Evolution of threat response-related polymorphisms at the SLC6A4 locus in callitrichid primates.

Variation in an upstream repetitive region at the SLC6A4 locus, which encodes the serotonin transporter, is associated with anxiety-related behaviour in a few primate species, including humans and rhesus macaques, and has been suggested to be related to ecological adaptability among macaques. In this study, we investigate evolution of SLC6A4 polymorphisms associated with anxiety-related behaviour in common marmosets (Callithrix jacchus). Assaying variation in the SLC6A4 repeat region across 14 species in eight genera of callitrichid primates (marmosets and tamarins), we find large interspecific variation in the number of repeats present (24-43). The black tufted-ear marmoset (C. penicillata) has sequence polymorphisms similar to those found in the common marmoset, which is its sister species, and no other species has intraspecific variation at these sites. We conclude that, similar to humans and macaques, the functional polymorphism at SLC6A4 in common marmosets has a recent evolutionary origin, and that the anxiety-related allele is evolutionarily derived. Common/black tufted-ear marmosets and rhesus/bonnet macaques share high ecological adaptability and behavioural flexibility that we propose may be related to the maintenance of the polymorphism.

Diet and the evolution of ADH7 across seven orders of mammals.

Dietary variation within and across species drives the eco-evolutionary responsiveness of genes necessary to metabolize nutrients and other components. Recent evidence from humans and other mammals suggests that sugar-rich diets of floral nectar and ripe fruit have favoured mutations in, and functional preservation of, the ADH7 gene, which encodes the ADH class 4 enzyme responsible for metabolizing ethanol. Here we interrogate a large, comparative dataset of ADH7 gene sequence variation, including that underlying the amino acid residue located at the key site (294) that regulates the affinity of ADH7 for ethanol. Our analyses span 171 mammal species, including 59 newly sequenced. We report extensive variation, especially among frugivorous and nectarivorous bats, with potential for functional impact. We also report widespread variation in the retention and probable pseudogenization of ADH7. However, we find little statistical evidence of an overarching impact of dietary behaviour on putative ADH7 function or presence of derived alleles at site 294 across mammals, which suggests that the evolution of ADH7 is shaped by complex factors. Our study reports extensive new diversity in a gene of longstanding ecological interest, offers new sources of variation to be explored in functional assays in future study, and advances our understanding of the processes of molecular evolution.

Ranking mAb-excipient interactions in biologics formulations by NMR spectroscopy and computational approaches.

Excipients are added to biopharmaceutical formulations to enhance protein stability and enable the development of robust formulations with acceptable physicochemical properties, but the mechanism by which they confer stability is not fully understood. Here, we aimed to elucidate the mechanism through direct experimental evidence of the binding affinity of an excipient to a monoclonal antibody (mAb), using saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopic method. We ranked a series of excipients with respect to their dissociation constant (KD) and nonspecific binding constants (Ns). In parallel, molecular dynamic and site identification by ligand competitive saturation (SILCS)-Monte Carlo simulations were done to rank the excipient proximity to the proteins, thereby corroborating the ranking by STD NMR. Finally, the excipient ranking by NMR was correlated with mAb conformational and colloidal stability. Our approach can aid excipient selection in biologic formulations by providing insights into mAb-excipient affinities before conventional and time-consuming excipient screening studies are conducted.

Symptomatic fractures in systemic sclerosis: A case-control study.

This case-control study analyzed risk factors for symptomatic fractures in a group of 52 patients with systemic sclerosis compared with a group of 104 patients without fractures, matched for sex and age, who were attended at a single systemic sclerosis outpatient clinic from 2010 to 2020. Fractures affected predominantly vertebral (65.4%), rib (13.5%), and hip (7.7%) joints, while the mean age of fracture was 55.3 ± 9.5 years. Age at disease onset, age at diagnosis, disease duration, age at menarche, and age at menopause were similar in both groups, and 58.9% of the patients were menopausal at the time of the fracture. The presence of fractures had a significant association with densitometric osteoporosis (p < 0.001), lower weight (p = 0.032), and bone mineral index (p = 0.044), anti-RNA polymerase III (p = 0.040), use of corticosteroids (p = 0.019), and bisphosphonates (p < 0.001), as well as with densitometric T-scores of lumbar spine (p < 0.001), femoral neck (p = 0.025), and total hip (p = 0.013). Multivariate analysis showed that the variables significantly associated with fractures were high doses of corticosteroids (odds ratio = 4.10; 95% confidence interval = 1.290-13.090; p = 0.017), bisphosphonates (odds ratio = 3.91; 95% confidence interval = 1.699-8.984; p = 0.001), negative anti-Scl70 (OR = 0.34; 95% confidence interval = 0.124-0.943; p = 0.038), and lumbar T-score (odds ratio = 0.39; 95% confidence interval = 0.034-0.460; p = 0.010). In conclusion, symptomatic fractures were associated predominantly with lower bone mineral density of lumbar spine and use of high doses of corticosteroids and bisphosphonates in this cohort.

Spontaneous object recognition in capuchin monkeys: assessing the effects of sex, familiarization phase and retention delay.

The spontaneous object recognition (SOR) task is a versatile and widely used memory test that was only recently established in nonhuman primates (marmosets). Here, we extended these initial findings by assessing the performance of adult capuchin monkeys on the SOR task and three potentially intervening task parameters-object familiarization phase, retention delay and sex. In Experiment 1, after an initial 10-min familiarization period with two identical objects and a pre-established retention delay (0.5, 6 or 24 h), the capuchins preferentially explored a new rather than the familiar object during a 10-min test trial, regardless of delay length. In Experiment 2, the capuchins were again exposed to two identical objects (but now for 10 or 20 min), then a 30-min retention delay and a 10-min test trial. An exploratory preference for the new over the familiar item was not affected by the length of the familiarization interval, possibly because overall exploration remained the same. However, the amount of initial object exploration was not related to task performance, and both males and females performed similarly on the SOR task with a 10-min familiarization, 30-min delay and 10-min test trial. Therefore, male and female capuchins recognize objects on the SOR task after both short and long delays, whereas a twofold increase in the familiarization phase does not affect task performance. The results also provide further support for the use of incidental learning paradigms to assess recognition memory in nonhuman primates.

A high-performance electrochemical sensor based on a mesoporous silica/titania material and cobalt(II) phthalocyanine for sensitive pentachlorophenol determination.

The synthesis and characterization of a novel titania/silica hybrid xerogel subsequently modified with 4-methylpyridine (4-Pic), named TiSi4Pic+Cl- is reported. The physicochemical, structural and thermal properties of TiSi4Pic+Cl- were characterized using several techniques. Anchoring cobalt(II) phthalocyanine (CoTsPc) in TiSi4Pic+Cl- showed greater electroanalytical sensitivity over other sensors built with these materials. A novel electroanalytical method was developed to quantify the noxious biocide pentachlorophenol (PCP) for environmental monitoring. The peak current intensity increased linearly with the analyte concentration in the range between 0.99 and 4.21 µmol L-1, based on the oxidation process (at + 0.81 V, vs. Ag/AgCl) of differential pulse voltammetry (DPV). The estimated limit of detection (LOD) was 29 nmol L-1. Recovery tests in environmental samples showed a PCP concentration of 2.05 ± 0.03 µmol L-1 (n = 3). The method was statistically validated by comparing the PCP concentrations with those obtained by molecular absorption spectrometry and high-performance liquid chromatography-diode array detection (HPLC-DAD). At a 95% confidence level, no difference between the results was found, therefore confirming the excellent accuracy of the proposed method.

Lower hand grip in rheumatoid arthritis patients is associated with low finite element analysis using high resolution peripheral quantitative computed tomography scan of the 2nd metacarpophalangeal joint.

AIM: To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs ≥18 kgf). A logistic regression was performed using hand grip test <18 kgf as a dependent variable. RESULTS: A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). CONCLUSION: Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.

A single brief stressful event time-dependently affects object recognition memory and promotes familiarity preference in marmoset monkeys.

A stressful experience can enhance information storage and impair memory retrieval in the rodent novel object recognition (NOR) task. However, recent conflicting results underscore the need for further investigation. Nonhuman primates may provide a unique, underexplored and more translational means to investigate stress-mediated changes in memory. Therefore, we assessed whether a single brief extrinsic stress event affects information encoding, storage and/or retrieval in adult marmoset monkeys submitted to the NOR task. This consisted of an initial 10 min familiarization period with two identical neutral objects. After a 6 h delay, a 10 min test trial was held where a new and familiar object could be explored. Stress was induced by a 15 min restraint event held before or after the encoding phase, or prior to retrieval. Pre-encoding stress had no effect on task performance, as this group displayed above-chance novelty preference similar to non-stressed controls. Post-encoding stress induced memory deficits, with both objects being explored equally. Interestingly, pre-retrieval stress induced an above-chance familiarity preference. A single brief stressful event thus affects recognition memory in a time-dependent manner. Also, negative discrimination ratios can be used as a measure of memory in the NOR task and a change in strategy may not mean memory failure in spontaneous learning paradigms.

Reliability of quantitative sensory testing on myofascial trigger points in the upper trapezius muscle of individuals with chronic neck pain.

OBJECTIVE: The objective of this study was to measure the intra- and inter-rater reliability of the quantitative sensory testing for measuring the thermal pain threshold on myofascial trigger points in the upper trapezius muscle of individuals with chronic neck pain. METHODS: Thirty female participants were included, aged between 18 and 45 years and with bilateral myofascial trigger points, active and centrally located in the upper trapezius muscle. Two measurements with quantitative sensory testing were performed by each examiner at an interval of 1 week between them. RESULTS: We observed substantial reliability for the intra-rater analysis (intraclass correlation coefficient ranging between 0.876 and 0.896) and excellent reliability for the inter-rater analysis (intraclass correlation coefficient ranging between 0.917 and 0.954). CONCLUSION: The measurement of the thermal pain threshold on myofascial trigger points in individuals with chronic neck pain has acceptable reliability values, supporting the use of the quantitative sensory testing in the research setting and the clinical environment.

Reliability of quantitative sensory testing on myofascial trigger points in the upper trapezius muscle of individuals with chronic neck pain

SUMMARY OBJECTIVE: The objective of this study was to measure the intra- and inter-rater reliability of the quantitative sensory testing for measuring the thermal pain threshold on myofascial trigger points in the upper trapezius muscle of individuals with chronic neck pain. METHODS: Thirty female participants were included, aged between 18 and 45 years and with bilateral myofascial trigger points, active and centrally located in the upper trapezius muscle. Two measurements with quantitative sensory testing were performed by each examiner at an interval of 1 week between them. RESULTS: We observed substantial reliability for the intra-rater analysis (intraclass correlation coefficient ranging between 0.876 and 0.896) and excellent reliability for the inter-rater analysis (intraclass correlation coefficient ranging between 0.917 and 0.954). CONCLUSION: The measurement of the thermal pain threshold on myofascial trigger points in individuals with chronic neck pain has acceptable reliability values, supporting the use of the quantitative sensory testing in the research setting and the clinical environment.

Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases.

BACKGROUND: Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. OBJECTIVE: This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. METHODS AND RESULTS: A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). CONCLUSION: Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. TRIAL REGISTRATION: This clinical trial was registered with Clinicaltrials.gov (#NCT03430388).

Scopolamine and MK-801 impair recognition memory in a new spontaneous object exploration task in monkeys.

The spontaneous object recognition (SOR) task is one of the most widely used behavioral protocols to assess visual memory in animals. However, only recently was it shown that nonhuman primates also perform well on this task. Here we further characterized this new monkey recognition memory test by assessing the performance of adult marmosets after an acute systemic administration of two putative amnesic agents: the competitive muscarinic acetylcholine receptor antagonist scopolamine (SCP; 0.05 mg/kg) and the noncompetitive N-methyl-d-aspartate glutamate receptor antagonist MK-801 (0.015 mg/kg). We also determined whether the acetylcholinesterase inhibitor donepezil (DNP; 0.50 mg/kg), a clinically-used cognitive enhancer, reverses memory deficits caused by either drug. The subjects had an initial 10 min sample trial where two identical neutral objects could be explored. After a 6 h retention interval, recognition was based on an exploratory preference for a new rather than familiar object during a 10 min test trial. Both SCP and MK-801 impaired the marmosets' performance on the SOR task, as both objects were explored equivalently. Co-administration of 0.50 mg/kg of DNP reversed the SCP- but not the MK-801-induced memory deficit. These results indicate that cholinergic and glutamatergic pathways mediate object recognition memory in the monkey SOR task.

The Perception of the Müller-Lyer Visual Illusion in Schizophrenics and Non-human Primates: A Translational Approach.

The Müller-Lyer Illusion (MLI) has been suggested as a potential marker for the perceptual impairments observed in schizophrenia patients. Along with some positive symptoms, these deficits are not easily modeled in rodent experiments, and novel animal models are warranted. Previously, MK-801 was shown to reduce susceptibility to MLI in monkeys, raising the prospects of an effective perception-based model. Here, we evaluate the translational feasibility of the MLI task under NMDA receptor blockage as a primate model for schizophrenia. In Experiment 1, eight capuchin monkeys (Sapajus spp.) were trained on a touchscreen MLI task. Upon reaching the learning criteria, the monkeys were given ketamine (0.3 mg/kg; i.m.) or saline on four consecutive days and then retested on the MLI task. In Experiment 2, eight chronic schizophrenia patients (and eight matching controls) were tested on the Brentano version of the MLI. Under saline treatment, monkeys were susceptible to MLI, similarly to healthy human participants. Repeated ketamine administrations, however, failed to improve their performance as previous results with MK-801 had shown. Schizophrenic patients, on the other hand, showed a higher susceptibility to MLI when compared to healthy controls. In light of the present and previous studies, the MLI task shows consistent results across monkeys and humans. In spite of potentially being an interesting translational model of schizophrenia, the MLI task warrants further refinement in non-human primates and a broader sample of schizophrenia subtypes.

Opalescence Measurements: Improvements in Fundamental Knowledge, Identifying Sources of Analytical Biases, and Advanced Applications for the Development of Therapeutic Proteins.

Opalescence of biopharmaceutical solutions can indicate suboptimal colloidal stability and is therefore a generally undesirable attribute that requires investigation and potentially remediation. While there are numerous instrumentation options available for measuring opalescence, cross-instrument comparisons and detailed knowledge of analytical biases have been limited.  Here, we highlight key findings from a multi-instrument investigation where differences in reported opalescence values are explained with particular emphasis on how the optical configuration and detector properties of each instrument affect the response of the sample and the primary formazin standards required for instrument calibration. In doing so, the particle size distribution, angular-dependent light scattering properties and refractive index of the primary formazin standard material are characterized and presented. Finally, the advanced application of a 90° angle light scattering instrument is presented as a suitable approach for making low volume, temperature controlled, nephelometric measurements of opalescence.  Moreover, we demonstrate how this approach enables the simultaneous evaluation of key physical properties, such as hydrodynamic size, that are pertinent to investigations of opalescent biopharmaceuticals but have historically required the use of separate instrumentation.  The findings reported here address key knowledge gaps and provide opportunities for improving the efficiency and inter-laboratory comparability of opalescence measurements for biopharmaceuticals.

Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory.

Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mechanisms of two different types of memory, such as appetitively and aversively motivated memory, which are considered to be mediated by different neural mechanisms. We found an association between superior performance in short- and long-term appetitively motivated learning and regionally enhanced neutral sphingomyelinase (NSM) activity. An opposite interaction was observed in an aversively motivated task. A valence-dissociating role of NSM in learning was confirmed in mice with genetically reduced NSM activity. This role may be mediated by the NSM control of N-methyl-d-aspartate receptor subunit expression. In a translational approach, we confirmed a positive association of serum NSM activity with long-term appetitively motivated memory in nonhuman primates and in healthy humans. Altogether, these data suggest a new sphingolipid mechanism of de-novo learning and memory, which is based on NSM activity.

Neutral ceramidase is a marker for cognitive performance in rats and monkeys.

BACKGROUND: Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates. METHODS: Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats. RESULTS: We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance. CONCLUSIONS: Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.

Social buffering of cortisol release and tympanic temperature asymmetries during novelty and isolation stress in marmoset monkeys.

Novel environments induce a conflicting emotional approach-withdrawal state that triggers stress-related reactions. Social support through the presence of a highly familiar conspecific buffers the individual against such challenges. Although aversive events seem to be predominantly processed by the right hemisphere, this is still under debate and little is known about functional cerebral asymmetries in nonhuman primates during novelty stress, isolation and social buffering. Here we isolated adult marmoset monkeys in a new open-field arena or in their familiar home-cages to establish hemisphere activity and whether the pairmate's presence buffers the response. Monkeys socially isolated in either location had higher circulating cortisol levels than non-isolated marmosets, but different hemisphere activity patterns indicated by changes in baseline tympanic membrane temperatures (TMT). The bilateral increase in the monkeys that were isolated in the unfamiliar location may reflect an approach-withdrawal conflict. The left-sided increase in the home-cage isolation group was negatively related to cortisol release, this being potentially associated with a more proactive/approach-prone temperament. Interestingly, TMT and cortisol were unaltered when the pairmate was present. Thus, positive social interaction reduces the perceived intensity of the threat, alters hemisphere asymmetries and blocks the hormonal response to novelty stress, consistent with a buffering effect.

Cocaine attenuates acid sphingomyelinase activity during establishment of addiction-related behavior-A translational study in rats and monkeys.

Cocaine addiction is a severe psychiatric condition for which currently no effective pharmacotherapy is available. Brain mechanisms for the establishment of addiction-related behaviors are still not fully understood, and specific biomarkers for cocaine use are not available. Sphingolipids are major membrane lipids, which shape neuronal membrane composition and dynamics in the brain. Here, we investigated how chronic cocaine exposure during establishment of addiction-related behaviors affects the activity of the sphingolipid rheostat controlling enzymes in the brain of rats. As we detected specific effects on several enzymes in the brain, we tested whether the activity of selected enzymes in the blood may serve as potential biomarker for cocaine exposure in non-human primates (Callithrix penicillata). We found that intravenous cocaine self-administration led to a reduced mRNA expression of Cers1, Degs1 and Degs2, and Smpd1 in the prefrontal cortex of rats, as well as a reduction of Cers4 expression in the striatum. These effects reversed after 10 days of abstinence. Monkeys showed a robust cocaine-induced place preference (CPP). This coincided with a reduction in blood acid sphingomyelinase (ASM) activity after CPP establishment. This effect normalized after 15 days of abstinence. Altogether, these findings suggest that the establishment of cocaine addiction-related behaviors coincides with changes in the activity of sphingolipid controlling enzymes. In particular, blood ASM levels may serve as a translational biomarker for recent cocaine exposure.

The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease.

Innate immunity is associated with Alzheimer's disease1, but the influence of immune activation on the production of amyloid-ß is unknown2,3. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-ß. Inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-ß. The expression of IFITM3 is increased with ageing and in mouse models that express familial Alzheimer's disease genes. Furthermore, knockout of IFITM3 reduces γ-secretase activity and the formation of amyloid plaques in a transgenic mouse model (5xFAD) of early amyloid deposition. IFITM3 protein is upregulated in tissue samples from a subset of patients with late-onset Alzheimer's disease that exhibit higher γ-secretase activity. The amount of IFITM3 in the γ-secretase complex has a strong and positive correlation with γ-secretase activity in samples from patients with late-onset Alzheimer's disease. These findings reveal a mechanism in which γ-secretase is modulated by neuroinflammation via IFITM3 and the risk of Alzheimer's disease is thereby increased.

Time-Dependent Changes in Cortisol and Tympanic Temperature Lateralization During Food Deprivation Stress in Marmoset Monkeys.

Temporal information about food availability can be easily entrained, as in the case of fixed feeding routines of captive animals. A sudden unintentional or deliberate delay (e.g., food deprivation-FD) leads to frustration and psychological stress due to the loss of temporal predictability. How marmosets-an increasingly used small primate-process and respond to FD stress has not been previously assessed. Here we delayed the routine feeding of adult captive marmosets for 3 or 6 h. Blood cortisol concentration was used as a hormonal measure of the stress response. Changes in the left/right baseline tympanic membrane temperature (TMT) were used as an indirect ipsilateral indicator of hemisphere activity. Marmosets that were deprived for 3 h had higher cortisol levels than non-deprived controls. Cortisol concentration in the marmosets deprived for 6 h did not differ from controls possibly due to adaptative mechanisms against the detrimental effects of prolonged high cortisol levels. Interestingly, FD stress may have been processed more symmetrically at first, as indicated by the bilateral increase in TMT at the 3 h interval. As the event progressed (i.e., 6 h), a clear rightward TMT bias suggests that hemisphere activity had become asymmetrical. Therefore, the sudden loss of temporal predictability of an entrained routine feeding schedule induces time-dependent changes in the cortisol stress response and shifts in the TMT (and potentially hemisphere activity) lateralization bias of adult captive marmosets.