Isolation and properties of a natural inhibitor of the chloroplast adenosine triphosphatase

The complete sequence of protein L17 which is a component of the large subunit of the E. coli ribosome has been determined. Peptides deriving from enzymatic hydrolysis with trypsin, thermolysin, chymotrypsin and S. aureus and A. mellea protease were isolated and sequenced by the DABITC/PITC double coupling method. Some overlapping peptides were obtained after mild acid cleavage of the protein. According to the amino acid sequence protein L17 contains 127 residues and has a molecular mass of 14 365. The primary structure of protein L17 agrees well with the amino acid analysis of the intact protein and its N-terminal sequence as derived from automatic sequencing in an improved Beckman sequencer. Secondary predictions and a search for homologous sequence stretches to other ribosomal proteins were made.     

Glycation as an atherogenic modification of LDL

PURPOSE OF REVIEW: To highlight the potential importance of glycation as an atherogenic modification of LDL in both diabetic and nondiabetic people. RECENT FINDINGS: Small dense LDL which is known to be most closely associated with atherogenesis is more susceptible to glycation than more buoyant LDL. Glycation and oxidation of LDL appear to be intimately associated. SUMMARY: Glycation of LDL occurs chiefly due to the nonenzymatic reaction of glucose and its metabolites with the free amino groups of lysine in which LDL is rich. Higher concentrations of glycated LDL are present in diabetic than in nondiabetic individuals, but even in the latter, there is generally more circulating glycated LDL than oxidatively modified LDL. Probably, oxidation and glycation of LDL are at least partially interdependent, but both prevent LDL receptor-mediated uptake and promote macrophage scavenger receptor uptake. The recognition that LDL glycation is at least as important as oxidation in atherogenesis may lead to improvements in our understanding of its mechanism and how to prevent it.     

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²–3×10⁻¹⁰), with heterogeneity detected only at the PSMB9/TAP1 locus (I² = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻⁴). A seven–SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²⁸). This model paralleled the known East–West gradient in disease risk. Moreover, the prediction of a South–North axis was confirmed by registry data showing that the prevalence of IgAN–attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.     

Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.     

Studies on the effect of certain enzymic poisons on the metabolism of storage organs IV. Respiration and nitrogen assimilation by radish root slices in relation to feeding with KCN

At low and high concentrations, respectively, KCN stimulatedand inhibited the CO₂ output of radish root slices. Analysisof tissue slices showed that CO₂ production is nearly accountedfor by the loss in carbohydrates. After 48 hr, the content ofprotein-N was slightly changed in all the cyanide-treated tissues;whereas, that of soluble-N decreased markedly at high cyanideconcentrations and hardly changed at low concentrations. Leakageof soluble-N occurred at high concentrations of cyanide. The nitrogen compounds taken up were incorporated into the nitrogenpool of radish slices. KCN retarded uptake of nitrogen compounds,inhibited their utilization and led to excessive leakage ofsoluble-N from the tissues into the media. Increased CO₂ outputof slices in nitrogen media was largely accounted for by theloss in carbohydrates from the tissues. High concentrations of cyanide are thought to inhibit CO₂ outputthrough inhibition of the oxidase system and accompanying phosphorylations.The present results with low concentrations further substantiatethe uncoupling theory as a main factor involved in respiration. ¹Permanent address: Department of Botany, Faculty of Science,University of A'in Shams, Abbassia, Cairo, Egypt, U.A.R. (Received October 3, 1969; )     

An Innovative Micro-Modelling of Simultaneous Heat and Moisture Transfer during Bread Baking Using the Lattice Boltzmann Method

A considerable fraction of the energy consumed in bread manufacturing is used for the baking process. A thorough understanding of internal moisture transfer mechanisms are important to optimise both the quality of the product and the economics of the process. From a transport phenomena point of view, bread baking has been considered as a simultaneous heat and mass transfer problem in a porous medium. Nevertheless, most efforts previously made have avoided modelling the phenomenon occurring in the microscale, although the mechanism occurs primarily in the microscale. In this work heat and moisture transfer models were developed to accomplish the mechanisms included, both in the microscale and the macroscale by means of Boltzmann’s equation. Modelling and predictions of moisture transfer, heat transfer, modelling of effective moisture diffusivity, thermal conductivity and diffusivity have been investigated in this work. The microstructure in the dough samples was obtained using micro-computer tomography images from the samples prior to baking. The models were quantified and validated with measurements from the literature in order to assess the predictive models. The simulated crust development has shown a crust thickness of 0.8 cm, which is slightly higher than similar experimental results in which a dehydrated thickness of 0.5–0.6 cm was reported. The crust over-estimation in this work fits to the overheating occurring in the model. Additionally, investigations were made on the influence of different porosities (11–16%) of the bread; the boundary layer temperature at a porosity of 11% was reached after 25 min and after 17.5 min at a porosity of 16%. Therewith, the results showed that, with increasing porosity, the heat transfer rate towards the centre was higher, which matches the knowledge of experienced bakers.     

Synthesis of 1′,2′-Seco-nucleoside Analogues of AZT

Abstract

1′,2′-Seco-AZT (3) and its 3′R,4′S diastereomer (19) were prepared and evaluated as antiviral agents. The chiral, acyclic side chains of these thymine acyclonuleosides were derived from D-isoascorbic acid. The two AZT analogues, 3 and 19, were screened against HIV, other RNA viruses, and two DNA viruses and they were found to be inactive.     

Influence of Different Intensities of Pesticide Management on the Structure of Ground Beetle Communities (Coleoptera; Carabidae) During a Crop Rotation

Investigations were lead through in the years 1992 to 1995 at Halle (Saale) on a stand 24ha in size. Aim of the survey was to record the effects of graduate intensities of pest management on ground beetles. For this purpose 6 plots were installed on the field, 72 ‐ 200m each. Two plots served as control areas, without any application of pesticides. On two other plots intensive chemical pest management was applied. On the last two plots treatments were lead through considering the economic thresholds for weeds, fungal and insect pests according to the rules of integrated pest management. Ground beetles were sampled by using pitfall traps. In 1992 complementary methods to the pitfall trap catches, pick up of beetles after pesticide applications and semi-field-tests, on all plots were lead through. The graduate pest management was carried out 1992 and 1993 in winter wheat and 1994 in sugar beet stands. The last crop in 1995 was summer barley. In this year all plots were treated conventionally. In 1992 the differences between the total catches of ground beetles on the experimental sites were not high. In the following year most species were predominant on the control sites. In 1994 in sugar beet mechanical weed control was carried out on the control plots. The intensity of pesticide management between intensive and integrated plots differs only small. The amounts of ground beetles reached similar values on all experimental sites. In contrast to the expections the trap catches of ground beetles in the final investigations in summer barley were highest in the plots which had been treated integrated in the years before. The smallest amount was sampled in the former intensively managed sites. Renunciation of pesticides often is connected with economic losses which are not tolerable. If management is conducted considering the economic thresholds corresponding to the principles of integrated pest management negative effects on the economy of nature should not be expected for the longer term.