A New Role for Plastid Thioredoxins in Seed Physiology in Relation to Hormone Regulation

In Arabidopsis seeds, ROS have been shown to be enabling actors of cellular signaling pathways promoting germination, but their accumulation under stress conditions or during aging leads to a decrease in the ability to germinate. Previous biochemical work revealed that a specific class of plastid thioredoxins (Trxs), the y-type Trxs, can fulfill antioxidant functions. Among the ten plastidial Trx isoforms identified in Arabidopsis, Trx y1 mRNA is the most abundant in dry seeds. We hypothesized that Trx y1 and Trx y2 would play an important role in seed physiology as antioxidants. Using reverse genetics, we found important changes in the corresponding Arabidopsis mutant seeds. They display remarkable traits such as increased longevity and higher and faster germination in conditions of reduced water availability or oxidative stress. These phenotypes suggest that Trxs y do not play an antioxidant role in seeds, as further evidenced by no changes in global ROS contents and protein redox status found in the corresponding mutant seeds. Instead, we provide evidence that marker genes of ABA and GAs pathways are perturbed in mutant seeds, together with their sensitivity to specific hormone inhibitors. Altogether, our results suggest that Trxs y function in Arabidopsis seeds is not linked to their previously identified antioxidant roles and reveal a new role for plastid Trxs linked to hormone regulation.     

Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages,Driving Them toward Gaucher Cells

Gaucher disease (GD) is caused by glucocerebrosidase deficiency leading to the accumulation of sphingolipids in macrophages named “Gaucher’s Cells”. These cells are characterized by deregulated expression of cell surface markers, abnormal secretion of inflammatory cytokines, and iron sequestration. These cells are known to infiltrate tissues resulting in hematological manifestations, splenomegaly, and bone diseases. We have already demonstrated that Gaucher red blood cells exhibit altered properties suggesting their key role in GD clinical manifestations. We hypothesized that Gaucher’s erythrocytes could be prone to premature destruction by macrophages contributing to the formation of altered macrophages and Gaucher-like cells. We conducted in vitro experiments of erythrophagocytosis using erythrocytes from Gaucher’s patients or healthy donors. Our results showed an enhanced erythrophagocytosis of Gaucher red blood cells compared to healthy red blood cells, which is related to erythrocyte sphingolipids overload and reduced deformability. Importantly, we showed elevated expression of the antigen-presenting molecules CD1d and MHC-II and of the iron-regulator hepcidin in macrophages, as well as enhanced secretion of the pro-inflammatory cytokine IL-1β after phagocytosis of GD erythrocytes. These results strongly suggested that erythrophagocytosis in GD contribute to phenotypic modifications in macrophages. This present study shows that erythrocytes-macrophages interactions may be crucial in GD pathophysiology and pathogenesis.     

MS565: A SPECT Tracer for Evaluating the Brain Penetration of BAF312 (Siponimod)

BAF312 (siponimod) is a sphingosine‐1‐phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 (fingolimod). Our aim was to develop a tracer to better quantify the penetration of BAF312 in the human brain, with the potential to be labeled for positron emission tomography (PET) or single‐photon emission computed tomography (SPECT). Although the PET radioisotopes ¹¹C and ¹⁸F could have been introduced in BAF312 without modifying its structure, they do not have decay kinetics compatible with the time required for observing the drug′s organ distribution in patients. In contrast, the SPECT radioisotope ¹²³I has a longer half‐life and would suit this purpose. Herein we report the identification of an iodinated derivative of BAF312, (E)‐1‐(4‐(1‐(((4‐cyclohexyl‐3‐iodobenzyl)oxy)imino)ethyl)‐2‐ethylbenzyl)azetidine‐3‐carboxylic acid ( 18 , MS565), as a SPECT tracer candidate with affinity, S1P receptor selectivity, overall physicochemical properties, and blood pharmacokinetics similar to those of the original molecule. A whole‐body autoradiography study performed with [¹⁴C]MS565 subsequently confirmed that its organ distribution is similar to that of BAF312. This validates the selection of MS565 for ¹²³I radiolabeling and for use in imaging studies to quantify the brain penetration of BAF312.     

Advanced thermal simulation of processes involving materials exhibiting fine-scale microstructures

Image-based simulation is being considered more and more in industrial applications, where more than simulate the expected reality it seems preferable to simulate the reality itself. For example, in heterogeneous composite materials more than assuming a particular distribution of the material constituents, it is preferable to solve the model in the real distribution, the one existing in the considered material that is accessible from an appropriate scanning technique. However such route requires, in many applications, advanced simulation techniques able to proceed in real time, looking for a synchronism with the scanning process itself. This constitutes a challenging issue due to the rate of image acquisition and the amount of information associated to each one. This work proposes an efficient strategy for solving thermal problems in two scales heterogeneous media in both the linear and the nonlinear case. In both cases the calculation of the homogenized thermal conductivity tensor requires the solution of many thermal problems defined at the microstructure level, here considered coming from digital images. For alleviating the computational cost and speeding up calculations to fulfill real time constraints, we propose an offline/online procedure for evaluating the homogenized thermal conductivities.     

A rule-based event detection system for real-life underwater domain

Understanding and analyzing fish behaviour is a fundamental task for biologists that study marine ecosystems because the changes in animal behaviour reflect environmental conditions such as pollution and climate change. To support investigators in addressing these complex questions, underwater cameras have been recently used. They can continuously monitor marine life while having almost no influence on the environment under observation, which is not the case with observations made by divers for instance. However, the huge quantity of recorded data make the manual video analysis practically impossible. Thus machine vision approaches are needed to distill the information to be investigated. In this paper, we propose an automatic event detection system able to identify solitary and pairing behaviours of the most common fish species of the Taiwanese coral reef. More specifically, the proposed system employs robust low-level processing modules for fish detection, tracking and recognition that extract the raw data used in the event detection process. Then each fish trajectory is modeled and classified using hidden Markov models. The events of interest are detected by integrating end-user rules, specified through an ad hoc user interface, and the analysis of fish trajectories. The system was tested on 499 events of interest, divided into solitary and pairing events for each fish species. It achieved an average accuracy of 0.105, expressed in terms of normalized detection cost. The obtained results are promising, especially given the difficulties occurring in underwater environments. And moreover, it allows marine biologists to speed up the behaviour analysis process, and to reliably carry on their investigations.     

Varifocal liquid lenses with integrated actuator, high focusing power and low operating voltage fabricated on 200 mm wafers

We developed an innovative type of varifocal liquid lens actuated by electrostatic parallel plates. The 3 mm diameter lens is made of a polymer membrane that encapsulates a high permittivity liquid in a cavity on top of a glass wafer. Annular electrodes situated below the membrane and on the glass wafer form the electrostatic parallel plates actuator. By applying a voltage between the electrodes, the electrostatic actuation generated reduces the gap and pushes the liquid towards the center of the lens changing the curvature of the membrane.Compared to previous liquid lenses, very compact devices (≤6 mm × 6 mm × 0.7 mm) working at a reduced supply voltage (<25 V) are demonstrated. Wave front measurements indicate an optical power change of 8 m⁻¹ at 22 V_RMS that can be further improved. The lenses were fabricated on 200 mm wafers using standard microelectronics processes that make our solution a promising small outline, low voltage and low cost candidate for auto-focus devices in camera phones.     

Local MST Computation with Short Advice

We use the recently introduced advising scheme framework for measuring the difficulty of locally distributively computing a Minimum Spanning Tree (MST). An (m,t)-advising scheme for a distributed problem ? is a way, for every possible input I of ?, to provide an “advice” (i.e., a bit string) about I to each node so that: (1) the maximum size of the advices is at most m bits, and (2) the problem ? can be solved distributively in at most t rounds using the advices as inputs. In case of MST, the output returned by each node of a weighted graph G is the edge leading to its parent in some rooted MST T of G. Clearly, there is a trivial (?log?n?,0)-advising scheme for MST (each node is given the local port number of the edge leading to the root of some MST T), and it is known that any (0,t)-advising scheme satisfies $t\geq\tilde{\Omega}(\sqrt{n})We use the recently introduced advising scheme framework for measuring the difficulty of locally distributively computing a Minimum Spanning Tree (MST). An (m,t)-advising scheme for a distributed problem ℘ is a way, for every possible input I of ℘, to provide an “advice” (i.e., a bit string) about I to each node so that: (1) the maximum size of the advices is at most m bits, and (2) the problem ℘ can be solved distributively in at most t rounds using the advices as inputs. In case of MST, the output returned by each node of a weighted graph G is the edge leading to its parent in some rooted MST T of G. Clearly, there is a trivial (⌈log n⌉,0)-advising scheme for MST (each node is given the local port number of the edge leading to the root of some MST T), and it is known that any (0,t)-advising scheme satisfies t 3 [(W)\tilde](?n)t\geq\tilde{\Omega}(\sqrt{n}). Our main result is the construction of an (O(1),O(log n))-advising scheme for MST. That is, by only giving a constant number of bits of advice to each node, one can decrease exponentially the distributed computation time of MST in arbitrary graph, compared to algorithms dealing with the problem in absence of any a priori information. We also consider the average size of the advices. On the one hand, we show that any (m,0)-advising scheme for MST gives advices of average size Ω(log n). On the other hand we design an (m,1)-advising scheme for MST with advices of constant average size, that is one round is enough to decrease the average size of the advices from log n to constant.     

Statistical analysis of "looked-but-failed-to-see" accidents: highlighting the involvement of two distinct mechanisms

Circumstances where "looked-but-failed-to-see" accidents arise are a particular subject of study. In order to better understand why normal drivers could miss a relevant event signaling danger, more than 500 accidents were analyzed in-depth with regard to driver-environment-goal interactions. Results show four typical situations that imply two distinct mechanisms. When a failure arose at the perceptual stage, drivers actually never saw the danger while they were going straight at a junction or turning left to park their car. When failure arose at the processing stage, there was evidence that drivers saw the danger even when their recall of it was lacking. In fact, drivers saw the danger too late to avoid collision when they were overtaking another road user or trying to find his/her way. These are called "looked-but-failed-to-see-accidents". Accident patterns are discussed according to driver's goal involvement and local setting to suggest directions for further investigation with a special emphasis on change blindness.