Thiago Mosqueiro

NOTCH1 is a mechanosensor in adult arteries

Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell–cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.The arterial wall is subjected to mechanical forces that modulate endothelial cell responses. Here, Mack and colleagues identify a novel role for Notch1 as a mechanosensor in adult arteries, where it ensures junctional integrity through modulation of calcium signalling and limits atherosclerosis.

Optimal Channel Efficiency in a Sensory Network

Spontaneous neural activity has been increasingly recognized as a subject of key relevance in neuroscience. It exhibits nontrivial spatiotemporal structure reflecting the organization of the underlying neural network and has proved to be closely intertwined with stimulus-induced activity patterns. As an additional contribution in this regard, we report computational studies that strongly suggest that a stimulus-free feature rules the behavior of an important psychophysical measure of the sensibility of a sensory system to a stimulus, the so-called dynamic range. Indeed in this paper we show that the entropy of the distribution of avalanche lifetimes (information efficiency, since it can be interpreted as the efficiency of the network seen as a communication channel) always accompanies the dynamic range in the benchmark model for sensory systems. Specifically, by simulating the Kinouchi-Copelli (KC) model on two broad families of model networks, we generically observed that both quantities always increase or decrease together as functions of the average branching ratio (the control parameter of the KC model) and that the information efficiency typically exhibits critical optimization jointly with the dynamic range (i.e., both quantities are optimized at the same value of that control parameter, that turns out to be the critical point of a nonequilibrium phase transition). In contrast with the practice of taking power laws to identify critical points in most studies describing measured neuronal avalanches, we rely on data collapses as more robust signatures of criticality to claim that critical optimization may happen even when the distribution of avalanche lifetimes is not a power law, as suggested by a recent experiment. Finally, we note that the entropy of the size distribution of avalanches (information capacity) does not always follow the dynamic range and the information efficiency when they are critically optimized, despite being more widely used than the latter to describe the computational capabilities of a neural network. This strongly suggests that dynamical rules allowing a proper temporal matching of the states of the interacting neurons is the key for achieving good performance in information processing, rather than increasing the number of available units.

Non-parametric change point detection for spike trains

Two techniques of non-parametric change point detection are applied to two different neuroscience datasets. In the first dataset, we show how the multivariate non-parametric change point detection can precisely estimate reaction times to input stimulation in the olfactory system using joint information of spike trains from several neurons. In the second example, we propose to analyze communication and sequence coding using change point formalism as a time segmentation of homogeneous pieces of information, revealing cues to elucidate directionality of the communication in electric fish. We are also sharing our software implementation Chapolins at GitHub.

A simple model for eletrocommunication - "refractoriness avoidance response"?

Weakly field electric fishes have an electric sense with two simultaneously processed tasks, called electrolocation and electrocommunication [1]. In pulse-type electric fishes, the first task is perceived by deformations of the self-generated electric field [2], and the later one by the precise timestamp of its own pulses and those generated by its conspecifics. Some observed changes in the timestamps of two communicating fish are different from those observed during the so called “Jamming Avoidance Response” of wave-type electric fishes [3]. Although in some fish there actually is a rate separation mechanism (coincidence avoidance), in most fish these rate changes are only transient [3] and has been reproduced using recursive models [4,5]. However it is well known that the electrosensory path of the fish is stimulated by the discharge of its conspecifics during the interval between two self-generated discharges (stimulus phase) [6]. Moreover, second order neurons responsible for the fishs self-detection show very long refractory period of about 10ms due to the activation of a low threshold K+ conductance [7]. This has led to hypothesis’ that there is not a coincidence avoidance effect, but instead an attempt to avoid firing just after its conspecific. Thus, a fish sensory processed signal is not jammed by a conspecific signal [6]. Agreeing with that, there is evidence that the fish adjusts its own signal to make the other one fire at a “preferential” phase [8], and this is probably related to dominance [3]. These effects can be observed in an integrate-and-fire model with non-linear inputs taking into account a phase preference for eliciting acceleration [9]. As the refractoriness of the fast electrosensory path is the most important jamming effect we call this effect “electrosensory refractoriness avoidance response” (RAR). Here, we extend this idea and test it using a simplified model that take this effects into account. We propose a model with two integrate-and-fire neurons per fish and a non-linear feedback loop between them. The first neuron represents the fishs pulse, and the other one a “sensory neuron”. The feedback is non-linear and has the effect of increase the frequency of firing. This model has been implemented both in an electronic hardware and in a computer simulation and allows us using it to mimic a conspecific during electro-communication encounters with real fish.

Exploring a Mathematical Model of Gain Control via Lateral Inhibition in the Antennal Lobe

Bioinspired Neural Networks have in many instances paved the way for significant discoveries in Statistical and Machine Learning. Among the many mechanisms employed by biological systems to implement learning, gain control is a ubiquitous and essential component that guarantees standard representation of patterns for improved performance in pattern recognition tasks. Gain control is particularly important for the identification of different odor molecules, regardless of their concentration. In this paper, we explore the functional impact of a biologically plausible model of the gain control on classification performance by representing the olfactory system of insects with a Single Hidden Layer Network (SHLN). Common to all insects, the primary olfactory pathway starts at the Antennal Lobes (ALs) and, then, odor identity is computed at the output of the Mushroom Bodies (MBs). We show that gain-control based on lateral inhibition in the Antennal Lobe robustly solves the classification of highly-concentrated odors. Furthermore, the proposed mechanism does not depend on learning at the AL level, in agreement with biological literature. Due to its simplicity, this bioinspired mechanism may not only be present in other neural systems but can also be further explored for applications, for instance, involving electronic noses.

Faster cloud Star Joins with Reduced Disk Spill and Network Communication

Combining powerful parallel frameworks and on-demand commodity hardware, cloud computing has made both analytics and decision support systems canonical to enterprises of all sizes. Associated with unprecedented volumes of data stacked by such companies, filtering and retrieving them are pressing challenges. This data is often organized in star schemas, in which Star Joins are ubiquitous and expensive operations. In particular, excessive disk spill and network communication are tight bottlenecks for all current MapReduce or Spark solutions. Here, we propose two efficient solutions that drop the computation time by at least 60%: the Spark Bloom-Filtered Cascade Join (SBFCJ) and the Spark Broadcast Join (SBJ). Conversely, a direct Spark implementation of a sequence of joins renders poor performance, showcasing the importance of further filtering for minimal disk spill and network communication. Finally, while SBJ is twice faster when memory per executor is large enough, SBFCJ is remarkably resilient to low memory scenarios. Both algorithms pose very competitive solutions to Star Joins in the cloud.

A comprehensive analysis of the usability and archival stability of omics computational tools and resources

Developing new software tools for analysis of large-scale biological data is a key component of advancing modern biomedical research. Scientific reproduction of published findings requires running computational tools on data generated by such studies, yet little attention is presently allocated to the installability and archival stability of computational software tools. Scientific journals require data and code sharing, but none currently require authors to guarantee the continuing functionality of newly published tools. We have estimated the archival stability of computational biology software tools by performing an empirical analysis of the internet presence for 36,702 omics software resources published from 2005 to 2017. We found that almost 28% of all resources are currently not accessible through URLs published in the paper they first appeared in. Among the 98 software tools selected for our installability test, 51% were deemed “easy to install,” and 28% of the tools failed to be installed at all due to problems in the implementation. Moreover, for papers introducing new software, we found that the number of citations significantly increased when authors provided an easy installation process. We propose for incorporation into journal policy several practical solutions for increasing the widespread installability and archival stability of published bioinformatics software.

Task allocation and site fidelity jointly influence foraging regulation in honeybee colonies

Variation in behaviour among group members often impacts collective outcomes. Individuals may vary both in the task that they perform and in the persistence with which they perform each task. Although both the distribution of individuals among tasks and differences among individuals in behavioural persistence can each impact collective behaviour, we do not know if and how they jointly affect collective outcomes. Here, we use a detailed computational model to examine the joint impact of colony-level distribution among tasks and behavioural persistence of individuals, specifically their fidelity to particular resource sites, on the collective trade-off between exploring for new resources and exploiting familiar ones. We developed an agent-based model of foraging honeybees, parametrized by data from five colonies, in which we simulated scouts, who search the environment for new resources, and individuals who are recruited by the scouts to the newly found resources, i.e. recruits. We varied the persistence of returning to a particular food source of both scouts and recruits and found that, for each value of persistence, there is a different optimal ratio of scouts to recruits that maximizes resource collection by the colony. Furthermore, changes to the persistence of scouts induced opposite effects from changes to the persistence of recruits on the collective foraging of the colony. The proportion of scouts that resulted in the most resources collected by the colony decreased as the persistence of recruits increased. However, this optimal proportion of scouts increased as the persistence of scouts increased. Thus, behavioural persistence and task participation can interact to impact a colonys collective behaviour in orthogonal directions. Our work provides new insights and generates new hypotheses into how variations in behaviour at both the individual and colony levels jointly impact the trade-off between exploring for new resources and exploiting familiar ones.

Automated pulse discrimination of two freely-swimming weakly electric fish and analysis of their electrical behavior during dominance contest

Electric fishes modulate their electric organ discharges with a remarkable variability. Some patterns can be easily identified, such as pulse rate changes, offs and chirps, which are often associated with important behavioral contexts, including aggression, hiding and mating. However, these behaviors are only observed when at least two fish are freely interacting. Although their electrical pulses can be easily recorded by non-invasive techniques, discriminating the emitter of each pulse is challenging when physically similar fish are allowed to freely move and interact. Here we optimized a custom-made software recently designed to identify the emitter of pulses by using automated chirp detection, adaptive threshold for pulse detection and slightly changing how the recorded signals are integrated. With these optimizations, we performed a quantitative analysis of the statistical changes throughout the dominance contest with respect to Inter Pulse Intervals, Chirps and Offs dyads of freely moving Gymnotus carapo. In all dyads, chirps were signatures of subsequent submission, even when they occurred early in the contest. Although offs were observed in both dominant and submissive fish, they were substantially more frequent in submissive individuals, in agreement with the idea from previous studies that offs are electric cues of submission. In general, after the dominance is established the submissive fish significantly changes its average pulse rate, while the pulse rate of the dominant remained unchanged. Additionally, no chirps or offs were observed when two fish were manually kept in direct physical contact, suggesting that these electric behaviors are not automatic responses to physical contact.

DYNAMICAL ASPECTS OF KINOUCHI-COPELLI MODEL: EMERGENCE OF AVALANCHES AT CRITICALITY

We analyze the behavior of bursts of neural activity in the Kinouchi-Copelli model, originally conceived to explain information processing issues in sensory systems. We show that, at a critical condition, power-law behavior emerges for the size and duration of the bursts (avalanches), with exponents experimentally observed in real biological systems.