The makings of a gradient: spatiotemporal distribution of gibberellins in plant development.

The gibberellin phytohormones regulate growth and development throughout the plant lifecycle. Upstream regulation and downstream responses to gibberellins vary across cells and tissues, developmental stages, environmental conditions, and plant species. The spatiotemporal distribution of gibberellins is the result of an ensemble of biosynthetic, catabolic and transport activities, each of which can be targeted to influence gibberellin levels in space and time. Understanding gibberellin distributions has recently benefited from discovery of transport proteins capable of importing gibberellins as well as novel methods for detecting gibberellins with high spatiotemporal resolution. For example, a genetically-encoded fluorescent biosensor for gibberellins was deployed in Arabidopsis and revealed gibberellin gradients in rapidly elongating tissues. Although cellular accumulations of gibberellins are hypothesized to regulate cell growth in developing embryos, germinating seeds, elongating stems and roots, and developing floral organs, understanding the quantitative relationship between cellular gibberellin levels and cellular growth awaits further investigation. It is also unclear how spatiotemporal gibberellin distributions result from myriad endogenous and environmental factors directing an ensemble of known gibberellin enzymatic and transport steps

Air quality modelling system over a central mediterranean region

This work presents a complex modelling system for air quality studies. The system couples meteorological models, emission preprocessors and dispersion models. Two meteorological models have been coupled in cascade: a mesoscale meteorological model and a 3D diagnostic micro-meteorological model, which is able to provide a realistic three-dimensional wind and temperature fields and two dimensional fields of boundary layer parameters. The emission data were obtained trough disaggregation of national emission inventory, by using a database related to all industrial sources, and through direct evaluation of road transport and biogenic emissions. Meteorological fields and emission data have been used by a photochemical model and by a Lagrangian puff dispersion model. The modelling system has been applied over Salento Peninsula, located in the south-east corner of Italy, in the Mediterranean central area in a real typical summer scenario.Este trabalho apresenta um complexo sitema de modelagem para estudos de qualidade do ar, acoplando modelos meteorológicos, preprocessadores de emissão e modelos de dispersão. Dois modelos meteorológicos foram acoplados em cascata: um modelo meteorológico de mesoescala e um modelo de diagnóstico micrometorólgico 3-D; capaz de gerar campos realísticos e tridimensionais de vento e temperatura e campos bidimensionais de parâmetros da camada limite planetária. Os dados de emissão foram obtidos do inventário nacional de emissão, que consiste em um banco de dados de todas as fontes industriais, e por estimativa direta da emissão de veículos e biogênica. Os campos meteorológicos e dados de emissão foram inseridos em um modelo fotoquímico e um modelo de dispersão puff-Lagrangeano. Todo o sistema foi então aplicado na Península de Salento, localizada no extremo sudeste da Itália, área central do Mar Mediterrâneo, para um cenário típico de verão

Visualizing Cellular Gibberellin Levels Using the nlsGPS1 Förster Resonance Energy Transfer (FRET) Biosensor.

The phytohormone gibberellin (GA) is a small, mobile signaling molecule that plays a key role in seed germination, cellular elongation, and developmental transitions in plants. Gibberellin Perception Sensor 1 (GPS1) is the first Förster resonance energy transfer (FRET)-based biosensor that allows monitoring of cellular GA levels in vivo. By measuring a fluorescence emission ratio of nuclear localized-GPS1 (nlsGPS1), spatiotemporal mapping of endogenously and exogenously supplied GA gradients in different tissue types is feasible at a cellular scale. This protocol will describe how to image nlsGPS1 emission ratios in three example experiments: steady-state, before-and-after exogenous gibberellin A4 (GA4) treatments, and over a treatment time-course. We also provide methods to analyze nlsGPS1 emission ratios using both Fiji and a commercial three-dimensional (3-D) micrograph visualization and analysis software and explain the limitations and likely pitfalls of using nlsGPS1 to quantify gibberellin levels.European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 759282

Differential biosynthesis and cellular permeability explain longitudinal gibberellin gradients in growing roots.

Control over cell growth by mobile regulators underlies much of eukaryotic morphogenesis. In plant roots, cell division and elongation are separated into distinct longitudinal zones and both division and elongation are influenced by the growth regulatory hormone gibberellin (GA). Previously, a multicellular mathematical model predicted a GA maximum at the border of the meristematic and elongation zones. However, GA in roots was recently measured using a genetically encoded fluorescent biosensor, nlsGPS1, and found to be low in the meristematic zone grading to a maximum at the end of the elongation zone. Furthermore, the accumulation rate of exogenous GA was also found to be higher in the elongation zone. It was still unknown which biochemical activities were responsible for these mobile small molecule gradients and whether the spatiotemporal correlation between GA levels and cell length is important for root cell division and elongation patterns. Using a mathematical modeling approach in combination with high-resolution GA measurements in vivo, we now show how differentials in several biosynthetic enzyme steps contribute to the endogenous GA gradient and how differential cellular permeability contributes to an accumulation gradient of exogenous GA. We also analyzed the effects of altered GA distribution in roots and did not find significant phenotypes resulting from increased GA levels or signaling. We did find a substantial temporal delay between complementation of GA distribution and cell division and elongation phenotypes in a GA deficient mutant. Together, our results provide models of how GA gradients are directed and in turn direct root growth

Asenapine in Clinical Practice: Responders Vs Non-responders

ntroduction Asenapine is a second-generation antipsychotic approved in Europe for the treatment of manic or mixed episodes. Objective To describe the clinical features of Asenapine responders and non-responders. Methods A naturalistic, observational study is ongoing in patients treated with Asenapine. We have already recruited 37 manic patients with a lifetime diagnosis of Bipolar I (BDI) or Schizoaffective Disorder referring to our Psychiatric Ward. Patients are assessed with the Young Mania Rating Scale (YMRS) at baseline (T0), and after 1 (T1) and 4 weeks (T2) of treatment. According to YMRS scores, patients are classified as responders and non-responders. Results The preliminary results highlight a significant improvement of the YMRS score from T0 to T2 in most patients. Asenapine seems particularly effective in patients with less severe manic symptoms, and responders are more likely to have lower baseline YMRS score. No correlation has currently emerged between responder status and diagnosis. Non-responders in our sample are females sharing some clinical features: early onset BDI diagnosis, several previous treatments (antipsychotics, mood stabilizers), initial cognitive impairment confirmed with the Mini Mental State Examination, Alzheimer Disease Assessment Scale and neuroimaging. Conclusions Elderly manic patients with neurological impairment and/or dementia may have poorer therapeutic outcomes and poorer response to pharmacological treatment, which may prove effective in reducing agitation but not mania ratings. Diagnosis (BDI or schizoaffective disorder) does not seem to have a significant impact on Asenapine efficacy. The further recruitment and assessment of patients is expected to support the results described above

Asenapine Effects On Peroxidation and Calcium Movements in HL-1 Cells

Introduction Bipolar patients are at higher risk for cardiovascular morbidity and mortality than their counterparts in the general population. In a recent in vitro study, Asenapine, a new antipsychotic for the treatment of mania/mixed mania, was found to keep physiological endothelial function by activation of eNOS-related NO release and to protect endothelial cells against peroxidation by interference with mitochondria, apoptosis and cell survival. Objectives To examine the cardiac protective effects elicited by Asenapine against peroxidation and on the Ca2+ movements. Methods In HL-1 that had undergone oxidative stress by 20 min hydrogen peroxide the effects of 30 min pre-treatment with Asenapine on survival and proliferation will be examined. In Fura-2AM loaded HL-1 we will next analyze the effects of Asenapine on Ca2+ movements and the related involvement of cAMP/PKA and PLC pathways, CaMKII, L and T type Ca2+ channels and 5HT1A receptors. The role of 'capacitative” Ca2+ entry, plasma-membrane Ca2+ pump inhibitor (PMCA) and Na+/Ca2+ exchanger will be analyzed. Changes of membrane potential caused by interference with K+ channels will be examined, as well. Results We expect to find a proliferative and anti-peroxidative effect of Asenapine in HL-1 cells. Asenapine could also affect Ca2+ movements through cAMP/PKA and PLC-dependent signalling and the involvement of 5HT1A receptors. The effects of Asenapine could also be related to changes of plasma membrane by interference with K+ channels and the modulation of PMCA activity and Na+/Ca2+ exchanger. Conclusions We expect to further confirm the protective effect of Asenapine against peroxidative injuries.Implications will be discusse

Research data supporting "Differential biosynthesis and cellular permeability explain longitudinal gibberellin gradients in growing roots"

Datasets in support of the figures of "Differential biosynthesis and cellular permeability explain longitudinal gibberellin gradients in growing roots" publication in PNAS 2021 with first author Annalisa Rizza. See file Rizza et al.,2021 metadata confocal imaging and phenotypes .xlsx for details on biological data. The dataset contains experimental data on Arabidopsis thaliana roots and consists primarily of microscopy imaging data presented as Leica files (.lif) and root growth phenotyping data presented as Excel files (.xlsx) or TIFF (.tiff) images. Most imaging files are organised by data acquired and phenotyping files are organised by corresponding Figure number from the publication. Detailed explanation is found in the metadata excel file. Additional imaging files are presented as TIFF images (Scanned plates zip files, .tiff) and imaging and phenotyping data analysis presented as Origin Pro files (.opju). Finally, a set of modeling program files relating to the mathematical modeling described in the publication are provided (Modeling Programs zip file, .mat, .m files).European Union's Horizon 2020 research and innovation program (grant agreement n° 759282 to Alexander Jones). Gatsby Charitable Foundation grant to Alexander Jones. Leverhulme Trust (Early Career Fellowship to Dr Leah Band, ECF-2012-681). Human Frontier Science Program (Young Investigator Grant, RGY0075/2020 to Leah Band)

Quantifying Phytohormones in Vivo with FRET Biosensors and the FRETENATOR Analysis Toolset.

The ABACUS1-2 μ (ABscisic Acid Concentration and Uptake Sensor 1-2 μ) and GPS1 (Gibberellin Perception Sensor 1) are direct Förster resonance energy transfer (FRET) biosensors that can be used to measure hormone levels in planta. We provide detailed protocols to image FRET biosensors under exogenously applied hormones in roots, either as a single time point or for treatment time courses before and after hormone application. A new, free, open-source analysis toolset for Fiji is introduced and used to get full 3D segmentation of images of nuclear localized FRET biosensors and calculate emission ratios on a per nucleus basis allowing in-depth analysis of biosensor data.Gatsby Charitable trust, European Research Counci

Dispositional optimism, depression, disability and quality of life in Parkinson’s disease

Very little research on dispositional optimism (DO) has been carried out in the field of Parkinson’s disease (PD). The present cross-sectional study, focusing on this personality trait, was performed with two main aims: i) to compare DO between patients with PD and a control group (CG); ii) to perform, in the PD group, a regression analysis including health-related variables, such as depression, anxiety, quality of life (QoL) and activities of daily living. Seventy PD participants and 70 healthy volunteers were enrolled in the study. The Mann-Whitney test was used to compare life orientation between the PD and CG groups. In the PD group, Pearson’s correlation analysis was used to investigate the relationship between the measures of DO and the other variables. Means of log-linear regression were also used. Mean ratios adjusted for sex, age, education, and severity of disease were estimated, with relative 95% confidence intervals and p-values. The main results were as follows: i) no significant difference in DO was found between the PD participants and the CG; ii) DO was positively associated with QoL and emotional distress and inversely correlated with the Unified Parkinson’s Disease Rating Scale; iii) DO was not correlated with disability. In conclusion, high DO predicts a satisfactory quality of life, low emotional distress and reduced disease severity in PD