Unusual D:B-friedobaccharane and oxygenated friedelane-type triterpenoids from Salvadorean Celastraceae species

Three new triterpenoids, including two rare D:B-friedobaccharanes (leonatriol, 1 and leonatriolone, 2) and a 2,3-seco-2,24-epoxy-3,24-olide-D:A-friedooleanane (cassinolide, 3) were isolated from the root bark of Cassine xylocarpa and Celastrus vulcanicola, collected in El Salvador. Their stereostructures were elucidated on the basis of spectroscopic analyses, mainly ¹D and ²D NMR techniques, spectrometric analyses, and comparison with data reported in the literature. The absolute configuration of 1 and 2 were determined by the application of the Riguera ester procedure and biogenetic considerations. The possible biogenetic pathway for cassinolide (3) is also discussed.     

Cross-linking of collagen in the X-linked Ehlers-Danlos Type V.

The activity and antigenicity of the collagen crosslinking enzyme, lysyl oxidase, and the proportions of reducible crosslink in skin biopsies from Ehlers-Danlos Type V subjects were equivalent to those of control skin. These results reveal that both the potential for crosslinking, and the ability to form reducible crosslinks is present in Ehlers-Danlos syndrome Type V subjects, clearly demonstrating that the defect in this disorder is not due to a defective crosslinking mechanism.     

Chick embryonic plasma proteins and binding capacity for corticosterone

Plasma was collected from White Leghorn embryos on alternate days from Day 4 of incubation to Day 22 (day after hatch). The plasma-binding capacity for corticosteroid was essentially zero before Day 10, but rose rapidly between Days 10 and 12. Binding capacity remained high until Day 16 and then declined before hatch. The increase after Day 10 was concurrent with the appearance of α-globulin whose rate of migration on acrylamide gel electrophoresis was similar to that of purified chicken corticosteroid binding globulin. Corticosterone, which was present in the plasma of the 4-day embryo, rose to its highest level on Day 20. The relatively high corticosterone concentration, with low plasma-binding capacity, suggests that in the chick embryo levels of free or active corticosterone are highest before Day 10 and just prior to hatching.     

A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation

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Calcium Ions Promote Superoxide Dismutase 1 (SOD1) Aggregation into Non-fibrillar Amyloid: A LINK TO TOXIC EFFECTS OF CALCIUM OVERLOAD IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)?*

Imbalance in metal ion homeostasis is a hallmark in neurodegenerative conditions involving protein deposition, and amyotrophic lateral sclerosis (ALS) is no exception. In particular, Ca²⁺ dysregulation has been shown to correlate with superoxide dismutase-1 (SOD1) aggregation in a cellular model of ALS. Here we present evidence that SOD1 aggregation is enhanced and modulated by Ca²⁺. We show that at physiological pH, Ca²⁺ induces conformational changes that increase SOD1 β-sheet content, as probed by far UV CD and attenuated total reflectance-FTIR, and enhances SOD1 hydrophobicity, as probed by ANS fluorescence emission. Moreover, dynamic light scattering analysis showed that Ca²⁺ boosts the onset of SOD1 aggregation. In agreement, Ca²⁺ decreases SOD1 critical concentration and nucleation time during aggregation kinetics, as evidenced by thioflavin T fluorescence emission. Attenuated total reflectance FTIR analysis showed that Ca²⁺ induced aggregates consisting preferentially of antiparallel β-sheets, thus suggesting a modulation effect on the aggregation pathway. Transmission electron microscopy and analysis with conformational anti-fibril and anti-oligomer antibodies showed that oligomers and amyloidogenic aggregates constitute the prevalent morphology of Ca²⁺-induced aggregates, thus indicating that Ca²⁺ diverts SOD1 aggregation from fibrils toward amorphous aggregates. Interestingly, the same heterogeneity of conformations is found in ALS-derived protein inclusions. We thus hypothesize that transient variations and dysregulation of cellular Ca²⁺ levels contribute to the formation of SOD1 aggregates in ALS patients. In this scenario, Ca²⁺ may be considered as a pathogenic effector in the formation of ALS proteinaceous inclusions.     

Distribution of Methylene Blue after Injection into the Epidural Space of Anaesthetized Pregnant and Non-Pregnant Sheep

The aim of the study was to determine the distribution of different volumes of methylene blue solution injected into the epidural space in anaesthetized pregnant and non-pregnant sheep, to evaluate its cranial distribution and to compare between them. Fifteen pregnant and fifteen non-pregnant sheep were included in the study. Sheep were anaesthetized and received 0.05, 0.1, or 0.2 mL/kg of a lumbosacral epidural solution containing 0.12% methylene blue in 0.9% saline. Thirty minutes after the epidural injection, the ewes were euthanized. The extension of the dye within the epidural space was measured, and the correlation between the volume of the dye injected and the number of stained vertebrae was evaluated. The cranial migration of the dye between pregnant and non-pregnant sheep was also compared. The results show that the volume of methylene blue injected epidurally into pregnant and non-pregnant sheep correlated directly with its cephalic distribution into the epidural space; and a volume of 0.1 mL/kg or 0.2 mL/kg stained up to the first lumbar segment in pregnant and non-pregnant sheep, respectively. Also, the results suggest that the volume of drugs administered into the epidural space of pregnant sheep should be half the volume that would be used in non-pregnant sheep.