Body mass and growth rates in captive chimpanzees (Pan troglodytes) cared for in African wildlife sanctuaries,zoological institutions,and research facilities

Captive chimpanzees (Pan troglodytes) mature earlier in body mass and have a greater growth rate compared to wild individuals. However, relatively little is known about how growth parameters compare between chimpanzees living in different captive environments. To investigate, body mass was measured in 298 African sanctuary chimpanzees and was acquired from 1030 zoological and 442 research chimpanzees, using data repositories. An analysis of covariance, adjusting for age, was performed to assess same-sex body mass differences between adult sanctuary, zoological, and research populations. Piecewise linear regression was performed to estimate sex-specific growth rates and the age at maturation, which were compared between sexes and across populations using extra-sum-of-squares F tests. Adult body mass was greater in the zoological and resarch populations compared to the sanctuary chimpanzees, in both sexes. Male and female sanctuary chimpanzees were estimated to have a slower rate of growth compared with their zoological and research counterparts. Additionally, male sanctuary chimpanzees were estimated to have an older age at maturation for body mass compared with zoological and research males, whereas the age at maturation was similar across female populations. For both the zoological and research populations, the estimated growth rate was greater in males compared to females. Together, these data contribute to current understanding of growth and maturation in this species and suggest marked differences between the growth patterns of chimpanzees living in different captive environments.     

The effects of varying concentrations of colchicine on the progression of grasshopper neuroblasts into metaphase

The effects of four concentrations of colchicine (2.5 x 10^-7, x 10^-5, x 10^-3, and x 10^-2 M) on the cell cycle of grasshopper neuroblasts have been determined by direct observations on living cells. The lowest concentration, 2.5 x 10^-7 M, does not completely disorganize the spindle but does retard its action. The three higher concentrations disorganize the spindle, so that all cells reaching metaphase are blocked in a c-mitotic condition throughout the period of observations (308 min at 38°C, the minimum duration of the cell cycle in untreated neuroblasts). Continuous treatment with all concentrations reduces the rate at which neuroblasts enter metaphase, the extent of the reduction being a function of increasing concentration and time of exposure. After a short exposure to 2.5 x 10^-5 M colchicine, the neuroblasts recover from the inhibiting effects on progression through the cycle to metaphase, but they show no recovery from the inhibiting effects on spindle formation for more than 3 hr. Apparent stimulation of progression rate occurs early in exposure to all concentrations and during recovery from a short exposure to 2.5 x 10^-5 M. Morphological alterations in the chromatin of telophase, interphase, and prophase cells are induced by the higher concentrations of colchicine. The data indicate that caution should be exercised in the use of colchicine for determining cell cycle duration and/or the effects of physical and chemical agents on the cycle.     

ISCOMATRIX vaccines mediate CD8+ T-cell cross-priming by a MyD88-dependent signaling pathway

Generating a cytotoxic CD8(+) T-cell response that can eradicate malignant cells is the primary objective of cancer vaccine strategies. In this study we have characterized the innate and adaptive immune response to the ISCOMATRIX adjuvant, and the ability of vaccine antigens formulated with this adjuvant to promote antitumor immunity. ISCOMATRIX adjuvant led to a rapid innate immune cell response at the injection site, followed by the activation of natural killer and dendritic cells (DC) in regional draining lymph nodes. Strikingly, major histocompatibility complex (MHC) class I cross-presentation by CD8α(+) and CD8α(-) DCs was enhanced by up to 100-fold when antigen was formulated with ISCOMATRIX adjuvant. These coordinated features enabled efficient CD8(+) T-cell cross-priming, which exhibited prophylactic and therapeutic tumoricidal activity. The therapeutic efficacy of an ISCOMATRIX vaccine was further improved when co-administered with an anti-CD40 agonist antibody, suggesting that ISCOMATRIX-based vaccines may combine favorably with other immune modifiers in clinical development to treat cancer. Finally, we identified a requirement for the myeloid differentiation primary response gene 88 (MyD88) adapter protein for both innate and adaptive immune responses to ISCOMATRIX vaccines in vivo. Taken together, our findings support the utility of the ISCOMATRIX adjuvant for use in the development of novel vaccines, particularly those requiring strong CD8(+) T-cell immune responses, such as therapeutic cancer vaccines.     

Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5

Broad, multispecific CD4⁺ and CD8⁺ T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of these responses in an ideal vaccine regimen, we have explored the use of recombinant HCV polypeptides combined with various Th1-type adjuvants and replication-defective alphaviral particles encoding HCV proteins in various prime/boost modalities in BALB/c mice. Defective chimeric alphaviral particles derived from the Sindbis and Venezuelan equine encephalitis viruses encoding either the HCV envelope glycoprotein gpE1/gpE2 heterodimer (E1E2) or nonstructural proteins 3, 4, and 5 (NS345) elicited strong CD8⁺ T-cell responses but low CD4⁺ T helper responses to these HCV gene products. In contrast, recombinant E1E2 glycoproteins adjuvanted with MF59 containing a CpG oligonucleotide elicited strong CD4⁺ T helper responses but no CD8⁺ T-cell responses. A recombinant NS345 polyprotein also stimulated strong CD4⁺ T helper responses but no CD8⁺ T-cell responses when adjuvanted with Iscomatrix containing CpG. Optimal elicitation of broad CD4⁺ and CD8⁺ T-cell responses to E1E2 and NS345 was obtained by first priming with Th1-adjuvanted proteins and then boosting with chimeric, defective alphaviruses expressing these HCV genes. In addition, this prime/boost regimen resulted in the induction of anti-E1E2 antibodies capable of cross-neutralizing heterologous HCV isolates in vitro. This vaccine formulation and regimen may therefore be optimal in humans for protection against this highly heterogeneous global pathogen.     

Sex reversal in pairs of Lythrypnus dalli: behavioral and morphological changes

In Lythrypnus dalli, the bluebanded goby, reproductive success is primarily determined by functional sex, and functional sex is determined largely by rank in the dominance hierarchy. In most natural social groups of L. dalli, one male is at the apex of the hierarchy, and 1 to 7 females are lower in rank. When a male exits the group, a female ascends to the top of the hierarchy and becomes a male. We have examined this process in a simplified environment--a pair of females--that allows us to identify behavior associated with the formation of a dominance relationship and any other phenotypic changes associated with dominance, sex change or both. We found that pairs of L. dalli females quickly and readily form stable dominance relationships, with the dominant fish changing sex into a male. This dominant animal also rapidly increases in body size and length of its dorsal fin. In summary, dominant L. dalli females change sex in this simplified environment, providing excellent opportunities to examine the early behavioral and morphological changes associated with dominance and sex change.     

Obesity among People with and without Mental Retardation across Adulthood

Objective: This study was designed to explore obesity during adulthood and the likelihood of moving out of obesity among 1809 adults without disability and 680 adults with mental retardation who received care at the same primary care practices during the period of 1990 to 2003. Research Method and Procedures: A retrospective observational design using medical records first identified patients with mental retardation (MR) and age‐matched controls without disabilities. Data on BMI collected during each primary care visit allowed exploration of obesity at three levels. Moving out of obesity was defined as having a BMI <25 kg/m². We also abstracted data on age, sex, race, and other medical conditions. Results: For adults 20 to 29 years of age, 33.1% of patients without disability and 21% of patients with MR had a BMI >30 kg/m². Between the ages of 50 and 59 years, 40.5% of the patients without disability and 35.2% of the patients with MR had a BMI >30 kg/m². Patients with mild MR had similar prevalence rates of obesity and patients with severe MR had significantly lower prevalence of obesity compared with the patients without disability through 50 years of age. Throughout the period from 20 to 60 years of age, between 15% and 40% of individuals with and without MR, who were previously obese, were not currently obese. Discussion: Throughout the adult years, an increasing proportion of individuals with and without MR are obese. However, obesity is not a chronic state; many people transition back to a normal body weight.     

Measuring thermal time constants of reptiles under conditions of linearly-varying ambient temperatures

This paper examines methods of measuring the thermal time constants of reptiles under ramp-function conditions. It is found that the “thermal lag” method, previously reported in the literature, can be used only under certain very limited conditions. A second method, referred to as the “ramp-compensation” method, is introduced and shown to be superior in many ways, particularly in telemetric applications.     

Common DISC1 polymorphisms disrupt Wnt/GSK3β signaling and brain development

Disrupted in Schizophrenia-1 (DISC1) is a candidate gene for psychiatric disorders and has many roles during brain development. Common DISC1 polymorphisms (variants) are associated with neuropsychiatric phenotypes including altered cognition, brain structure, and function; however, it is unknown how this occurs. Here, we demonstrate using mouse, zebrafish, and human model systems that DISC1 variants are loss of function in Wnt/GSK3β signaling and disrupt brain development. The DISC1 variants A83V, R264Q, and L607F, but not S704C, do not activate Wnt signaling compared with wild-type DISC1 resulting in decreased neural progenitor proliferation. In zebrafish, R264Q and L607F could not rescue DISC1 knockdown-mediated aberrant brain development. Furthermore, human lymphoblast cell lines endogenously expressing R264Q displayed impaired Wnt signaling. Interestingly, S704C inhibited the migration of neurons in the developing neocortex. Our data demonstrate DISC1 variants impair Wnt signaling and brain development and elucidate?a possible mechanism for their role in neuropsychiatric phenotypes.     

Genomic analysis of detoxification genes in the mosquito Aedes aegypti

Annotation of the recently determined genome sequence of the major dengue vector, Aedes aegypti, reveals an abundance of detoxification genes. Here, we report the presence of 235 members of the cytochrome P450, glutathione transferase and carboxy/cholinesterase families in Ae. aegypti. This gene count represents an increase of 58% and 36% compared with the fruitfly, Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae, respectively. The expansion is not uniform within the gene families. Secure orthologs can be found across the insect species for enzymes that have presumed or proven biosynthetic or housekeeping roles. In contrast, subsets of these gene families that are associated with general xenobiotic detoxification, in particular the CYP6, CYP9 and alpha esterase families, have expanded in Ae. aegypti. In order to identify detoxification genes associated with resistance to insecticides we constructed an array containing unique oligonucleotide probes for these genes and compared their expression level in insecticide resistant and susceptible strains. Several candidate genes were identified with the majority belonging to two gene families, the CYP9 P450s and the Epsilon GSTs. This 'Ae. aegypti Detox Chip' will facilitate the implementation of insecticide resistance management strategies for arboviral control programmes.     

Variability of the QuantiFERON?-TB Gold In-Tube Test Using Automated and Manual Methods

Background

The QuantiFERON®-TB Gold In-Tube test (QFT-GIT) detects Mycobacterium tuberculosis (Mtb) infection by measuring release of interferon gamma (IFN-γ) when T-cells (in heparinized whole blood) are stimulated with specific Mtb antigens. The amount of IFN-γ is determined by enzyme-linked immunosorbent assay (ELISA). Automation of the ELISA method may reduce variability. To assess the impact of ELISA automation, we compared QFT-GIT results and variability when ELISAs were performed manually and with automation.

Methods

Blood was collected into two sets of QFT-GIT tubes and processed at the same time. For each set, IFN-γ was measured in automated and manual ELISAs. Variability in interpretations and IFN-γ measurements was assessed between automated (A1 vs. A2) and manual (M1 vs. M2) ELISAs. Variability in IFN-γ measurements was also assessed on separate groups stratified by the mean of the four ELISAs.

Results

Subjects (N = 146) had two automated and two manual ELISAs completed. Overall, interpretations were discordant for 16 (11%) subjects. Excluding one subject with indeterminate results, 7 (4.8%) subjects had discordant automated interpretations and 10 (6.9%) subjects had discordant manual interpretations (p = 0.17). Quantitative variability was not uniform; within-subject variability was greater with higher IFN-γ measurements and with manual ELISAs. For subjects with mean TB Responses ±0.25 IU/mL of the 0.35 IU/mL cutoff, the within-subject standard deviation for two manual tests was 0.27 (CI₉₅ = 0.22–0.37) IU/mL vs. 0.09 (CI₉₅ = 0.07–0.12) IU/mL for two automated tests.

Conclusion

QFT-GIT ELISA automation may reduce variability near the test cutoff. Methodological differences should be considered when interpreting and using IFN-γ release assays (IGRAs).