Dynamics of optic canal and orbital cavity development revealed by microCT.

PURPOSE: Numerous studies have attempted to clarify the exact anatomy and variations of the optic canal with non-conclusive results due to its close proximity to many vulnerable structures. We sought to determine the dynamics of growth and development of these structures on fetal skulls, which will help us to better understand of gender and age-dependent variations, as well as fatal malformations. METHODS: Fifteen previously macerated fetal frontal and sphenoid bones were analyzed and the diameters of optic canal, and distance of orbit from frontomaxillary suture to frontozygomatic suture were measured using 3D reconstruction images obtained by micro-CT. RESULTS: Average diameter of the optic canal in 300 mm fetus was measured to be 1,546 ± 36 µm, in 400 mm fetus 2,470 ± 123 µm and in 500 mm fetus 3,757 ± 203 µm. This trend indicates a linear enlargement of optic canal during the fetal period. During the same time period, diameter of the orbit enlarges from 12,319 ± 559 µm in 300 mm fetus to 19,788 ± 736 µm in 500 mm fetus. Growth curve is significantly lower in comparison with the same curve in optic canal data. We also calculated the ratio of orbit diameter and optic canal diameter between those groups which decreased from a value of 7.9 ± 0.4 for 300 mm fetus to 5.3 ± 0.2 for 500 mm fetus. CONCLUSION: Dynamics of optic canal and orbital cavity development is different in early and late fetal period. Diameters of those structures are in better correlation with the fetal length.

Bone morphogenetic protein (BMP)1-3 enhances bone repair.

Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFß, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair.

Wss1 Promotes Replication Stress Tolerance by Degrading Histones.

Timely completion of DNA replication is central to accurate cell division and to the maintenance of genomic stability. However, certain DNA-protein interactions can physically impede DNA replication fork progression. Cells remove or bypass these physical impediments by different mechanisms to preserve DNA macromolecule integrity and genome stability. In Saccharomyces cerevisiae, Wss1, the DNA-protein crosslink repair protease, allows cells to tolerate hydroxyurea-induced replication stress, but the underlying mechanism by which Wss1 promotes this function has remained unknown. Here, we report that Wss1 provides cells tolerance to replication stress by directly degrading core histone subunits that non-specifically and non-covalently bind to single-stranded DNA. Unlike Wss1-dependent proteolysis of covalent DNA-protein crosslinks, proteolysis of histones does not require Cdc48 nor SUMO-binding activities. Wss1 thus acts as a multi-functional protease capable of targeting a broad range of covalent and non-covalent DNA-binding proteins to preserve genome stability during adverse conditions.

SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks.

Ruijs-Aalfs syndrome is a segmental progeroid syndrome resulting from mutations in the SPRTN gene. Cells derived from patients with SPRTN mutations elicit genomic instability and people afflicted with this syndrome developed hepatocellular carcinoma. Here we describe the molecular mechanism by which SPRTN contributes to genome stability and normal cellular homeostasis. We show that SPRTN is a DNA-dependent mammalian protease required for resolving cytotoxic DNA-protein crosslinks (DPCs)- a function that had only been attributed to the metalloprotease Wss1 in budding yeast. We provide genetic evidence that SPRTN and Wss1 function distinctly in vivo to resolve DPCs. Upon DNA and ubiquitin binding, SPRTN can elicit proteolytic activity; cleaving DPC substrates and itself. SPRTN null cells or cells derived from patients with Ruijs-Aalfs syndrome are impaired in the resolution of covalent DPCs in vivo. Collectively, SPRTN is a mammalian protease required for resolving DNA-protein crosslinks in vivo whose function is compromised in Ruijs-Aalfs syndrome patients.

Sinus pericranii in the left frontal region involving the superior eyelid: a case report.

BACKGROUND: Sinus pericranii is a rare asymptomatic communication between the intracranial and extracranial venous drainage pathways. The venous flow in this condition circulates through abnormal dilated veins in both directions. PATIENT/METHODS: We describe an unusual location of an accessory sinus pericranii that involved the left frontal bone along with the superior orbital rim and the upper eyelid, with special focus on therapy. RESULTS: The patient did not have any complication during the first and second surgery. Final outcome was excellent. The patient did not show any evidence of disease recurrence 1 year after the surgery. CONCLUSION: We propose a multidisciplinary approach in the treatment of such lesions with a two-step surgery. Excision of the sinus pericranii is possible if the sinus pericranii is not a major venous outflow channel of the brain, which can be evaluated by angiography.