Biology subjects

Scheid, B.

Publications and source records attributed to Scheid, B..

4 recordsLinked to original sources

bioRxiv2024

Reversal of vein of Galen aneurysmal malformation by stimulation of flow-mediated vessel fusion

Congenital vascular malformations arise from defective homeostatic development of the vascular tree1. The aneurysmal malformation of the Vein of Galen (VGAM) is the most frequent neurovascular malformation in neonates, with limited therapeutic options and poor outcomes in the most severe cases2. This congenital disease is consecutive to germline genetic mutation of RASA1 or EPHB43,4, but little is known about the mechanisms leading to its development. We generated mutant rasa1a and ephb4a deficiency models in zebrafish reproducing the genetic and structural characteristics of the VGAM in the dorsal longitudinal vein of the cerebral vasculature. We link the development of the malformation to a failure of the fusion of precursor blood vessels into a draining vessel for the choroidal type malformations and to a failure to constrict for the mural type malformations. The fusion process is driven by blood flow, sensed and integrated by endothelial cells. RASA1 deficiency destabilizes the homeostatic response to blood flow and contributes to impaired flow-mediated activation of MAPK and PI3K signaling. We targeted these defective mechanotransduction mechanisms pharmacologically in both rasa1a and ephb4a mutant models, successfully reestablishing the fusion and constriction processes in preexisting malformations. This work identifies molecular actors of the flow-mediated blood vessel fusion mechanism, a specific angiogenetic program, and provides ground for treating VGAM and other vascular remodeling disorders.

developmental biology↗

bioRxiv2024

Epileptiform activity and seizure risk follow long-term non-linear attractor dynamics

Many biological systems display circadian and slow multi-day rhythms, such as hormonal and cardiac cycles. In patients with epilepsy, these cycles also manifest as slow cyclical fluctuations in seizure propensity. However, such fluctuations in symptoms are consequences of the complex interactions between the underlying physiological, pathophysiological, and external causes. Therefore, identifying an accurate model of the underlying system that governs the multi-day rhythms allows for a more reliable seizure risk forecast and targeted interventions. To achieve this goal, we adopt the Hankel alternative view of Koopman (HAVOK) analysis to approximate a linear representation of nonlinear seizure propensity dynamics. The HAVOK framework leverages Koopman theory and delay-embedding to decompose chaotic dynamics into a linear system of leading delay-embedded coordinates driven by the low-energy coordinate (i.e., forcing). Our findings reveal the topology of attractors underlying multi-day seizure cycles, showing that seizures tend to occur in regions of the manifold with strongly nonlinear dynamics. Moreover, we demonstrate that the identified system driven by forcings with short periods up to a few days accurately predicts patients slower multi-day rhythms, which improves seizure risk forecasting.

neuroscience↗

bioRxiv2020

Mosquito densoviruses: the revival of a biological control agent against urban Aedes vectors of arboviruses

Urban Aedes mosquitoes are vectors of many viruses affecting human health such as Dengue, Chikungunya and Zika viruses. Insecticide resistance and environmental toxicity risks hamper the effectiveness of chemical control against these mosquito vectors. Alternative control methods, such as the use of mosquito-specific entomopathogenic viruses should be explored. Numerous studies have focused on evaluating the potential of different densoviruses species as biological control agent. However, knowledge on the extent of inter- and intra-specific variations in the susceptibility of Aedes mosquitoes to infection by different densoviruses remains insufficient. In this study, we compared infection and mortality rates induced by the Aedes albopictus densovirus 2 in different strains of Aedes albopictus and Aedes aegypti mosquitoes. The two Aedes species were different in terms of susceptibility to viral infection. Under laboratory conditions, Aedes albopictus densovirus 2 appeared more virulent for the different strains of Aedes aegypti tested than for those of Aedes albopictus. In addition, we also found significant intra-specific variation in infection and mortality rates. Thus, although even if Aedes albopictus densoviruses could be powerful biocontrol agents used in the management of urban Aedes populations, our results also call into question the use of single viral isolate as biocontrol agents.

microbiology↗

bioRxiv2020

Synchronized genetic activities in Alzheimer's brains revealed by heterogeneity-capturing network analysis

It is becoming increasingly evident that the efficacy of single-gene computational analyses for complex traits is nearly exhausted and future advances hinge on unraveling the intricate combinatorial interactions among multiple genes. However, the discovery of modules of genes working in concert to manifest a complex trait has been crippled by combinatorial complexity, genetic heterogeneity, and validation biases. We introduce Maestro, a novel network approach that employs a multifaceted correlation measure, which captures heterogeneity, and a rigorous validation method. Maestros utilization for Alzheimers disease (AD) reveals an expression pattern that has virtually zero probability of simultaneous expression by an individual, assuming independence. Yet this pattern is exhibited by 19.0% of AD cases and 7.3% of controls, establishing an unprecedented pattern of synchronized genetic activities in the human brain. This pattern is significantly associated with AD, with an odds ratio of 3.0. This study substantiates Maestros power for discovery of orchestrated genetic activities underlying complex traits. More generally, Maestro can be applied in diverse domains in which heterogeneity exists. HighlightsO_LISynchronized genetic activities associated with Alzheimers disease C_LIO_LINovel vector-based correlation measure that captures genetic heterogeneity C_LIO_LIEnhanced network model for revealing combinatorial genetic interactions C_LIO_LIPro-survival genetic activities associated with Alzheimers disease C_LIO_LIGeneral approach for revealing patterns in data subject to heterogeneity C_LI

bioinformatics↗