VERNALIZATION2 (VRN2), an angiosperm-specific subunit of the polycomb repressive complex 2 (PRC2), is an oxygen (O2 )-regulated target of the PCO branch of the PRT6 N-degron pathway of ubiquitin-mediated proteolysis. How this post-translational regulation coordinates VRN2 activity remains to be fully established. Here we use Arabidopsis thaliana ecotypes, mutants and transgenic lines to determine how control of VRN2 stability contributes to its functions during plant development. VRN2 localizes to endogenous hypoxic regions in aerial and root tissues. In the shoot apex, VRN2 differentially modulates flowering time dependent on photoperiod, whilst its presence in lateral root primordia and the root apical meristem negatively regulates root system architecture. Ectopic accumulation of VRN2 does not enhance its effects on flowering, but does potentiate its repressive effects on root growth. In late-flowering vernalization-dependent ecotypes, VRN2 is only active outside meristems when its proteolysis is inhibited in response to cold exposure, as its function requires concomitant cold-triggered increases in other PRC2 subunits and cofactors. We conclude that the O2 -sensitive N-degron of VRN2 has a dual function, confining VRN2 to meristems and primordia, where it has specific developmental roles, whilst also permitting broad accumulation outside of meristems in response to environmental cues, leading to other functions. https://www.selleckchem.com/products/4-hydroxynonenal.html © 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.In the colon of patients with ulcerative colitis (UC), decreased function of the paracellular barrier, especially hypofunction of the tight junction, is associated with pathological conditions. However, there has been no report to date on the function of tight junctions in the small intestine. Here, we focused on the barrier function of the small intestine, especially in tight junctions, and compared it with that of the colon. Dextran sulfate sodium (DSS) was used to induce ulcerative colitis in rats in order to evaluate the function of the paracellular barrier in the jejunum, ileum, and colon. An in vitro diffusion chamber method was used to evaluate membrane resistance, which is an index of tight junction function and mucosal permeability, using 6-carboxyfluorescein (6-CF), a paracellular marker. In the jejunum and colon, with decrease of membrane resistance in the DSS group, mucosal permeability increased, whereas no marked difference was observed in the ileum. In the in situ closed-loop method, absorption of 6-CF from the jejunum was higher than that from the ileum. Immunohistochemical staining of claudin-4 showed heterogeneous attenuation of claudin-4 in the jejunum. Pharmacokinetic parameters were calculated from the blood concentration after intravenous injection and oral administration of 6-CF. In the DSS group, there was a delay in the elimination phase, suggesting a decrease in renal function, and an increase in maximum blood concentration, associated with an increased absorption rate constant. The increased absorption and decreased renal function due to decreased paracellular barrier function in the small intestine and colon may cause fluctuations in drug efficacy and side effects. © 2020 John Wiley & Sons, Ltd.AIMS Reduction mammoplasty (RM) is one of the most common plastic surgeries in the US. We aimed to demonstrate the rate of incidental atypical and malignant breast lesions (AMBL) found in RM specimens and the impact of the number of submitted tissue sections on the rate of ABL. METHODS AND RESULTS We analyzed our database for patients who underwent reduction mammoplasty between 2000 and 2018. Patients with a history of breast cancer were excluded from the study. All pathology reports were analyzed for AMBL (ALH, LCIS, FEA, ADH, DCIS, invasive carcinoma). The grossing protocol was to submit ten sections from each breast between 2000 and 2013, and six sections between 2014 and 2018. One hundred and sixty-nine of 5208 patients (3.3%) and 216 of 10,340 RM specimens (2.1%) showed at least one AMBL. Nineteen (0.36%) patients had incidental cancer. The median age of patients with AMBL was significantly higher than patients without ABL (59 vs. 45 years old). There was no cancer in patients 30 years old and two sections from each breast for patients less then 30 years old would be sufficient. © 2020 John Wiley & Sons Ltd.Behavior requires an actor. Two experiments using complex conditional action discriminations examined whether pigeons privilege information related to the digital actor who is engaged in behavior. In Experiment 1, each of two video displays contained a digital model, one an actor engaged in one of two behaviors (Indian dance or martial arts) and one a neutrally posed bystander. To correctly classify the display, the pigeons needed to conditionally process the action in conjunction with distinctive physical features of the actor or the bystander. Four actor-conditional pigeons learned to correctly discriminate the actions based on the identity of the actors, whereas four bystander-conditional birds failed to learn. Experiment 2 established that this failure was not due to the latter group's inability to spatially integrate information across the distance between the two models. Potentially, the colocalization of the relevant model identity and the action was critical due to a fundamental configural or integral representation of these properties. These findings contribute to our understanding of the evolution of action recognition, the recognition of social behavior, and forms of observational learning by animals.Pet dogs are known to be responsive to human pointing gestures, but shelter dogs have repeatedly demonstrated poor abilities to follow human pointing, although they can be explicitly trained quickly. This study evaluated the time course in which shelter dogs learn to follow points without explicit training, when given typical interactions with humans. In a longitudinal evaluation, the development of point following was tracked in seven shelter dogs in a training program (enriched human exposure), seven dogs in a traditional shelter (control population), and evaluated once in pet dogs. Twice a week for 6 weeks, shelter dogs' point-following performance was evaluated in 10 probe trials in which an experimenter pointed to one of two containers equidistant from the dog. To avoid direct training, dogs were given a treat for approaching and touching either container; although correct responses were recorded for touching the pointed-towards container within 30 s. Pet dogs were tested in only one session. All shelter dogs initially showed the expected poor performance.
VERNALIZATION2 (VRN2), an angiosperm-specific subunit of the polycomb repressive complex 2 (PRC2), is an oxygen (O2 )-regulated target of the PCO branch of the PRT6 N-degron pathway of ubiquitin-mediated proteolysis. How this post-translational regulation coordinates VRN2 activity remains to be fully established. Here we use Arabidopsis thaliana ecotypes, mutants and transgenic lines to determine how control of VRN2 stability contributes to its functions during plant development. VRN2 localizes to endogenous hypoxic regions in aerial and root tissues. In the shoot apex, VRN2 differentially modulates flowering time dependent on photoperiod, whilst its presence in lateral root primordia and the root apical meristem negatively regulates root system architecture. Ectopic accumulation of VRN2 does not enhance its effects on flowering, but does potentiate its repressive effects on root growth. In late-flowering vernalization-dependent ecotypes, VRN2 is only active outside meristems when its proteolysis is inhibited in response to cold exposure, as its function requires concomitant cold-triggered increases in other PRC2 subunits and cofactors. We conclude that the O2 -sensitive N-degron of VRN2 has a dual function, confining VRN2 to meristems and primordia, where it has specific developmental roles, whilst also permitting broad accumulation outside of meristems in response to environmental cues, leading to other functions. https://www.selleckchem.com/products/4-hydroxynonenal.html © 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.In the colon of patients with ulcerative colitis (UC), decreased function of the paracellular barrier, especially hypofunction of the tight junction, is associated with pathological conditions. However, there has been no report to date on the function of tight junctions in the small intestine. Here, we focused on the barrier function of the small intestine, especially in tight junctions, and compared it with that of the colon. Dextran sulfate sodium (DSS) was used to induce ulcerative colitis in rats in order to evaluate the function of the paracellular barrier in the jejunum, ileum, and colon. An in vitro diffusion chamber method was used to evaluate membrane resistance, which is an index of tight junction function and mucosal permeability, using 6-carboxyfluorescein (6-CF), a paracellular marker. In the jejunum and colon, with decrease of membrane resistance in the DSS group, mucosal permeability increased, whereas no marked difference was observed in the ileum. In the in situ closed-loop method, absorption of 6-CF from the jejunum was higher than that from the ileum. Immunohistochemical staining of claudin-4 showed heterogeneous attenuation of claudin-4 in the jejunum. Pharmacokinetic parameters were calculated from the blood concentration after intravenous injection and oral administration of 6-CF. In the DSS group, there was a delay in the elimination phase, suggesting a decrease in renal function, and an increase in maximum blood concentration, associated with an increased absorption rate constant. The increased absorption and decreased renal function due to decreased paracellular barrier function in the small intestine and colon may cause fluctuations in drug efficacy and side effects. © 2020 John Wiley & Sons, Ltd.AIMS Reduction mammoplasty (RM) is one of the most common plastic surgeries in the US. We aimed to demonstrate the rate of incidental atypical and malignant breast lesions (AMBL) found in RM specimens and the impact of the number of submitted tissue sections on the rate of ABL. METHODS AND RESULTS We analyzed our database for patients who underwent reduction mammoplasty between 2000 and 2018. Patients with a history of breast cancer were excluded from the study. All pathology reports were analyzed for AMBL (ALH, LCIS, FEA, ADH, DCIS, invasive carcinoma). The grossing protocol was to submit ten sections from each breast between 2000 and 2013, and six sections between 2014 and 2018. One hundred and sixty-nine of 5208 patients (3.3%) and 216 of 10,340 RM specimens (2.1%) showed at least one AMBL. Nineteen (0.36%) patients had incidental cancer. The median age of patients with AMBL was significantly higher than patients without ABL (59 vs. 45 years old). There was no cancer in patients 30 years old and two sections from each breast for patients less then 30 years old would be sufficient. © 2020 John Wiley & Sons Ltd.Behavior requires an actor. Two experiments using complex conditional action discriminations examined whether pigeons privilege information related to the digital actor who is engaged in behavior. In Experiment 1, each of two video displays contained a digital model, one an actor engaged in one of two behaviors (Indian dance or martial arts) and one a neutrally posed bystander. To correctly classify the display, the pigeons needed to conditionally process the action in conjunction with distinctive physical features of the actor or the bystander. Four actor-conditional pigeons learned to correctly discriminate the actions based on the identity of the actors, whereas four bystander-conditional birds failed to learn. Experiment 2 established that this failure was not due to the latter group's inability to spatially integrate information across the distance between the two models. Potentially, the colocalization of the relevant model identity and the action was critical due to a fundamental configural or integral representation of these properties. These findings contribute to our understanding of the evolution of action recognition, the recognition of social behavior, and forms of observational learning by animals.Pet dogs are known to be responsive to human pointing gestures, but shelter dogs have repeatedly demonstrated poor abilities to follow human pointing, although they can be explicitly trained quickly. This study evaluated the time course in which shelter dogs learn to follow points without explicit training, when given typical interactions with humans. In a longitudinal evaluation, the development of point following was tracked in seven shelter dogs in a training program (enriched human exposure), seven dogs in a traditional shelter (control population), and evaluated once in pet dogs. Twice a week for 6 weeks, shelter dogs' point-following performance was evaluated in 10 probe trials in which an experimenter pointed to one of two containers equidistant from the dog. To avoid direct training, dogs were given a treat for approaching and touching either container; although correct responses were recorded for touching the pointed-towards container within 30 s. Pet dogs were tested in only one session. All shelter dogs initially showed the expected poor performance.
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