Brassinosteroids modulate autophagy through phosphorylation of RAPTOR1B by the GSK3-like kinase BIN2 in Arabidopsis.

Macroautophagy/autophagy is a conserved recycling process that maintains cellular homeostasis during environmental stress. Autophagy is negatively regulated by TOR (target of rapamycin), a nutrient-regulated protein kinase that in plants is activated by several phytohormones, leading to increased growth. However, the detailed molecular mechanisms by which TOR integrates autophagy and hormone signaling are poorly understood. Here, we show that TOR modulates brassinosteroid (BR)-regulated plant growth and stress-response pathways. Active TOR was required for full BR-mediated growth in Arabidopsis thaliana. Autophagy was constitutively up-regulated upon blocking BR biosynthesis or signaling, and down-regulated by increasing the activity of the BR pathway. BIN2 (brassinosteroid-insensitive 2) kinase, a GSK3-like kinase functioning as a negative regulator in BR signaling, directly phosphorylated RAPTOR1B (regulatory-associated protein of TOR 1B), a substrate-recruiting subunit in the TOR complex, at a conserved serine residue within a typical BIN2 phosphorylation motif. Mutation of RAPTOR1B serine 916 to alanine, to block phosphorylation by BIN2, repressed autophagy and increased phosphorylation of the TOR substrate ATG13a (autophagy-related protein 13a). By contrast, this mutation had only a limited effect on growth. We present a model in which RAPTOR1B is phosphorylated and inhibited by BIN2 when BRs are absent, activating the autophagy pathway. When BRs signal and inhibit BIN2, RAPTOR1B is thus less inhibited by BIN2 phosphorylation. This leads to increased TOR activity and ATG13a phosphorylation, and decreased autophagy activity. Our studies define a new mechanism by which coordination between BR and TOR signaling pathways helps to maintain the balance between plant growth and stress responses.

Participant characteristics predicting communication outcomes in AAC implementation for individuals with ASD and IDD: a systematic review and meta-analysis.

This meta-analysis examined communication outcomes in single-case design studies of augmentative and alternative communication (AAC) interventions and their relationship to participant characteristics. Variables addressed included chronological age, pre-intervention communication mode, productive repertoire, and pre-intervention imitation skills. Investigators identified 114 single-case design studies that implemented AAC interventions with school-aged individuals with autism spectrum disorder and/or intellectual disability. Two complementary effect size indices, Tau(AB) and the log response ratio, were applied to synthesize findings. Both indices showed positive effects on average, but also exhibited a high degree of heterogeneity. Moderator analyses detected few differences in effectiveness when comparing across diagnoses, age, the number and type of communication modes, participant's productive repertoires, and imitation skills to intervention. A PRISMA-compliant abstract is available: https://bit.ly/30BzbLv.

FERONIA functions through Target of Rapamycin (TOR) to negatively regulate autophagy.

FERONIA (FER) receptor kinase plays versatile roles in plant growth and development, biotic and abiotic stress responses, and reproduction. Autophagy is a conserved cellular recycling process that is critical for balancing plant growth and stress responses. Target of Rapamycin (TOR) has been shown to be a master regulator of autophagy. Our previous multi-omics analysis with loss-of-function fer-4 mutant implicated that FER functions in the autophagy pathway. We further demonstrated here that the fer-4 mutant displayed constitutive autophagy, and FER is required for TOR kinase activity measured by S6K1 phosphorylation and by root growth inhibition assay to TOR kinase inhibitor AZD8055. Taken together, our study provides a previously unknown mechanism by which FER functions through TOR to negatively regulate autophagy.

Integration of multi-omics data reveals interplay between brassinosteroid and Target of Rapamycin Complex signaling in Arabidopsis.

Brassinosteroids (BRs) and Target of Rapamycin Complex (TORC) are two major actors coordinating plant growth and stress responses. Brassinosteroids function through a signaling pathway to extensively regulate gene expression and TORC is known to regulate translation and autophagy. Recent studies have revealed connections between these two pathways, but a system-wide view of their interplay is still missing. We quantified the level of 23 975 transcripts, 11 183 proteins, and 27 887 phosphorylation sites in wild-type Arabidopsis thaliana and in mutants with altered levels of either BRASSINOSTEROID INSENSITIVE 2 (BIN2) or REGULATORY ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), two key players in BR and TORC signaling, respectively. We found that perturbation of BIN2 or RAPTOR1B levels affects a common set of gene-products involved in growth and stress responses. Furthermore, we used the multi-omic data to reconstruct an integrated signaling network. We screened 41 candidate genes identified from the reconstructed network and found that loss of function mutants of many of these proteins led to an altered BR response and/or modulated autophagy activity. Altogether, these results establish a predictive network that defines different layers of molecular interactions between BR- or TORC-regulated growth and autophagy.

Integrated omics reveal novel functions and underlying mechanisms of the receptor kinase FERONIA in Arabidopsis thaliana.

The receptor kinase FERONIA (FER) is a versatile regulator of plant growth and development, biotic and abiotic stress responses, and reproduction. To gain new insights into the molecular interplay of these processes and to identify new FER functions, we carried out quantitative transcriptome, proteome, and phosphoproteome profiling of Arabidopsis (Arabidopsis thaliana) wild-type and fer-4 loss-of-function mutant plants. Gene ontology terms for phytohormone signaling, abiotic stress, and biotic stress were significantly enriched among differentially expressed transcripts, differentially abundant proteins, and/or misphosphorylated proteins, in agreement with the known roles for FER in these processes. Analysis of multiomics data and subsequent experimental evidence revealed previously unknown functions for FER in endoplasmic reticulum (ER) body formation and glucosinolate biosynthesis. FER functions through the transcription factor NAI1 to mediate ER body formation. FER also negatively regulates indole glucosinolate biosynthesis, partially through NAI1. Furthermore, we found that a group of abscisic acid (ABA)-induced transcription factors is hypophosphorylated in the fer-4 mutant and demonstrated that FER acts through the transcription factor ABA INSENSITIVE5 (ABI5) to negatively regulate the ABA response during cotyledon greening. Our integrated omics study, therefore, reveals novel functions for FER and provides new insights into the underlying mechanisms of FER function.

Interactions between autophagy and phytohormone signaling pathways in plants.

Autophagy is a conserved recycling process with important functions in plant growth, development, and stress responses. Phytohormones also play key roles in the regulation of some of the same processes. Increasing evidence indicates that a close relationship exists between autophagy and phytohormone signaling pathways, and the mechanisms of interaction between these pathways have begun to be revealed. Here, we review recent advances in our understanding of how autophagy regulates hormone signaling and, conversely, how hormones regulate the activity of autophagy, both in plant growth and development and in environmental stress responses. We highlight in particular recent mechanistic insights into the coordination between autophagy and signaling events controlled by the stress hormone abscisic acid and by the growth hormones brassinosteroid and cytokinin and briefly discuss potential connections between autophagy and other phytohormones.

Functional outcomes following fixation of a marginal distal radius fracture with two commonly used volar locking plates: a retrospective cohort study.

INTRODUCTION: The volar locking plate has been widely used for unstable distal radius fractures to provide early recovery of wrist function. Volar plate prominence to the watershed line has been reported to be related to flexor tendon irritation, and avoid implant prominence in this area was suggested. On the other hand, marginal distal radius fracture patterns required the plate to cross the watershed line, making conflict over plate positioning on marginal distal radius fractures. This study compared functional outcomes in patients with marginal distal radius fractures treated with two different implants. MATERIALS AND METHODS: A retrospective study was conducted, all patients who received a Synthes 2.4 mm LCP or an Acumed Acu-Loc VLP between January 2015 and December 2018 were reviewed. The marginal distal radius fracture pattern was the most distal horizontal fracture line within 10 mm of the lunate fossa's joint line. The primary outcomes including patient-reported pain scores, range of motion, and grip strength were assessed. Secondary outcomes included patient-based subjective satisfaction scores of the injured wrist and hand function. The Mayo Wrist Score and the requirement for a secondary procedure related to hardware complications were also recorded. RESULTS: Forty-two patients met our inclusion criteria. Twenty-one patients were treated with the Synthes 2.4 mm LCP, and 21 patients with the Acumed Acu-Loc VLP. The primary outcome revealed that post-operative range of motion (P = 0.016) and grip strengths (P = 0.014) were significantly improved in the Acu-Loc VLP group. The MAYO wrist score in the Acu-Loc VLP group was also significantly better (P = 0.006). CONCLUSIONS: Despite advances in implant designs, flexor tendon irritation or rupture is still a complication following distal radius's volar plating. We believe the Acumed Acu-Loc VLP design provided better functional outcomes than the Synthes 2.4 mm LCP if appropriately and carefully placed into its designed-for position. This positioning results in promising patient satisfaction when treating marginal distal radius fractures.

Respiratory muscle training in stroke patients with respiratory muscle weakness, dysphagia, and dysarthria - a prospective randomized trial.

OBJECTIVE: To examine the efficacy of combined inspiratory and expiratory respiratory muscle training (RMT) with respect to the swallowing function, pulmonary function, functional performance, and dysarthria in patients with stroke. DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary hospital. PARTICIPANTS: The trial included 21 subjects (12 men, 9 women) aged 35 to 80 years presenting with 6 months history of unilateral stroke, respiratory muscle weakness (≥70% predicted maximal inspiratory pressure (MIP) and/or ≤70% maximal expiratory pressure (MEP)), dysphagia, or dysarthria. These subjects were randomly assigned to the control (n = 10, rehabilitation) and experimental (n = 11, rehabilitation with RMT) groups. INTERVENTION: Inspiratory RMT starting from 30% to 60% of MIP and expiratory RMT starting from 15% to 75% of MEP for 5 days/week for 6 weeks. MAIN OUTCOME MEASURES: MIP, MEP, pulmonary function, peak cough flow, perception of dyspnea, Fatigue Assessment Scale, Modified Rankin Scale, Brunnstrom stage, Barthel index, Functional Oral Intake Scale (FOIS), and parameters of voice analysis. RESULTS: Significant differences were observed between both groups in terms of MIP, forced vital capacity (FVC), and forced expiratory volume per second (FEV1) of the percentage predicted. Significant difference was found with respect to the change in fatigue, shimmer percent, amplitude perturbation quotient, and voice turbulence index (VTI) according to the acoustic analysis in the RMT group. The FEV1/FVC ratio was negatively correlated with jitter percent, relative average perturbation, pitch perturbation quotient, and VTI; the maximum mid-expiratory flow (MMEF) and MMEF% were also negatively correlated with VTI. Significant differences among participants of the same group were observed while comparing the Brunnstrom stage before and after training of the affected limbs and the Barthel scale and FOIS scores in both the groups. CONCLUSIONS: Altogether, 6-week combined inspiratory and expiratory RMT is feasible as adjuvant therapy for stroke patients to improve fatigue level, respiratory muscle strength, lung volume, respiratory flow, and dysarthria.Clinical trial registration number (Clinical Trial Identifier): NCT03491111.

Combating stress: the interplay between hormone signaling and autophagy in plants.

Autophagy is a conserved recycling process in which cellular components are delivered to and degraded in the vacuole/lysosome for reuse. In plants, it assists in responding to dynamic environmental conditions and maintaining metabolite homeostasis under normal or stress conditions. Under stress, autophagy is activated to remove damaged components and to recycle nutrients for survival, and the energy sensor kinases target of rapamycin (TOR) and SNF-related kinase 1 (SnRK1) are key to this activation. Here, we discuss accumulating evidence that hormone signaling plays critical roles in regulating autophagy and plant stress responses, although the molecular mechanisms by which this occurs are often not clear. Several hormones have been shown to regulate TOR activity during stress, in turn controlling autophagy. Hormone signaling can also regulate autophagy gene expression, while, reciprocally, autophagy can regulate hormone synthesis and signaling pathways. We highlight how the interplay between major energy sensors, plant hormones, and autophagy under abiotic and biotic stress conditions can assist in plant stress tolerance.

Overexpression of trans-Golgi network t-SNAREs rescues vacuolar trafficking and TGN morphology defects in a putative tethering factor mutant.

The trans-Golgi network (TGN) is a major site for sorting of cargo to either the vacuole or apoplast. The TGN-localized coiled-coil protein TNO1 is a putative tethering factor that interacts with the TGN t-SNARE SYP41 and is required for correct localization of the SYP61 t-SNARE. An Arabidopsis thaliana tno1 mutant is hypersensitive to salt stress and partially mislocalizes vacuolar proteins to the apoplast, indicating a role in vacuolar trafficking. Here, we show that overexpression of SYP41 or SYP61 significantly increases SYP41-SYP61 complex formation in a tno1 mutant, and rescues the salt sensitivity and defective vacuolar trafficking of the tno1 mutant. The TGN is disrupted and vesicle budding from Golgi cisternae is reduced in the tno1 mutant, and these defects are also rescued by overexpression of SYP41 or SYP61. Our results suggest that the trafficking and Golgi morphology defects caused by loss of TNO1 can be rescued by increasing SYP41-SYP61 t-SNARE complex formation, implicating TNO1 as a tethering factor mediating efficient vesicle fusion at the TGN.