Atypical experiences of captive chimpanzees (Pan troglodytes) are associated with higher hair cortisol concentrations as adults.

Experiences during early development are influential on the lives of human and non-human primates into adulthood. The population of captive chimpanzees in the USA can provide insight into this relationship, as collectively they have experienced a wide range of exposure to both conspecifics (those raised in natal groups) and humans (those raised as personal pets or performers). Our study investigated chimpanzee exposure to humans using a continuous measure of categorization, the chimpanzee-human interaction index, and the relationship between this experience and cortisol concentrations in adulthood. Historical records and hair samples were collected from 60 chimpanzees which were socially housed in 13 zoos and sanctuaries. We found that more human exposure throughout the life of a chimpanzee was associated with higher hair cortisol concentrations in adulthood. Sex was also a significant factor affecting cortisol concentration, with male chimpanzees having higher cortisol concentrations than female chimpanzees. These results build upon the extensive literature about aversive effects of atypical social histories for chimpanzees and emphasize to managers the importance of monitoring potential negative health consequences and social deficits these individuals may exhibit.

Space use selectivity by chimpanzees and gorillas in an indoor-outdoor enclosure.

Understanding the relationship between physical environments and nonhuman primate behavior is a key element for effective care and management in a range of settings. The physical features of the captive environment, including not only gross useable space but also environmental complexity, can have a significant influence on primate behavior and ultimately, animal welfare. But despite this connection, there remains relatively little conclusive data on how captive primates, especially great apes, use the spaces provided to them, especially in modern, indoor-outdoor enclosures that have become more prevalent in recent years. In this study, we used four years of detailed data on where 23 great apes (chimpanzees and gorillas) positioned themselves within a modern, indoor-outdoor zoo enclosure to determine not only how the apes utilized their space but also how access to outdoor areas affected their spatial selectivity. We found that both species used relatively little of their available space: chimpanzees and gorillas spent half their time in only 3.2 and 1.5% of their useable three-dimensional space, respectively. Chimpanzees utilized the outdoor space more than gorillas, but access to the outdoors did not affect space selectivity in the indoor area for either species. Although both species of ape were highly selective in their space use, consideration should be given to the importance of providing the choice to locate in a variety of spaces, including outdoor areas. These data represent an extremely detailed account of space selectivity by great apes in an indoor-outdoor environment and have substantial implications for future facility design and captive primate management.

Impact of immunosuppressive therapy on hepatitis C infection after renal transplantation.

BACKGROUND: Among patients after renal transplantation (NTx), hepatitis C virus (HCV) infection is a risk factor for graft loss and patient death caused by hepatic decompensation. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. Therefore, the aim of this retrospective cohort study was to determine the effects of the widely used calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus (Tac) on hepatitis C virus replication, inflammatory activity, development of liver fibrosis, and long-term renal graft function. SUBJECTS AND METHODS: A cohort of 71 patients with HCV infection after kidney transplantation under immunosuppression with either CsA or Tac were analyzed for viral kinetics and serum transaminases. In addition, presence of liver fibrosis was detected by non-invasive measurements using the FibroScan. Graft function was determined biochemically. Patients with interferon therapy prior to transplantation were excluded from the study in order to avoid any impact of the antiviral therapy on outcomes. RESULTS: In the early period after transplantation, hepatitis C viral load was lower in patients treated with Tac as compared to CsA. This effect became negligible 3 months after transplantation. However, hepatic inflammatory activity was reduced in the CsA-treated group. Extent of liver fibrosis was similar in both groups of HCV-infected patients as well as in a control group of non-HCV-infected patients after renal transplantation (NTx), respectively. Renal function and glomerular filtration rate, as calculated by the modification of diet in renal disease (MDRD) formula, were significantly better in patients treated with Tac. CONCLUSIONS: During long-term immunosuppression, the CNIs cyclosporine A versus tacrolimus showed no significant differences in HCV-infected patients after renal transplantation with respect to viral replication and development of liver fibrosis. However, function of the renal graft is significantly better preserved in patients receiving tacrolimus.

Preliminary assessment of methods used to demonstrate nut-cracking behavior to five captive chimpanzees (Pan troglodytes).

Chimpanzees acquire nut-cracking skills by observation and trial and error. Studies of captive chimpanzees have shown the effectiveness of a skilled demonstrator. We examined the effectiveness of 3 live demonstration forms from which subjects could learn nut-cracking skills: a video of proficient conspecifics, human demonstration and the presence of a skilled conspecific performing the task. A male subject did not learn to crack open nuts after viewing a video of proficient conspecifics but quickly learned the skill following a demonstration by a human facilitator. Subsequently, 4 female chimpanzees were given the opportunity to learn the skill from the now proficient male, as well as from a video and human demonstration, but failed to do so.

Ape behavior in two alternating environments: comparing exhibit and short-term holding areas.

In many facilities, primates are voluntarily transferred between different enclosures on a daily basis to facilitate animal husbandry and exhibit maintenance. This procedure is particularly relevant in the management of great apes living in zoos, where the requirements of functional management must be balanced with the desire to maintain enriching and naturalistic exhibit enclosures that benefit ape residents and attract the visiting public. In these settings, examinations of ape behavior and welfare typically focus exclusively on activity in the primary exhibit area. However, physical, social and sensory experiences unique to each area may shape different patterns of behavior. In the current study, zoo-living chimpanzees and gorillas were moved each day from exhibit areas to off-exhibit holding areas for a short duration as a part of regular management procedures. Behavioral data indicated species-specific reactions to the holding area, including increased aggression and self-directed behavior by chimpanzees and increased activity and prosocial behavior among gorilla subjects. Both species showed more feeding-foraging behavior while in the exhibit enclosure. Results suggest that holding areas may not meet all behavior needs of captive great apes and demonstrate the importance of including all components of the captive enclosure in comprehensive analyses of great ape behavior and welfare.

The influence of captive adolescent male chimpanzees on wounding: management and welfare implications.

Adolescence, the period lasting from the onset of puberty to the emergence of physical and sexual maturity, is a period of social change for many species including chimpanzees. Several reports have implicitly linked the physiological changes that occur during male chimpanzee adolescence to significant disruption in the social group, which in turn may result in serious agonism and wounding. To assess the association between adolescent males and wounding rates, 38 institutions housing 399 chimpanzees among 59 social groups, recorded all wounds incurred by chimpanzees over a 6-month period. The rate of wounding did not differ between groups with or without adolescent males. Adolescent males received the most wounds, but were no more likely to cause wounds than group members of any other sex-age class. Social groups with multiple adult males experienced lower wounding rates than those with a single adult male. Results indicate that (1) adolescent male chimpanzees may receive, but not inflict, more wounds than chimpanzees in other sex-age classes; and (2) management strategies that support natural social groupings may control and limit group agonism.

Interactions between zoo-housed great apes and local wildlife.

Although there are published reports of wild chimpanzees, bonobos, and orangutans hunting and consuming vertebrate prey, data pertaining to captive apes remain sparse. In this survey-based study, we evaluate the prevalence and nature of interactions between captive great apes and various indigenous wildlife species that range into their enclosures in North America. Our hypotheses were threefold: (a) facilities housing chimpanzees will report the most frequent and most aggressive interactions with local wildlife; (b) facilities housing orangutans and bonobos will report intermediate frequencies of these interactions with low levels of aggression and killing; and (c) facilities housing gorillas will report the lowest frequency of interactions and no reports of killing local wildlife. Chimpanzees and bonobos demonstrated the most aggressive behavior toward wildlife, which matched our predictions for chimpanzees, but not bonobos. This fits well with expectations for chimpanzees based on their natural history of hunting and consuming prey in wild settings, and also supports new field data on bonobos. Captive gorillas and orangutans were reported to be much less likely to chase, catch and kill wildlife than chimpanzees and bonobos. Gorillas were the least likely to engage in aggressive interactions with local wildlife, matching our predictions based on natural history. However unlike wild gorillas, captive gorillas were reported to kill (and in one case, eat) local wildlife. These results suggest that some behavioral patterns seen in captive groups of apes may be useful for modeling corresponding activities in the wild that may not be as easily observed and quantified. Furthermore, the data highlight the potential for disease transmission in some captive settings, and we outline the associated implications for ape health and safety.

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer.

Mouse mammary tumour virus (MMTV) causes breast cancer in mice, and MMTV-specific antibodies develop to high titers among mice infected as adults. Whether MMTV or a related virus infects humans is uncertain, because MMTV DNA sequences have been detected inconsistently and because serologic methods have varied widely. The current study used immunoblot and immunoprecipitation with four strains of MMTV (RIII, FM, C3H, and LA) to detect specific antibodies in 92 sera from US women with breast cancer and in masked dilutions of monoclonal hybridoma and hyperimmunised goat positive-control reagents. In these positive controls, MMTV antibodies of the expected molecular weights were detected at high titer (1 : 100 in the monoclonal reagent, 1 : 10000 in the hyperimmunised goat serum). Nearly 30% of the sera from women with breast cancer had at least one faint band on an immunoblot, but none of these matched the molecular weight of bands revealed by probing the same blot strips with the goat serum. The goat serum readily immunoprecipitated MMTV antigens from all four strains of MMTV, but MMTV antigens were not immunoprecipitated by any of the six breast cancer sera that had four or more nonspecific immunoblot bands. Thus, among women with breast cancer, we found no MMTV-specific antibodies. The upper 95% confidence limit implies that MMTV seroprevalence among breast cancer patients does not exceed 3%.

The effect of addressing demand for as well as supply of emergency obstetric care in Dinajpur, Bangladesh.

PURPOSE: The Dinajpur SafeMother Initiative (DSI) was designed to test the impact of several interventions on use of obstetric services in government health facilities in Northwestern Bangladesh during 1998-2001. INTERVENTION: Facility-based interventions included upgrading health facilities. The sub-district hospitals or Upazila Health Centers (UHCs) had earlier been upgraded to provide basic emergency obstetric care (BEmOC). This project undertook activities designed to improved the quality of care in the facilities which included team-building among providers, case reviews and a stakeholders' committee. CARE introduced a community mobilization intervention, which included birth planning, community support systems for funding, transportation, blood donation etc. for care of women with complications. METHODS: The intervention area received all interventions. The only intervention in the comparison area was the upgrading of the health facilities to provide basic EmOC. There were no interventions in the control area. RESULTS: Met need increased by 13% in comparison area but nearly 24% in intervention area. There was no substantial change in the control area. At the end of the project, knowledge of obstetric danger signs was much greater in intervention area than in the other 2 areas. CONCLUSION: We conclude, therefore, that the best results are achieved through a combination of facility improvement, quality of care activities and targeted community mobilization activities.

Cellular ITAM-containing proteins are oncoproteins in nonhematopoietic cells.

Immunoreceptor tyrosine-based activation motifs (ITAMs) are involved in the transduction of signals necessary for activation, differentiation, and survival in hematopoietic cells. Several viruses have been shown to encode ITAM-containing transmembrane proteins. Although expression of these viral proteins has in some cases been shown to transform nonhematopoietic cells, a causal role for a functional ITAM in this process has not been elucidated. To examine the potential transforming properties of ITAM-containing proteins, a recombinant protein consisting of ITAM-containing cytoplasmic regions of the B-cell antigen receptor was expressed in immortalized murine mammary epithelial and fibroblast cells. Mammary epithelial cells expressing this construct exhibited depolarized morphology in three-dimensional cultures. This transformed phenotype was characterized by a loss of anchorage dependence and hallmarks of epithelial to mesenchymal transition. Fibroblasts expressing this ITAM construct also lost contact inhibition and anchorage dependence. The transformed phenotype seen in both cell types was abrogated upon tyrosine to phenylalanine substitutions of the ITAMs. Inhibition of Syk tyrosine kinase, which associates with the ITAM, also prevented cell transformation. Our results indicate that expression of a nonviral ITAM-containing protein is sufficient for cell transformation. Despite lacking intrinsic enzymatic activity, ITAM-containing proteins can function as potent oncoproteins by scaffolding downstream mediators.

Detecting incomplete effort on the MMPI-2: an examination of the Fake-Bad Scale in mild head injury.

The current study is an investigation of the MMPI-2 Fake Bad Scale ( FBS ) in the detection of incomplete effort in mild head injury (MHI). Using ROC curve analysis, we found that a cutoff score of 21 had a sensitivity of 90% and specificity of 90%, providing an overall correct classificatory rate of 90%. In addition, traditional indices of faking bad on the MMPI-2, the F and F-K indices, fared relatively poorly by comparison and added no predictive power over the FBS. Finally, multivariate analyses revealed that although the FBS shares a number of items with Hs and Hy scales, the FBS carried the majority of variance in predicting incomplete effort in our MHI sample. Overall, these findings indicate that the FBS has high sensitivity and specificity in identifying incomplete effort in mild head injury.

Neonatal weight loss in breast and formula fed infants.

OBJECTIVE: To define the range of neonatal weight loss in a population relative to feeding method. DESIGN: Prospective observational cohort study. SETTING: Maternity service providing geographically defined, community based newborn follow up. PARTICIPANTS: 971 consecutive term newborns of birth weight > or = 2500 g during the first 2-3 weeks of life; 34 excluded (inadequate data). 937 included: 45% breast fed, 42% formula fed, 13% breast and formula fed. OUTCOME MEASURES: Maximum weight loss and timing, age on regaining birth weight. RESULTS: Median weight loss: formula fed 3.5%, breast fed 6.6%. Upper centiles for maximum weight loss differ considerably (95th centiles: breast fed = 11.8%, formula fed = 8.4%; 97.5th centiles: breast fed = 12.8%, formula fed = 9.5%). Median time of maximum weight loss: 2.7 days for breast fed and formula fed. Recovery of birth weight: breast fed median 8.3 days, 95th centile 18.7 days, 97.5th centile 21.0 days; formula fed median 6.5 days, 95th centile 14.5 days, 97.5th centile 16.7 days. The time taken to regain birth weight correlates with both the degree and timing of initial weight loss for all groups. CONCLUSIONS: Early neonatal weight loss is defined allowing identification of infants who merit closer assessment and support.

The Memory Assessment Scales in the detection of incomplete effort in mild head injury.

Despite differences in the constructs measured, the Memory Assessment Scales (MAS) remain an alternative to the Wechsler Memory Scales (WMS) as a broad-band instrument for assessing multiple aspects of attention and memory. Although a number of studies have examined indices of the WMS as indicators of malingering, few studies have similarly investigated the MAS. In this study, we examined the degree to which the MAS was effective in detecting incomplete effort in a clinical sample of patients referred for neuropsychological evaluation after mild head injury. Included in the sample were 21 financially compensable (FC) participants with alleged mild head injury and 21 participants who were not involved in litigation and suffered more serious head injuries. Examination of the four MAS domain indices indicated that Short-Term Memory was most useful at identifying incomplete effort. We also examined subscales of the MAS. Consistent with previous findings, brief tests such as Verbal and Visual Span had high rates of diagnostic sensitivity and specificity. Although tests based on a forced-choice recognition paradigm (e.g., Immediate and Delayed Visual Recognition) predicted group membership above chance levels, they failed to significantly add to prediction above Verbal and Visual Span subtests.

Interleukin-4 up-regulates mouse mammary tumor virus expression yet is not required for in vivo virus spread.

The mouse mammary tumor virus (MMTV) superantigen induces T-cell production of cytokines, such as interleukin-4, which in turn increase MMTV transcription. However, interleukin-4 is not required for in vivo virus spread, because mice lacking interleukin-4 or the STAT6 transcription factor showed wild-type infection of lymphoid and mammary tissue. In spite of this, mammary tumor incidence was decreased in STAT6 null mice.

Promoter function of the angiogenic inducer Cyr61gene in transgenic mice: tissue specificity, inducibility during wound healing, and role of the serum response element.

The cysteine-rich angiogenic protein 61 (Cyr61) is an extracellular matrix-associated, heparin-binding protein that mediates cell adhesion, stimulates cell migration, and enhances growth factor-induced cell proliferation. Cyr61 also promotes chondrogenic differentiation and induces neovascularization. In this study, we show that a 2-kb fragment of the Cyr61 promoter, which confers growth factor-inducible expression in cultured fibroblasts, is able to drive accurate expression of the reporter gene lacZ in transgenic mice. Thus, transgene expression was observed in the developing placenta and embryonic cardiovascular, skeletal, and central and peripheral nervous systems. The sites of transgene expression are consistent with those observed of the endogenous Cyr61 gene as determined by in situ hybridization and immunohistochemistry. The transgene expression in the cardiovascular system does not require the serum response element, a promoter sequence essential for transcriptional activation of Cyr61 by serum growth factors in cultured fibroblasts. Because the serum response element contains the CArG box, a sequence element implicated in cardiovascular-specific gene expression, the nonessential nature of this sequence for cardiovascular expression of Cyr61 is unexpected. Furthermore, the Cyr61 promoter-driven lacZ expression is inducible in granulation tissue during wound healing, as is synthesis of the endogenous Cyr61 protein, suggesting a role for Cyr61 in wound healing. Consistent with this finding, purified Cyr61 protein promotes the healing of a wounded fibroblast monolayer in culture. In addition, we mapped the mouse Cyr61 gene to the distal region of chromosome 3. Together, these results define the functional Cyr61 promoter in vivo, and suggest a role of Cyr61 in wound healing through its demonstrated angiogenic activities upon endothelial cells and its chemotactic and growth promoting activities upon fibroblasts.

Using genetics to probe host-virus interactions; the mouse mammary tumor virus model.

It is clear that there is genetic variation among different individuals in their susceptibility to infection by viruses and other pathogens. Identification of the genes involved in conferring resistance or susceptibility to viral infection will allow us to understand both mechanisms of infection and pathogenesis and to develop reagents for treating or preventing them. Because of the large number of genetically well-characterized inbred mouse strains and the ability to generate targeted germ line mutations, this species is particularly well-suited for such analysis. This review focuses on how the use of genetics to study the retrovirus mouse mammary tumor virus allowed the dissection of both the viral infection pathway and the response of the host to this infection.

Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene.

Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (HP)] for tumorigenicity in mice from two distinct genetic backgrounds. All three viruses were tumor causing in BALB/cJ mice. However, only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated expression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtv1 provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity of MMTV(C3H) to the gag region of the retrovirus.