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Biology subjects

Avraham, C.

Publications and source records attributed to Avraham, C..

5 recordsLinked to original sources

Feedback-Feedforward Dynamics Shape De Novo Motor Learning

Many real-world motor skills require continuous control under substantial sensorimotor delays, necessitating the coordination of reactive feedback and predictive feedforward control. How these complementary control processes emerge and interact during the acquisition of a novel continuous motor skill remains unclear. We addressed this question by examining how feedback and feedforward control evolve over five days of continuous visuomotor mirror reversal learning. To directly dissociate feedback- and feedforward-related contributions during learning, we combined frequency-domain analyses of continuous tracking with independent behavioral probes of online feedback responses (brief cursor perturbations) and predictive feedforward control (initial movement direction during point-to-point reaches). We found that learning exhibited both temporal and frequency-dependent shifts in the relative contributions of feedback and feedforward control. Early improvements were dominated by rapid online feedback corrections expressed primarily at low movement frequencies, whereas predictive feedforward control emerged more gradually and became increasingly important at higher frequencies, where delayed feedback is insufficient for accurate control. A recurrent neural network model, in which an adaptive cerebellar-like feedback controller provides a teaching signal to a recurrent cortical predictive controller, reproduced these key behavioral signatures, supporting a mechanistic framework in which feedback-driven error signals facilitate the gradual emergence of predictive control. Together, these findings demonstrate that continuous motor learning arises through distinct but interacting feedback and feedforward processes that co-evolve across practice under the constraints imposed by sensorimotor delays.

neuroscience↗

TIR domains produce histidine-ADPR conjugates as immune signaling molecules in bacteria

TIR domains are central components of pattern recognition immune proteins across all domains of life. In both bacteria and plants, TIR-domain proteins were shown to recognize pathogen invasion and then produce immune signaling molecules exclusively comprising nucleotide moieties. Here we show that the TIR domain protein of the type II Thoeris defense system in bacteria produces a unique signaling molecule comprising the amino acid histidine conjugated to ADP-ribose (His-ADPR). His-ADPR is generated in response to phage infection and activates the cognate Thoeris effector by binding a Macro domain located at the C-terminus of the effector protein. By determining the crystal structure of a ligand-bound Macro domain, we describe the structural basis for His-ADPR recognition. Our analyses furthermore reveal a family of phage proteins that bind and sequester His-ADPR signaling molecules, allowing phages to evade TIR- mediated immunity. These data demonstrate diversity in bacterial TIR signaling and reveal a new class of TIR-derived immune signaling molecules combining nucleotide and amino acid moieties.

microbiology↗

Artificial Tactile Stimulation Provides Haptic Cuing in Force Field Adaptation

When interacting with objects with unfamiliar dynamics, the sensorimotor system uses haptic information to develop internal representations of the new dynamics. These representations are subsequently used to manipulate the objects by applying predictive forces that comply with the mechanical properties of the objects. In a recent study (Farajian et al. 2020), we showed that when participants evaluated the stiffness of elastic objects, adding artificial tactile stimulation created an illusion of higher stiffness, increasing the grip force control used to interact with the object. Here, we took a step further in understanding how kinesthetic and tactile information is integrated into the control of objects. Specifically, we examined how added skin stretch influenced the learning of novel forces. We found that the extent of force compensation that the participants exhibited depended on the direction of the artificial skin stretch applied simultaneously with the force; learning was enhanced when the skin was stretched in the opposite direction to the external force and diminished when the skin was stretched in the same direction. Strikingly, when the skin stretch stimulation was delivered during probe trials in which the force perturbation was absent, the behavior pattern was flipped, with an increase in force compensation for the same-direction skin stretch stimulation and vice versa. Modeling suggests that these results reflect a unique effect of tactile stimulation during the learning of novel forces; rather than becoming integrated with the dynamic information, it is used by the sensorimotor system as a guidance cue, possibly through explicit mechanisms, providing information on the way to compensate for the forces and optimize movements. We believe that these findings propose a novel instructive role of tactile stimulation during interaction with a dynamic object. This provides a significant potential to leverage these effects in the development of devices aiming to assist and guide users in many human-in-the-loop applications, such as rehabilitation and surgical robotics.

neuroscience↗

Phages overcome bacterial immunity via diverse anti-defense proteins

It was recently shown that bacteria employ, apart from CRISPR-Cas and restriction systems, a considerable diversity of phage resistance systems, but it is largely unknown how phages cope with this multilayered bacterial immunity. Here, we analyzed groups of closely related Bacillus phages that showed differential sensitivity to bacterial defense systems, and identified multiple families of anti-defense proteins that inhibit the Gabija, Thoeris, and Hachiman systems. We show that these proteins efficiently cancel the defensive activity when co-expressed with the respective defense system or introduced into phage genomes. Homologs of these anti-defense proteins are found in hundreds of phages that infect taxonomically diverse bacterial species. We show that an anti-Gabija protein, denoted Gad1, blocks the ability of the Gabija defense complex to cleave phage-derived DNA. Our data further reveal an anti-Thoeris protein, denoted Tad2, which is a "sponge" that sequesters the immune signaling molecules produced by Thoeris TIR-domain proteins in response to phage. Our results demonstrate that phages encode an arsenal of anti-defense proteins that can disable a variety of bacterial defense mechanisms.

genetics↗

Adaptation to a Space-variant Visuomotor Delay can Cause Neglect-like Effects on Drawing Symmetry

In daily interactions, our sensorimotor system accounts for spatial and temporal discrepancies between the senses. Functional lateralization between hemispheres causes differences in attention and control of action. In addition, differences in transmission delays between modalities affects motor control. Studies on hemispatial neglect syndrome suggest a link between temporal processing and lateral spatial biases. To understand this link, we studied participants who performed lateral reaching, and adapted to delayed visual feedback in either left, right, or both workspaces. We tested transfer of adaptation to blind drawing, and found that adaptation to left or both delay caused selective leftward elongation. In contrast, adaptation to right delay caused elongation in both directions. Arm dynamics alone cannot explain these findings, but a model of a combined attentional-motor asymmetry across the hemispheres explains our observations. This suggests a possible connection between laterality in delay processing and motor performances observed in cases of hemispatial neglect.

neuroscience↗