The energy cost of the tonoplast futile sodium leak.

Active removal of Na+ from the cytosol into the vacuole plays a critical role in salinity tissue tolerance, but another, often neglected component of this trait is Na+ retention in vacuoles. This retention is based on an efficient control of Na+ -permeable slow- and fast-vacuolar channels that mediate the back-leak of Na+ into cytosol and, if not regulated tightly, could result in a futile cycle. This Tansley insight summarizes our current knowledge of regulation of tonoplast Na+ -permeable channels and discusses the energy cost of vacuolar Na+ sequestration, under different scenarios. We also report on a phylogenetic and bioinformatic analysis of the plant two-pore channel family and the difference in its structure and regulation between halophytes and glycophytes, in the context of salinity tolerance.

Energy costs of salt tolerance in crop plants.

Agriculture is expanding into regions that are affected by salinity. This review considers the energetic costs of salinity tolerance in crop plants and provides a framework for a quantitative assessment of costs. Different sources of energy, and modifications of root system architecture that would maximize water vs ion uptake are addressed. Energy requirements for transport of salt (NaCl) to leaf vacuoles for osmotic adjustment could be small if there are no substantial leaks back across plasma membrane and tonoplast in root and leaf. The coupling ratio of the H+ -ATPase also is a critical component. One proposed leak, that of Na+ influx across the plasma membrane through certain aquaporin channels, might be coupled to water flow, thus conserving energy. For the tonoplast, control of two types of cation channels is required for energy efficiency. Transporters controlling the Na+ and Cl- concentrations in mitochondria and chloroplasts are largely unknown and could be a major energy cost. The complexity of the system will require a sophisticated modelling approach to identify critical transporters, apoplastic barriers and root structures. This modelling approach will inform experimentation and allow a quantitative assessment of the energy costs of NaCl tolerance to guide breeding and engineering of molecular components.

Resource allocation to growth or luxury consumption drives mycorrhizal responses.

Highly variable phenotypic responses in mycorrhizal plants challenge our functional understanding of plant-fungal mutualisms. Using non-invasive high-throughput phenotyping, we observed that arbuscular mycorrhizal (AM) fungi relieved phosphorus (P) limitation and enhanced growth of Brachypodium distachyon under P-limited conditions, while photosynthetic limitation under low nitrogen (N) was exacerbated by the fungus. However, these responses were strongly dependent on host genotype: only the faster growing genotype (Bd3-1) utilised P transferred from the fungus to achieve improved growth under P-limited conditions. Under low N, the slower growing genotype (Bd21) had a carbon and N surplus that was linked to a less negative growth response compared with the faster growing genotype. These responses were linked to the regulation of N : P stoichiometry, couples resource allocation to growth or luxury consumption in diverse plant lineages. Our results attest strongly to a mechanism in plants by which plant genotype-specific resource economics drive phenotypic outcomes during AM symbioses.

Quality of critical care clinical practice guidelines: Assessment with AGREE II instrument.

STUDY OBJECTIVE: Clinical practice guidelines (CPGs) are cornerstones for the management of critically ill patients. Numerous CPGs have been generated in critical care medicine, but their qualities have never been systematically appraised. The aim of the present study was to systematically assess the quality of critical care CPGs. DESIGN: A systematic electronic search was performed in PubMed and Scopus. All critical care CPGs were included for analysis. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTION: None. MEASUREMENTS: The Appraisal of guidelines for research & evaluation II (AGREE II) instrument was employed to appraise the quality. CPGs were assessed independently by three raters and intraclass correlation coefficient to represent the agreement among raters. MAIN RESULTS: A total of 89 CPGs were included for quantitative analysis. The results showed that domain 1 (scope and purpose) had the highest scores (0.93, IQR: 0.89-0.98) and domain 2 (stakeholder involvement) had the lowest scores (0.37, IQR: 0.30-0.46). The overall score was 0.83 (IQR: 0.67-0.83). Publication year was not associated with scaled scores in each domain. Domain 2 (stakeholder involvement) was significantly associated with the number of societies (coefficient: 0.702, p = 0.033). Also, greater number of societies were associated with higher scaled scores of domain 3 (coefficient: 0.768, p = 0.027), 4 (coefficient: 0.730, p = 0.029) and 5 (coefficient: 0.995, p = 0.023). CONCLUSIONS: The study showed that the reporting quality of critical care CPGs were suboptimal. The reporting quality varied across the six domains, with the highest quality in domain 1 and lowest quality in domain 2. Strenuous efforts need to be made to improve the reporting of critical care CPGs.

Development and validation of a LC-MS/MS method for quantification of hetrombopag for pharmacokinetics study.

Hetrombopag as the derivative of ethylidene hydrazine carboxamide was recently developed into a novel patented non-peptide thrombopoietin mimetic and thrombopoietin receptor agonist to treat idiopathic thrombocytopenic purpura. To study the pharmacokinetics of hetrombopag, a highly sensitive, rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of hetrombopag in rat plasma. After protein precipitation extraction, the chromatography separation of analyte and internal standard named eltrombopag as an marketed analog of hetrombopag was performed on an Synergi Polar-RP column at the flow rate of 0.5 mL/min, and the determination was conducted on an API4000 triple quadrupole mass spectrometry in the multiple reaction monitoring mode using the respective [M+H](+) ions m/z 459.2 â†’ 200.9 for hetrombopag and m/z 443.2 â†’ 229.0 for IS. The lower limit of quantification was established to be 1 ng/mL, and the linear scope of standard curve was 1-1000 ng/mL. Both the precision (RSD%) and accuracy (RE%) were within the acceptable criterion of below 15 %. The validated method was successfully applied to quantify hetrombopag in the rat plasma and investigate the pharmacokinetics.