Ontogeny of the human fetal, neonatal, and infantile basioccipital bone: Traditional and extended eigenshape geometric morphometric analysis.

The basioccipital bone is an essential developmental component to the occipital bone, occipital condyles, foramen magnum, clivus, and cranial base. The basioccipital bone joins each exoccipital bone with a basiexoccipital synchondrosis and the basisphenoid/sphenoid bone with a spheno-occipital synchondrosis. The basioccipital is found intermediate to the petrous temporal bones and forms the bilateral petrooccipital/petroclival fissures otherwise known as the petrooccipital complex. Thus, the basioccipital bone is a central component to the developing cranial base. Despite the importance of basioccipital development in cranial ontogeny, there has been limited study of basioccipital ontogeny. This study assessed 98 disarticulated human basioccipital bones from a perinatal population ranging in age-at-death from 5-months intrauterine to 5-months post-natal development. Size and shape of basioccipital bones were assessed with traditional and extended eigenshape geometric morphometric analysis. The results of this study demonstrate that the basioccipital bone grows in width at a faster rate than it grows in length. The maximum basioccipital width surpassed the midsagittal length at approximately 7-months intrauterine development. Canonical variate analysis revealed statistically significant shape change occurring from a relatively narrow/elongate (anterior-to-posterior) basiocciput shape with mild concavity at the foramen magnum in the fifth and sixth intrauterine months to a relatively broad/stout basiocciput shape with more pronounced concavity in the postnatal months. Likewise, growth rate in total length was greater than midsagittal length, demonstrating enlargement of concavity in the anterior foramen magnum over time. This report provides insight into cranial development and aids in estimating age-at-death among fetuses and infants.

Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin.

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin.