Inhibition of ascorbate oxidation by urate

Cupric sulfate is reduced by ascorbate to the cuprous ion. The cuprous ion is then oxidized back to the cupric form by oxygen. A steady state concentration of the cupric ion is thus established to maintain a continuous oxidation of ascorbate in the presence of a trace amount of copper. In the presence of urate there is an instantaneous oxidation of ascorbate by the cupric ion. However, urate complexes with the cuprous ion and thus reduces the steady state concentration of the cupric ion. This decrease in cupric ion concentration interrupts ascorbate oxidation. The interaction of urate and cuprous ion was documented by analysis of uv absorption spectrum and the isolation of urate-Cu⁺ by high-pressure liquid chromatography.     

Activation of hormone-sensitive lipase from adipose tissue by cyclic AMP-dependent protein kinase

Lipase activation requiring cyclic-3′,5′-adenosine monophosphate and ATP was demonstrated in crude fractions of human adipose tissue homogenates. Activation was totally blocked by addition of the specific protein kinase inhibitor. Levels of endogenous protein kinase were adequate to support clear-cut activation but in partially purified preparations addition of exogenous (rabbit muscle) kinase further enhanced activation. When tissue was treated with epinephrine prior to homogenization the degree of activation in partially purified fractions was distinctly reduced. The mechanism of activation of hormone-sensitive lipase in human adipose tissue is thus shown, like that in rat adipose tissue, to be linked to a cyclic AMP-dependent protein kinase.     

Amphetamine modulates human incentive processing

Research suggests that psychostimulants can physiologically alter dopamine kinetics in the ventral striatum (VS) and psychologically enhance mood and attention. Using event-related functional magnetic resonance imaging (fMRI), we conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity and affect during incentive processing. In two counterbalanced scanning sessions 60-180 min after ingesting AMPH or PLAC, 8 healthy volunteers played a game involving anticipation and receipt of monetary gains and losses. Group and volume of interest analyses suggested that by enhancing tonic over phasic activation, AMPH treatment "equalized" levels of VS activity and positive arousal during anticipation of both gain and loss. These findings suggest that therapeutic effects of amphetamine on incentive processing may involve reducing the difference between anticipation of gains and losses.     

Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro

Human skeletal muscle is an essential source of various cellular progenitors with potential therapeutic perspectives. We first used extracellular markers to identify in situ the main cell types located in a satellite position or in the endomysium of the skeletal muscle. Immunohistology revealed labeling of cells by markers of mesenchymal (CD13, CD29, CD44, CD47, CD49, CD62, CD73, CD90, CD105, CD146, and CD15 in this study), myogenic (CD56), angiogenic (CD31, CD34, CD106, CD146), hematopoietic (CD10, CD15, CD34) lineages. We then analysed cell phenotypes and fates in short- and long-term cultures of dissociated muscle biopsies in a proliferation medium favouring the expansion of myogenic cells. While CD56⁺ cells grew rapidly, a population of CD15⁺ cells emerged, partly from CD56⁺ cells, and became individualized. Both populations expressed mesenchymal markers similar to that harboured by human bone marrow-derived mesenchymal stem cells. In differentiation media, both CD56⁺ and CD15⁺ cells shared osteogenic and chondrogenic abilities, while CD56⁺ cells presented a myogenic capacity and CD15⁺ cells presented an adipogenic capacity. An important proportion of cells expressed the CD34 antigen in situ and immediately after muscle dissociation. However, CD34 antigen did not persist in culture and this initial population gave rise to adipogenic cells. These results underline the diversity of human muscle cells, and the shared or restricted commitment abilities of the main lineages under defined conditions.     

Plant low-molecular-weight phospholipase A2s (PLA2s) are structurally related to the animal secretory PLA2s and are present as a family of isoforms in rice (Oryza sativa)

Recently, we purified to homogeneity and characterized a low-molecular-weight calcium-dependent phospholipase A₂ (PLA₂) from developing elm seed endosperm. This represented the first purified and characterized PLA₂ from a plant tissue. The full sequences of two distinct but homologous rice (Oryza sativa) cDNAs are given here. These encode mature proteins of 119 amino acids (PLA₂-I, preceded by a 19 amino acid signal peptide) and 128 amino acids (PLA₂-II, preceded by a 25 amino acid signal peptide), and were derived from four expressed sequence tag (EST) clones. Both proteins were homologous to the N-terminal amino acid sequence of the elm PLA₂. They contained twelve conserved cysteine residues and sequences that are likely to represent the Ca²⁺-binding loop and active-site motif, which are characteristic of animal secretory PLA₂s. A soluble PLA₂ activity was purified 145 000-fold from green rice shoots. This had the same biochemical characteristics as the elm and animal secretory PLA₂s. The purified rice PLA₂ consisted of two proteins, with a molecular weight of 12 440 and 12 920, that had identical N-terminal amino acid sequences. This sequence was different from but homologous to the PLA₂-I and PLA₂-II sequences. Taken together, the results suggest that at least three different low-molecular-weight PLA₂s are expressed in green rice shoots. Southern blot analysis suggested that multiple copies of such genes are likely to occur in the rice and in other plant genomes.     

Antifungal Activity of Baicalein Against Candida krusei Does Not Involve Apoptosis

The present study was designed to evaluate the antifungal activity of baicalein against Candida krusei isolates. Using a broth microdilution assay, baicalein exhibited potent in vitro antifungal activity against C. krusei isolates with a minimum inhibitory concentration of 2.7 μg/ml. Flow cytometric study indicated that baicalein depolarized mitochondrial membrane potential in a concentration-dependent manner. However, mechanistic analyses showed that the intracellular reactive oxygen species (ROS) level was virtually unchanged, and massive DNA fragmentation was not observed in C. krusei isolates after baicalein treatment even at a concentration which was apoptotic in C. albicans. Taken together, we conclude that the antifungal activity of baicalein in C. krusei isolates occurs through perturbation in mitochondrial homeostasis without causing elevation of the intracellular ROS level and does not involve apoptosis.     

A regulatory role of polycystin-1 on cystic fibrosis transmembrane conductance regulator plasma membrane expression.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by genetic mutations in either PKD1 or PKD2, the genes that encode polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively. ADPKD is characterized by the formation of multiple, progressive, fluid-filled renal cysts. To elucidate the mechanism of fluid secretion by ADPKD cysts, we examined the effect of PC-1 on the plasma membrane expression of cystic fibrosis transmembrane conductance regulator (CFTR), a key Cl(-) secretory protein. Five stably transfected MDCK lines were used in this study: two transfected with empty vector (control cells) and three expressing human PC-1 (PC-1 cells). The cAMP-induced endogenous short circuit currents (I(sc)) were smaller in PC-1 cells than in control cells. Compared to control cells, PC-1 cells transiently expressing pEGFP-CFTR showed significant reduction of whole cell cAMP-activated Cl(-) currents. Cell surface biotinylation experiments also indicated a reduction in surface expression of CFTR in PC-1 cells compared to control. Furthermore, studies using CHO cells transiently expressing PC-1 and CFTR suggest the importance of the PC-1 COOH-terminus in the observed reduction of CFTR plasma membrane expression. No differences in either endogeneous K(+) currents or P2Y receptor responses were observed between PC-1 and control cells, indicating the specificity of PC-1's action. These results indicate that PC-1 selectively maintains low cell surface expression of CFTR. Moreover, these findings suggest that the malfunction of PC-1 enhances plasma membrane expression of CFTR, thus causing abnormal Cl(-)secretion into the cyst lumen.     

The Synergistic Effect of Functional Status and Comorbidity Burden on Mortality: A 16-Year Survival Analysis

Objectives

The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty.

Design

National data were retrospectively extracted from medical records of community hospital.

Data Sources

There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011.

Outcome Measure

Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality.

Results

During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25–1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29–1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05–1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45–1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13–2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12–2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15–8.37).

Conclusions

Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.     

Dental histology of Coelophysis bauri and the evolution of tooth attachment tissues in early dinosaurs

Studies of dinosaur teeth have focused primarily on external crown morphology and thus, use shed or in situ tooth crowns, and are limited to the enamel and dentine dental tissues. As a result, the full suites of periodontal tissues that attach teeth to the jaws remain poorly documented, particularly in early dinosaurs. These tissues are an integral part of the tooth and thus essential to a more complete understanding of dental anatomy, development, and evolution in dinosaurs. To identify the tooth attachment tissues in early dinosaurs, histological thin sections were prepared from the maxilla and dentary of a partial skull of the early theropod Coelophysis bauri from the Upper Triassic (Rhaetian‐ 209–201 Ma) Whitaker Quarry, New Mexico, USA. As one of the phylogenetically and geologically oldest dinosaurs, it is an ideal candidate for examining dental tissues near the base of the dinosaurian clade. The teeth of C. bauri exhibited a fibrous tooth attachment in which the teeth possessed five tissues: enamel, dentine, cementum, periodontal ligament (PDL), and alveolar bone. Our findings, coupled with those of more recent studies of ornithischian teeth, indicate that a tripartite periodontium, similar to that of crocodilians and mammals, is the plesiomorphic condition for dinosaurs. The occurrence of a tripartite periodontium in dinosaurs adds to the growing consensus that the presence of these tissues is the plesiomorphic condition for the major amniote clades. Furthermore, this study establishes the relative timing of tissue development and growth directions of periodontal tissues and provides the first comparative framework for future studies of dinosaur periodontal development, tooth replacement, and histology. J. Morphol. 277:916–924, 2016. © 2016 Wiley Periodicals, Inc.