Expression of bond-related behaviors affects titi monkey responsiveness to oxytocin and vasopressin treatments.

Social bonds influence physiology and behavior, which can shape how individuals respond to physical and affective challenges. Coppery titi monkey (Plecturocebus cupreus) offspring form selective bonds with their fathers, making them ideal for investigating how father-daughter bonds influence juveniles' responses to oxytocin (OT) and arginine-vasopressin (AVP) manipulations. We quantified the expression of father-daughter bond-related behaviors in females (n = 10) and gave acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or an OT receptor antagonist (OTA) to subjects prior to a parent preference test. While females spent more time in proximity to their parents than strangers, we found a large degree of individual variation. Females with greater expression of bonding behaviors responded to OT treatments in a dose-dependent manner. Subjects also spent less time in proximity to strangers when treated with High OT (p = 0.003) and Low OT (p = 0.007), but more time when treated with High AVP (p = 0.007), Low AVP (p = 0.009), and OTA (p = 0.001). Findings from the present study suggest that variation in the expression of bond-related behaviors may alter responsiveness to OT and AVP, increasing engagement with unfamiliar social others. This enhanced sociality with strangers may promote the formation of pair bonds with partners.

Intranasal oxytocin does not change partner preference in female titi monkeys (Plecturocebus cupreus), but intranasal vasopressin decreases it.

Strong social bonds are critical to human health; however, the mechanisms by which social bonds are formed and maintained are still being elucidated. The neurohormones oxytocin (OT) and vasopressin (AVP) are considered likely candidates. Primate females, both human and nonhuman, remain understudied populations. Here, we conducted a pharmacological study coupled with a behavioral partner preference test (PPT) to better understand the mechanistic basis of attachment in adult female titi monkeys (Plecturocebus cupreus). This pair-bonding species shares a conserved form of oxytocin with humans and is an excellent model organism to study the neural basis of social bonding. We performed intranasal administration of three doses of oxytocin (IN-OT), two doses of vasopressin (IN-AVP), one dose of an oxytocin antagonist (IN-OTA) and one dose of a saline treatment. We found that compared to the saline control, the IN-AVP treatment (lower dose, 40 IU/kg) decreased the time spent in proximity to the partner and increased lip-smacking toward the stranger. We found no effects of IN-OT or IN-OTA manipulation on partner preference. In contrast, low-dose IN-AVP weakened the partner preference in female titi monkeys.

Titi monkey father-daughter bond-related behaviors explain stress response variability.

Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds. We established a method for quantifying variability in expression of bond-related behaviors in females (n = 12), and the present study is the second to use this method for explaining titi monkey responses to behavioral tests. We also investigated how manipulations of oxytocin (OT) and vasopressin (AVP) influenced juvenile behavior and physiology. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT receptor antagonist (OTA) prior to an acute social separation. General linear mixed-effects model results revealed fathers were significant behavioral and physiological stress buffers for their daughters, as evidenced by fewer distress vocalizations (p < 0.001), less locomotion (p < 0.001), and lower plasma cortisol (p < 0.001) in a social separation paradigm. Females vocalized less if they exhibited greater expression of bond-related behaviors with their fathers as infants (p = 0.01), and this stress-buffering effect remained even when the daughter was separated from the father (p = 0.001). While treatments did not alter behaviors, OTA treatment caused the largest rise in plasma cortisol (p < 0.001), suggesting blockade of OT receptors can inhibit fathers' stress-buffering effects. Remarkably, females with greater expression of father-daughter bond-related behaviors exhibited an overall reduced physiological separation distress response (p = 0.04). Findings from the present study advance current knowledge of the neurobiological mechanisms foundational to female bonds and help inform how social disruptions may differently impact individuals based on expression of bond-related behaviors.

Initial compatibility during a "Speed-Dating" test predicts postpairing affiliation in titi monkeys (Plecturocebus cupreus).

Behavioral compatibility plays a critical role in shaping how potential mates interact with and evaluate each other and whether they choose to pursue a relationship. Compatibility is especially important for mate choice and relationship quality in pair-bonding species that form long-term attachments between mates. Although this process has been studied in humans and birds, relatively few studies have investigated it in non-human primates. In this study, we investigated whether pairing titi monkeys (Plecturocebus cupreus) based on initial compatibility increased postpairing affiliation between mates. Subjects were 12 unpaired adult titi monkeys (two cohorts of three males and three females). We determined each subject's initial interest in each opposite-sex potential mate in their cohort across a series of six 30-min interaction periods (i.e., "speed-dates"). To determine initial compatibility, we used the Social Relations Model to calculate relationship effects in initial interest (how much each subject uniquely preferred each potential mate beyond their own affiliative disposition and their partner's popularity). We then paired monkeys in a way that maximized net relationship effects between pairs, and measured longitudinal pair affiliation (Proximity, Contact, Tail Twining, and Combined Affiliation) for 6 months postpairing using daily scan-sample observations and monthly home-cage video recordings. Multilevel models showed that, on average, the six speed-dating pairs exhibited higher levels of Tail Twining (determined from scan-sample observations; ß = 0.31) compared to a group of 13 age-matched colony pairs that were determined quasi-randomly without quantifying compatibility. The degree of initial compatibility within speed-dating pairs also predicted higher levels of Combined Affiliation (determined from video recordings) at earlier post-pairing time points, with the association peaking at 2 months postpairing (ß = 0.57). These findings suggest that initial compatibility facilitates pair bonding in titi monkeys. We conclude by discussing how the speed-dating design can be used for colony management to inform pair-housing decisions.

Effects of aging on glucose and lipid metabolism in mice.

Aging is accompanied by multiple molecular changes that contribute to aging-associated pathologies, such as accumulation of cellular damage and mitochondrial dysfunction. Tissue metabolism can also change with age, in part because mitochondria are central to cellular metabolism. Moreover, the co-factor NAD+, which is reported to decline across multiple tissue types during aging, plays a central role in metabolic pathways such as glycolysis, the tricarboxylic acid cycle, and the oxidative synthesis of nucleotides, amino acids, and lipids. To further characterize how tissue metabolism changes with age, we intravenously infused [U-13C]-glucose into young and old C57BL/6J, WSB/EiJ, and Diversity Outbred mice to trace glucose fate into downstream metabolites within plasma, liver, gastrocnemius muscle, and brain tissues. We found that glucose incorporation into central carbon and amino acid metabolism was robust during healthy aging across these different strains of mice. We also observed that levels of NAD+, NADH, and the NAD+/NADH ratio were unchanged in these tissues with healthy aging. However, aging tissues, particularly brain, exhibited evidence of up-regulated fatty acid and sphingolipid metabolism reactions that regenerate NAD+ from NADH. Because mitochondrial respiration, a major source of NAD+ regeneration, is reported to decline with age, our data supports a model where NAD+-generating lipid metabolism reactions may buffer against changes in NAD+/NADH during healthy aging.

Pairing status and stimulus type predict responses to audio playbacks in female titi monkeys.

Some paired primates use complex, coordinated vocal signals to communicate within and between family groups. The information encoded within those signals is not well understood, nor is the intricacy of individuals' behavioral and physiological responses to these signals. Considering the conspicuous nature of these vocal signals, it is a priority to better understand paired primates' responses to conspecific calls. Pair-bonded titi monkeys (Plecturocebus cupreus) sing duets comprised of the male and female's long call. Here, we use a playback study to assess female titi monkeys' responses to different vocal stimuli based on the subject's pairing status. Six adult female titi monkeys participated in the study at two timepoints--pre-pairing and post-pairing. At each timepoint, subjects underwent three distinct playbacks--control recording, male solo vocalization, and pair duet. Behaviors such as locomotion and vocalizations were scored during and after the playback, and cortisol and androgen values were assessed via a plasma blood sample. Female titi monkeys attended more to social signals compared to the control, regardless of pairing status. However, in the time immediately following any playback type, female titi monkeys trilled more and spent a greater proportion of time locomoting during pre-pairing timepoints (compared to post-pairing). Female titi monkeys' behavioral responses to social audio stimuli, combined with subjects' increases in cortisol and androgens as paired individuals, imply female titi monkeys attend and respond to social signals territorially.

Room size and offspring presence impact pair-bonded primate affiliation.

Primates live in a variety of social groupings and vary in the expression of species-typical behaviors depending upon social conditions. Coppery titi monkeys (Plecturocebus cupreus) are pair-bonding, territorial primates often used to study neurobiology and social behavior in captivity at the California National Primate Research Center (CNPRC). At the center, titi monkeys are housed in cages of standardized size. However, the number of cages--and thus families--per room varies based upon the room size (small or large). Anecdotal evidence suggests titi monkeys behave differently in the two different room sizes. To empirically test this, we measured rates of pair-bonding related affiliation in 23 pairs of titi monkeys. We predicted that monkeys in small rooms would show higher rates of affiliation compared to large rooms. We used a between- and within- subjects design in which all subjects moved from either small to large or large to small rooms. Affiliative behavior was recorded via bihourly instantaneous scan samples. We found that titi monkey pairs affiliated significantly more in small rooms compared to large rooms (partial R2 = 0.1468, t(33) = -3.729, p-value < .0005). We also confirmed that the presence of offspring negatively impacts pair affiliation rates (partial R2 = 0.2240, t(33) = -0.181, p-value = 0.0011). The results of this study suggest that titi monkey pair behavior is influenced by room size, and thus the number of neighboring groups. Management decisions should consider the implications that housing may have on the results of social behavior research.

Effects of Chronic and Acute Intranasal Oxytocin Treatments on Temporary Social Separation in Adult Titi Monkeys (Plecturocebus cupreus).

In socially monogamous titi monkeys, involuntary separation from a pair mate can produce behavioral distress and increased cortisol production. The neuropeptide oxytocin (OXT) is thought to play an important role in the separation response of pair-bonded species. Previous studies from our lab have shown that chronic intranasal oxytocin (IN OXT) during development can have long-term effects on adult social behavior. In the current study, we examined the chronic and acute effects of IN OXT or Saline (SAL) on the subjects' response to a brief separation from their pair mates. Subjects with a history of chronic IN OXT or SAL treatment during development received a single dose of OXT or SAL as adults 30 min before being separated from their pair mate. Chronic treatment consisted of a daily dose of IN OXT (0.8 IU/kg) or SAL (control) from 12 to 18 months of age. Subjects (N = 29) were introduced to a pair mate at 30 months of age. After the pairs had cohabitated for 5 months, pairs underwent two "Brief Separation" (OXT and SAL) and two "Non-Separation" (OXT and SAL) test sessions. Vocalizations and locomotion were measured as behavioral indices of agitation or distress during the Brief Separation and Non-Separation periods (30 min each). We collected blood samples after the Brief Separation and Non-Separation periods to measure cortisol levels. Our results showed subjects treated with chronic OXT had a reduction in long call and peep vocalizations compared to subjects treated with chronic SAL. Subjects treated with chronic SAL and acute OXT produced more peeps and long calls compared to animals treated with acute SAL; however, patterns in this response depended on sex. Cortisol and locomotion were significantly higher during the Brief Separation period compared to the Non-Separation period; however, we did not find any treatment or sex effects. We conclude that chronic IN OXT given during development blunts the separation response, while acute OXT in chronic SAL subjects had sexually dimorphic effects, which could reflect increased partner seeking behaviors in males and increased anxiety in females.

Effects of pairing on color change and central gene expression in lined seahorses.

Social monogamy is a reproductive strategy characterized by pair living and defense of a common territory. Pair bonding, sometimes displayed by monogamous species, is an affective construct that includes preference for a specific partner, distress upon separation, and the ability of the partner to buffer against stress. Many seahorse species show a monogamous social structure in the wild, but their pair bond has not been well studied. We examined the gene expression of lined seahorses (Hippocampus erectus) during and after the process of pairing in the laboratory as well as color change (luminance), a potential form of social communication and behavioral synchrony between pair mates. When a seahorse of either sex was interacting with its pair mate, their changes in luminance ("brightness") were correlated and larger than when interacting with an opposite-sex stranger. At the conclusion of testing, subjects were euthanized, RNA was extracted from whole brains and analyzed via RNA sequencing. Changes in gene expression in paired males versus those that were unpaired included processes governing metabolic activity, hormones and cilia. Perhaps most interesting is the overlap in gene expression change induced by pairing in both male seahorses and male prairie voles, including components of hormone systems regulating reproduction. Because of our limited sample size, we consider our results and interpretations to be preliminary, and prompts for further exploration. Future studies will expand upon these findings and investigate the neuroendocrine and genetic basis of these behaviors.

Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors.

Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Nontransformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide cofactors we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells. This suggests that metabolic interaction between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.

Moderate evidence for heritability in the duet contributions of a South American primate.

Acoustic signals are ubiquitous across mammalian taxa. They serve a myriad of functions related to the formation and maintenance of social bonds and can provide conspecifics information about caller condition, motivation and identity. Disentangling the relative importance of evolutionary mechanisms that shape vocal variation is difficult, and little is known about heritability of mammalian vocalizations. Duetting--coordinated vocalizations within male and female pairs--arose independently at least four times across the Primate Order. Primate duets contain individual- or pair-level signatures, but the mechanisms that shape this variation remain unclear. Here, we test for evidence of heritability in two call types (pulses and chirps) from the duets of captive coppery titi monkeys (Plecturocebus cupreus). We extracted four features--note rate, duration, minimum and maximum fundamental frequency--from spectrograms of pulses and chirps, and estimated heritability of the features. We also tested whether features varied with sex or body weight. We found evidence for moderate heritability in one of the features examined (chirp note rate), whereas inter-individual variance was the most important source of variance for the rest of the features. We did not find evidence for sex differences in any of the features, but we did find that body weight and fundamental frequency of chirp elements covaried. Kin recognition has been invoked as a possible explanation for heritability or kin signatures in mammalian vocalizations. Although the function of primate duets remains a topic of debate, the presence of moderate heritability in titi monkey chirp elements indicates duets may serve a kin recognition function.

Parenting costs time: Changes in pair bond maintenance across pregnancy and infant rearing in a monogamous primate (Plecturocebus cupreus).

Relationships support social animals' health, but maintaining relationships is challenging. When transitioning to parenthood, new parents balance pair-bond maintenance with infant care. We studied pair-bond maintenance via affiliation in 22 adult titi monkey pairs (Plecturocebus cupreus) for 16 months centered around their first offspring's birth. Pair affiliation peaked during pregnancy, decreased across the postpartum period, and rose after reaching minimum affiliation 32.6 weeks postpartum. Pairs in which fathers carry infants more than average had lower affiliation at the infant's birth and return to an increase in affiliation sooner. Parents of infants who were slow to independence had higher rates of affiliation. Titi monkey infants actively prefer their fathers; mothers may avoid their infant-carrying mate, suggesting infants play an active role in parental affiliative decline. Our data supports previous findings that affiliation between partners declines following an infant's birth, but demonstrates new knowledge about the extent and duration of affiliative decline.

Low glycaemic diets alter lipid metabolism to influence tumour growth.

Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1-5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6-8, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth. These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth.

Relationships between cortisol and urinary androgens in female titi monkeys (Plecturocebus cupreus).

Steroid hormones are critical to the regulation of sociosexual behavior. Their role in the formation of pair bonds is complicated by the relative scarcity of this social system in mammals, as well as species and taxonomic differences in endocrine systems. In the present study, we experimentally manipulated the hypothalamic-pituitary-adrenal axis in female titi monkeys (Plecturocebus cupreus), a neotropical monkey studied for its strong, selective pair bonds. We validated an assay for plasma and urinary cortisol in this species, showing a strong suppression of cortisol following dexamethasone injection, and a significant but somewhat blunted response to adrenocorticotrophin hormone (ACTH) stimulation. Urinary androgens did not change in response to dexamethasone or ACTH. Plasma and urinary cortisol were moderately correlated, whereas urinary cortisol and androgens were only correlated when extreme cortisol values were included. In this study, we laid groundwork for studying the role of glucocorticoids and androgens (and eventually, their interactions with peptides) in the behavioral endocrinology of pair bonds in female titi monkeys.

What is a pair bond?

Pair bonding is a psychological construct that we attempt to operationalize via behavioral and physiological measurements. Yet, pair bonding has been both defined differently in various taxonomic groups as well as used loosely to describe not just a psychological and affective phenomenon, but also a social structure or mating system (either social monogamy or just pair living). In this review, we ask the questions: What has been the historical definition of a pair bond? Has this definition differed across taxonomic groups? What behavioral evidence do we see of pair bonding in these groups? Does this observed evidence alter the definition of pair bonding? Does the observed neurobiology underlying these behaviors affect this definition as well? And finally, what are the upcoming directions in which the study of pair bonding needs to head?

Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells.

Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studies on enriched ECM from samples of progressive PDAC stages reveal that the C-terminal prodomains of fibrillar collagens are partially uncleaved in PDAC ECM, suggesting reduced procollagen C-proteinase activity. We further show that the enzyme responsible for procollagen C-proteinase activity, bone morphogenetic protein1 (BMP1), selectively suppresses tumor growth and metastasis in cells expressing high levels of COL1A1. Although BMP1, as a secreted proteinase, promotes fibrillar collagen deposition from both cancer cells and stromal cells, only cancer-cell-derived procollagen cleavage and deposition suppresses tumor malignancy. These studies reveal a role for cancer-cell-derived fibrillar collagen in selectively restraining tumor growth and suggest stratification of patients based on their tumor epithelial collagen I expression when considering treatments related to perturbation of fibrillar collagens.

Titi monkey neophobia and visual abilities allow for fast responses to novel stimuli.

The Snake Detection Theory implicates constricting snakes in the origin of primates, and venomous snakes for differences between catarrhine and platyrrhine primate visual systems. Although many studies using different methods have found very rapid snake detection in catarrhines, including humans, to date no studies have examined how quickly platyrrhine primates can detect snakes. We therefore tested in captive coppery titi monkeys (Plecturocebus cupreus) the latency to detect a small portion of visible snake skin. Because titi monkeys are neophobic, we designed a crossover experiment to compare their latency to look and their duration of looking at a snake skin and synthetic feather of two lengths (2.5 cm and uncovered). To test our predictions that the latency to look would be shorter and the duration of looking would be longer for the snake skin, we used survival/event time models for latency to look and negative binomial mixed models for duration of looking. While titi monkeys looked more quickly and for longer at both the snake skin and feather compared to a control, they also looked more quickly and for longer at larger compared to smaller stimuli. This suggests titi monkeys' neophobia may augment their visual abilities to help them avoid dangerous stimuli.

Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast-Driven Nutritional Support and Immunosuppression.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multiplex data from patient tissue, three-dimensional coculturing in vitro assays, and orthotopic murine models, we identified Netrin G1 (NetG1) as a promoter of PDAC tumorigenesis. We found that NetG1+ cancer-associated fibroblasts (CAF) support PDAC survival, through a NetG1-mediated effect on glutamate/glutamine metabolism. Also, NetG1+ CAFs are intrinsically immunosuppressive and inhibit natural killer cell-mediated killing of tumor cells. These protumor functions are controlled by a signaling circuit downstream of NetG1, which is comprised of AKT/4E-BP1, p38/FRA1, vesicular glutamate transporter 1, and glutamine synthetase. Finally, blocking NetG1 with a neutralizing antibody stunts in vivo tumorigenesis, suggesting NetG1 as potential target in PDAC. SIGNIFICANCE: This study demonstrates the feasibility of targeting a fibroblastic protein, NetG1, which can limit PDAC tumorigenesis in vivo by reverting the protumorigenic properties of CAFs. Moreover, inhibition of metabolic proteins in CAFs altered their immunosuppressive capacity, linking metabolism with immunomodulatory function.See related commentary by Sherman, p. 230.This article is highlighted in the In This Issue feature, p. 211.

Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma.

Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.

Tumors contain a mixture of many different types of cells, including cancer cells and non-cancer cells. The interactions between these two groups of cells affect how the cancer cells use nutrients, which, in turn, affects how fast these cells grow and divide. Furthermore, different cell types may use nutrients in diverse ways to make other molecules ­ known as metabolites ­ that the cell needs to survive. Fibroblasts are a subset of non-cancer cells that are typically found in tumors and can help them form. Separating fibroblasts from cancer cells in a tumor takes a lot longer than the chemical reactions in each cell of the tumor that produce and use up nutrients, also known as the cell's metabolism. Therefore, measuring the levels of glucose (the sugar that is the main energy source for cells) and other metabolites in each tumor cell after separating them does not necessarily provide accurate information about the tumor cell's metabolism. This makes it difficult to study how cancer cells and fibroblasts use nutrients differently. Lau et al. have developed a strategy to study the metabolism of cancer cells and fibroblasts in tumors. Mice with tumors in their pancreas were provided glucose that had been labelled using biochemical techniques. As expected, when the cell processed the glucose, the label was transferred into metabolites that got used up very quickly. But the label also became incorporated into larger, more stable molecules, such as proteins. Unlike the small metabolites, these larger molecules do not change in the time it takes to separate the cancer cells from the fibroblasts. Lau et al. sorted cells from whole pancreatic tumors and analyzed large, stable molecules that can incorporate the label from glucose in cancer cells and fibroblasts. The experiments showed that, in cancer cells, these molecules were more likely to have labeling patterns that are characteristic of two specific enzymes called pyruvate carboxylase and malic enzyme 1. This suggests that these enzymes are more active in cancer cells. Lau et al. also found that pancreatic cancer cells needed these two enzymes to metabolize glucose and to grow into large tumors. Pancreatic cancer is one of the most lethal cancers and current therapies offer limited benefit to many patients. Therefore, it is important to develop new drugs to treat this disease. Understanding how cancer cells and non-cancer cells in pancreatic tumors use nutrients differently is important for developing drugs that only target cancer cells.

New approaches to quantify social development in rhesus macaques (Macaca mulatta): Integrating eye tracking with traditional assessments of social behavior.

The nonhuman primate provides a sophisticated animal model system both to explore neurobiological mechanisms underlying complex behaviors and to facilitate preclinical research for neurodevelopmental and neuropsychiatric disease. A better understanding of evolutionarily conserved behaviors and brain processes between humans and nonhuman primates will be needed to successfully apply recently released NIMH guidelines (NOT-MH-19-053) for conducting rigorous nonhuman primate neurobehavioral research. Here, we explore the relationship between two measures of social behavior that can be used in both humans and nonhuman primates-traditional observations of social interactions with conspecifics and eye gaze detection in response to social stimuli. Infant male rhesus macaques (Macaca mulatta) serving as controls (N = 14) for an ongoing study were observed in their social rearing groups and participated in a noninvasive, longitudinal eye-tracking study. We found significant positive relationships between time spent viewing eyes of faces in an eye tracker and number of initiations made for social interactions with peers that is consistent with similar observations in human populations. Although future studies are needed to determine if this relationship represents species-typical social developmental processes, these preliminary results provide a novel framework to explore the relationship between social interactions and social attention in nonhuman primate models for neurobehavioral development.