Subchronic toxicity evaluation of glucosamine and glucosamine in combination with chondroitin sulfate in obese Zucker rats.

D-glucosamine is a widely consumed dietary supplement used to promote joint health and treat osteoarthritis. It also stimulates intracellular hexosamine flux and increases transforming growth factor ß1 (TGFß1) mRNA expression and insulin resistance in animal studies. The effects of D-glucosamine exposure were investigated in obese Zucker rats. Male (leprfa/leprfa) Zucker rats were exposed to 30, 120, 300 and 600 mg D-glucosamine HCl per kg/day either alone or with chondroitin sulfate (24, 96, 240 and 480 mg/kg/day respectively) for 90 days. After 4 weeks exposure, these doses produced CmaxD-glucosamine concentrations of up to 24 µM in tail vein serum concurrent with a transient 30% increase in blood glucose concentration in the 600 mg/kg/day dose group. D-Glucosamine did not significantly alter body weight, blood glucose or serum insulin levels at any dose tested after 13 weeks exposure, but did increase urinary TGFß1 concentrations. The Zucker rats developed nephropathy and scrotal sores that were related to their hyperglycemia and obesity, and D-glucosamine exposure exacerbated these conditions to a small extent. The incidence of pulmonary osseous metaplasia was increased in rats exposed to D-glucosamine and a single incidence of adrenal osseous metaplasia was noted in one animal exposed to 600/480 mg D-glucosamine HCl/chondroitin sulfate. These lesions may have been treatment related. These studies suggest that the risk of adverse effects of oral D-glucosamine is small compared to that of hyperglycemia in these animals, but the potential for TGFß1-mediated pathologies, such as osseous metaplasia and renal nephropathy may be increased.

The physical chemistry of the enigmatic phospholipid diacylglycerol pyrophosphate.

Phosphatidic acid (PA) is a lipid second messenger that is formed transiently in plants in response to different stress conditions, and plays a role in recruiting protein targets, ultimately enabling an adequate response. Intriguingly, this increase in PA concentration in plants is generally followed by an increase in the phospholipid diacylglycerolpyrophosphate (DGPP), via turnover of PA. Although DGPP has been shown to induce stress-related responses in plants, it is unclear to date what its molecular function is and how it exerts its effect. Here, we describe the physicochemical properties, i.e., effective molecular shape and charge, of DGPP. We find that unlike PA, which imparts a negative curvature stress to a (phospho)lipid bilayer, DGPP stabilizes the bilayer phase of phosphatidylethanolamine (PE), similar to the effect of phosphatidylcholine (PC). DGPP thus has zero curvature. The pKa(2) of the phosphomonoester of DGPP is 7.44 ± 0.02 in a PC bilayer, compared to a pKa(2) of 7.9 for PA. Replacement of half of the PC with PE decreases the pKa(2) of DGPP to 6.71 ± 0.02, similar to the behavior previously described for PA and summarized in the electrostatic-hydrogen bond switch model. Implications for the potential function of DGPP in biomembranes are discussed.

Most morphologic features in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not reliably predict underlying FISH genetics or immunoglobulin heavy chain variable region somatic mutational status.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is common in the Western world. Genetic abnormalities detected by fluorescence in situ hybridization (FISH) and immunoglobulin heavy chain variable gene region (IGHV) mutational status are well-known independent prognostic indicators in CLL/SLL. Given the requirement for specialized testing to detect such aberrations, we investigated whether morphologic features may predict the presence of a more or less favorable genetic profile. Forty-one SLL cases were morphologically evaluated for expanded proliferation centers, increased large cells outside of proliferation centers, and nuclear contour irregularities (NCI) in small and large tumor cells. ZAP-70 immunohistochemistry and FISH (deletions of 13q14, p53 and ATM and trisomy 12) were successful in all cases. IGHV mutational status was determined in 26/41 cases. Significant NCI in both small and large cells correlated with the presence of an unfavorable FISH abnormality (ie, ATM or p53 deletions). However, despite good specificity (94%), the sensitivity (57%) of this finding is inadequate for routine use. No other significant associations with morphologic features were identified. Strong ZAP-70 positivity correlated with unmutated IGHV (P=0.001), rendering ZAP-70 IHC a useful surrogate for IGHV mutational status. ZAP-70 positivity predicted against finding a favorable FISH deletion 13q14 (P=0.023). Although we only studied 41 cases, we corroborated their validity using Kaplan-Meier overall survival analysis. In conclusion, morphologic features in SLL are not a reliable predictor of underlying genetic status. Thus, we propose a practical, cost-effective approach to the work-up of these cases, which should be driven by clinical necessity.

A gene-shuffled glyphosate acetyltransferase protein from Bacillus licheniformis (GAT4601) shows no evidence of allergenicity or toxicity.

The glyphosate acetyltransferase (gat) gene from Bacillus licheniformis was subjected to multiple rounds of gene shuffling to optimize kinetics of corresponding GAT proteins to acetylate the herbicide active ingredient glyphosate. Genetically modified soybeans expressing the gat4601 gene (356043 soybeans) are tolerant to the application of glyphosate. The current manuscript reports the outcome of the allergenicity and toxicity assessment for the GAT4601 protein. Bioinformatic comparison of the amino acid sequence of GAT4601 did not identify similarities to known allergenic or toxic proteins. In vitro studies conducted with heterologously produced GAT4601 protein demonstrated that it was rapidly degraded in simulated gastric fluid containing pepsin (< 30 s) and in simulated intestinal fluid containing pancreatin (< 2 min) and completely inactivated at temperatures above 56 degrees C. The GAT4601 protein expressed in planta is not glycosylated and similar protein profiles were observed in flour extracts from 356043 soybeans and nontransgenic near isoline comparator soybeans (Jack) using serum from soy allergic persons. No evidence of adverse effects was observed in mice following acute oral exposure to 2000 mg/kg of GAT4601 protein or in a repeated dose dietary exposure study at doses of 800-1000 mg/kg/day. This comprehensive assessment demonstrates that the GAT4601 protein does not present a risk for adverse effects in humans when used in the context of agricultural biotechnology.

A unique eclipsed 2-D coordination polymer with removable iodine molecules in the open-channel structure.

The first removable solid-state iodine inclusion eclipsed two-dimensional coordination polymer with an unusually stable open-channel structure has been synthesized and characterized by X-ray diffraction technique.

An extremely stable open-framework metal-organic polymer with expandable structure and selective adsorption capability.

A novel porous framework polymer with expandable structure, over 8% volume expansion upon inclusion, has been characterized.

A simultaneous reduction, substitution, and self-assembly reaction under hydrothermal conditions afforded the first diiodopyridine copper(I) coordination polymer.

A simultaneous reduction of copper(II) to copper(I) by pyridinecarboxylate and the substitution of carboxylato groups by iodo nucleophiles in a self-assembly process under hydrothermal conditions afforded a new iodine-inclusion coordination polymer [CuI(C5H3NI2)*1/2I2] 1. The synthetic studies of the substitution process produced a new supramolecular compound [IC5H3NCOOH] 2 and revealed that the catalytic properties of copper ions in redox and substitution reactions under hydrothermal conditions are attractive. Crystal data for [CuI(C5H3NI2)*1/2I2]: triclinic, space group P1; cell dimensions a = 4.216(1) A, b = 11.254(2) A, c = 12.196(2) A, alpha = 80.34(3) degrees, beta = 88.44(3) degrees, gamma = 83.10(3); V = 566.2(2) A(3), Z = 2. Crystal data for [IC(5)H(3)NCOOH]: monoclinic, space group P2(1)/c; cell dimensions a = 5.041(1) A, b = 17.313(2) A, c = 8.639(1) A, beta = 95.042(2) degrees; V = 751.02(13) A(3), Z = 4.

Las aventuras de Julia y René : Los mellizos desastre

Cuento sobre la importancia de la preparación ante situaciones de emergencia o desastres a través de historias cortas para niños y niñas sobre la tormenta de nieve, la crecida del río, la tarde del tornado, unas vacaciones temblorosas, y la temporada de huracanes.