Relationships In Nonhuman Primates Research Articles

Social and economic interdependence as a basis for peaceful between-group relationships in nonhuman primates and humans.

Glowacki asserts that interdependent relationships beyond group boundaries are exceptionally rare among nonhuman mammals. However, rudimentary forms of interdependence can be seen in primate species that form multilevel societies, that is, core social units embedded within higher-level grouping categories. Studies of primate multilevel societies can enrich discussions about the evolutionary origins of peaceful between-group interactions in humans.

Generation of Half-Life Extended Anti-BCMA Bite® Antibody Construct Compatible with Once-Weekly Dosing for Treatment of Multiple Myeloma (MM)

Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of abnormal plasma cells in the bone marrow. Although several treatment options are available, patients frequently develop relapsed/refractory disease leading to significant morbidity and mortality. More effective induction and elimination of residual disease are required for curative treatments. One potential strategy for improving patient outcomes is the use of T cell engaging agents such as BiTE® antibody constructs and CAR-T cells.The bispecific T cell engager (BiTE®) antibody construct blinatumomab, which targets CD19-positive cells, has demonstrated efficacy in treating certain CD19-positive hematological malignancies. Blinatumomab comprises a single chain variable fragment (scFv) that binds CD19 on B cells and a scFv that targets the T cell CD3 protein. The short serum half-life of blinatumomab necessitates administration by continuous IV infusion to maintain therapeutic serum concentrations. To enable once-weekly dosing, next generation BiTE® antibody constructs have been modified by fusion to an Fc domain to extend half-life.BCMA, a member of the TNF receptor super family, supports plasma cell survival, and is widely expressed on MM and normal plasma cells. A half-life extended (HLE) anti-BCMA BiTE® was generated and evaluated in vitro, in mouse xenograft models and in non-human primates (NHP). In vitro assays evaluated 1) binding to both human and NHP BCMA and CD3 proteins, and 2) cytotoxicity using human and NHP target and effector cells. The anti-BCMA BiTE® demonstrated picomolar binding affinity and efficacy in cytotoxicity assays. In a mouse xenograft model in which BCMA-positive NCI-H929 cells and human PBMC were co-administered SC, the anti-BCMA HLE BiTE® completely inhibited tumor formation in contrast to vehicle control-treated groups with or without PBMC. BCMA cell surface protein expression was assessed by flow cytometry and observed on NHP bone marrow plasma cells but not on blood or bone marrow B cells. The serum half-life in NHP was 112 hours following a single 15 µg/kg dose. The PK/PD relationship in NHP was subsequently evaluated in a repeat-dose study. To assess elimination of BCMA-positive plasma cells in blood and bone marrow, a sensitive and specific ddPCR-based method was developed. Robust depletion of BCMA mRNA was observed in NHP following anti-BCMA BiTE® treatment, indicating effective elimination of BCMA-positive plasma cells from blood and bone marrow. These results demonstrate that HLE anti-BCMA BiTE® is effective in vitro and in vivo, and may be suitable for once-weekly dosing in MM patients. DisclosuresGoyos:Amgen: Employment. Li:Amgen, Inc.: Employment. Deegen:Amgen: Employment. Bogner:Amgen: Employment. Thomas:Amgen Research (Munich): Employment. Matthias:Amgen: Employment. Wahl:Amgen Research (Munich): Employment. Goldstein:Amgen: Employment. Coxon:Amgen, Inc.: Employment. Balazs:Amgen Inc.: Employment, Equity Ownership. Chapman-Arvedson:Amgen, Inc.: Employment, Equity Ownership.

IOP, IOP Transient Impulse, Ocular Perfusion Pressure, and Mean Arterial Pressure Relationships in Nonhuman Primates Instrumented With Telemetry.

PurposeTo characterize relationships between intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP), IOP transient impulse, and IOP baseline impulse using continuous telemetry in nonhuman primates.MethodsWe used our validated implantable telemetry system to wirelessly record bilateral IOP and arterial BP at 500 Hz in 7 eyes of 4 male rhesus macaques, aged 4 to 5 years. IOP, MAP, OPP, IOP transient impulse, and IOP baseline impulse were averaged into 1-hour periods over 20 days for each NHP. IOP transient impulse was defined as the portion of total IOP due to transient IOP fluctuations <0.5 seconds duration alone and IOP baseline impulse as the remaining area under the IOP versus time curve. OPP was defined as arterial BP-IOP (calculated continuously), and MAP was the hourly average of the continuous BP curve. Relationships between the variables were analyzed for each 24-hour period using either multivariate linear regression or Spearman Correlation Coefficients as appropriate.ResultsOver twenty 24-hour periods, IOP transient impulse and OPP showed significant positive relationship in all eyes, which was driven largely by the data during waking hours. There was no significant relationship between IOP and MAP, IOP transient impulse and MAP, or IOP baseline impulse and IOP transient impulse.ConclusionsThere are significant positive relationships between the frequency and/or size of transient IOP fluctuations (IOP transient impulse) and OPP. A possible explanation of this finding is that higher OPP, as well as a greater number of blinks and saccades (the primary sources of IOP transients), are associated with increased activity.

Abstract LB-299: Cynomolgus monkey plasma cell gene signature to quantify the in vivo activity of a half-life extended anti-BCMA BiTE® for the treatment of multiple myeloma

Abstract Background: Multiple myeloma (MM) is a hematologic malignancy where abnormal plasma cells (PC) accumulate in the bone marrow (BM). Patients often develop relapsed/refractory disease leading to significant morbidity and mortality. Elimination of residual disease is required for curative treatments. Patient outcome can be improved by using T-cell engaging agents, such as bispecific T-cell engager (BiTE®) antibody constructs, to redirect T cells to tumor cells. B-cell maturation antigen (BCMA), a TNF receptor superfamily member, supports PC survival and is widely expressed on MM and normal PC. Methods: A half-life extended (HLE) anti-BCMA BiTE® (BCMA HLE-BiTE®) antibody construct was generated and characterized in vitro, and in vivo in a mouse xenograft model and in non-human primates (NHP). To quantify on-target activity of the BCMA HLE-BiTE® in NHP it was necessary to follow changes in PC numbers. Because PC are rare (0.1 - 3%) in the BM and blood, detection using traditional assays is not possible. To address this limitation, a PC gene signature was defined and used to develop a quantitative ddPCR assay (sensitivity = 0.01%) to assess the effect of the BCMA HLE-BiTE® in a 12-day repeat-dose NHP study. Results: A BCMA HLE-BiTE® was selected that demonstrated cytotoxic activity using human effector cells (EC50: 0.13 ± 0.07 pM in MM.1R cells) and comparable activity using NHP effector cells. In a sub-cutaneous mouse xenograft model in which BCMA-positive NCI-H929 cells and human PBMC were co-administered, the BCMA HLE-BiTE® completely inhibited tumor formation, in contrast to vehicle controls with/without PBMC. The serum half-life of the BCMA HLE-BiTE® in NHP was 112 hours following a single 15 µg/kg IV dose. The PK/PD relationship in NHP was next evaluated in a 12-day repeat-dose study. A dose-dependent PK behavior as well as depletion of PC in blood and BM was observed, reaching 93% depletion in the blood and 85% in the BM in the high-dose group on day 12. Conclusions: These results demonstrate that the BCMA HLE-BiTE® is potent and effective at inducing cytotoxicity of target cells in vitro and in vivo, and may be suitable for once-weekly dosing in MM patients. This molecule is being evaluated in humans: trial NCT03287908. Citation Format: Ana Goyos, Chi-Ming Li, Petra Deegen, Pamela Bogner, Oliver Thomas, Joachim Wahl, Rebecca Goldstein, Maththias Friedrich, Angela Coxon, Mercedesz Balazs, Tara Arvedson. Cynomolgus monkey plasma cell gene signature to quantify the in vivo activity of a half-life extended anti-BCMA BiTE® for the treatment of multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-299.

Sex roles and adult sex ratios: insights from mammalian biology and consequences for primate behaviour.

Theoretical models and empirical studies in various taxa have identified important links between variation in sex roles and the number of adult males and females (adult sex ratio (ASR)) in a population. In this review, I examine these relationships in non-human primates. Because most existing theoretical models of the evolution of sex roles focus on the evolutionary origins of sex-biased behaviour, they offer only a general scaffold for predicting variation in sex roles among and within species. I argue that studies examining sex role variation at these more specific levels need to take social organization into account to identify meaningful levels for the measurement of ASR and to account for the fact that ASR and sex roles mutually influence each other. Moreover, taxon-specific life-history traits can constrain sex role flexibility and impact the operational sex ratio (OSR) by specifying the minimum length of female time outs from reproduction. Using examples from the primate literature, I highlight practical problems in estimating ASR and OSR. I then argue that interspecific variation in the occurrence of indirect forms of paternal care might indeed be linked to variation in ASR. Some studies also indicate that female aggression and bonding, as well as components of inter-sexual relationships, are sensitive to variation in ASR. Thus, links between primate sex roles and sex ratios merit further study, and such studies could prompt the development of more specific theoretical models that make realistic assumptions about taxon-specific life history and social organization.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'.

The relationship between event-based prospective memory and ongoing task performance in chimpanzees (Pan troglodytes).

Prospective memory is remembering to do something at a future time. A growing body of research supports that prospective memory may exist in nonhuman animals, but the methods used to test nonhuman prospective memory differ from those used with humans. The current work tests prospective memory in chimpanzees using a method that closely approximates a typical human paradigm. In these experiments, the prospective memory cue was embedded within an ongoing task. Tokens representing food items could be used in one of two ways: in a matching task with pictures of items (the ongoing task) or to request a food item hidden in a different location at the beginning of the trial. Chimpanzees had to disengage from the ongoing task in order to use the appropriate token to obtain a higher preference food item. In Experiment 1, chimpanzees effectively matched tokens to pictures, when appropriate, and disengaged from the ongoing task when the token matched the hidden item. In Experiment 2, performance did not differ when the target item was either hidden or visible. This suggested no effect of cognitive load on either the prospective memory task or the ongoing task, but performance was near ceiling, which may have contributed to this outcome. In Experiment 3, we created a more challenging version of the task. More errors on the matching task occurred before the prospective memory had been carried out, and this difference seemed to be limited to the hidden condition. This finding parallels results from human studies and suggests that working memory load and prospective memory may have a similar relationship in nonhuman primates.

Relationship between Age and Neurogenesis in Old World Monkeys

Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously studied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear significant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout adulthood and begins to decline in middle age in bonnet macaques.

Comparisons of Intraunit Relationships in Nonhuman Primates Living in Multilevel Social Systems

Multilevel social systems have evolved in several species of cercopithecoid primates and appear to be an effective means of changing group size amid variation in environmental conditions. Larger groupings of these species fission and fuse, making intraunit relationships essential to maintain the integrity of the smallest social units. We examine these intraunit relationships in four primates with multilevel social systems: proboscis monkeys (Nasalis larvatus), snub-nosed monkeys (Rhinopithecus roxellana), hamadryas baboons (Papio hamadryas), and geladas (Theropithecus gelada), using social network analysis. The proboscis monkeys and hamadryas baboons were wild and unprovisioned, whereas the snub-nosed monkeys and geladas were partly provisioned. Comparison of eigenvector centrality coefficients revealed a phylogenetic difference in the key individuals maintaining social networks between the colobines and the cercopithecines: females were more central in proboscis and snub-nosed monkeys, with males generally peripheral to social interaction, whereas males were more central than females in geladas and hamadryas. A comparison of sex differences in clustering coefficients, however, revealed a significant difference only in geladas, suggesting that one-male–multifemale units in this species become more unstable when females, but not males, are removed from social networks. Taken together, our results reveal the strongest differences between geladas, characterized by female philopatry and male dispersal, and the three species with bisexual dispersal. These results demonstrate the potential for social network analysis to reveal the social bonds most important for maintaining cohesion of the smallest units of primate multilevel societies. This, in turn, can serve as a proxy, in the absence of long-term data, for underlying patterns of sex-biased dispersal and philopatry.

The influences of perinatal challenge persist into the adolescent period in socially housed bonnet macaques (Macaca radiata).

Social challenges during the perinatal period influence the mother-infant relationship in nonhuman primates and may affect the offspring's response to later social challenge(s). Relocation of a breeding colony of monkeys (Macaca radiata) created two groups of infants: one group experienced social group relocation to a new housing facility during the perinatal period (ATYPICAL) and the second group developed within a constant environment (TYPICAL). At a mean age of 25 months, all animals were removed from their natal group and placed in same sex adolescent social groups. Behavioral observations were collected after group formation or introduction to a new group. ATYPICAL subjects showed increased aggression and reduced affiliation compared to TYPICAL subjects. Hair cortisol in male subjects collected 6 months after introduction was elevated in the ATYPICAL subjects compared to TYPICAL subjects. These findings demonstrate that early life challenges affect behavior as well as stress hormone responses to social challenge in adolescence.

Perseveration on a reversal-learning task correlates with rates of self-directed behavior in nonhuman primates

In humans and several nonhuman animals, repetitive behavior is associated with deficits on executive function tasks involving response inhibition. We tested for this relationship in nonhuman primates by correlating rates of normative behavior to performance on a reversal-learning task in which animals were required to inhibit a previously learned rule. We focused on rates of self-directed behavior (scratch, autogroom, self touch and manipulation) because these responses are known indicators of arousal or anxiety in primates, however, we also examined rates of other categories of behavior (e.g., locomotion). Behavior rates were obtained from 14 animals representing three nonhuman primate species (Macaca silenus, Saimiri sciureus, Cebus apella) living in separate social groups. The same animals were tested on a reversal-learning task in which they were presented with a black and a grey square on a touch screen and were trained to touch the black square. Once animals learned to select the black square, reward contingencies were reversed and animals were rewarded for selecting the grey square. Performance on the reversal-learning task was positively correlated to self-directed behavior in that animals that exhibited higher rates of self-directed behavior required more trials to achieve reversal. Reversal learning was not correlated to rates of any other category of behavior. Results indicate that rates of behavior associated with anxiety and arousal provide an indicator of executive function in nonhuman primates. The relationship suggests continuity between nonhuman primates and humans in the link between executive functioning and repetitive behavior.

Dose response results of self complementary adeno‐associated virus (AAV) vector‐mediated factor IX gene transfer in non‐human primates

Objective: In anticipation of opening a phase I/II clinical trial of adeno‐associated virus (AAV) vector‐mediated factor IX (FIX) gene transfer in subjects with severe haemophilia B, we have recently evaluated the vector dose‐response relationship in nonhuman primates. Our approach differs from prior studies in that the vector (scAAV2/8‐LP1‐hFIXco) used, will: (i) be pseudotyped with serotype 8 capsid; (ii) be delivered by peripheral vein; and (iii) have a self‐complementary genome.Methods: The vector scAAV2/8‐LP1‐hFIXco was produced by calcium phosphate mediated two plasmid transient transfection of 293T cells with the virus then being purified using group separation and ion exchange chromatography in our GMP facility, using exactly the same methodology that we propose to use for production of the clinical lot. The titre of the vector prep was determined by qPCR analysis. Male rhesus macaques, previously screened for the absence of serotype 8 humoral immunity, received vector via bolus infusion over 15 min through a peripheral vein. Human FIX expression in the rhesus plasma collected at serial time points following vector administration was determined by our previously validated ELISA.Summary: We used four vector dose levels, 2 × 1010, 6 × 1010, 2 × 1011 and 2 × 1012 vg kg−1 body weight, in cohorts of three or four macaques each. No overt toxicity or perturbation in serum biochemistries or other laboratory values was noted in any animal. A nearly linear dose‐response relationship between vector administered and hFIX expression was observed. Mean levels of human FIX 3 weeks following vector administration, expressed as a percentage of normal (5ug mL−1), was as follows: 2% (2 × 1010), 6% (6 × 1010), 25% (2 × 1011) and 200% (2 × 1012) and has remained relatively stable. Of the four macaques given a dose of 2 × 1010 vg kg−1, one initially had a FIX level of nearly 10% that has remained at 8% for several weeks. A second animal peaked at 1% but hFIX is now undetectable. Two macaques never had detectable hFIX expression. Tissue biopsies have demonstrated by qPCR analysis that the vast majority of vector genomes are found in the liver, although they can be detected at other sites including the testis.Conclusions: Based on these results, we plan to use 2 × 1010 vg kg−1 as the starting dose in our upcoming clinical trial. We believe that some participants may achieve the target level of 3% hFIX expression at this dose, if we can extrapolate the information we have obtained in rhesus macaques to humans. However, we are prepared to quickly dose‐escalate if this is not the case. Our maximal clinical dose will be 2 × 1011 vg kg−1, 10‐fold lower than the highest dose in this preclinical study (2 × 1012 vg kg−1), a dose that was found to be safe and without toxicity.

Mother–infant interactions in free-ranging rhesus macaques: Relationships between physiological and behavioral variables

Studies of mother–infant relationships in nonhuman primates have increasingly attempted to understand the neuroendocrine bases of interindividual variation in mothering styles and the mechanisms through which early exposure to variable mothering styles affects infant behavioral development. In this study of free-ranging rhesus macaques on Cayo Santiago, Puerto Rico, we aimed to: 1) compare lactating and nonlactating females to investigate whether lactation is associated with changes in plasma cortisol, prolactin and oxytocin, as well as changes in CSF levels of serotonin and dopamine metabolites (5-HIAA and HVA); 2) examine the extent to which interindividual variation in maternal physiology is associated with variation in maternal behavior; 3) examine the extent to which interindividual variation in infant physiology and behavior is accounted for by variation in maternal physiology and behavior. Lactating females had higher plasma concentrations of cortisol, prolactin, and oxytocin but lower CSF concentrations of HVA than nonlactating females. Variation in maternal rejection behavior was positively correlated with variation in maternal plasma cortisol levels and in CSF 5-HIAA levels while variation in the time spent nursing and grooming was associated with maternal plasma oxytocin levels. Infants who were protected more by their mothers had higher cortisol levels than those who were protected less, while infants who were rejected more had lower CSF 5-HIAA than infants who were rejected less. Since exposure to high levels of maternal protectiveness and rejection is known to affect the offspring's behavior and responsiveness to the environment later in life, our results are consistent with the hypothesis that these effects are mediated by long-term changes in the activity of the offspring's HPA axis and brain serotonergic system.

Cerebrospinal fluid concentrations of large neutral and basic amino acids in Macaca mulatta: diurnal variations and responses to chronic changes in dietary protein intake

In rats, dietary protein intake influences brain concentrations of tryptophan, tyrosine, and other large neutral amino acids (LNAAs) and the neurotransmitters to which they are linked. Few experiments have examined these dietary protein–amino acid relationships in nonhuman primates, in relation to time of day or dietary protein content. We therefore examined the effect in monkeys of changes in chronic protein intake on 24-hour plasma and cerebrospinal fluid (CSF) concentrations of LNAAs (tyrosine, phenylalanine, branched-chain amino acids) and basic amino acids. Juvenile male monkeys ( Macaca mulatta) consumed for sequential 4-week periods diets differing in protein content (∼23% → ∼16% → ∼10% → ∼6% protein [percentage of energy]). The daily ration was presented as a morning meal of fruit and an afternoon meal of fruit and a commercial diet to mimic feeding patterns in the wild. During week 4 on each diet, blood and CSF were sampled repeatedly over a 48-hour period via indwelling catheters. Plasma and CSF LNAA concentrations varied markedly with time of day and dietary protein content, showing up to 4-fold variations. Diurnal variations in plasma and CSF basic amino acids were smaller in magnitude and generally not strongly linked to dietary protein content. A measure of the competitive transport of LNAAs across the blood-brain barrier, calculated using plasma concentrations of the LNAAs and their blood-brain barrier kinetic constants, predicted the observed CSF concentration of each LNAA examined remarkably well, except for phenylalanine. Based on observations in rats, the variations in the CSF concentrations of the LNAAs in monkeys may be large enough to influence metabolic and signaling pathways in brain to which they have been linked.

Functional analysis of the gibbon foot during terrestrial bipedal walking: Plantar pressure distributions and three‐dimensional ground reaction forces

This paper gives a detailed analysis of bipedal walking in the white-handed gibbon, based on collected pressure and force data. These data were obtained from four gibbons in the Wild Animal Park, Planckendael, Belgium, by using a walkway with integrated force plate and pressure mat. This is the first study that collects and describes dynamic plantar pressure data of bipedally walking gibbons, and combines these with force plate data. The combination of these data with previously described roll-off patterns of gibbons, based on general observations, video images, force plates, and EMG data, gives us a detailed description of foot function during gibbon bipedalism. In addition, we compare the observed characteristics of hylobatid bipedalism with the main characteristics of bonobo and human bipedalism. We found that gibbons are midfoot/heel plantigrade, and lack the typical heel-strike of other hominoids. The hallux is widely abducted and touches down at the onset of the stance phase, which results in an L-shaped course of the center of pressure. The vertical force curve is trapezoid to triangular in shape, with high peak values compared to humans. The braking component is shorter than the accelerating component, and shortens further at higher walking velocities. Speed has a significant influence on the forefoot peak pressures and on most of the defined gait parameters (e.g., vertical force peak), and it alters the foot contact pattern as well. The investigation of existing form-function relationships in nonhuman primates is essential for the interpretation of fossil remains, and might help us understand the evolution of habitual bipedal walking in hominids.

Reciprocity and interchange in the social relationships of wild male chimpanzees

Social relationships in nonhuman primates result from investments that individuals make while pursuing fitness-maximizing strategies. These strategies sometimes include social exchange, either reciprocity (exchange of the same acts) or interchange (exchange of different acts). Individuals in many species may negotiate for services in biological markets, particularly grooming and agonistic support. They also may compete for access to valuable social partners. Abundant evidence for reciprocity in grooming and in support and for competition over partners exists, notably for females in some cercopithecines. However, evidence for interchange of grooming and support is scarcer, and apparent interchange may be a byproduct of correlations between grooming or support and some third variable (e.g. dominance rank). Chimpanzees have been prominent in discussions of social exchange, especially because male chimpanzees cooperate in many ways. Most analyses of interchange have used data on captive chimpanzees; these provide good evidence for reciprocity, but ambiguity with regard to interchange. Data on an unusually large chimpanzee community at Ngogo, Kibale National Park, Uganda, strongly support the argument that social exchange is prominent in social relationships among males. Males at Ngogo show reciprocity in grooming and support. They also interchange grooming given and support received, as well as grooming received and support given, independently of reciprocity in grooming and support and of correlations of support and grooming with dominance rank. However, most cooperation in contests with third parties took low risk forms (e.g. both participants outranked their opponent). In this, males at Ngogo resemble captive chimpanzees and female cercopithecines. Reciprocity and interchange in this context may be important in the maintenance of social bonds between males, and in attainment and maintenance of high dominance rank, but probably represent mutualism, not reciprocal altruism.

The evolution of female social relationships in nonhuman primates

Considerable interspecific variation in female social relationships occurs in gregarious primates, particularly with regard to agonism and cooperation between females and to the quality of female relationships with males. This variation exists alongside variation in female philopatry and dispersal. Socioecological theories have tried to explain variation in female-female social relationships from an evolutionary perspective focused on ecological factors, notably predation and food distribution. According to the current “ecological model”, predation risk forces females of most diurnal primate species to live in groups; the strength of the contest component of competition for resources within and between groups then largely determines social relationships between females. Social relationships among gregarious females are here characterized as Dispersal-Egalitarian, Resident-Nepotistic, Resident-Nepotistic-Tolerant, or Resident-Egalitarian. This ecological model has successfully explained differences in the occurrence of formal submission signals, decided dominance relationships, coalitions and female philopatry. Group size and female rank generally affect female reproduction success as the model predicts, and studies of closely related species in different ecological circumstances underscore the importance of the model. Some cases, however, can only be explained when we extend the model to incorporate the effects of infanticide risk and habitat saturation. We review evidence in support of the ecological model and test the power of alternative models that invoke between-group competition, forced female philopatry, demographic female recruitment, male interventions into female aggression, and male harassment. Not one of these models can replace the ecological model, which already encompasses the between-group competition. Currently the best model, which explains several phenomena that the ecological model does not, is a “socioecological model” based on the combined importance of ecological factors, habitat saturation and infanticide avoidance. We note some points of similarity and divergence with other mammalian taxa; these remain to be explored in detail.

Attacking Feminism is No Substitute for Good Scholarship

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Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol

Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.

Experimental maternal and neonatal folate status relationships in nonhuman primates

The influence of maternal dietary folic acid intake on folate status was studied in Cebus albifrons monkeys by feeding 10 or 250 micrograms/100 kcal dietary folic acid during pregnancy and 4 wk postpartum. Maternal, infant, and nonpregnant hematologic indices; blood and liver folate concentrations; and urinary formiminoglutamic acid excretion all varied with dietary folate intake and pregnancy status as did milk folate concentration in lactating dams. Maternal folate status, determined by plasma, red blood cell, and milk folate concentrations, as well as urinary formiminoglutamic acid excretion, all were correlated significantly with liver folate concentrations in neonates (r = 0.740, r = 0.919, r = 0.936, and r = -0.851, respectively). Results in these primates showed that neonatal folate status was related significantly to the dietary folate intake and folate status of the mother during pregnancy and lactation.

Bladder and Ureteral Pressure Relationships in Nonhuman Primates

Bladder pressures during filling are precisely paralleled by ureteral resistance to perfusion. The pressure relationships are identical in normal, spinal and decentralized nonhuman primates, none of which had vesicoureteral reflux. Intravesical and thus intraureteral pressures are higher in animals with neurological lesions, particularly decentralization.