The best-characterized members of the plant-specific SIAMESE-RELATED (SMR) family of cyclin-dependent kinase inhibitors regulate the transition from the mitotic cell cycle to endoreplication, also known as endoreduplication, an altered version of the cell cycle in which DNA is replicated without cell division. Some other family members are implicated in cell cycle responses to biotic and abiotic stresses. However, the functions of most SMRs remain unknown, and the specific cyclindependent kinase complexes inhibited by SMRs are unclear. Here, we demonstrate that a diverse group of SMRs, including an SMR from the bryophyte Physcomitrella patens, can complement an Arabidopsis thaliana siamese (sim) mutant and that both Arabidopsis SIM and P. patens SMR can inhibit CDK activity in vitro. Furthermore, we show that Arabidopsis SIM can bind to and inhibit both CDKA;1 and CDKB1;1. Finally, we show that SMR2 acts to restrict cell proliferation during leaf growth in Arabidopsis and that SIM, SMR1/LGO, and SMR2 play overlapping roles in controlling the transition from cell division to endoreplication during leaf development. These results indicate that differences in SMR function in plant growth and development are primarily due to differences in transcriptional and posttranscriptional regulation, rather than to differences in fundamental biochemical function.

No abstract

Precise cell-cycle control is critical for plant development and responses to pathogen invasion. Two homologous cyclindependent kinase inhibitor genes, SIAMESE (SIM) and SIM-RELATED 1 (SMR1), were recently shown to regulate Arabidopsis (Arabidopsis thaliana) defense based on phenotypes conferred by a sim smr1 double mutant. However, whether these two genes play differential roles in cell-cycle and defense control is unknown. In this report, we show that while acting synergistically to promote endoreplication, SIM and SMR1 play different roles in affecting the ploidy of trichome and leaf cells, respectively. In addition, we found that the smr1-1 mutant, but not sim-1, was more susceptible to a virulent Pseudomonas syringae strain, and this susceptibility could be rescued by activating salicylic acid (SA)-mediated defense. Consistent with these results, smr1-1 partially suppressed the dwarfism, high SA levels, and cell death phenotypes in acd6-1, a mutant used to gauge the change of defense levels. Thus, SMR1 functions partly through SA in defense control. The differential roles of SIM and SMR1 are due to differences in temporal and spatial expression of these two genes in Arabidopsis tissues and in response to P. syringae infection. In addition, flow-cytometry analysis of plants with altered SA signaling revealed that SA is necessary, but not sufficient, to change cell-cycle progression. We further found that a mutant with three CYCD3 genes disrupted also compromised disease resistance to P. syringae. Together, this study reveals differential roles of two homologous cyclin-dependent kinase inhibitors in regulating cell-cycle progression and innate immunity in Arabidopsis and provides insights into the importance of cell-cycle control during host-pathogen interactions.

The three-site approach to steroid instillation in frozen shoulder is a safe method and provides early recovery and better improvement in shoulder function with less relapses.

No abstract

The root cap, a small tissue at the tip of the root, protects the root from environmental stress and functions in gravity perception. To perform its functions, the position and size of the root cap remains stable throughout root growth. This occurs due to constant root cap cell turnover, in which the last layer of the root cap is released, and new root cap cells are produced. Cells in the last root cap layer are known as border cells or border-like cells, and have important functions in root protection against bacterial and fungal pathogens. Despite the importance of root cap cell release to root health and plant growth, the mechanisms regulating this phenomenon are not well understood. Recent work identified several factors including transcription factors, auxin, and small peptides with roles in the production and release of root cap cells. Here, we review the involvement of the known players in root cap cell release, compare the release of border-like cells and border cells, and discuss the importance of root cap cell release to root health and survival.

Background The programmed cell death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2 are immune checkpoints that suppress anti-cancer immunity. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their activity. Recently, PD-1 expression has also been found in cancer cells. Here, we analysed expression and functions of PD-1 in thyroid cancer (TC). Methods PD-1 expression was evaluated by immunohistochemistry on human TC samples and by RT-PCR, western blot and FACS on TC cell lines. Proliferation and migration of TC cells in culture were assessed by BrdU incorporation and Boyden chamber assays. Biochemical studies were performed by western blot, immunoprecipitation, pull-down and phosphatase assays. TC cell tumorigenicity was assessed by xenotransplants in nude mice. Results Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 was also constitutively expressed on TC cell lines. PD-1 overexpression/stimulation promoted TC cell proliferation and migration. Accordingly, PD-1 genetic/pharmacologic inhibition caused the opposite effects. Mechanistically, PD-1 recruited the SHP2 phosphatase to the plasma membrane and potentiated its phosphatase activity. SHP2 enhanced Ras activation by dephosphorylating its inhibitory tyrosine 32, thus triggering the MAPK cascade. SHP2, BRAF and MEK were necessary for PD-1-mediated biologic functions. PD-1 inhibition decreased, while PD-1 enforced expression facilitated, TC cell xenograft growth in mice by affecting tumour cell proliferation. Conclusions PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the SHP2/Ras/MAPK signalling pathway.

The use of extremophyte models to select growth promoting traits during environmental stresses is a recognized yet an underutilized strategy to design stress-resilient plants. Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its life cycle under multiple environmental stresses, including high salinity. While S. parvula is equipped with foundational genomic resources to identify genetic clues that potentially lead to stress adaptations at the phenome level, a comprehensive physiological and structural characterization of salt stress responses throughout its lifecycle is absent. We aimed to identify the influential traits that lead to resilient growth and strategic decisions to ensure survival of the species in an extreme environment, and examined salt-induced changes in the physiology and anatomy of S. parvula throughout its life cycle across multiple tissues. We found that S. parvula maintains or even enhances growth during various developmental stages at salt stress levels known to inhibit growth in Arabidopsis thaliana and most crops. The resilient growth of S. parvula was associated with key traits synergistically allowing continued primary root growth, expansion of xylem vessel elements across the root-shoot continuum, and the high capacity to maintain tissue water levels by developing larger and thicker leaves while facilitating continued photosynthesis during salt stress. In turn, the stress-resilient growth during the vegetative phase of S. parvula allowed a successful transition to a reproductive phase via early flowering followed by the development of larger siliques with viable seeds on salt-treated plants. Additionally, the success of self-fertilization in early flowering stages was dependent on salt-induced filament elongation. Our results suggest that the maintenance of leaf water status and enhancement of selfing in early flowers to ensure reproductive success are among the most influential traits that contribute to the extremophilic lifestyle of S. parvula in its natural habitat.