdominant alleles resulting from increased homozygosity, but these genetic models cannot fully explain the phenomenon. Here, we report epigenetic links to inbreeding depression in maize. Teosinte branched1/cycloidea/proliferating cell factor (TCP) transcription factors control plant development. During successive inbreeding among inbred lines, thousands of genomic regions across TCP-binding sites (TBS) are hypermethylated through the H3K9me2-mediated pathway. These hypermethylated regions are accompanied by decreased chromatin accessibility, increased levels of the repressive histone marks H3K27me2 and H3K27me3, and reduced binding affinity of maize TCP-proteins to TBS. Consequently, hundreds of TCP-target genes involved in mitochondrion, chloroplast, and ribosome functions are down-regulated, leading to reduced growth vigor. Conversely, random mating can reverse corresponding hypermethylation sites and TCP-target gene expression, restoring growth vigor. These results support a unique role of reversible epigenetic modifications in inbreeding depression.
Extremely low currents synthesis of molecular sieve films by controlling the interfacial microenvironment with catalytic efficiency of 105 is explored.
Display omitted
•Extremely low currents applied ...for the synthesis of AEL molecular sieve films.•Water and ionic liquid cation are linked by hydrogen bonding in microenvironment.•The catalytic efficiency in the synthesis is defined as high as 105.
Minimizing electric currents in the electrosynthesis of molecular sieve films is critically challenging. Herein we demonstrate the electric currents can be significantly minimized to catalyze AEL molecular sieve films nucleation in ionic liquids by the control of interfacial microenvironment. In the local microenvironment, the nucleation promoter of water and structure directing agents of ionic liquids are believed to be linked via hydrogen bonding in the electrical double layer, thus lowering the currents to 10e-8 A. The corresponding catalytic efficiency reaches up to as high as 105. This study sheds lights on manipulating the local chemical domain in the interfacial structure using extremely low currents for the synthesis chemistry.
Based on three-dimensional seismic interpretation, structural and sedimentary feature analysis, and examination of fluid properties and production dynamics, the regularity and main controlling ...factors of hydrocarbon accumulation in the Tazhong uplift, Tarim Basin are investigated. The results show that the oil and gas in the Tazhong uplift has the characteristics of complex accumulation mainly controlled by faults, and more than 80% of the oil and gas reserves are enriched along fault zones. There are large thrust and strike-slip faults in the Tazhong uplift, and the coupling relationship between the formation and evolution of the faults and accumulation determine the difference in complex oil and gas accumulations. The active scale and stage of faults determine the fullness of the traps and the balance of the phase, that is, the blocking of the transport system, the insufficient filling of oil and gas, and the unsteady state of fluid accumulation are dependent on the faults. The multi-period tectonic sedimentary evolution controls the differences of trap conditions in the fault zones, and the multi-phase hydrocarbon migration and accumulation causes the differences of fluid distribution in the fault zones. The theory of differential oil and gas accumulation controlled by fault is the key to the overall evaluation, three-dimensional development and discovery of new reserves in the Tazhong uplift.
Abstract
Background
High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our ...multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections.
Methods
The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression.
Results
The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of
Klebsiella pneumoniae
. The mean duration of PMB therapy was 11 days (range 7–38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 10
9
/l vs 9.28 × 10
9
/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%).
Conclusions
Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.
To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct ...therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China.
This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected.
Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH
O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital.
Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China.
Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.
•Data on polymyxin B pharmacokinetics (PK) in patients undergoing continuous renal replacement therapy are very limited.•Population PK models were performed with 53 patients undergoing continuous ...venovenous haemofiltration (CVVH).•Clearance of polymyxin B was higher among patients on CCVH compared with patients off CVVH, accounting for 65% of total polymyxin B clearance.•A loading dose of polymyxin B 200 mg plus a fixed maintenance dose of 150 mg q12h for patients on CVVH would be an optimal regimen.
Antibiotic dosing in critically ill patients undergoing continuous renal replacement therapy is considered challenging. This study aimed to analyse the population pharmacokinetics of polymyxin B in patients receiving continuous venovenous haemofiltration (CVVH), and to optimize individual dosing regimens in specific clinical scenarios. Patients treated with CVVH and polymyxin B for multi-drug-resistant Gram-negative bacterial infections were enrolled from two hospitals. Blood samples were collected during and outside CVVH, and assayed using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Phoenix NLME software. In total, 53 patients were included. The area under the concentration curve across 24 hours at steady state (AUCss,24h) of polymyxin B during CVVH was 27.94 ± 10.92 mg‧h/L, which was significantly lower than that outside CVVH (77.89 ± 35.66 mg‧h/L) (P=1.65 × 10−8). The population pharmacokinetic model revealed that CVVH significantly increased the clearance of polymyxin B. Monte Carlo simulations showed that for patients on CVVH, a loading dose of 200 mg plus a fixed maintenance dose of 150 mg every 12 h had a high probability of achieving AUCss,24h of 50–100 mg•h/L and the pharmacokinetic/pharmacodynamic target with a minimum inhibitory concentration ≤0.5 mg/L. For patients undergoing CVVH, high doses of polymyxin B and a dose-adjustment regimen based on therapeutic drug monitoring should be considered to improve efficacy.