Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Frontolimbic Response to Negative Feedback in Clinical Depression.

Functional neuroimaging suggests that limbic regions of the medial frontal cortex may be abnormally active in individuals with depression. These regions, including the anterior cingulate cortex, are engaged in both action regulation, such as monitoring errors and conflict, and affect regulation, such as responding to pain. The authors examined whether clinically depressed subjects would show abnormal sensitivity of frontolimbic networks as they evaluated negative feedback. Depressed subjects and matched control subjects performed a video game in the laboratory as a 256-channel EEG was recorded. Speed of performance on each trial was graded with a feedback signal of A, C, or F. By 350 ms after the feedback signal, depressed subjects showed a larger medial frontal negativity for all feedback compared with control subjects with a particularly striking response to the F grade. This response was strongest for moderately depressed subjects and was attenuated for subjects who were more severely depressed. Localization analyses suggested that negative feedback engaged sources in the anterior cingulate and insular cortices. These results suggest that moderate depression may sensitize limbic networks to respond strongly to aversive events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Results from the monitoring of pesticide residues in fruit and vegetables on the Danish market, 2000-01

To check compliance with the maximum residue levels in foods and to monitor the residue levels to enable an evaluation of the exposure of the Danish population to pesticides, a monitoring programme for pesticides residues in fruit and vegetables was performed. Sampling plans were designed based on previous findings and on consumption data. Samples (n = 4404) of mainly fresh conventionally and organically grown fruit and vegetables were collected at wholesalers and importers and at food processing companies. Of the samples, 3% were frozen products and 5% organically grown. Of the samples, 34% were of Danish origin, with 66% from other countries. Two accredited laboratories performed analyses of the samples using capillary gas chromatography, liquid chromatography and a spectrophotometric method. Reporting levels were set at the lowest calibration level or at the limit of determination. Residues were found in 60% of the samples of fruit but in only 18% of the vegetable samples. Residues above the maximum residue levels were found in 6% of all samples of fruit and in 2% of the vegetable samples.     

Safety evaluation of substances consumed as technical ingredients (food additives)

The different types of acceptable daily intakes (ADIs) are described as used by the FAO/WHO Expert Committee on Food Additives (JECFA) and the EEC Scientific Committee for Food (SCF). The allocation is discussed of a full ADI or a temporary ADI, and examples are given for the establishment (or withdrawal) of these ADIs. The flavours cinnamyl anthranillate and the solvent 2-nitropropane (both withdrawn), the sweeteners cyclamate and saccharin and the antioxidant BHA (all three changed) but not abolished. For BHA and saccharin the ADI was retained by both committees in spite of some evidence of carcinogenicity to experimental animals. ADI--'not specified' is specially discussed and it is recommended that numerical ADIs are used whenever possible. With an ADI--'not specified' it should be stated which use (and intake) levels are toxicologically acceptable. Some compounds evaluated by the two committees are discussed, e.g. the colours: Allura red AC, erythrosine, canthaxanthin and the caramels; three anti-oxidants: BHA, BHT and the gallates; the sweeteners: polyols, aspartame, saccharin and cyclamates. Four recommendations are made: (1) a numerical basis be given for the levels allocated an ADI--'not specified' or 'acceptable'; (2) lowering of the conventional safety factor be considered when the effects found are trivial--higher safety factors be considered when the toxic effects are serious or even irreversible; (3) ADIs should, whenever possible, be based on a combination of human and animal data; (4) ADIs might be allocated to compounds indicating animal carcinogenicity, if the compound is non-genotoxic, the mechanism clearly secondary and/or species-specific.     

A Bethe theory for the directional dependence of stopping by molecules

We derive a Bethe formula for the stopping of swift ions by target molecules oriented with respect to the beam. The theory is characterized by a directional mean excitation energy formed from transition energies and dipole matrix elements. The expression for the mean excitation energy is similar to the one for an isotropic sample but the dipole matrix elements corresponding to the various transition moment directions carry unequal weights which depend on the orientation of the molecule with respect to the beam. For a large class of molecules, the logarithm of the mean excitation energy is linear in sin² θ, where θ denotes the angle between the beam and the principal molecular axis. We illustrate the properties of the theory in the simple case of a diatomic molecule.     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.     

Group codes on certain algebraic curves with many rational points

We construct a series of algebraic geometric codes using a class of curves which have many rational points. We obtain codes of lengthq ² over _q , whereq = 2q ₀ ² andq ₀ = 2 ⁿ , such that dimension + minimal distance q ² + 1 – q ₀ (q – 1). The codes are ideals in the group algebra _q [S], whereS is a Sylow-2-subgroup of orderq ² of the Suzuki-group of orderq ² (q ² + 1)(q – 1). The curves used for construction have in relation to their genera the maximal number of GF _q -rational points. This maximal number is determined by the explicit formulas of Weil and is effectively smaller than the Hasse—Weil bound.Supported by Deutsche Forschungsgemeinschaft while visiting Essen University