Fusion of interleukin-2 to subunit antigens increase their antigenicity in vitro due to an interleukin-2 receptor beta-mediated antigen uptake mechanism

Subunit vaccines, based on one or more epitopes, offer advantages over whole vaccines in terms of safety but are less antigenic. We investigated whether fusion of the cytokine interleukin-2 (IL-2) to influenza-derived subunit antigens could increase their antigenicity. The fusion of IL-2 to the subunit antigens increased their antigenicity in vitro. Encapsulation of the subunit antigen in liposomes also increased its antigenicity in vitro, yet encapsulation of the subunit IL-2 fusion did not. The use of anti-IL-2 receptor beta (IL-2Rbeta) antibody to block the receptor subunit on macrophages suggested that the adjuvancy exerted by IL-2 in our in vitro system is due to, at least in part, a previously unreported IL-2Rbeta-mediated antigen uptake mechanism.

Nonbreeding Eastern Curlews Numenius madagascariensis Do Not Increase the Rate of Intake or Digestive Efficiency before Long-Distance Migration because of an Apparent Digestive Constraint

The possibility of premigratory modulation in gastric digestive performance was investigated in a long-distance migrant, the eastern curlew (Numenius madagascariensis), in eastern Australia. The rate of intake in the curlews was limited by the rate of digestion but not by food availability. It was hypothesized that before migration, eastern curlews would meet the increased energy demand by increasing energy consumption. It was predicted that (1) an increase in the rate of intake and the corresponding rate of gastric throughput would occur or (2) the gastric digestive efficiency would increase between the mid-nonbreeding and premigratory periods. Neither crude intake rate (the rate of intake calculated including inactive pauses; 0.22 g DM [grams dry mass] or 3.09 kJ min(-1)) nor the rate of gastric throughput (0.15 g DM or 2.85 kJ min(-1)) changed over time. Gastric digestive efficiency did not improve between the periods (91%) nor did the estimated overall energy assimilation efficiency (63% and 58%, respectively). It was concluded that the crustacean-dominated diet of the birds is processed at its highest rate and efficiency throughout a season. It appears that without a qualitative shift in diet, no increase in intake rate is possible. Accepting these findings at their face value poses the question of how and over what time period the eastern curlews store the nutrients necessary for the ensuing long, northward nonstop flight.

Neurally-mediated increase in calcineurin activity regulates cardiac contractile function in absence of hypertrophy

Objective: The calcineurin pathway has been involved in the development of cardiac hypertrophy, yet it remains unknown whether calcineurin activity can be regulated in myocardium independently from hypertrophy and cardiac load. Methods: To test that hypothesis, we measured calcineurin activity in a rat model of infrarenal aortic constriction (IR), which affects neurohormonal pathways without increasing cardiac afterload. Results: In this model, there was no change in arterial pressure over the 4-week experimental period, and the left ventricle/body weight ratio did not increase. At 2 weeks after IR, calcineurin activity was increased 1.8-fold (P

Using identity-by-de scent information in affected sib pairs to increase the efficiency of genetic association studies

T he aim of this study was to determine whether identity-by-descent (IBD) information for affected sib pairs (ASPs) can be used to select a sample of cases for a genetic case-control study which will provide more power for detecting association with loci in a known linkage region. By modeling the expected frequency of the disease allele in ASPs showing IBD sharing of 0, 1, or 2 alleles, and considering additive, recessive, and dominant disease models, we show that cases selected from IBD 2 families are best for this purpose, followed by those selected from IBD 1 families; least useful are cases selected from IBD 0 families.

Is quantitative interpretation likely to increase sensitivity of dobutamine stress echocardiography? A study of false-negative results

Background: False-negative interpretations of do-butamine stress echocardiography (DSE) may be associated with reduced wall stress. using measurements of contraction, we sought whether these segments were actually ischemic but unrecognized or showed normal contraction. Methods. We studied 48 patients (29 men; mean age 60 +/- 10 years) with normal regional function on the basis of standard qualitative interpretation of DSE. At coronary angiography within. 6 months of DSE, 32 were identified as having true-negative and 16 as having false-negative results of DSE. Three apical views were used to measure regional function with color Doppler tissue, integrated backscatter, and strain rate imaging. Cyclic variation of integrated backscatter was measured in 16 segments, and strain rate and peak systolic strain was calculated in 6 walls at rest and peak stress. Results. Segments with false-negative results of DSE were divided into 2 groups with and without low wall stress according to previously published cut-off values. Age, sex, left ventricular mass, left ventricular geometric pattern, and peak workload were not significantly different between patients with true and false-negative results of DSE. Importantly, no significant differences in cyclic variation and strain parameters at rest and peak stress were found among segments with true-and false-negative results of DSE with and without low wall stress. Stenosis severity had no influence on cyclic variation and strain parameters at peak stress. Conclusions: False-negative results of DSE reflect lack of ischemia rather than underinterpretation of regional left ventricular function. Quantitative markers are unlikely to increase the sensitivity of DSE.

Costs increase as ritualized fighting progresses within and between phases in the sierra dome spider, Neriene litigiosa

Magnitudes and patterns of energy expenditure in animal contests are seldom measured, but can be critical for predicting contest dynamics and understanding the evolution of ritualized fighting behaviour. In the sierra dome spider, males compete for sexual access to females and their webs. They show three distinct phases of fighting behaviour, escalating from ritualized noncontact display (phase 1) to cooperative wrestling (phase 2), and finally to unritualized, potentially fatal fighting (phase 3). Using CO2 respirometry, we estimated energetic costs of male-male combat in terms of mean and maximum metabolic rates and the rate of increase in energy expenditure. We also investigated the energetic consequences of age and body mass, and compared fighting metabolism to metabolism during courtship. All three phases involved mean energy expenditures well above resting metabolic rate (3.5 X, 7.4 X and 11.5 X). Both mean and maximum energy expenditure became substantially greater as fights escalated through successive phases. The rates of increase in energy use during phases 2 and 3 were much higher than in phase 1. In addition, age and body mass affected contest energetics. These results are consistent with a basic prediction of evolutionarily stable strategy contest models, that sequences of agonistic behaviours should be organized into phases of escalating energetic costs. Finally, higher energetic costs of escalated fighting compared to courtship provide a rationale for first-male sperm precedence in this spider species. (C) 2004 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Cutaneous stimulation from patella tape causes a differential increase in vasti muscle activity in people with patellofemoral pain

Patella taping reduces pain ill individuals with patellofemoral pain (PFP), although the mechanism remains unclear. One possibility is that patella taping modifies vasti muscle activity via stimulation of cutaneous afferents. The aim of this study was to investigate the effect of stretching the skin over the patella on vasti Muscle activity in people with PFP. Electromyographic activity (EMG) of individual motor units in vastus medialis obliquus (VMO) was recorded via a needle electrode and from Surface electrodes placed over VMO and vastus lateralis (VL). A tape was applied to the skin directly over the patella and stretch was applied via the tape in three directions, while subjects maintained a gentle isometric knee extension effort at constant force. Recordings were made from five separate motor units in each direction. Stretch applied to the skin over the patella increased VMO surface EMG and was greatest with lateral stretch. There was no change in VL surface EMG activity. While there was no net increase in motor unit firing rate, it was increased in the majority of motor units during lateral stretch. Application of stretch to the skin over VMO via the tape can increase VMO activity, suggesting that cutaneous stimulation may be one mechanism by which patella taping produces a clinical effect. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Is the increase in coronary events on Mondays an artifact?

Background: The aim of this article was to investigate the size and possible causes of the reported excess in coronary events on Mondays. Methods: We conducted a metaanalysis of data from the World Health Organization (WHO) MONICA Project, which monitored trends and determinants in cardiovascular disease. The MONICA Project was undertaken in 21 countries from 1980 to 1995. Results: We found a small overall excess rate of coronary events on Mondays. In a population experiencing 100 events per week, we estimate there would be approximately I more event on Monday than on any other day. Hierarchical logistic regression showed that the Monday excess was greater in centers with less thorough data collection procedures. Conclusions: The excess of coronary events on Mondays is probably an artifact resulting from events with uncertain dates being coded as taking place on Mondays.

An orthodontic information package designed to increase patient awareness

BACKGROUND: Most patients and their parents experience difficulty in fully appreciating the implications and demands of orthodontic treatment. This is largely because of inadequate understanding of the process of treatment or the commitment required. OBJECTIVES: To determine if a specifically developed video information package could significantly increase patient awareness of the implications of a full course of orthodontic treatment. Changes in attitude to orthodontic treatment after viewing the package were also measured. METHODS: Year 7 (12 year-old) students in two primary schools in the City of Gold Coast, Australia were randomly allocated to either a study group or a control group. Knowledge of and attitude to orthodontic treatment were measured with self-administered questionnaires before and after viewing the information package. RESULTS: The intervention group showed a 15 per cent gain in knowledge (p < 0.001). There was no gain in knowledge for the 45 students in the control group. There was no measured change in perception of need for orthodontic treatment in the study group. There was, however, an increase in potential compliance and positive attitude to the appearance of orthodontic appliances. There was a small increase in willingness to undertake treatment, but this was not statistically significant. CONCLUSIONS: The information package developed for this study increased awareness of the implications and practical difficulties which may be encountered during a course of orthodontic treatment, and produced some changes in attitude to treatment.

Increase of a Caribbean leatherback turtle Dermochelys coriacea nesting population linked to long-term nest protection

The leatherback turtle Dermochelys coriacea is considered to be at serious risk of global extinction, despite ongoing conservation efforts. Intensive long-term monitoring of a leatherback nesting population on Sandy Point (St. Croix, US Virgin Islands) offers a unique opportunity to quantify basic population parameters and evaluate effectiveness of nesting beach conservation practices. We report a significant increase in the number of females nesting annually from ca. 18-30 in the 1980s to 186 in 2001, with a corresponding increase in annual hatchling production from ca. 2000 to over 49,000. We then analyzed resighting data from 1991 to 2001 with an open robust-design capture-mark-recapture model to estimate annual nester survival and adult abundance for this population. The expected annual survival probability was estimated at ca. 0.893 (95% CL 0.87-0.92) and the population was estimated to be increasing ca. 13% pa since the early 1990s. Taken together with DNA fingerprinting that identify mother-daughter relations, our findings suggest that the increase in the size of the nesting population since 1991 was probably due to an aggressive program of beach protection and egg relocation initiated more than 20 years ago. Beach protection and egg relocation provide a simple and effective conservation strategy for this Northern Caribbean nesting population as long as adult survival at sea remains relatively high. (c) 2005 Elsevier Ltd. All rights reserved.

Was an increase in cocaine use among injecting drug users in New South Wales, Australia, accompanied by an increase in violent crime?

Background: A sharp reduction in heroin supply in Australia in 2001 was followed by a large but transient increase in cocaine use among injecting drug users (IDU) in Sydney. This paper assesses whether the increase in cocaine use among IDU was accompanied by increased rates of violent crime as occurred in the United States in the 1980s. Specifically, the paper aims to examine the impact of increased cocaine use among Sydney IDU upon police incidents of robbery with a weapon, assault and homicide. Methods: Data on cocaine use among IDU was obtained from the Illicit Drug Reporting System (IDRS). Monthly NSW Police incident data on arrests for cocaine possession/ use, robbery offences, homicides, and assaults, were obtained from the Bureau of Crime Statistics and Research. Time series analysis was conducted on the police data series where possible. Semi-structured interviews were conducted with representatives from law enforcement and health agencies about the impacts of cocaine use on crime and policing. Results: There was a significant increase in cocaine use and cocaine possession offences in the months immediately following the reduction in heroin supply. There was also a significant increase in incidents of robbery where weapons were involved. There were no increases in offences involving firearms, homicides or reported assaults. Conclusion: The increased use of cocaine among injecting drug users following the heroin shortage led to increases in violent crime. Other States and territories that also experienced a heroin shortage but did not show any increases in cocaine use did not report any increase in violent crimes. The violent crimes committed did not involve guns, most likely because of its stringent gun laws, in contrast to the experience of American cities that have experienced high rates of cocaine use and violent crime.

Acute exposure to cyclosporine does not increase plasma homocysteine in rats

There is interest in the postulate that cyclosporine a (CsA) contributes to the elevated homocysteine levels seen in organ transplant recipients, as hyperhomocysteinemia is now considered an independent risk factor for cardiovascular disease (CVD) and may partially explain the increased prevalence of CVD in this population. The main purpose of this investigation was to determine the effect of CsA administration on plasma homocysteine. Eighteen female Sprague Dawley rats (4 months old) were randomly assigned to either a treatment or a control group. For 18 days the treatment group received of CsA (25 mg/kg/d) while the control group received the same volume of the vehicle. Blood samples obtained following sacrifice to measure CsA, total homocysteine, and plasma creatinine. There were no significant differences in plasma homocysteine (mean values SD: treatment = 4.79 +/- 0.63 mu mol/L, control = 4.46 +/- 0.75 mu mol/L; P = .37). Homocysteine was not significantly correlated with final CsA concentrations (r = .17; P = .69). There was a significant difference in plasma creatinine values between the two groups (treatment = 60.44 +/- 7.68 mu mol/L, control = 46.33 +/- 1.66 mu mol/L; P < .001). Furthermore, plasma homocysteine and creatinine were positively correlated with the treatment group (r = .73; P < .05) but not the controls (r = -.10; P = .81). In conclusion, CsA does not influence plasma homocysteine concentrations in rats.

Potential to increase yield in lucerne (Medicago sativa subsp sativa) through introgression of Medicago sativa subsp falcata into Australian adapted material

The effect of interspecific heterosis in crosses between Medicago sativa subsp. sativa and M. sativa subsp. falcata was assessed. Three sativa and 3 falcata plants were crossed in a diallel design. Progeny dry matter yield and natural plant height were assessed in a replicated field experiment at Gatton, Queensland. Yield data were analysed using the method of residual maximum likelihood (REML) and Griffing's model 1. There were significant differences between the reciprocal, general combining ability (GCA), and specific combining ability (SCA) effects. As expected, S-1 populations were lower yielding than their respective intraspecific cross and falcata x falcata crosses were significantly lower yielding than sativa x sativa crosses. Some of the interspecific crosses indicated substantial SCA effects, yielding at least as well as the best sativa x sativa crosses. We have demonstrated the potential usefulness of unselected M. sativa subsp. falcata as a heterotic group in the improvement of yield in northern Australian adapted lucerne material, and discuss how it could be incorporated into future breeding to overcome the yield stagnation currently being experienced in Australian programs.