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Biology subjects

Salomon, T.

Publications and source records attributed to Salomon, T..

7 recordsLinked to original sources

Clinical grade cryopreservation unlocks transplant ready human pancreatic and stem cell derived islets for diabetes therapy

Pancreatic islet transplantation can restore endogenous insulin production and offers a potential cure for diabetes, but its clinical impact has been limited by the inability to preserve large numbers of functional islets for timely use. Cryopreservation could provide an on-demand supply, yet conventional methods cause ice formation, cell injury, and loss of insulin secretion. We developed CryoMesh, a vitrification platform that combines a low-toxicity cryoprotectant with a thermally conductive, biocompatible mesh to enable ultra-rapid cooling and rewarming for ice-free cryopreservation. This approach supports long-term, clinical-scale preservation of both human pancreatic and stem cell-derived islets while maintaining viability, architecture, mitochondrial integrity, and glucose-responsive insulin secretion. Human islets preserved for up to one year restored normoglycemia in diabetic mice, with complete recovery of function and no increase in immunogenicity or loss of potency. The combination of high viability, recovery, and functional preservation at clinical scale has not been achieved previously. By decoupling islet isolation and manufacture from transplantation, CryoMesh enables extended quality, potency, and safety testing, cost-effective batch production, and global banking and distribution. These capabilities remove a major barrier to curative cell therapy for diabetes and establish a generalizable strategy for preserving complex multicellular therapeutics. One Sentence SummaryA clinical scale vitrification platform enables long-term banking of human pancreatic and stem cell-derived islets for transplantation.

cell biology↗

High avidity phase-separated RNA-protein sialogranules sense lectins and inhibit influenza infection

We previously developed synthetic RNA-protein (sRNP) granules as stable, programmable, genetically encoded nanoparticles. Here, we adapt this platform into high-avidity sialogranules that inhibit influenza virus entry. Natural or synthetic 2,6-sialylated proteins and peptides were fused to RNA-binding domains and assembled with synthetic long non-coding RNA to form phase-separated glyco-nanoparticles. Using the sialic-acid-binding lectin Sambucus nigra agglutinin (SNA), we identified a selective transition from sialogranules to tri-component multiphasic biocondensates that occurs only for sialylated constructs. The structural features of this transition quantitatively correlate with predicted sialylation density, enabling extraction of an effective avidity constant. Enzymatic desialylation with neuraminidase or Endo H abolished SNA binding and restored native granule morphology. Guided by this assay, LAMP1-based sialogranules were selected and inhibited influenza entry by [~]50% in cell culture. These results establish sRNP sialogranules as programmable glyco-nanoparticles integrating glycan sensing with antiviral decoy activity.

synthetic biology↗

Synthetic RNA-protein decoy granules to prevent SARS-CoV-2 infection

Synthetic receptor decoys offer a promising strategy to block viral entry but are often limited by instability and rapid clearance. Here we introduce AntiCoV decoy particles: phase-separated synthetic RNA-protein nanoparticles that display multivalent human ACE2 and act as robust decoy receptors for SARS-CoV-2. The granules remain structurally stable for at least two weeks at room temperature. Using confocal imaging and FRET, we show that the SARS-CoV-2 receptor-binding domain is absorbed into the granule matrix with nanometer-scale proximity to ACE2. In viral entry assays with Delta and Omicron (BA.1) variants, AntiCoV decoy particles achieve complete inhibition of infection at low micromolar concentrations and outperform soluble ACE2, which also exhibits infection enhancement at low doses. A minimal kinetic model suggests a multistep spike-priming mechanism that reconciles this biphasic response. AntiCoV decoy particles therefore provide a stable, modular, and pan-variant antiviral platform with potential for low-cost, room-temperature-stable prophylaxis.

synthetic biology↗

A passive computational marker for individual differences in non-reinforced learning

Cue-Approach Training (CAT) is a paradigm that enhances preferences without external reinforcmeents, suggesting a potential role for internal learning processes. Here, we developed a novel Bayesian computational model to quantify anticipatory response patterns during the training phase of CAT. This phase includes individual items and thus this marker is potentially of internal learning signals at the item level. Our model, fitted to meta-analysis data from 29 prior CAT experiments, was able to predict individual differences in non-reinforced preference changes using a key computational marker. Crucially, two new experiments manipulated the training procedure to influence the models predicted learning marker. As predicted and preregistered, the manipulation successfully induced differential preference changes, supporting a causal role of our model. These findings demonstrate powerful potential of our computational framework for investigating intrinsic learning processes. This framework could be used to predict preference changes and opens new avenues for understanding intrinsic motivation and decision-making. TeaserBayesian modeling of response time predicts individual differences in non reinforced preference change.

neuroscience↗

Brain volumetric changes in the general population following the COVID-19 outbreak and lockdown

The COVID-19 outbreak introduced unprecedented health-risks, as well as pressure on the financial, social, and psychological well-being due to the response to the outbreak. Here, we examined the manifestations of the COVID-19 outbreak on the brain structure in the healthy population, following the initial phase of the pandemic in Israel. We pre-registered our hypothesis that the intense experience of the outbreak potentially induced stress-related brain modifications. Volumetric changes in n = 50 participants who were scanned before and after the COVID-19 outbreak and lockdown, were compared with n = 50 control participants who were scanned twice prior to the pandemic. The pandemic provided a rare opportunity to examine brain plasticity in a natural experiment. We found volumetric increases in bilateral amygdalae, putamen, and the anterior temporal cortices. Changes in the amygdalae diminished as time elapsed from lockdown relief, suggesting that the intense experience associated with the pandemic outbreak induced transient volumetric changes in brain regions commonly associated with stress and anxiety.

neuroscience↗

Memory for Individual Items is Related to Non-Reinforced Preference Change

It is commonly assumed that memories contribute to value-based decisions. Nevertheless, most theories of value-based decision-making do not account for memory influences on choice. Recently, new interest has emerged in the interactions between these two fundamental processes, mainly using reinforcement-based paradigms. Here, we aimed to study the role memory processes play in preference change following the non-reinforced cue-approach training (CAT) paradigm. In CAT, the mere association of cued items with a speeded motor response influences choices. Previous studies with this paradigm showed that a single training session induces a long-lasting effect of enhanced preferences for high-value trained stimuli, that is maintained for several months. We hypothesized that CAT influences memory accessibility for trained items, leading to enhanced accessibility of their positive associative memories and in turn to preference changes. In two pre-registered experiments, we tested whether memory for trained items was enhanced following CAT, in the short and in the long-term, and whether memory modifications were related to choices. We found that memory was enhanced for trained items and that better memory was correlated with enhanced preferences at the individual item level, both immediately and one month following CAT. Our findings show that memory plays a central role in value-based decision-making following CAT, even in the absence of external reinforcements. These findings contribute to new theories relating memory and value-based decision-making and set the groundwork for the implementation of novel behavioral interventions that lead to long-lasting behavioral change.

neuroscience↗

Perceptual and memory neural processes underlie short and long-term non-reinforced behavioral change

Behavioral change studies and interventions focus on self-control and external reinforcements as means to influence preferences. Cue-approach training (CAT) has been shown to induce preference changes lasting months following a mere association of items with a neutral cue and a speeded response, without external reinforcements. We utilized this paradigm to study preference representation and modification in the brain without external reinforcements. We scanned 36 participants with fMRI during a novel passive viewing task before, after and 30 days following CAT. We pre-registered the predictions that activity in regions related to memory, top-down attention and value processing underlie behavioral change. We found that bottom-up neural mechanisms, involving visual processing regions, were associated with immediate behavioral change, while reduced top-down parietal activity and enhanced hippocampal activity were related to the long-term change. Enhanced activity in value-related regions was found both immediately and in the long-term. Our findings suggest a novel neural mechanism of preference representation and modification. We suggest that non-reinforced change occurs initially in perceptual representation of items, which putatively lead to long-term changes in memory and top-down processes. These findings could lead to implementation of bottom-up instead of top-down targeted interventions to accomplish long-lasting behavioral change.

neuroscience↗