Characterization of the work-time relationship during cross-country ski ergometry.

The purpose of this study was to examine the validity and reliability of estimated parameters of the work-time relationship during cross-country ski ergometry using the traditional multi-trial critical power (CP) test and a 3 min 'all-out' test (3MT). Fourteen recreationally active male participants (mean ± SD; age: 22.14 ± 2.85 yrs; height: 177.09 ± 6.57 cm; weight: 85.68 ± 13.56 kg) completed three testing visits. All testing was conducted using an upper-body ergometer (SkiErg, Concept2, Inc., Morrisville, VT). A graded exercise test was used to determined maximal oxygen uptake (VO2peak). Two separate 3MT sessions were used to determine oxygen uptake (VO23MT), end-test power (EP), work above end-test power (WEP) and end stroke rate (ESR). Additionally, three time trials completed in a single day at simulated distances of 300 m, 650 m and 1000 m were used to estimate CP, W' and critical stroke rate (CSR). VO2peak (3.65 ± 0.50 l · min(-1)) and VO23MT (3.59 ± 0.4 l · min(-1)) were not significantly different (p = 0.162). Intraclass correlation coefficients for EP, WEP and ESR were 0.809, 0.611 and 0.783, respectively. EP (148 ± 33 W) and CP (157 ± 49 W), were not significantly different between the testing methodologies (p = 0.290) and were highly correlated (r = 0.780). WEP (8.4 ± 3.0 kJ) and W' (8.3 ± 3.0 kJ) were similar (p = 0.947) but not related (r = 0.119), while ESR (45 ± 7 spm) and CSR (47 ± 7 spm) values were not significantly different (p = 0.238) and moderately correlated (r = 0.498). The 3MT using ski ergometry was shown to produce concurrently valid results with the traditional multi-trial CP test for CP and CSR, but not W', and elicited similar maximal oxygen uptake values when compared to a graded exercise test.

Sex Ratio, Conflict Dynamics, and Wounding in Rhesus Macaques (Macaca mulatta).

Rhesus macaques, like many other primates, live in stable, multi-male multi-female groups in which adult females typically outnumber adult males. The number of males in multi-male/multi-female groups is most commonly discussed in terms of mate competition, where the sex ratio is a function of an adult male's ability to monopolize a group of females. However, the relationship between sex ratio and group stability is unclear because the presence of many males may either reduce stability by increasing mate competition or may improve stability if adult males are key conflict managers. We investigated the relationship between sex ratio, male intervention behavior, and trauma in seven groups of captive rhesus macaques. Our results show that high-ranking adult males intervene twice as frequently as adult females (P<0.0001) and are about twice as successful (P<0.0001). Furthermore, the type of adult males present in the group affects the relationship between intervention behavior and rate of traumas: males must be unrelated to the highest-ranking matrilines. Groups with a lower ratio of females per male unrelated to the alpha and beta matrilines had better intervention success (P<0.04) and fewer traumas requiring veterinary care (P=0.003). We conclude that conflict management behavior by adult males, particularly those unrelated to the highest-ranking matrilines, is the mechanism by which sex ratio influences the frequency of traumas, and thus group stability. We therefore suggest that monitoring and managing the sex ratio of captive primate groups is one of many measurements to predict group stability.

Effects of natal male alliances on aggression and power dynamics in rhesus macaques.

In the wild, male rhesus macaques disperse at sexual maturity. In captivity, however, males cannot disperse from their natal groups. Thus, the presence of natal males in captive rhesus social groups is unnatural and has the potential to negatively influence group dynamics and stability. A primary difference between natal males and non-natal (immigrant) males is that natal males have the opportunity to form long-term alliances with their maternal kin as well as nonkin. We investigated the factors associated with natal males' kin alliances and the impact of these alliances on measures of natal male behavior, group dynamics, and group stability. We found that natal males more frequently formed alliances with maternal kin when they were from high-ranking matrilines, had more siblings, and were younger. More frequent kin alliances were associated with more frequent use of intense aggression, higher individual rank, and higher degree of integration within the male displacement network. Thus, it seems that natal males use their alliances to be more active and influential in the social group, which may affect group stability. It appears that juvenile natal males from high-ranking matrilines, in particular, have the largest impact on group stability. Younger natal males from high-ranking matrilines formed alliances with kin more frequently and used intense aggression more frequently than older or lower ranking males. Furthermore, groups with a higher proportion of juvenile males from high-ranking matrilines also had higher rates of wounding. We suggest that the presence of natal males in rhesus groups may act in opposition to group stability.

A dose-response study with the feed enzyme beta-mannanase in broilers provided with corn-soybean meal based diets in the absence of antibiotic growth promoters.

An experiment was designed to assess the effects of graded levels of beta-mannanase on performance and body weight uniformity of male broilers provided with diets based on corn and soybean meal and devoid of antibiotic growth promoters or coccidiostats. Four dietary treatments contained 0, 50, 80, and 110 MU of Hemicell/ ton (where 1 MU = 10(6) enzyme activity units, 100 MU/ton is manufacturer's recommendation). Each treatment contained 15 pens with 40 birds/pen. Individual bird weights were determined on d 0, 21, and 42. From 21 to 42 d of age, feed intake for the 80 MU/ton treatment was significantly greater than the 50 MU/ton treatment. beta-Mannanase inclusion at 80 or 110 MU/ton induced improvements (P < 0.05) in weight gain (3.9 to 4.8%) and feed efficiency (3.5 to 3.8%) over the control, whereas inclusion of 50 MU/ton resulted in no significant benefit. There were no significant differences between 80 or 110 MU/ton. The experiment demonstrated that dietary inclusion of beta-mannanase at approximately 50 MU/ton is not sufficient for maximum response. Inclusion at 80 MU/ ton improved broiler gains and feed conversion and increasing to 110 MU/ton resulted in no significant additional response.

Beneficial effect of beta-mannanase feed enzyme on performance of chicks challenged with Eimerla sp. and Clostridium perfringens.

Two experiments were conducted to determine the effect of a beta-mannanase feed enzyme on the performance of broiler chicks subject to a necrotic enteritis disease challenge model involving oral inoculation of Eimeria sp. and Clostridium pefringens. Beta-mannanase is known to improve productive performance when added to poultry and swine diets. In both experiments, disease challenge in the absence of feed additives demonstrated significant reductions in performance as measured by weight gain, feed conversion, and the incidence of coccidial lesion scores. Significant mortality was also observed in challenged groups in Experiment 1. The disease challenge model was therefore judged as highly effective. Additions of a commonly used antibiotic, bacitracin methylene disalicilate (BMD), and coccidiostat, salinomycin, were highly effective in partially counteracting negative effects of the disease challenge. In both experiments, addition of beta-mannanase significantly improved performance and reduced lesion scores in disease-challenged groups. The degree of improvement was somewhat less than that afforded by a combination of BMD and salinomycin in Experiment 1 but was not different from that afforded by BMD alone in Experiment 2. We conclude that the beta-mannanase enzyme can play a role in circumstances where the use of antibiotics is not desired.

Analysis of the frequency response of the saccadic circuit: system behavior.

To more thoroughly describe the system dynamics for the saccadic circuit in monkeys, we have determined the frequency response by applying a frequency modulated train of microstimulation pulses in the superior colliculus. The resulting eye movements reflect the transfer function of the saccadic circuit. Below input modulations of 5 cycles/s, the saccadic circuit increasingly oscillates with multiple high-frequency, low-amplitude movements reminiscent of the "staircase saccades" evoked during the sustained step response. Between 5 and 20 cycles/s, the circuit entrains well to the input, exhibiting one saccadic response to each sinusoidal input. Within this range there are systematic frequency-dependent changes in movement amplitudes, including super-normal saccades at some input frequencies. Above 20 cycles/s, the saccadic circuit increasingly exhibits periodic failures at rates of 1:2 or higher. In addition, the circuit exhibits predictable amplitude-modulated interference patterns in response to a combined step and frequency-modulated input. These experimental results provide insight into several biological mechanisms and serve as benchmark tests of viable models of the saccadic system. The data are consistent with negative feedback models of the saccadic system that operate as a displacement controller and inconsistent with theories that put the superior colliculus within the lowest-order, local feedback loop. The data support theories that the circuit feedback operates with dynamics that simulate a "leaky integrator." In addition, the results demonstrate how the temporal output of the superior colliculus interacts with recurrent inhibition to influence the eye movement dynamics.

Stimulation of prefrontal cortex at physiologically relevant frequencies inhibits dopamine release in the nucleus accumbens.

The prefrontal cortex (PFC) is thought to provide an excitatory influence on the output of mesoaccumbens dopamine neurons. The evidence for this influence primarily arises from findings in the rat that chemical or high-intensity and high-frequency (60-200 Hz) electrical stimulations of PFC increase burst activity of midbrain dopamine neurons, and augment terminal release of dopamine in the nucleus accumbens. However, PFC neurons in animals that are engaged in PFC-dependent cognitive tasks increase their firing frequency from a baseline of 1-3 Hz to 7-10 Hz, suggesting that the commonly used high-frequency stimulation parameters of the PFC may not be relevant to the behavioral states that are associated with PFC activation. We investigated the influence of PFC activation at lower physiologically relevant frequencies on the release of dopamine in the nucleus accumbens. Using rapid (5-min) microdialysis measures of extracellular dopamine in the nucleus accumbens, we found that although PFC stimulation at 60 Hz produces the expected increases in accumbal dopamine release, the same amplitude of PFC stimulation at 10 Hz significantly decreased these levels. These results indicate that activation of PFC, at frequencies that are associated with increased cognitive demand on this region, inhibits the mesoaccumbens dopamine system.

Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex.

A dynamic interaction between the prefrontal cortex (PFC), amygdala, and nucleus accumbens (NAc) may be fundamental to regulation of goal-directed behavior by affective and cognitive processes. This study demonstrates that a mechanism for this triadic relationship is an inhibitory control by prefrontal cortex on accumbal dopamine release during amygdala activation. In freely moving rats, microstimulation of basolateral amygdala at intensities that produced mild behavioral activation produced an expected rapid increase in glutamate efflux in the prefrontal cortex and the nucleus accumbens shell region of the ventral striatum. However, during the stimulation, dopamine release increased only in the prefrontal cortex, not in the nucleus accumbens. An increase in accumbal dopamine release was observed during the stimulation if glutamate activation in the prefrontal cortex was inhibited at either presynaptic or postsynaptic levels. Some behaviors expressed during the stimulation were intensified in animals in which prefrontal cortex glutamate activation was blocked. In addition, these animals continued to express stimulus-induced behaviors after the termination of stimulation, whereas normal poststimulus behaviors such as ambulation and grooming were not displayed as frequently. Considering that dopamine neurotransmission in the nucleus accumbens is thought to play an integral role in goal-directed motor behavior, these findings suggest that the prefrontal cortex influences the behavioral impact of amygdala activation via a concomitant active suppression of accumbal dopamine release. Absence of this cortical influence appears to result in an aberrant pattern of behavioral expression in response to amygdala activation, including behavioral perseveration after stimulus termination.

Analysis of the frequency response of the saccadic circuit: numerical simulations.

Fundamental mechanisms of a brain circuit's operation can be revealed by quantitative analysis of the system's dynamic behavior. This approach is particularly useful for investigation of motor circuits, which generate machine-like outputs and where systems control techniques can be applied to reveal the circuit behavior outside the dynamic range of volitional activation. As an extension of our previous study of the step response of the saccadic motor system, this paper presents analytical and numerical considerations for the frequency response of the saccadic circuit-the system response to a steady-state sinusoidal input. Consideration of these responses provides mechanistic explanation for several aspects of the biological circuit and formalizes constraints for viable models of the saccadic circuit. Most importantly, these studies provide quantitative predictions for comparison with experimental data in vivo and make explicit hypotheses about biological mechanisms for experimental verification.

British Society for Immunology: vaccines and mucosal immunity.

The Annual Congress of the British Society for Immunology was well attended with over 1000 British scientists converging on the small Yorkshire town of Harrogate. Wide-ranging and varied, the topics covered included the biochemistry of signaling as well as sessions examining dietary influences upon mucosal immunity. The plenary session on the morning of Wednesday 6 December focused on immunology at the cell surface, where many speakers discussed the role of lipid rafts in immune cell signaling. A session of particular interest followed the plenary session, hosted by the Vaccine Immunology Group. Discussion centered around a number of novel vaccines currently under development, with the emphasis on finding alternatives to the use of hypodermic needles. A number of interesting posters affiliated to this session reflected the high quality of the research presented at the meeting in general.

Shared responsibility in home birth practice: collaborating with clients.

The home setting not only provides a special environment for birth and the practice of midwifery, but also has an impact on the processes used in clinical decision making. This article focuses on collaboration between the midwife and the birthing woman and also discusses the collaborative relationship between midwives and obstetric consultants. A home birth case study illustrates the interactions among the midwife, the woman, and the medical system. These critical relationships provide structure for safe, effective clinical practice in planned home birth when practice boundaries are not defined by institutional walls.

The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum.

To investigate the role of the KDEL receptor in the retrieval of protein toxins to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the KDEL receptor was confirmed by immunofluorescence. When such cells were challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 (SLT-1), there was no observable difference in their sensitivities as compared to cells which did not express these exogenous proteins. By contrast, the cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing lysozyme-KDEL, which causes a redistribution of the KDEL receptor from the Golgi complex to the ER, and cells are sensitised to this toxin when they express additional KDEL receptors. These data suggest that, in contrast to SLT-1, PE can exploit the KDEL receptor in order to reach the ER lumen where it is believed that membrane transfer to the cytosol occurs. This contention was confirmed by microinjecting into Vero cells antibodies raised against the cytoplasmically exposed tail of the KDEL receptor. Immunofluorescence confirmed that these antibodies prevented the retrograde transport of the KDEL receptor from the Golgi complex to the ER, and this in turn reduced the cytotoxicity of PE, but not that of SLT-1, to these cells.

Effects of beta-mannanase in corn-soybean meal diets on laying hen performance.

Recently, a patented enzyme product (beta-Mannanase, Hemicell) has been shown to improve feed conversion in corn-soybean diets fed to broilers and swine. The mechanism of beta-Mannanase is to degrade beta-mannan, which is an antinutritional factor existing in many legumes, including soybean and canola meals. The objective of this study was to determine whether or not performance can be improved by including beta-Mannanase in diets of commercial laying hens, 18 through 66 wk of age. A 2 x 2 x 2 factorial arrangement of treatments was employed. There were two energy sequences of 2,926-2,907-2,885 and 2,827-2,808-2,786 kcal ME/kg, which changed at 33 and 43 wk of age respectively; two dietary enzyme levels (0 and 110 units/g); and two Hy-Line strains (W36 and W77). Hen-day production, hen-housed production, BW, feed intake, mortality, egg weight, and specific gravity data were collected biweekly. Data were analyzed in four cycles (each with six 2-wk periods) and also for the whole experiment. beta-Mannanase increased egg weight from 51.4 to 51.7 g/egg (P < 0.05) in the first 12-wk cycle. This effect was consistent across energy levels. beta-Mannanase significantly improved hen-day and hen-housed production after the first cycle. Hen-day production of the beta-Mannanase group was 0.70, 1.07, and 1.5% greater than the control for cycles two, three, and four, respectively (P < 0.01). After 30 wk of age, average hen-day production of hens fed the low-energy diets with beta-Mannanase was similar or superior to that of hens fed the high-energy diets without the enzyme. The study indicates that beta-Mannanase is capable of increasing egg weight in commercial layers at early stages of production, and increasing egg production, particularly delaying the postpeak decline in productivity.

Numerical simulation of nonlinear feedback model of saccade generation circuit implemented in the LabView graphical programming language.

The object-oriented graphical programming language LabView was used to implement the numerical solution to a computational model of saccade generation in primates. The computational model simulates the activity and connectivity of anatomical strictures known to be involved in saccadic eye movements. The LabView program provides a graphical user interface to the model that makes it easy to observe and modify the behavior of each element of the model. Essential elements of the source code of the LabView program are presented and explained. A copy of the model is available for download from the internet.

Neural activity in SII modifies sensory evoked potentials in SI in awake rats.

The function of the projection from the secondary somatosensory cortex (SII) to the primary somatosensory cortex (SI) in rats was investigated by recording sensory evoked potentials (SEP) in SI during glutamate activation and lidocaine blockade of SII. In anesthetized animals, glutamate stimulation of SII decreased SEP latency and increased SEP amplitude, whereas no changes were evident during lidocaine blockade of SII. In awake animals, a second, later component of the SEP appeared. This second component was almost completely eliminated during lidocaine blockade of SII. We conclude that the projection from SII to SI in rats slightly facilitates the SEP response in anesthetized animals and is responsible for a major portion of the late component of the SEP in awake animals.

The BPV-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates transcription from the LCR of BPV-4.

Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of neoplasias of the upper alimentary canal of cattle. The flavonoid quercetin is one of the most potent and best characterised mutagens present in the fern. We have shown that transfection with BPV-4 DNA and exposure to a single dose of quercetin leads to tumorigenic transformation of primary bovine cells. We now show that quercetin induces cell cycle arrest and up-regulates transcription from the BPV-4 long control region (LCR). This up-regulation is mediated by a 21 nucleotide-long cis-element in the LCR, designated QRE-1, which is located immediately downstream of the TATA box. Cellular proteins bind to QRE-1 and removal or substitution of QRE-1 lead to the abrogation of the response to quercetin. As expression of the viral oncogenes is controlled by the LCR, perturbation in this control and increased oncoprotein expression are likely to contribute to fully malignant cell transformation by overcoming the cell cycle arrest induced by quercetin, thus forcing damaged cells to proliferate.

The impact of female caregivers' employment status on patterns of formal and informal eldercare.

This article uses data from the 1989 National Long-Term Care Survey and its companion Informal Caregivers Survey to investigate how the employment of female primary caregivers (FPCGs) affects hours of care received by disabled elderly care recipients (CRs). Multivariage analyses controlling for key FPCG and CR characteristics indicate that when FPCGs are employed they provide significantly fewer hours of care personally; however, their CRs also receive significantly more hours of help from other sources. When FPCGs work more than 17 hours per week, their CRs receive significantly fewer total weekly hours of care than would otherwise be the case.

The role of exogenous p53 and E6 oncoproteins in in vitro transformation by bovine papillomavirus type 4 (BPV-4): significance of the absence of an E6 ORF in the BPV-4 genome.

Bovine papillomavirus type 4 (BPV-4) does not possess an E6 ORF. The E6 oncoprotein of human papillomavirus (HPV) binds and degrades the tumour suppressor protein p53, thus contributing to tumour progression. Since BPV-4 lacks E6, it is unknown how the virus evades the tumour suppressor properties of p53 in the induction of tumours of the gastrointestinal tract. Mutations in the p53 gene have been detected both in papillomas and carcinomas, suggesting that p53 dysfunction plays a part in these neoplasias. BPV-4 can transform primary foetal bovine cells (PalFs) in cooperation with an activated ras gene, but the transformed cells are neither immortal nor tumorigenic. Co-transfection with the HPV-16 E6 (16E6) ORF confers immortality but not tumorigenicity. To investigate the role of p53 in BPV-4 cell transformation in vitro, we transfected PalFs and p53-null mouse fibroblasts with BPV-4 DNA in combinations with ras, 16E6 ORF and mutant (V143A) p53 cDNA. Transfection of PalFs with BPV-4 DNA, ras and mutant p53 led to cell immortalization, indicating that 16E6 and mutant p53 are functionally equivalent in conferring immortality. However, co-transfection of PalFs with BPV-4 DNA, ras, and both mutant p53 cDNA and 16E6 ORF resulted in cells which were fully transformed to tumorigenicity. In p53-null mouse fibroblasts, BPV-4 DNA induced transformation by itself, but the transformed cells were incapable of suspension growth. The co-transfection of BPV-4 DNA with 16E6 ORF produced many more transformed colonies and the cells were capable of growing in suspension. In this system, therefore, 16E6 confers anchorage-independence to BPV-4-transformed cells in a p53-independent fashion.

Risk of behavior problems among nursing home residents in the United States.

This study identified personal risk factors associated with behavior problems among nursing home residents using data based on a national survey of nursing home residents. Data are based on the Institutional Population Component of the 1987 National Medical Expenditure Survey and include nursing home residents living in licensed facilities on January 1, 1987. Multiple regression analyses were conducted to examine characteristics of residents that place them at risk of behavior problems. Independent variables include physical functioning, sensory impairment, cognitive impairment, psychiatric diagnoses, and demographics. Eleven behavior problems grouped into four categories based on factor analysis serve as dependent variables: wandering/safety, aggressive behaviors, collecting behaviors, and delusions/hallucinations. Risk factors emerging as predictors included sex (male), cognitive impairment, ADL dependency, incontinence, psychiatric history, receptive communication, walking, and difficulty seeing. Risk factors differ by type of behavior problem. Results suggest a multiple etiology in which biological, psychological, and sociocultural factors all play a role in generating behavior problems in the long-term care setting.

Evaluation of simplified compartmental models of reconstructed neocortical neurons for use in large-scale simulations of biological neural networks.

The electrotonic properties of the complex arborizations of neurons can be simulated by creating compartmental models based on the morphology of real neurons. These models can be very detailed with thousands of individual compartments and active channels. Large numbers of these models can be linked together into biologically realistic, large-scale neural networks with which to obtain a better understanding of the interactions among real neurons. However, the use of detailed compartmental models in such large networks is hindered by long computation times. Methods exist to reduce the complex morphology of detailed compartmental models to simpler reconstructions that retain many of the electrotonic properties of the original model yet are computationally efficient. However, little work exists that evaluates the limitations and performance of such reduced models with realistic active conductances modeled in both the soma and the dendrites to ensure that they are appropriate for use in biologically realistic network models. We have created detailed and reduced models of reconstructed dye-filled neurons from rat somatosensory neocortex and evaluated the ability of the reduced models to faithfully reproduce the input-output functions of the more detailed models. We find that the reduced models are not capable of perfectly reproducing the exact output of the detailed models using identical parameters. However, if the parameters are adjusted the reduced models are certainly capable of providing input-output patterns that are well within an acceptable range of known neural activity. The limitations and the benefits of such models are discussed.