To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16-deficient (p16-/- ) mice, homozygous Bmi1-deficient (Bmi1-/- ) mice, double homozygous Bmi1 and p16-deficient (Bmi1-/- p16-/- ) mice to those of their wild-type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1-/- mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice. Compared to Bmi1-/- mice, the mandible mineral density, cortical thickness, alveolar bone volume, osteoblast number and activity, alkaline phosphatase positive area were all increased significantly in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve mandible growth in Bmi1 knockout mice. Furthermore, the protein expression levels of cyclin D, CDK4 and p53 were increased significantly in p16-/- mice compared with those from wild-type mice; the protein expression levels of cyclin D and CDK4 were decreased significantly, whereas those of p27 and p53 were increased significantly in Bmi1-/- mice; these parameters were partly rescued in Bmi1-/- p16-/- mice compared with those from Bmi1-/- mice. Therefore, our results indicate that Bmi1 plays roles in regulating tooth and mandible development by inhibiting p16 signal pathway which initiated entry into cell cycle.Invasive ants shape assemblages and interactions of native species, but their effect on fundamental ecological processes is poorly understood. In East Africa, Pheidole megacephala ants have invaded monodominant stands of the ant-tree Acacia drepanolobium, extirpating native ant defenders and rendering trees vulnerable to canopy damage by vertebrate herbivores. We used experiments and observations to quantify direct and interactive effects of invasive ants and large herbivores on A. drepanolobium photosynthesis over a 2-year period. Trees that had been invaded for ≥ 5 years exhibited 69% lower whole-tree photosynthesis during key growing seasons, resulting from interaction between invasive ants and vertebrate herbivores that caused leaf- and canopy-level photosynthesis declines. We also surveyed trees shortly before and after invasion, finding that recent invasion induced only minor changes in leaf physiology. Our results from individual trees likely scale up, highlighting the potential of invasive species to alter ecosystem-level carbon fixation and other biogeochemical cycles.Existing criteria for inclusion in the European baseline series are summarized. Additional criteria are developed to aid decision making where the current criteria do not yield an unequivocal result. These include a consideration of whether an allergen (hapten) is better placed in a special series and the frequency with which an allergen cross-reacts with existing markers in the baseline series. Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na channel inhibitors are in general ineffective against the seizures in LGS. https://www.selleckchem.com/products/uk5099.html Rufinamide is a new Na channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASDs) according to simplistic categorical grouping. The effect of rufinamide on the Na channel, cellular discharges, and seizure behaviors was quantitatively characterized in native neurons and mammalian models of epilepsy, and compared with the other Na channel inhibitors. With a much faster binding rate to the inactivated Na channel than phenytoin, rufinamide is distinctively effective if the seizure discharges chiefly involve short bursts interspersed with hyperpolarized interburst intervals, exemplified by spike and wave discharges (SWDs) on electroencephalograms. Consistently, rufinamide, but not phenytoin, suppresses SWD-associated seizures in pelarized, phenytoin could be better because of the higher affinity. Na+ channel inhibitors with different binding kinetics and affinity to the inactivated channels may have different antiseizure scope. A rational choice of ASDs according to in-depth molecular pharmacology and the attributes of ictal discharges is advisable. ANN NEUROL 2021;891099-1113.ROS are known to be accumulated in stigmas of different species and can possibly perform different functions important for plant reproduction. Here we tested the assumption that one of their functions is to control membrane potential and provoke synthesis of unique proteins in germinating pollen. We used spectrofluorometry and spectrophotometry to detect H2 O2 in stigma exudate, quantitative fluorescent microscopy of pollen tubes and flow cytometry of pollen protoplasts to reveal effects on membrane potential, and a label-free quantification approach to study pollen proteome changes after H2 O2 treatment. We found that in both growing pollen tubes and pollen protoplasts exudate causes plasmalemma hyperpolarization similar to that provoked by H2 O2 . This effect is abolished by catalase treatment and the ROS quencher, MnTMPP. Inhibitory analysis indicates probable participation of Ca2+ - and K+ -conducting channels in the observed hyperpolarization. For a deeper understanding of pollen response, we analysed proteome alterations in H2 O2 -treated pollen grains. We found 50 unique proteins and 20 differently accumulated proteins that are mainly involved in cell metabolism, energetics, protein synthesis and folding. Observed hyperpolarization and proteome alterations agree well with previously reported stimulation of pollen germination by H2 O2 and sensitivity of Ca2+ - and K+ -conducting channels to this ROS. Thus, H2 O2 is one of the active substances in tobacco stigma exudate that stimulates various physiological processes in germinating pollen.