Asma, B. | bioRxiv Science

bioRxiv2023

Allele mining of eukaryotic translation initiation factor genes in Prunus species for the identification of new sources of resistance to sharka

BackgroundMembers of the eukaryotic translation initiation complex are co-opted in viral infection, leading to susceptibility in many crop species, including stone fruit trees (Prunus spp). Therefore, modification of one of those eukaryotic translation initiation factors or changes in their gene expression may result in resistance. ObjectiveWe searched the crop and wild Prunus germplasm from the Armeniaca and Amygdalus taxonomic sections for allelic variants in the eIF4E and eIFiso4E genes, to identify alleles potentially linked to resistance to the Plum Pox Virus (PPV). Methodology and resultsOver one thousand stone fruit accessions (1,397) were screened for variation in eIF4E and eIFiso4E transcript sequences which are in single copy within the diploid Prunus genome. We identified new alleles for both genes that are not evident in haplotypes associated with PPV susceptible individuals. Overall, analyses showed that eIFiso4E is genetically more constrained since it displayed less polymorphism than eIF4E. We also demonstrated more variation at both loci in the related wild species than in crop species. As the eIFiso4E translation initiation factor was identified as indispensable for PPV infection in Prunus species, a selection of ten different eIFiso4E haplotypes along 13 individuals were tested by infection with PPV and eight of them displayed a range of reduced susceptibility to resistance, indicating new potential sources of resistance to sharka.

genetics↗

bioRxiv2019

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia--thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of \"disconnection\" simulations, we showed that these changes in interactive profiles of the basal ganglia--thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

neuroscience↗