Cuticle chirality and body handedness in Caenorhabditis elegans

BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate.     

Modelling the kinetics of antigen-antibody reactions at particle enhanced optical immunoassays

Functionalized latexes coated by antibodies are used in diagnostic tests for the detection of antigens in biological fluids. A simple kinetic model is presented which is related to the optical monitoring of the formation of specific complexes between antigen and antibody amplified by latex beads. The antibodies are chemically coupled onto chloromethylstyrene (CMST) particles. The kinetic model is able to describe the immunoprecipitin curves of immunolatex beads. The number of fitting parameters is relatively reduced (only three), and the meaning of these parameters can be interpreted in terms of the chemical equilibrium constant, the percentage of active IgG on the latex beads, and optical response. The model explains very well the optical response of immunolatex prepared by covalent coupling of antibodies on polymer carriers.     

Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease

The HIV-1 transframe region (TFR) is between the structural and functional domains of the Gag-Pol polyprotein, flanked by the nucleocapsid and the protease domains at its N and C termini, respectively. Transframe octapeptide (TFP) Phe-Leu-Arg-Glu-Asp-Leu-Ala-Phe, the N terminus of TFR, and its analogues are competitive inhibitors of the action of the mature HIV-1 protease. The smallest, most potent analogues are tripeptides: Glu-Asp-Leu and Glu-Asp-Phe with Ki values of approximately 50 and approximately 20 microM, respectively. Substitution of the acidic amino acids in the TFP by neutral amino acids and d or retro-d configurations of Glu-Asp-Leu results in an >40-fold increase in Ki. Protease inhibition by Glu-Asp-Leu is dependent on a protonated form of a group with a pKa of 3.8; unlike other inhibitors of HIV-1 protease which are highly hydrophobic, Glu-Asp-Leu is extremely soluble in water, and its binding affinity decreases with increasing NaCl concentration. However, Glu-Asp-Leu is a poor inhibitor (Ki approximately 7.5 mM) of the mammalian aspartic acid protease pepsin. X-ray crystallographic studies at pH 4.2 show that the interactions of Glu at P2 and Leu at P1 of Glu-Asp-Leu with residues of the active site of HIV-1 protease are similar to those of other product-enzyme complexes. It was not feasible to understand the interaction of intact TFP with HIV-1 protease under conditions of crystal growth due to its hydrolysis giving rise to two products. The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-1 replication.     

Putting occupation into practice: occupation as ends, occupation as means

We have investigated the effect of 5-HT2 receptor agonist or antagonist administration on postsynaptic 5-HT1A receptor sensitivity assessed by two behavioral measures, reciprocal forepaw treading or hypothermia induced by acute injection of the 5-HT1A receptor agonist 8-OH-DPAT. The effectiveness of these drug treatments to downregulate 5-HT2A receptors was confirmed by measuring the binding of [3H]-ketanserin in cortical homogenates, because all of these drug treatments have been shown to result in the downregulation of 5-HT2A receptor sites. Acute or chronic treatment of rats with the 5-HT2 receptor antagonist mianserin, or chronic administration of the 5-HT2A receptor antagonist ketanserin, did not alter 8-OH-DPAT-induced hypothermia or forepaw treading. These data indicate that downregulation of 5-HT2A receptors is not sufficient to alter these postsynaptic 5-HT1A receptor-mediated responses. Chronic treatment of rats with the 5-HT2 receptor agonist DOI, however, resulted in the attenuation of both 5-HT1A receptor-mediated responses measured in separate experimental groups. The apparent desensitization of 5-HT1A receptors following chronic DOI treatment was not accompanied by a change in either the number or affinity of 5-HT1A receptor sites as measured by the binding of [3H]-8-OH-DPAT in hippocampal homogenates. Chronic activation of 5-HT2 receptors may be one mechanism by which the sensitivity postsynaptic 5-HT1A receptors can be regulated.     

Geographic variations in the composition of ivory of the African elephant (Loxodonta africana)

OBJECTIVES: The purpose of the present study was to compare the inclination of the occlusal plane with occlusal guidance as a contributing factor to masticatory movement. METHODS: Masticatory movements of 41 young adults were measured using a 3-D mandibular movement analysing system. The inclination of the occlusal plane was measured in the sagittal plane using a 3-D digitizer. The contribution of the occlusal guidance and the inclination of the occlusal plane to the direction of the masticatory path of closure was evaluated at various closing levels. RESULTS: The masticatory path of closure outside the intercuspal range was influenced mainly by the inclination of the occlusal plane, and the masticatory path of closure near the intercuspal range was only influenced by occlusal guidance. The so-called gliding type masticatory pattern was observed predominantly in subjects with a posteriorly inclined occlusal plane. In contrast, a chopping type masticatory pattern was observed predominantly in subjects with an anteriorly inclined occlusal plane. CONCLUSIONS: The contribution of the inclination of the occlusal plane to masticatory movement was greater than that of occlusal guidance throughout the closing phase except near the intercuspal range.     

Mechanisms of insulin resistance in experimental hyperinsulinemic dogs

The aim of this work was to identify which proteins in horse dander extracts are allergens and to characterise them. Two-dimensional PAGE showed that horse dander preparations are composed of up to 50 proteins, all having acidic isoelectric points in the pH range 3-4.5. Immunoblots of two-dimensional PAGE were used to compare the reactivity of the proteins with IgE from 23 allergic patients. Patient sera were divided into two main groups recognising either allergens of 18.5 kDa or proteins of 27-29 and 31 kDa. The proteins of 27-29 kDa and 31 kDa were all N-glycosylated and their glycan chains seem to play a role in the binding of IgE from allergic patients. The sugar composition of their carbohydrate moiety was determined and lectin-binding experiments indicated presence of terminal sialic acid linked alpha-(2-->6) to galactose, galactose linked beta-(1-->4) to N-acetylglucosamine, and possibly presence of sialic acid linked alpha-(2-->3) to galactose. The 27-29-kDa glycoproteins had heterogeneous isoelectric points, most probably due to different degrees of sialylation in their oligosaccharide chains. The two 18.5-kDa allergens exhibited slightly different isoelectric points and their N-terminal sequences were identical, showing that they most likely were isoforms of the same protein. Sequence analyses revealed that their N-terminal sequences are similar to proteins belonging to the lipocalin family. We named the two 18.5-kDa proteins Equ c 2.0101 and Equ c 2.0102, according to International Allergen Nomenclature recommendations [King, T. P., Hoffman, D., Lowenstein, H., Marsh, D. G., Platts-Mills, T. A. E. & Thomas, W. (1995) J. Allergy Clin. Immunol. 96, 5-14]. The N-terminal of the allergens of 27-29 kDa were blocked and their sequences were not determined. Their amino acid compositions were determined and comparison with acidic mammalian proteins in the Swiss-Prot database revealed high scores with lipocalin proteins. This suggests that the glycosylated horse dander allergens belong to the lipocalin family, like Equ c 2.0101 and Equ c 2.0102.     

Evidence into practice. Prescribing selective serotonin reuptake inhibitors

Sex differences in rotational behavior have been most clearly established in laboratory rats with females exhibiting a turning bias. Here, using an automated open-field apparatus, locomotor activity and spontaneous rotational behavior were examined in diurnally crepuscularly active reproductive male and female meadow voles (Microtus pennsylvanicus). Meadow voles, being induced ovulators, permitted analysis of females in constant behavioral estrous. Males displayed significantly greater levels of activity and also significantly greater levels of clockwise but not counterclockwise rotational behavior relative to the females. Rotational behavior was less strongly related to activity levels in female as compared to male voles. In addition, females displayed an overall turning bias. These results contrast with findings from laboratory rats in which females are reported to display greater levels of both locomotor activity and rotational behavior. They are, however, consistent with the rotational bias evident in female rats. The present findings confirm the presence of sex differences in rotational behavior and indicate that factors other than activity levels are involved in the generation and/or expression of these sex differences. Sex differences in anxiety and routine-like behavior (i.e., asymmetry in movement) are discussed as possible factors contributing to these male-female differences in rotational behavior.     

Quantitative measurement of a new synthetic hetrazepine derivative, BN50730, in human plasma and urine by combined liquid chromatography-negative chemical ionization mass spectrometry using a particle beam interface

A new simple and sensitive assay has been developed for the quantitative measurement of BN50730 at the picomole level in human plasma and urine. The drug and the internal standard (BN50765) were measured by combined liquid chromatography-negative chemical ionization mass spectrometry with methane as the reagent gas. A simple solid-liquid extraction procedure was used to isolate BN50730 from complex biological matrices. Mild operating conditions were required to assay the parent drug with a particle beam interface from Hewlett-Packard. The mass spectrometer was tuned to monitor the intense ion m/z 333, which was generated in the ion source by a dissociative capture process. This assay was performed with 1 ml of plasma or 0.1 ml of urine, and the quantification limit of the method was statistically calculated as 1 ng ml-1. The very low relative standard deviation and mean percentage of error calculated during the different within-day or between-day repeatability assays clearly demonstrate the ruggedness of the technique for the routine determination of BN50730 in the biological fluids. Some preliminary results on the pharmacokinetics of the drug are presented to illustrate the applicability of this new powerful LC-MS method.     

Risk stratification using the Society of Thoracic Surgeons Program

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.