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Hwang, G. M.

Publications and source records attributed to Hwang, G. M..

2 recordsLinked to original sources

Febrile temperature enhances Plasmodium falciparum cytoadhesion by disrupting the endothelial glycocalyx

Fever, a universal host defense response in infection and inflammation, paradoxically contributes to neurological complications in malaria. Febrile temperatures are known to enhance parasite virulence protein expression, but direct effects on the human endothelium remain unknown. We found that a 1-hour exposure to 40 {degrees}C, representative of fever in children with cerebral malaria, increased adhesion of Plasmodium falciparum-infected red blood cells and neutrophils to 3D brain microvascular models displaying a wide wall shear stress gradient. Mechanistically, this brief hyperthermia triggered rapid endothelial glycocalyx shedding, exposing endothelial receptors for binding. This response was more pronounced in brain than in pulmonary microvessels, revealing a greater vulnerability of the cerebral vasculature to fever. Pharmacological inhibition of matrix metalloproteinase activity preserved glycocalyx integrity and abolished the temperature-induced increase in adhesion. These findings identify fever as a host-specific amplifier of malaria-associated microvascular pathology, highlighting the importance of antipyretic strategies to mitigate disease severity.

microbiology↗

Recurrent connections enable point attractor dynamics and dimensionality reduction in a connectome-constrained model of the insect learning center

The learning center in the insect, the mushroom body (MB) with its predominant population of Kenyon Cells (KCs), is a widely studied model system to investigate neural processing principles, both experimentally and theoretically. While many computational models of the MB have been studied, the computational role of recurrent connectivity between KCs remains inadequately understood. Dynamical point attractors are a candidate theoretical framework where recurrent connections in a neural network can enable a discrete set of stable activation patterns. However, given that detailed, full recurrent connectivity patterns in biological neuron populations are mostly unknown, how theoretical models are substantiated by specific networks found in biology has not been clear. Leveraging the recent release of the full synapse-level connectivity of the MB in the fly, we performed a series of analyses and network model simulations to investigate the computational role of the recurrent KC connections, especially their significance in attractor dynamics. Structurally, the recurrent excitation (RE) connections are highly symmetric and balanced with feedforward input. In simulations, RE facilitates dimensionality reduction and allows a small set of self-sustaining point attractor states to emerge. To further quantify the possible range of network properties mediated by RE, we systematically explored the dynamical regimes enabled by changing recurrent connectivity strength. Finally, we establish connections between our findings and potential functional or behavioral implications. Overall, our work provides quantitative insights into the possible functional role of the recurrent excitatory connections in the MB by quantifying the point attractor network dynamics within a full synapse-level connectome-constrained highly recurrent network model. These findings advance our understanding of how biological neural networks may utilize point attractor dynamics. Author summaryPoint attractor neural networks are widely used theoretical models of associative memory, where recurrent connections between neurons enable a discrete set of stable activation patterns that can recover a full pattern based on partial cues. The detailed full recurrent connectivity patterns in biological neuron populations are largely unknown, however, raising questions about the precise correspondence between theoretical point attractor models and neural networks found in biology. Recent breakthroughs have unveiled the synapse-level connectivity of all neurons within the learning center of an insect, including recurrent connections between the primary neuron type--a crucial component with an elusive computational role. In this work, we perform analyses of these recurrent connectivity patterns and simulate neural network models that have these biologically constrained neural network patterns. We find that these recurrent connections are highly symmetric and balanced with input to the memory center. In simulations, we find that these recurrent connections perform dimensionality reduction and enable a small set of point attractor states. We additionally characterize how the strength of these recurrent connections affects network properties and downstream behavioral consequences. Overall, this work advances an understanding of the insect learning center as well as the relationship between theoretical and biological recurrent networks.

neuroscience↗