Purification and molecular structure of digalactosyl myo-inositol (DGMI), trigalactosyl myo-inositol (TGMI), and fagopyritol B3 from common buckwheat seeds by NMR

Three galactosyl cyclitols, digalactosyl myo-inositol (assigned the trivial name DGMI), trigalactosyl myo-inositol (assigned the trivial name TGMI), and trigalactosyl D-chiro-inositol (fagopyritol B3), were isolated from common buckwheat (Fagopyrum esculentum Moench) seeds. Structures of the three compounds were determined by 2D NMR spectroscopy. DGMI is alpha-D-galactopyranosyl-(1 -> 6)-alpha-D-galactopyranosyl-(1 -> 1)-1L-myo-inositol, TGMI is alpha-D-galactopyranosyl-(1 -> 6)-alpha-D-galactopyranosyl-(1 -> 6)-alpha-D-galactopyranosyl-(1 -> 1)-1L-myo-inositol, and fagopyritol B3 is alpha-D-galactopyranosyl-(1 -> 6)-alpha-D-galactopyranosyl-(1 -> 6)-alpha-D-galactopyranosyl-(1 -> 2)-1D-chiro-inositol. DGMI and TGMI are higher oligomers of galactinol, a major galactosyl donor in plant seeds. Fagopyritol B3 is a higher oligomer of the fagopyritol B series and one of six fagopyritols found in buckwheat seeds and in the bran milling fraction. Samples of TGMI and fagopyritol B3 also contained the compounds N-(beta-glucopyranosyl)-nicotinic acid and beta-D-apiofuranosyl-(1 -> 6)-beta-D-(1-O-methyl)-glucopyranoside. (C) 2013 Elsevier Ltd. All rights reserved

Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome

Meckel-Gruber syndrome (MKS) is a recessive disorder resulting in multiple birth defects that are associated with mutations affecting ciliogenesis. We recovered a mouse mutant with a mutation in the Mks1 gene (Mks1del64-323) that caused a 260-amino-acid deletion spanning nine amino acids in the B9 domain, a protein motif with unknown function conserved in two other basal body proteins. We showed that, in wild-type cells, Mks1 was localized to the mother centriole from which the cilium was generated. However, in mutant Mks1del64-323 cells, Mks1 was not localized to the centriole, even though it maintained a punctate distribution. Resembling MKS patients, Mks1 mutants had craniofacial defects, polydactyly, congenital heart defects, polycystic kidneys and randomized left-right patterning. These defects reflected disturbance of functions subserved by motile and non-motile cilia. In the kidney, glomerular and tubule cysts were observed along with short cilia, and cilia were reduced in number to a near-complete loss. Underlying the left-right patterning defects were fewer and shorter nodal cilia, and analysis with fluorescent beads showed no directional flow at the embryonic node. In the cochlea, the stereocilia were mal-patterned, with the kinocilia being abnormally positioned. Together, these defects suggested disruption of planar cell polarity, which is known to regulate node, kidney and cochlea development. In addition, we also showed that Shh signaling was disrupted. Thus, in the neural tube, the floor plate was not specified posteriorly even as expression of the Shh mediator Gli2 increased. By contrast, the Shh signaling domain was expanded in the anterior neural tube and anterior limb bud, consistent with reduced Gli3-repressor (Gli3R) function. The latter probably accounted for the preaxial digit duplication exhibited by the Mks1del64-323 mutants. Overall, these findings indicate that centriole localization of Mks1 is required for ciliogenesis of motile and non-motile cilia, but not for centriole assembly. On the basis of these results, we hypothesize a role for the B9 domain in mother centriole targeting, a possibility that warrants further future investigations

Trends in Ductus Arteriosus Stent Versus Blalock‐Taussig‐Thomas Shunt Use and Comparison of Cost, Length of Stay, and Short‐Term Outcomes in Neonates With Ductal‐Dependent Pulmonary Blood Flow: An Observational Study Using the Pediatric Health Information Systems Database

Background The modified Blalock‐Taussig‐Thomas shunt is the gold standard palliation for securing pulmonary blood flow in infants with ductal‐dependent pulmonary blood flow. Recently, the ductus arteriosus stent (DAS) has become a viable alternative. Methods and Results This was a retrospective multicenter study of neonates ≤30 days undergoing DAS or Blalock‐Taussig‐Thomas shunt placement between January 1, 2017 and December 31, 2020 at hospitals reporting to the Pediatric Health Information Systems database. We performed generalized linear mixed‐effects modeling to evaluate trends in intervention and intercenter variation, propensity score adjustment and inverse probability weighting with linear mixed‐effects modeling to analyze length of stay and cost of hospitalization, and generalized linear mixed modeling to analyze differences in 30‐day outcomes. There were 1874 subjects (58% male, 61% White) from 45 centers (29% DAS). Odds of DAS increased with time (odds ratio [OR] 1.23, annually, P<0.01 [95% CI, 1.10–1.38]) with significant intercenter variation (median OR, 3.81 [95% CI, 2.74–5.91]). DAS was associated with shorter hospital length of stay (ratio of geometric means, 0.76 [95% CI, 0.63–0.91]), shorter intensive care unit length of stay (ratio of geometric means, 0.77 [95% CI, 0.61–0.97]), and less expensive hospitalization (ratio of geometric means, 0.70 [95% CI, 0.56–0.87]). Intervention was not significantly associated with odds of 30‐day transplant‐free survival (OR,1.18 [95% CI, 0.70–1.99]) or freedom from catheter reintervention (OR, 1.02 [95% CI, 0.65–1.58]), but DAS was associated with 30‐day freedom from composite adverse outcome (OR, 1.51 [95% CI, 1.11–2.05]). Conclusions Use of DAS is increasing, but there is variability across centers. Though odds of transplant‐free survival and reintervention were not significantly different after DAS, and DAS was associated with shorter length of stay and lower in‐hospital costs