TMK1-based auxin signaling regulates abscisic acid responses via phosphorylating ABI1/2 in Arabidopsis.

Differential concentrations of phytohormone trigger distinct outputs, which provides a mechanism for the plasticity of plant development and an adaptation strategy among plants to changing environments. However, the underlying mechanisms of the differential responses remain unclear. Here we report that a high concentration of auxin, distinct from the effect of low auxin concentration, enhances abscisic acid (ABA) responses in Arabidopsis thaliana, which partially relies on TRANS-MEMBERANE KINASE 1 (TMK1), a key regulator in auxin signaling. We show that high auxin and TMK1 play essential and positive roles in ABA signaling through regulating ABA INSENSITIVE 1 and 2 (ABI1/2), two negative regulators of the ABA pathway. TMK1 inhibits the phosphatase activity of ABI2 by direct phosphorylation of threonine 321 (T321), a conserved phosphorylation site in ABI2 proteins, whose phosphorylation status is important for both auxin and ABA responses. This TMK1-dependent auxin signaling in the regulation of ABA responses provides a possible mechanism underlying the high auxin responses in plants and an alternative mechanism involved in the coordination between auxin and ABA signaling.

Pharmaceutical care of rituximab in the treatment of children with refractory anti-NMDAR encephalitis: A case report.

RATIONALE: Anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis is a rare disease of nervous system, which is mediated by autoimmune mechanisms. The treatment of anti-NMDAR encephalitis includes Immunotherapy, symptomatic and supportive treatment for seizures and psychiatric symptoms. There are many kinds of drugs, so drug treatment management and pharmaceutical care for children are particularly important. At present, there are few reports on pharmaceutical care for children with this disease. Clinical pharmacists participated in the pharmaceutical care of a child with refractory anti-NMDAR encephalitis treated with rituximab, conducted drug treatment management on the dosage, administration method, complications and other aspects of off-label use of rituximab, combined with the children's clinical manifestations, inflammatory indicators, pathogenic detection, blood concentration, liver and kidney functions, drug interactions and other factors. The treatment plan of anti-infective drugs shall be adjusted, and attention shall be paid to whether there are adverse reactions during the treatment. PATIENT CONCERNS: A 4-year-old girl presented with epileptic seizure, intermittent recurrent fever, high inflammatory markers, abnormal psychiatric function/cognitive impairment, language disorder, consciousness disturbance, and movement disorder/involuntary movement. DIAGNOSIS: Refractory anti-NMDAR encephalitis. INTERVENTIONS: The patient was given first-line (3 rounds of methylprednisolone pulse therapy and gamma globulin) and second-line (rituximab) immunotherapy. On the advice of a clinical pharmacist, the patient wasn't given Advanced antibacterial agents (voriconazole, vancomycin) therapy. On the 41st day of admission, the patient's temperature and inflammatory indicators were normal, CD19 + B cells were reduced to 0. OUTCOMES: The patient consciousness level, cognition and orientation were gradually improved, mental disorder was improved, involuntary movement was obviously controlled, no seizure occurred again, and the patient was discharged with stable condition. LESSONS: Clinical pharmacists ensure the safety, effectiveness and economy of patients' medication by carrying out the whole process of individualized drug treatment management and care for patients.