Biology subjects

Schiff, H.

Publications and source records attributed to Schiff, H..

4 recordsLinked to original sources

bioRxiv2025

SIMAIS: A swarm intelligence inspired biosensor for rapid protein detection

Swarm intelligence, the collective behaviour of animals such as birds, fish, and ants, arises from simple local interactions and enables survival, efficient foraging, and decision-making without central control. Inspired by this principle, we aimed to harness swarm intelligence for biosensing applications. Conventional assays often struggle with limited sensitivity, long processing times, and the need for specialised instruments, restricting their use in decentralised healthcare. Here we developed a swarm intelligence of microbead-inspired, artificial intelligence (AI)-assisted, and smartphone-based (SIMAIS) biosensing platform that can transform invisible molecular recognition into visible, macroscale patterns. Millions of antibody-coated magnetic microbeads (MBs) organise into magnetically induced structures upon binding protein biomarkers, with the resulting patterns correlating directly to biomarker concentration. Using interferon-gamma (IFN-{gamma}) as a model biomarker, we demonstrate that this approach delivers results within 10 minutes and achieves a tenfold increase in sensitivity compared to conventional lateral flow assays. Robust performance in human serum and urine confirms clinical applicability. By mimicking natural swarm behaviour, this platform introduces a new biosensing paradigm that bridges biology and engineering. Its versatility, speed, and ease of use highlight its potential for decentralised diagnostics, early disease detection, and broader applications in point-of-care healthcare.

biophysics↗

bioRxiv2025

Postnatal development of pyramidal neurons excitability and synaptic inputs in mouse gustatory cortical circuits

Cortical neurons in sensory areas undergo a protracted process of postnatal maturation that includes changes in membrane properties, synaptic drive and connectivity. The completion of this process is associated with the closure of sensitive windows for experience-dependent plasticity. Weaning is a critical time in the development of taste circuits as animals transition from depending on the mother for nutrition to eating independently. While there is some evidence for developmental changes in taste bud innervation and in membrane properties of neurons in brainstem circuits for taste, very little is known about postnatal changes in the gustatory cortex (GC), the primary cortical region for taste and taste-guided behaviors. Here, we focused on pyramidal neurons in the deep layers of GC and compared their membrane properties in pre- and postweaning age groups. We report dynamic changes in intrinsic excitability and a progressive shift of the excitation/inhibition (E/I) balance toward inhibition as pyramidal neurons reach their young adult properties. The increase in inhibitory drive accompanied a protracted process of postnatal maturation of inhibitory circuits mediated by parvalbumin expressing neurons (PV neurons) that showed a progressive increase in their association with perineuronal nets (PNNs) and refinement of their connectivity onto pyramidal neurons. Together, our results indicate that GC neurons undergo protracted postnatal maturation that may influence taste response properties at the transition to independent feeding. Significance StatementWe show that the circuit in the gustatory cortex undergoes a protracted maturation process that extends into adulthood and progressively shifts the excitability of GC toward inhibition through changes in pyramidal neurons membrane properties, increased inhibitory synaptic drive and refinement of parvalbumin neurons connectivity. This maturation process extends beyond the developmental windows previously reported for other sensory cortical circuits and overlaps with the recently identified critical period for the development of taste preferences. As finding nutritious food sources may require the integration of vision, audition, somatosensation and olfaction, the extended maturation process for taste cortical circuits may facilitate the integration of sensory information for the identification of food and the decision to ingest it.

neuroscience↗

bioRxiv2024

Amyloid beta glycation leads to neuronal mitochondrial dysfunction and Alzheimers pathogenesis through VDAC1-dependent mtDNA efflux

Glycation, the non-enzymatic attachment of reactive dicarbonyls to proteins, lipids, or nucleic acids, contributes to the formation of advanced glycation end-products (AGEs). In Alzheimers disease (AD), amyloid-beta (A{beta}) undergoes post-translational glycation to produce glycated A{beta} (gA{beta}), yet its pathological role remains poorly understood. Here, we demonstrate that gA{beta} promotes neuronal mitochondrial DNA (mtDNA) efflux via a VDAC1-dependent mechanism, activating the innate immune cGAS-STING pathway. Using aged AD mice and human AD brain samples, we observed cGAS-mtDNA binding and cGAS-STING activation in the neuronal cytoplasm. Knockdown of RAGE, cGAS, or STING, as well as pharmacological inhibition of VDAC1, protected APP mice from mitochondrial dysfunction and Alzheimers-like pathology. Neuron-specific cGAS knockdown confirmed its pivotal role in driving neuroinflammation and cognitive deficits. Treatment with ALT-711, an AGE cross-link breaker, alleviated gA{beta}-associated pathology. Furthermore, RAGE inhibition in APP knock-in mice suppressed innate immune activation and disease-associated gene expression, as revealed by spatially resolved transcriptomics. Collectively, our findings establish a mechanistic link between gA{beta} and innate immune activation, identifying VDAC1, the AGE-RAGE axis, and the cGAS-STING pathway as promising therapeutic targets in AD. Significance StatementThis study reveals how a modified form of amyloid-beta disrupts mitochondrial function in neurons, triggering innate immunity and disease progression. We show that this modified amyloid-beta damages mitochondria, activating a specific immune response in the brain. By identifying the key molecules involved, we provide potential targets for new Alzheimers treatments aimed at preventing mitochondrial damage and cognitive decline. This research offers fresh insights into Alzheimers development and highlights new therapeutic pathways.

neuroscience↗

bioRxiv2017

The central amygdala controls learning in the lateral amygdala

Both the lateral and the central nuclei of the amygdala are required for adaptive behavioral responses to environmental cues predicting threats. While experience-driven synaptic plasticity in the lateral amygdala is thought to underlie the formation of association between a sensory stimulus and an ensuing threat, how the central amygdala participates in such learning process remains unclear. Here we show that a specific class of central amygdala neurons, the protein kinase C-{delta}-expressing neurons, is essential for the synaptic plasticity underlying learning in the lateral amygdala, as it is required for lateral amygdala neurons to respond to unconditioned stimulus, and furthermore carries information about the unconditioned stimulus to instruct learning. Our results uncover an amygdala functional organization that may play a key role in diverse learning processes.

neuroscience↗