Preterm Delivery Disrupts the Developmental Program of the Cerebellum

A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. The goal of this study was to characterize the impact of preterm delivery on the developmental program of the human cerebellum. Still born infants, which meant that all development up to that age had taken place in-utero, were age paired with preterm delivery infants, who had survived in an ex-utero environment, which meant that their development had also taken place outside the uterus. The two groups were assessed on quantitative measures that included molecular markers of granule neuron, purkinje neuron and bergmann glia differentiation, as well as the expression of the sonic hedgehog signaling pathway, that is important for cerebellar growth. We report that premature birth and development in an ex-utero environment leads to a significant decrease in the thickness and an increase in the packing density of the cells within the external granular layer and the inner granular layer well, as a reduction in the density of bergmann glial fibres. In addition, this also leads to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that the developmental program of the cerebellum is specifically modified by events that follow preterm delivery

Host-dependence of in vitro reassortment dynamics among the Sathuperi and Shamonda Simbuviruses

Orthobunyaviruses are arboviruses (Arthropod Borne Virus) and possess multipartite genomes made up of three negative RNAs corresponding to the small (S), medium (M) and large (L) segments. Reassortment and recombination are evolutionary driving forces of such segmented viruses and lead to the emergence of new strains and species. Retrospective studies based on phylogenetical analysis are able to evaluate these mechanisms at the end of the selection process but fail to address the dynamics of emergence. This issue was addressed using two Orthobunyaviruses infecting ruminants and belonging to the Simbu serogroup: the Sathuperi virus (SATV) and the Shamonda virus (SHAV). Both viruses were associated with abortion, stillbirth and congenital malformations occurring after transplacental transmission and were suspected to spread together in different ruminant and insect populations. This study showed that different viruses related to SHAV and SATV are spreading simultaneously in ruminants and equids of the Sub-Saharan region. Their reassortment and recombination potential was evaluated in mammalian and in insect contexts. A method was set up to determine the genomic background of any clonal progeny viruses isolated after in vitro coinfections assays. All the reassortment combinations were generated in both contexts while no recombinant virus was isolated. Progeny virus populations revealed a high level of reassortment in mammalian cells and a much lower level in insect cells. In vitro selection pressure that mimicked the host switching (insect-mammal) revealed that the best adapted reassortant virus was connected with an advantageous replicative fitness and with the presence of a specific segment

Host-dependence of in vitro reassortment dynamics among the Sathuperi and Shamonda Simbuviruses

Orthobunyaviruses are arboviruses (Arthropod Borne Virus) and possess multipartite genomes made up of three negative RNAs corresponding to the small (S), medium (M) and large (L) segments. Reassortment and recombination are evolutionary driving forces of such segmented viruses and lead to the emergence of new strains and species. Retrospective studies based on phylogenetical analysis are able to evaluate these mechanisms at the end of the selection process but fail to address the dynamics of emergence. This issue was addressed using two Orthobunyaviruses infecting ruminants and belonging to the Simbu serogroup: the Sathuperi virus (SATV) and the Shamonda virus (SHAV). Both viruses were associated with abortion, stillbirth and congenital malformations occurring after transplacental transmission and were suspected to spread together in different ruminant and insect populations. This study showed that different viruses related to SHAV and SATV are spreading simultaneously in ruminants and equids of the Sub-Saharan region. Their reassortment and recombination potential was evaluated in mammalian and in insect contexts. A method was set up to determine the genomic background of any clonal progeny viruses isolated after in vitro coinfections assays. All the reassortment combinations were generated in both contexts while no recombinant virus was isolated. Progeny virus populations revealed a high level of reassortment in mammalian cells and a much lower level in insect cells. In vitro selection pressure that mimicked the host switching (insect-mammal) revealed that the best adapted reassortant virus was connected with an advantageous replicative fitness and with the presence of a specific segment