The Coumarin Glucoside, Esculin, Reveals Rapid Changes in Phloem-Transport Velocity in Response to Environmental Cues

The study of phloem transport and its vital roles in long-distance communication and carbon allocation have been hampered by a lack of suitable tools that allow high-throughput, real-time studies. Esculin, a fluorescent coumarin glucoside, is recognized by Suc transporters, including AtSUC2, which loads it into the phloem for translocation to sink tissues. These properties make it an ideal tool for use in live-imaging experiments, where it acts as a surrogate for Suc. Here, we show that esculin is translocated with a similar efficiency to Suc and, because of its ease of application and detection, demonstrate that it is an ideal tool for in vivo studies of phloem transport. We used esculin to determine the effect of different environmental cues on the velocity of phloem transport. We provide evidence that fluctuations in cotyledon Suc levels influence phloem velocity rapidly, supporting the pressure-flow model of phloem transport. Under acute changes in light levels, the phloem velocity mirrored changes in the expression of AtSUC2. This observation suggests that under certain environmental conditions, transcriptional regulation may affect the abundance of AtSUC2 and thus regulate the phloem transport velocity

ANHEDONIA IN THE PSYCHOSIS RISK SYNDROME: STATE AND TRAIT CHARACTERISTICS

Background: Previous studies reported deficits in pleasure experience in schizophrenia, but little is known about anhedonia in psychosis risk syndrome. Aim of this study was: (1) to assess anhedonia in distinct help-seeking subgroups of young people identified through the Ultra-High Risk (UHR) criteria, (2) to explore its association with functioning and psychopathology in the UHR group, and (3) to monitor longitudinally its stability in UHR individuals along 1-year follow-up period. Subjects and methods: All participants (78 UHR, 137 with a First Episode Psychosis (FEP), and 95 non-UHR/FEP), aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Beck Depression Inventory-II (BDI-II), the Schizotypal Personality Questionnaire - Brief version (SPQ-B), the Brief O-LIFE questionnaire (BOL), and the World Health Organization Quality of Life - Brief version (WHOQOL-BREF). We adopted two different indexes of anhedonia: i.e. CAARMS “Anhedonia” item 4.3 and BOL “Introvertive Anhedonia” subscale scores. Results: In comparison with non-UHR/FEP, UHR individuals showed higher baseline CAARMS item 4.3 and BOL “Introvertive Anhedonia” subscale scores. No difference in anhedonia scores between UHR and FEP patients was found. After 1-year follow up period, UHR subjects had a significant decrease in severity exclusively on CAARMS item 4.3 subscore. Conclusions: In the UHR group, CAARMS anhedonia showed significant correlations with functioning deterioration, negative symptoms, and comorbid depression (including suicide ideation), while BOL anhedonia with a poorer self-perceived quality of life and specific schizotypal personality traits (i.e. interpersonal deficits and disorganization). Anhedonia is prominent in the psychosis risk syndrome and its severity is indistinguishable from that of FEP patients

Intercellular trafficking via plasmodesmata: molecular layers of complexity.

Plasmodesmata are intercellular pores connecting together most plant cells. These structures consist of a central constricted form of the endoplasmic reticulum, encircled by some cytoplasmic space, in turn delimited by the plasma membrane, itself ultimately surrounded by the cell wall. The presence and structure of plasmodesmata create multiple routes for intercellular trafficking of a large spectrum of molecules (encompassing RNAs, proteins, hormones and metabolites) and also enable local signalling events. Movement across plasmodesmata is finely controlled in order to balance processes requiring communication with those necessitating symplastic isolation. Here, we describe the identities and roles of the molecular components (specific sets of lipids, proteins and wall polysaccharides) that shape and define plasmodesmata structural and functional domains. We highlight the extensive and dynamic interactions that exist between the plasma/endoplasmic reticulum membranes, cytoplasm and cell wall domains, binding them together to effectively define plasmodesmata shapes and purposes

Anhedonia and suicidal ideation in young people with early psychosis: Further findings from the 2-year follow-up of the ReARMS program.

Hedonic deficits have been extensively studied in schizophrenia, but little is known about their association with suicidal ideation in early psychosis. The aim of this research was to examine the relationship between anhedonia and suicidal thoughts across a 2-year follow-up period in people with First Episode Psychosis (FEP) and at Ultra High Risk (UHR) of psychosis. Ninty-six UHR and 146 FEP, aged 13–35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Beck Depression Inventory-II (BDI-II). The BDI-II “Anhedonia” subscale score to assess anhedonia and the CAARMS “Depression” item 7.2 subscore to measure depression were used across the 2 years of follow-up. Hierarchical regression analyses were performed. No difference in anhedonia scores between FEP and UHR individuals was found. In the FEP group, a significant enduring association between anhedonia and suicidal ideation was found at baseline and across the follow-up, independent of clinical depression. In the UHR subgroup, the enduring relationship between anhedonia and suicidal thoughts were not completely independent from depression severity. Anhedonia is relevant in predicting suicidal ideation in early psychosis. Specific pharmacological and/or psychosocial interventions on anhedonia within specialized EIP program could reduce suicide risk overtime

Insights into Ligand–Protein Binding from Local Mechanical Response

Computational studies of ligand–protein binding are crucial for properly designing novel compounds of potential pharmacological interest. In this respect, researchers are increasingly interested in steered molecular dynamics for ligand–protein binding and unbinding studies. In particular, it has been suggested that analyzing the work profiles along the ligand–protein undocking paths could be fruitful. Here, we propose that small portions of work profiles, termed “local mechanical responses” of the system to a steering force, could serve as a universal measure for capturing relevant information about the system under investigation. Specifically, we first collected a high number of steering trajectories using two biological systems of increasing complexity (i.e., alanine dipeptide and (R)-roscovitine/CDK5 complex). Then, we devised a novel postprocessing tool to be applied to the local mechanical responses, to extract structural information related to the biological processes under investigation. Despite the out-of-equilibrium character of the trajectories, the analysis carried out on the work profiles provided pivotal information about the investigated biological processes. This could eventually be applied to drug design

A multiscale study of plasmodesmata: from channel ultrastructure to plant architecture

Plasmodesmata are nanoscale, membrane lined pores that span the cell wall of neighbouring plant cells. The presence of these structures enables cell-cell movement of substances important for plant growth and development. This thesis describes the nature of plasmodesmata and explores their importance at various biological scales within the model plant Arabidopsis thaliana. The first two experimental chapters focus on selected molecular components of individual plasmodesmata. I show that sphingolipids, a lipid class enriched in the membranes of these structures, have a functional role in shaping the pores. Sphingolipid alterations resulting from mutation in the PHLOEM UNLOADING MEDIATOR gene or in the LONG CHAIN BASE KINASE 1 gene result in plasmodesmata morphological changes with consequences on cell-cell permeability. Moving to the protein component of plasmodesmata, I highlight that the family of MULTIPLE C2 AND TRANSMEMBRANE REGION PROTEINS influences long distance movement in the phloem, a vascular conduit in plants. I also show that loss of selected members of the family causes severe developmental phenotypes. Additionally, my results suggest potential interactions between sphingolipids and these proteins. The following experimental chapters look at increasingly larger biological scales. Employing serial block electron microscopy, I develop computational tools to study the distribution and density of plasmodesmata over entire cellular interfaces, and the thickness of the wall they span. The proof of concept examples interestingly show differences in spatial patterns, depending on the interface, and suggest an influence of sphingolipids on cell wall thickness. I move to the tissue scale, focusing on movement in the phloem, and identify EMS-MUTAGENIZED BRI1 SUPPRESSOR 3 as a suppressor of restricted phloem unloading in lines that over-accumulate callose, a polysaccharide occluding plasmodesmata. The protein might specifically control correct folding of callose synthase enzymes within the endoplasmic reticulum. Lastly, looking at the whole plant level, I show that induced closure of plasmodesmata within a specific phloem vascular domain, that of SISTER OF APL, can have reproducible impacts on the rate of growth of axillary buds into branches. The effect is observed in a range of genetic backgrounds and might involve PIN-FORMED proteins

Computational Tools for Serial Block Electron Microscopy Reveal Plasmodesmata Distributions and Wall Environments

Plasmodesmata are small channels that connect plant cells. While recent technological advances have facilitated analysis of the ultrastructure of these channels, there are limitations to efficiently addressing their presence over an entire cellular interface. Here, we highlight the value of serial block electron microscopy for this purpose. We developed a computational pipeline to study plasmodesmata distributions and detect the presence/absence of plasmodesmata clusters, or pit fields, at the phloem unloading interfaces of Arabidopsis (Arabidopsis thaliana) roots. Pit fields were visualized and quantified. As the wall environment of plasmodesmata is highly specialized, we also designed a tool to extract the thickness of the extracellular matrix at and outside of plasmodesmata positions. We detected and quantified clear wall thinning around plasmodesmata with differences between genotypes, including the recently published plm-2 sphingolipid mutant. Our tools open avenues for quantitative approaches in the analysis of symplastic trafficking.Peer reviewe

Risk minimization in multi-factor portfolios: What is the best strategy?

Exposures to risk factors, as opposed to individual securities or bonds, can lead to an ex-ante improved risk management and a more transparent and cheaper way of devel- oping active asset allocation strategies. This paper provides an extensive analysis of eight state-of-the-art risk-minimization schemes and compares risk factor performance in a condi- tional performance analysis, contrasting good and bad states of the economy. The investment universe spans a total of 25 risk factors, including size, momentum, value, high profitability and low investments, from five non-overlapping regions (i.e., USA, UK, Japan, Developed Europe ex. UK and, Asia ex. Japan). Considering as investment period the interval from May 2004 to June 2015, our results show that each single factor yields positive premia in exchange for risk, which can lead to considerable underperformance and extensive recovery periods during times of crisis. The best factor investments can be found in Asia ex. Japan and the US. However, risk factor based portfolio construction across the various regions enables the investor to exploit low correlation structures, reducing the overall volatility, as well as tail- and extreme risk measures. Finally, the empirical results point towards the long-only global minimum variance portfolio, as the best risk minimization strategy