Common endocrine and genetic mechanisms of behavioral development in male and worker honey bees and the evolution of division of labor.

Temporal polyethism is a highly derived form of behavioral development displayed by social insects. Hormonal and genetic mechanisms regulating temporal polyethism in worker honey bees have been identified, but the evolution of these mechanisms is not well understood. We performed three experiments with male honey bees (drones) to investigate how mechanisms regulating temporal polyethism may have evolved because, relative to workers, drones display an intriguing combination of similarities and differences in behavioral development. We report that behavioral development in drones is regulated by mechanisms common to workers. In experiment 1, drones treated with the juvenile hormone (JH) analog methoprene started flying at significantly younger ages than did control drones, as is the case for workers. In experiment 2, there was an age-related increase in JH associated with the onset of drone flight, as in workers. In experiment 3, drones derived from workers with fast rates of behavioral development themselves started flying at younger ages than drones derived from workers with slower rates of behavioral development. These results suggest that endocrine and genetic mechanisms associated with temporal polyethism did not evolve strictly within the context of worker social behavior.

Impairment of Intrinsically Photosensitive Retinal Ganglion Cells Associated With Late Stages of Retinal Degeneration

Purpose. To evaluate quantitative and qualitative age-related changes in intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) in transgenic P23H rats, an animal model of autosomal dominant retinitis pigmentosa (RP) was examined. Methods. ipRGC density, morphology, and integrity were characterized by immunohistochemistry in retinas extracted from P23H and Sprague–Dawley (SD) rats aged 4, 12, and 18 months. Differences between SD and P23H rats throughout the experimental stages, as well as the interactions among them, were morphologically evaluated. Results. In rat retinas, we have identified ipRGCs with dendrites stratifying in either the outer margin (M1) or inner side (M2) of the inner plexiform layer, and in both the outer and inner plexuses (M3). A small group of M1 cells had their somas located in the inner nuclear layer (M1d). In SD rats, ipRGCs showed no significant changes associated with age, in terms of either mean cell density or the morphologic parameters analyzed. However, the mean density of ipRGCs in P23H rats fell by approximately 67% between 4 and 18 months of age. Moreover, ipRGCs in these animals showed a progressive age-dependent decrease in the dendritic area, the number of branch points and terminal neurite tips per cell, and the Sholl area. Conclusions. In the P23H rat model of retinitis pigmentosa, density, wholeness, and dendritic arborization of melanopsin-containing ganglion cells decrease in advanced stages of the degenerative disease.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects.

(Table 1) Organohalogen contaminants in adipose tissue of captive sledge dogs (Canis familiaris) fed with whale blubber or pork fat

Studies on the fate of organohalogen contaminants (OHCs) in wild top predator mammals in the Arctic have often been a challenge due to important knowledge deficiencies in the life history of the sampled animals. The present study investigated the influence of age, dietary and trans-generational factors on the fate of major lipophilic chlorinated and brominated OHCs in adipose tissue of a potential surrogate captive species for the polar bear (Ursus maritimus), the sledge dog (Canis familiaris) in West Greenland. Adult female sledge dogs (P) and their sexually-mature (F1) and/or pre-weaning pups (F1-MLK) were divided into an exposed group (EXP) fed blubber from a Greenland minke whale (Balaenoptera acutorostrata) and a control group (CON) given commercially available pork fat. Large dietary treatment-related differences in summed and individual congener/compound adipose tissue concentrations of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), chlordanes (CHLs) and polychlorinated biphenyls (PCBs) were found between the EXP and CON groups for all the sledge dog cohorts. However, among the F1-MLK, F1 and P dogs in both of the EXP and CON groups, little or no difference existed in PBDE, HCB, CHL and PCB concentrations, suggesting higher state of equilibrium in adipose tissue concentrations from a very early stage of life. In contrast, the distribution pattern (proportions to the summed concentrations) of OHC classes, and the major congeners/ compounds constituting those classes, varied on a dietary group- and/or cohort-dependent manner. The present captive sledge dog study demonstrated the importance of the confounding effects of diet composition, mother-pup association (maternal transfer), reproductive status (nursing), and to a lesser extent age in the fate of OHCs in adipose tissue of a large top carnivore mammal.

Role of oxidative stress in age-associated chronic kidney pathologies

The kidneys exhibit age-associated deterioration in function via a loss of 20% to 25% kidney mass, particularly from the renal cortex and increased fibrosis. Oxidative stress has been found to mediate age-associated renal cell injury and cell death, particularly apoptosis. Oxidative stress results from an imbalance between the levels of free radicals generated during aerobic metabolism, inflammation, and infection and the safe breakdown of these species by endogenous and exogenous scavengers. Other factors may influence these pathologies. For example, growth hormone and caloric restriction have been shown to influence life span, although neither method of prolonging life is likely to find general acceptance in humans. Some genetic knockout models offer promise; for example, knockout of the p66 isoform of the Shc gene in mice increases life span by 30%, but appetite, size, and fertility are retained. Whether the increase in life span is via increased kidney health is not yet clear, but decreasing the age-related renal pathologies will no doubt aid in increasing life span and health in general. This review looks at the role and modulation of factors that influence life span, in particular modulation of oxidative stress, with particular relevance to age-related renal pathologies. (C) 2005 by the National Kidney Foundation, Inc.

Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy

Aim Cardiovascular disease (CVD) rates are substantially higher among patients with Type 2 diabetes than in the general population. The objective of this study was to identify the determinants of carotid intima media thickness (IMT) in patients with Type 2 diabetes. Methods We measured the thickness of the intima media layer of the carotid artery, a strong predictor of the risk of future vascular events, in 397 Type 2 diabetic patients drawn from the Fenofibrate Intervention and Event Lowering in Diabetes study, prior to treatment allocation. Results The mean IMT was 0.78 mm [interquartile range (IQR) 0.23 mm], and the maximum IMT was 1.17 mm (IQR 0.36 mm). By multivariate analysis, age, sex, duration of diabetes, triglycerides, and total cholesterol were independently correlated with IMT, as was urine albumin-creatinine ratio (ACR) (P < 0.001). The effect of ACR on IMT was further examined by tertile. Clinically significant differences in IMT were associated with ACR > 0.65 mg/mmol, approximately one-fifth the standard clinical threshold for microalbuminuria (P < 0.01). Long-term diabetes, independent of other parameters, was associated with a 50% increase in age-related thickening. Conclusions IMT in people with Type 2 diabetes is independently and continuously related to urine albumin levels and to the duration of diabetes. These results support previous data linking urine albumin measurements within the normal range with increased ischaemic cardiac mortality in the setting of Type 2 diabetes, and strongly suggest that urine albumin levels within this range should trigger a formal evaluation for CVD.

Pharmacokinetic considerations relating to tacrolimus dosing in the elderly

Relaxation of the upper age limits for solid organ transplantation coupled with improvements in post-transplant survival have resulted in greater numbers of elderly patients receiving immunosuppressant drugs such as tacrolimus. Tacrolimus is a potent agent with a narrow therapeutic window and large inter- and intraindividual pharmacokinetic variability. Numerous physiological changes occur with aging that could potentially affect the pharmacokinetics of tacrolimus and, hence, patient dosage requirements. Tacrolimus is primarily metabolised by cytochrome P450 (CYP) 3A enzymes in the gut wall and liver. It is also a substrate for P-glycoprotein, which counter-transports diffused tacrolimus out of intestinal cells and back into the gut lumen. Age-associated alterations in CYP3A and P-glycoprotein expression and/or activity, along with liver mass and body composition changes, would be expected to affect the pharmacokinetics of tacrolimus in the elderly. However, interindividual variation in these processes may mask any changes caused by aging. More investigation is needed into the impact aging has on CYP and P-glycoprotein activity and expression. No single-dose, intense blood-sampling study has specifically compared the pharmacokinetics of tacrolimus across different patient age groups. However, five population pharmacokinetic studies, one in kidney, one in bone marrow and three in liver transplant recipients, have investigated age as a co-variate. None found a significant influence for age on tacrolimus bioavailability, volume of distribution or clearance. The number of elderly patients included in each study, however, was not documented and may have been only small. It is likely that inter- and intraindividual pharmacokinetic variability associated with tacrolimus increase in elderly populations. In addition to pharmacokinetic differences, donor organ viability, multiple co-morbidity, polypharmacy and immunological changes need to be considered when using tacrolimus in the elderly. Aging is associated with decreased immunoresponsiveness, a slower body repair process and increased drug adverse effects. Elderly liver and kidney transplant recipients are more likely to develop new-onset diabetes mellitus than younger patients. Elderly transplant recipients exhibit higher mortality from infectious and cardiovascular causes than younger patients but may be less likely to develop acute rejection. Elderly kidney recipients have a higher potential for chronic allograft nephropathy, and a single rejection episode can be more devastating. There is a paucity of information on optimal tacrolimus dosage and target trough concentration in the elderly. The therapeutic window for tacrolimus concentrations may be narrower. Further integrated pharmacokinetic-pharmaco-dynamic studies of tacrolimus are required. It would appear reasonable, based on current knowledge, to commence tacrolimus at similar doses as those used in younger patients. Maintenance dose requirements over the longer term may be lower in the elderly, but the increased variability in kinetics and the variety of factors that impact on dosage suggest that patient care needs to be based around more frequent monitoring in this age group.

Victim-perpetrator differences in reports of hurtful events

This research project addressed limitations identified in previous studies of role differences (victim vs. perpetrator) in evaluations of hurtful events. The study employed multiple methods (open-ended and structured retrospective reports and experience-sampling diary records), and involved a community sample of both dating and married couples. Retrospective reports indicated that the extent and direction of role-related differences varied markedly across dependent measures. Further, role differences were moderated by forgiveness, but not relationship status, relationship satisfaction, or event severity. Diary records pointed to the ambiguity inherent in many communication acts as contributing to differing perceptions of hurtful events. Results are discussed in terms of theories of interdependence and self-presentation and in terms of the complex and often ambiguous nature of couples' communication processes.

Searching for the trace: The influence of age, lexical activation and working memory on sentence processing

To investigate the stability of trace reactivation in healthy older adults, 22 older volunteers with no significant neurological history participated in a cross-modal priming task. Whilst both object relative center embedded (ORC) and object relative right branching (ORR) sentences is-ere employed, working memory load was reduced by limiting the number of wordy separating the antecedent front the gap for both sentence types. Analysis of the results did not reveal any significant trace reactivation for the ORC or ORR sentences. The results did reveal, however, a positive correlation between age and semantic printing at the pre-gap position and a negative correlation between age and semantic printing at the gap position for ORC sentences. In contrast, there was no correlation between age and priming effects for the ORR sentences. These results indicated that trace reactivation may be sensitive to a variety of age related factors, including lexical activation and working memory. The implications of these results for sentence processing in the older population arc discussed.

Dietary habits are major determinants of the plasma antioxidant status in healthy elderly subjects

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and α-carotene. Protein carbonyls were inversely correlated with γ-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life. © The Authors 2005.

New investigations into macular pigment optical density

Macular pigment (MP) is the collective name for three carotenoids, lutein, zeaxanthin and meso-zeaxanthin, which are found at high concentrations in the central macula. The macular carotenoids, like all carotenoids, are entirely of dietary origin. The term ‘macular pigment optical density’ (MPOD) refers to the peak concentration of MP in the retina, which varies from one individual to the next and is measurable in vivo. On account of its blue-light-filtering and antioxidant properties, MP has become a subject of interest with respect to age-related macular degeneration (AMD), the hypothesis being that MP helps to protect against AMD; the higher the MPOD, the lower the risk for AMD. Recently, a new MPOD-measuring device, the MPS 9000 (MPS), entered the ophthalmic market. Using this device, the research described here aimed to contribute new information to the MP literature. A second MPOD instrument, the Macular Pigment Reflectometer, was also used at times, but a reliability study (included in the thesis) demonstrated that it was unsuitable for use on its own. First, a series of exploratory investigations were undertaken to maximize the accuracy and consistency of MPOD measurements taken with the MPS; a protocol was established that substantially improved repeatability. Subsequently, a series of MPOD-based studies were conducted on anisometropia, South Asian race, blue-light-filtering contact lenses, and dietary modification with kale. The principle findings were as follows: interocular MPOD differences were not attributable to interocular refractive error differences; young adults of South Asian origin had significant gender-related MPOD differences (males>females, p<0.01), and they also had significantly higher MPOD than Caucasians (p<0.0005); wearing blue-light-filtering contact lenses for eight months did not affect MPOD; and dietary modification with kale for 16 weeks did not increase MPOD. This body of research adds new insights to MP knowledge, which in turn may contribute to MP knowledge in the context of AMD.

The effect of age, gender and driver status on pedestrians' intentions to cross the road in risky situations

The theory of planned behaviour (TPB) has been used successfully in the past to account for pedestrians' intentions to cross the road in risky situations. However, accident statistics show age and gender differences in the likelihood of adult pedestrian accidents. This study extends earlier work by examining the relative importance of the model components as predictors of intention to cross for four different adult age groups, men, women, drivers and nondrivers. The groups did not differ in the extent to which they differentiated between two situations of varying perceived risk. The model fit was good, but accounted for less of the variance in intention for the youngest group (17-24) than for other age groups. Differences between the age groups in intention to cross seemed to be due to differences in perceived value of crossing rather than differences in perceived risk. Women were less likely to intend to cross than men and perceived more risk, and there were important age, gender and driver status differences in the importance of the TPB variables as predictors of intention. A key implication of these findings is that road safety interventions need to be designed differently for different groups. © 2006 Elsevier Ltd. All rights reserved.

In vivo measurement of regional variation in anterior scleral resistance to Schiotz indentation

Purpose: Recent studies indicate that ocular and scleral rigidity is pertinent to our understanding of glaucoma, age related macular degeneration and the development and pathogenesis of myopia. The principal method of measuring ocular rigidity is by extrapolation of data from corneal indentation tonometry (Ko) using Friedenwald’s transformation algorithms. Using scleral indentation (Schiotz tonometry) we assess whether regional variations in resistance to indentation occur in vivo across the human anterior globe directly, with reference to the deflection of Schiotz scale readings. Methods: Data were collected from both eyes of 26 normal young adult subjects with a range of refractive error (mean spherical equivalent ± S.D. of -1.77 D ± 3.28 D, range -10.56 to +4.38 D). Schiotz tonometry (5.5 g & 7.5 g) was performed on the cornea and four scleral quadrants; supero-temporal (ST) and -nasal (SN), infero-temporal (IT) and -nasal (IN) approximately 8 mm posterior to the limbus. Results: Values of Ko (mm3)-1 were consistent with those previously reported (mean 0.0101 ± 0.0082, range 0.0019–0.0304). In regards to the sclera, significant differences (p < 0.001) were found across quadrants with indentation readings for both loads between means for the cornea and ST; ST and SN; ST and IT, ST and IN. Mean (±S.D.) scale readings for 5.5 g were: cornea 5.93 ± 1.14, ST 8.05 ± 1.58, IT 7.03 ± 1.86, SN 6.25 ± 1.10, IN 6.02 ± 1.49; and 7.5 g: cornea 9.26 ± 1.27, ST 11.56 ± 1.65, IT 10.31 ± 1.74, SN 9.91 ± 1.20, IN 9.50 ± 1.56. Conclusions: Significant regional variation was found in the resistance of the anterior sclera to indentation produced by the Schiotz tonometer.

The influence of patient and doctor gender on diagnosing coronary heart disease

Using novel methods, this paper explores sources of uncertainty and gender bias in primary care doctors' diagnostic decision-making about coronary heart disease (CHD). Claims about gendered consultation styles and quality of care are re-examined, along with the adequacy of CHD models for women. Randomly selected doctors in the UK and the US (n=112, 56 per country, stratified by gender) were shown standardised videotaped vignettes of actors portraying patients with CHD. Patients' age, gender, ethnicity and social class were varied systematically. During interviews, doctors gave free-recall accounts of their decision-making, which were analysed to determine patient and doctor gender effects. We found differences in male and female doctors' responses to different types of patient information. Female doctors recall more patient cues overall, particularly about history presentation, and particularly amongst women. Male doctors appear less affected by patient gender but both male and especially female doctors take more account of male patients' age, and consider more age-related disease possibilities for men than women. Findings highlight the need for better integration of knowledge about female presentations within accepted CHD risk models, and do not support the contention that women receive better-quality care from female doctors.

Beta-amyloid (beta/A4) deposition in the medial temporal lobe in Down's syndrome: effects of brain region and patient age

The density of diffuse, primitive, classic and compact beta-amyloid (beta/A4) deposits was studied in the medial temporal lobe in 12 cases of Down's syndrome (DS) from 38 to 67 years of age. Total beta/A4 deposit density was greater in the adjacent cortex compared with regions of the hippocampus, and these differences were similar within each age group of patients. The ratio of the primitive to diffuse deposits was greater in the hippocampus than in the adjacent cortex. Total beta/A4 density did not vary significantly with patient age. However, the density of the diffuse deposits exhibited a parabolic, and the primitive, classic and compact deposits an inverted parabolic, response with age. Hence, in DS, (1) beta/A4 density remains relatively constant with age, (2) differences in beta/A4 density between the hippocampus and adjacent cortex are established at an early age, and (3) mature beta/A4 subtype formation depends on brain region and patient age.