Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides

The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc-GlcA-Glc-sequenced and one Glc-IdoA-Glc-sequenced non-glycosaminoglycan, heparin-related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non-cancerous cell lines. Two d -glucuronate-containing tetra-O-sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.     

Dietary fat composition and tocopherol requirement: IV. Safety of polyunsaturated fats

In a long-term multigeneration study, conducted in our laboratories for 32-years, with occasional longevity and histopathological evaluations included, rats of our own inbred strain (originally of Wistar derivation) were fed semisynthetic diets comprising whole wheat, skim milk powder, and fat in the form of margarine products. The total source of tocopherols was the dietary fat itself. Saturated fatty acid content (S) remained relatively constant at about 20% of the fat and total tocopherol level also remained constant at about 0.12% of the fat. Polyunsaturated fatty acid (P) content, however, progressively increased almost fourfold, from 7.5% to 28.5% and alphatocopherol levels decreased to one-half level, from 0.033% to 0.016% of the fat. Hence, the ratio of polyunsaturated fatty acids to alpha-tocopherol content changed markedly from 227∶1 to 1780∶1, with other factors (relative to fat composition) held constant during the 32-year period of feedings and observations. Fat level in the diet increased over the years from 9.2% to 16.0% or from about 21% to about 33% of the caloric intake. Thus, quality and quantity of the fat in the diet progressively changed, and the impact of these changes was evaluated by comparing biological performances of the successive generations. Growth and reproduction and lactation performances were noted to be regularly satisfactory and comparable from generation to generation throughout the experimental period. Longevity studies conducted on arbitrarily selected generations also provided data showing no deleterious effects associated with a dietary change. Histopathological examinations of tissue revealed minimal myocarditis and no malignant tumors which could be attributed to a dietary factor. No vitamin E deficiencies were observed. Even the in vitro peroxide hemolysis values for the red blood cells of the animals, fed the diets containing the higher levels of polyunsaturated fatty acids, were low, indicating that the dietary fats provided sufficient absorbable tocopherol to protect the potentially oxidizable unsaturated fatty acids in the erythrocyte membrane. Biochemical data reflected responses to aging and not to any specific diet fed. It is concluded that a diet providing as much as 33% of the calories as a fat, the latter containing up to 28.5% polyunsaturated fatty acids, substantially of the essential fatty acid type, with a P/S ratio of up to 1.6∶1 and a polyunsaturated fatty acid to alphatocopherol ratio as high as 1780∶1] produces no undesirable effects in the rat. Presented in part at a symposium entitled “Long Term Nutritional Effects of Dietary Fats” at the International Society for Fat Research World Congress, September 30, 1970, Chicago, Illinois.     

Primary structure of water buffalo alpha-lactalbumin variants A and B

A novel electrophoretic alpha-lactalbumin (alpha-la) variant was detected in the Italian water buffalo breed. The isoelectric point of the variant, labelled A, was lower than the most frequent variant B. It presented an allelic frequency of 0.5% compared with the 97.1% of the BB allele. From Liquid Chromatography-Electrospray Ionization/Mass spectrometry, the molecular mass of the two alpha-la A and B variants were measured as 14,235.1+/-0.8 and 14,236.1+/-0.9 Da, respectively. The two proteins were sequenced and differentiated from one another by a single amino acid substitution, Asn45(B)-->Asp45(A). As this amino acid substitution altered the N-glycosylation sequence consensus Asn45-X-Ser46 it may be deduced that the protein glycosylation level of the alpha-la A would decrease.     

Functional properties of protein preparations from amaranth seeds in model system

The gross chemical composition and functional properties (solubility, emulsifying and foaming properties) of different amaranth protein preparations were studied in model systems and were compared to those of casein and soy protein isolates. Preparations of alkaline-soluble total protein, albumin, globulin, and glutelin-like alkaline-soluble residual protein were produced from two different types of defatted amaranth meals by extraction and fractionation. Although similarity can be shown between protein patterns of legumes (including soy) and amaranth, the emulsifying and foaming properties of amaranth protein preparations are relatively poor in comparison to the reference proteins, except foaming properties of albumin preparations. Nevertheless, taking in mind that these properties depend on interactions with other food components and textural requirements of individual food products, the amaranth protein preparations may be treated as potential protein sources and food ingredients.     

Early and late effects of absorbable poly(vinyl alcohol) hernia mesh to tissue reconstruction

Hernia is a defect of the abdominal wall. Treatment is principally surgical mesh implantation. Non‐degradable surgical meshes produce numerous complications and side‐effects such as inflammatory response, mesh migration and chronic pain. In contrast, the biodegradable, poly (vinyl alcohol) (PVA) based polymers have excellent chemical, mechanical and biological properties and after their degradation no chronic pain can be expected. The toxicology of PVA solution and fibers was investigated with Human dermal fibroblast‐ Adult cell line. Implantation tests were observed on long‐term contact (rat) and large animal (swine) models. To measure the adhesion formation, Diamond and Vandendael score were used. Macroscopical and histological responses were graded from the samples. In vitro examination showed that PVA solution and fibers are biocompatible for the cells. According to the implantation tests, all samples were integrated into the surrounding tissue, and there was no foreign body reaction. The average number of adhesions was found on the non‐absorbable suture line. The biocompatibility of the PVA nanofiber mesh was demonstrated. It has a non‐adhesive, non‐toxic and good quality structure which has the potential to be an alternative solution for the part of the hernia mesh.     

The Hydrophilic Loop of Arabidopsis PIN1 Auxin Efflux Carrier Harbors Hallmarks of an Intrinsically Disordered Protein

Much of plant development depends on cell-to-cell redistribution of the plant hormone auxin, which is facilitated by the plasma membrane (PM) localized PIN FORMED (PIN) proteins. Auxin export activity, developmental roles, subcellular trafficking, and polarity of PINs have been well studied, but their structure remains elusive besides a rough outline that they contain two groups of 5 alpha-helices connected by a large hydrophilic loop (HL). Here, we focus on the PIN1 HL as we could produce it in sufficient quantities for biochemical investigations to provide insights into its secondary structure. Circular dichroism (CD) studies revealed its nature as an intrinsically disordered protein (IDP), manifested by the increase of structure content upon thermal melting. Consistent with IDPs serving as interaction platforms, PIN1 loops homodimerize. PIN1 HL cytoplasmic overexpression in Arabidopsis disrupts early endocytic trafficking of PIN1 and PIN2 and causes defects in the cotyledon vasculature formation. In summary, we demonstrate that PIN1 HL has an intrinsically disordered nature, which must be considered to gain further structural insights. Some secondary structures may form transiently during pairing with known and yet-to-be-discovered interactors.     

Ozonolysis of α-PINENE, β-PINENE,d- and l-Turpentine Oil Studied by Chirooptical Methods; Some Implications on the Atmospheric Chemistry of Biogenic Volatile Organic Compounds

The main constituents of biogenic volatile organic compounds (BVOC) released in the atmosphere from vegetation are terpenes. The most common terpenes are α-pinene and β-pinene. These molecules react with ozone, forming oxidized derivatives which have low vapor pressure and which nucleate into secondary organic aerosol (SOA). Such aerosol-forming reactions have been simulated in the gas phase on laboratory scale with the visualization of the formation of SOA. Electronic absorption spectroscopy shows that the UV peak of pinenes at 205 nm is shifted to 225 nm during and after ozonolysis and is accompanied by a series of spectral features in the near infrared region (between 850 nm and 1100 nm). Optical rotatory dispersion (ORD) spectra were recorded on pure β(+)pinene and β(?)pinene. After ozonolysis β-pinene enantiomers are converted into nopinone enantiomers. The ORD spectra of both (?)nopinone and (+)nopinone respectively were recorded. The former showed a peak at 453 nm, an inflection point at 430 nm and a trough at 405 nm. The ORD spectrum of (?)-nopinone appears completely symmetrical to that of (+)nopinone. Thus, ORD spectroscopy can distinguish between BVOC and oxidized BVOC quite easily at least in the case of β-pinene. The ORD spectra of α-pinene enantiomers are different from those of β-pinene enantiomers and although the ORD spectra of ozonized α-pinene are not easily distinguishable from those of the primary compounds, they are completely different from those of ozonized β-pinene enantiomers. A reasonable natural model of BVOC is offered by l- and d-turpentine oil whose composition reflects that of the BVOC from conifer forests. The ORD spectra of ozonized l- and d-turpentine has permitted to distinguish between the levorotatory and dextrorotatory oxidation products and showing the ketone peak at about 367–380 nm, thus permitting in a real model to distinguish between primary BVOC (turpentine) and oxidized BVOC (or SOA) corresponding to ozonized turpentine. It has been proposed that ORD spectra in the gas phase could be used to detect chiral BVOC and oxidized chiral BVOC.     

On the combinatorics of suffix arrays

We present a bijective characterization of suffix array permutations obtained from a characterization of Burrows–Wheeler arrays given in [1]. We show that previous characterizations [2], [3], [4], or their analogs, can be obtained in a simple and elegant way using this relationship. To demonstrate the usefulness of our approach, we obtain simpler proofs for some known enumeration results about suffix arrays [3]. Our characterization of suffix arrays is the first based on their relationship with Burrows–Wheeler permutations.     

Radiation-Induced Synthesis of Fullerene-Silica Hybrid Nanomaterials

C₆₀ fullerene has been radiation grafted on bare and functionalized silica surface with mercaptopropyl moieties in toluene solution. The resulting fullerene-silica hybrid nanomaterials have been characterized by FT-IR and solid state ¹³C CP-MAS NMR spectroscopy and compared to the radiolysis products of C₆₀ in toluene. It has been found that fullerene is grafted on silica surface but, because the radiation grafting has been conducted in toluene, fullerene results arylated from radicals derived from toluene radiolysis. The fullerene-silica hybrid nanomaterials cannot be extracted by warm decalin, demonstrating that the fullerene cage is chemically bonded on the silica surface. The thermal behavior of fullerene-silica hybrid nanomaterials has been studied by thermogravimetric analysis (TGA) and differential thermal analysis (DTA) in air flow.     

Nutritional evaluation of inter-esterified fats

Studies with inter-esterified fats prepared to maintain a high level of linoleic acid content have been undertaken in several series of experiments with rats. These fats are as digestible as the liquid nonhydrogenated oils and the biological value of the linoleic acid is not impaired by the inter-esterification. Investigations involving growth, reproduction and lactation, longevity, tissue cholesterol levels and histological tissue examination have revealed that these inter-esterified fats are utilized by the animal similarly to cottonseed oil. No tissue pathology or interferences with any of the nutritional indices are observed. When the inter-esterified fats are included in atherogenic diets, the atheroselerotic lesions which develop in the coronary arteries and aorta of the animals are similar to, but less marked than, those found when animals are fed cholesterol-containing diets with butter oil or conventional margarine oil of the all-hydrogenated type. It is concluded that these inter-esterified fats are at least nutritionally equal to other similar edible fats of equivalent essential fatty acid content.