Callithrix Research Papers - Academia.edu (original) (raw)

Non-human primate models of human disease have an important role in the translation of a new scientific finding in lower species into an effective treatment. In this study, we tested a new therapeutic antibody against the IL-7 receptor α... more

Non-human primate models of human disease have an important role in the translation of a new scientific finding in lower species into an effective treatment. In this study, we tested a new therapeutic antibody against the IL-7 receptor α chain (CD127), which in a C57BL/6 mouse model of experimental autoimmune encephalomyelitis (EAE) ameliorates disease, demonstrating an important pathogenic function of IL-7. We observed that while the treatment was effective in 100 % of the mice, it was only partially effective in the EAE model in common marmosets (Callithrix jacchus), a smallbodied Neotropical primate. EAE was induced in seven female marmoset twins and treatment with the anti-CD127 mAb or PBS as control was started 21 days after immunization followed by weekly intravenous administration. The anti-CD127 mAb caused functional blockade of IL-7 signaling through its receptor as shown by reduced phosphorylation of STAT5 in lymphocytes upon stimulation with IL-7. Groupwise analysis showed no significant effects on the clinical course and neuropathology. However, paired twin analysis revealed a delayed disease onset in three twins, which were high responders to the immunization. In addition, we observed markedly opposite effects of the antibody on pathological changes in the spinal cord in high versus low responder twins. In conclusion, promising clinical effect of CD127 blockade observed in a standard inbred/SPF mouse EAE model could only be partially replicated in an outbred/non-SPF non-human primate EAE model. Only in high responders to the immunization we found a positive response to the treatment. The mechanism underpinning this dichotomous response will be discussed.

. The localization and distribution of non-phosphorylated neurofilaments NP-NF in the upper and lower motor neurons was investigated in the rat, the common marmoset, the rhesus monkey and man using the SMI-32 antibody. Within the spinal... more

. The localization and distribution of non-phosphorylated neurofilaments NP-NF in the upper and lower motor neurons was investigated in the rat, the common marmoset, the rhesus monkey and man using the SMI-32 antibody. Within the spinal cord of all species studied, the most intense NP-NF immunoreactivity was observed within the ventral horn a-motor neurons. Concurrent staining for Ž . the cholinergic marker choline acetyltransferase ChAT demonstrated that virtually all of the ChAT-positive a-motor neurons contain NP-NF immunoreactivity. Although NP-NF staining was also observed in other neurons within the ventral and intermediate horns, these neurons were loosely scattered and contained a considerably lower staining intensity. The only other prominent NP-NF staining in the spinal cord occurred within the neurons of the dorsal nucleus of Clark and the intermediolateral cell column. Phosphorylated Ž . neurofilament P-NF immunoreactivity was found primarily in neuronal processes. Occasionally, a solitary motor neuron contained weak P-NF immunoreactivity. Within the brainstem, neurons in all cranial nerve motor nuclei contained intense NP-NF immunoreactivity. The distribution and apparent density of NP-NF immunoreactive neurons in these nuclei was virtually identical to that observed for neurons immunoreactive for ChAT. NP-NF immunoreactive neurons of relatively lower intensity were found in many other regions of the Ž . brainstem. All of the giant Betz cells of layer L V in the motor cortex contained dark NP-NF immunoreactivity. Within the spinal cord Ž . of amyotrophic lateral sclerosis ALS patients, both Nissl and NP-NF staining demonstrated the dramatic loss of a-motor neurons characteristic of this disorder. Some of the remaining motor neurons contained intense P-NF immunoreactivity. These observations suggest that NP-NF immunoreactivity is a good marker for motor neurons in health and disease and may be a useful tool for studies of Ž . motor neuron degeneration MND . q

Increasing evidence suggests that personality structure differs between species, but the evolutionary reasons for this variation are not fully understood. We built on earlier research on New World monkeys to further elucidate the... more

Increasing evidence suggests that personality structure differs between species, but the evolutionary reasons for this variation are not fully understood. We built on earlier research on New World monkeys to further elucidate the evolution of personality structure in primates. We therefore examined personality in 100 family-reared adult common marmosets (Callithrix jacchus) from 3 colonies on a 60-item questionnaire. Principal components analyses revealed 5 domains that were largely similar to those found in a previous study on captive, ex-pet, or formerly laboratory-housed marmosets that were housed in a sanctuary. The interrater reliabilities of domain scores were consistent with the interrater reliabilities of domain scores found in other species, including humans. Four domainsdmdash;conscientiousness, agreeableness, inquisitiveness, and assertiveness-resembled personality domains identified in other nonhuman primates. The remaining domain, patience, was specific to common marmos...

lion years ago (Strickberger, 1990). The karyotype of Regions of DNA homology between human and mar-Callithrix jacchus was first studied in 1962 by Bemoset (Callithrix jacchus) chromosomes have been nirschke et al., who showed this... more

lion years ago (Strickberger, 1990). The karyotype of Regions of DNA homology between human and mar-Callithrix jacchus was first studied in 1962 by Bemoset (Callithrix jacchus) chromosomes have been nirschke et al., who showed this species to have a dipdemonstrated using fluorescence in situ hybridizaloid number of 46: 22 pairs of autosomes, a submetation. All 24 chromosome paints and two centromere centric X, and an acrocentric Y. The chromosomes repeat sequences from Homo sapiens (HSA) have been were first banded in 1974 by Perrotez, who carried annealed to previously G-banded metaphase spreads out R-banding and proposed a basic nomenclature. In of Callithrix jacchus. All human paint probes, except 1981, Dutrillaux and Couturier, using various band-Y, successfully hybridized to marmoset chromosomes. ing techniques, verified the universal presence of 22 Fifteen of them hybridized to one region only, seven to pairs of autosomes and two sex chromosomes per cell. two regions, and paint 1 to three regions. Homologies They proposed an alternative nomenclature based on proposed from previous banding comparisons have euchromatin segments, which are not variable. They been confirmed for HSA 2, 4-6, 10 -12, 18, 19, 21, and X also proposed a possible evolutionary process deriving and partially confirmed for HSA 1 and 3, but were not the present human and marmoset karyotypes, by rearin agreement for HSA 14 and 17. Human centromere rangements of ancestral chromosomes. In 1982, repeat sequences for X and 18 did not hybridize to mar-Soares et al. published a different nomenclature, moset chromosomes. Because, at present, there is the which was also followed by Seuanez et al. in 1988. A confusing situation of several different numbering sysfurther G-band nomenclature was presented by Nagatems for marmoset chromosomes, we propose a new simpler nomenclature based on descending order of machi et al. (1988), which was followed in a more rechromosome size. ᭧

Digestive tract morphology and function were studied in the common marmoset (Callithrix jacchus), a small (350 g) exudivore with a well-developed caecum. Transit times (times of first appearance of the markers in the faeces following a... more

Digestive tract morphology and function were studied in the common marmoset (Callithrix jacchus), a small (350 g) exudivore with a well-developed caecum. Transit times (times of first appearance of the markers in the faeces following a pulse dose in the food) were similar for Co-EDTA, which marks the fluid phase of the digesta, and Cr-mordanted cell walls, which marked the large (600–1200 μm) particulate phase of the digesta. However, mean retention time (the average time taken for the markers to transverse the whole digestive tract) for Co-EDTA was significantly longer than for Cr-cell walls, indicating selective retention of fluid digesta relative to large particles, probably in the caecum. These data are consistent with a digestive strategy of the common marmoset that appears to be based on rapid digestion of higher quality foods (animal prey, fruits) in the small intestine, followed by microbial fermentation of the complex polysaccharides of plant exudates in the caecum, which would allow for considerable dietary flexibility in its natural habitat of scrub forests.

This study on common marmosets Callithrix jacchus is the first to examine noise-dependent mechanisms of vocal plasticity in a New World monkey. Since acoustic communication can be considerably impaired by environmental noise, some animals... more

This study on common marmosets Callithrix jacchus is the first to examine noise-dependent mechanisms of vocal plasticity in a New World monkey. Since acoustic communication can be considerably impaired by environmental noise, some animals have evolved adaptations to counteract its masking effects. The studied marmosets increased the sound level of their spontaneous calls in response to increased levels of white noise broadcast to them. Possibly, such noise-dependent adjustment of vocal amplitude serves to maintain a specific signal-to-noise ratio that is favourable for signal production. Concurrently, the adjustment of vocal amplitude can maintain a given active space for communication. In contrast to some bird species, no noiseinduced increase in the number of syllables per call series could be found, showing that an increased serial redundancy of vocal signals was not used to communicate under noisy conditions. Finally, we examined a possible noise-dependent prolongation of vocal signals. This approach was guided by the findings of perceptional studies, which suggest an increased detection probability of prolonged signals in noise by temporal summation. Marmosets indeed increased the duration of their call syllables along with increasing background noise levels. This is the first evidence of such mechanism of vocal plasticity in an animal communication system.

Current therapies for Parkinson's disease (PD) like L-dopa and dopamine (DA) agonists have declined efficacy after long term use. Therefore, research towards supplementary or alternative medication is needed. The implementation in PD can... more

Current therapies for Parkinson's disease (PD) like L-dopa and dopamine (DA) agonists have declined efficacy after long term use. Therefore, research towards supplementary or alternative medication is needed. The implementation in PD can be expedited by application of compounds already used in the clinic. In this study the therapeutic effects of the psychoactive compounds Δ 9tetrahydrocannabinol (Δ 9 -THC) and modafinil were tested in the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-marmoset model for PD. The anti-parkinson effects of Δ 9 -THC (4 mg/kg) and modafinil (100 mg/kg) in parkinsonian marmosets were assessed with two behavioral rating scales covering parkinsonian symptoms and involuntary movements and two test systems assessing the locomotor activity and hand-eye coordination. Δ 9 -THC improved activity and hand-eye coordination, but induced compound-related sideeffects. Modafinil improved activity and observed parkinsonian symptoms but not hand-eye coordination. It can be concluded that both compounds have therapeutic values and could supplement existing therapies for PD.

The increasing popularity of marmoset monkeys (Callithrix jacchus) in anatomical, behavioral, and electrophysiological studies has called for a detailed analysis of their natural behavior within limited spaces. In the present study, the... more

The increasing popularity of marmoset monkeys (Callithrix jacchus) in anatomical, behavioral, and electrophysiological studies has called for a detailed analysis of their natural behavior within limited spaces. In the present study, the authors analyzed hand movements during horizontal and vertical progressions in a cylinder. The trajectory of each hand covered the entire cylinder floor during horizontal progressions and the entire cylinder wall during vertical progressions. Different marmosets have different patterns of hand movement. The average maximum angle of hand movements for all marmosets during horizontal and vertical progressions oscillates, although the average over time is constant and similar for both hands, whereas head movements during horizontal progressions become smaller with successive progressions. Another observed difference between rats and monkeys was in the size of head and hand movements at the beginning of each experimental session. During the 1st horizontal progression, all marmosets moved their heads to a greater extent than their hands. This sequential head and hand movement is referred as bistable behavior. The bistable pattern of motor behavior, which was also observed in successive progressions, may be derived from an inherent fear of predators or exploratory interest of a novel environment.

Common marmosets (Callithrix jacchus, n ⍧ 18) were impaired in recall and acquisition of CD tasks, but recall of SDs was not significantly disrupted. Both grafted trained to discriminate between rewarded and nonrewarded objects (simple... more

Common marmosets (Callithrix jacchus, n ⍧ 18) were impaired in recall and acquisition of CD tasks, but recall of SDs was not significantly disrupted. Both grafted trained to discriminate between rewarded and nonrewarded objects (simple discriminations, SDs) and to groups of marmosets showed improvement to control level in recall of CDs. They were significantly slower in make conditional discriminations (CDs) when presented sequentially with two different pairs of identical objects learning the first new CD task, but mastered the remaining tasks as efficiently as controls and were substantially signifying reward either in the right or left food well of the Wisconsin General Test Apparatus. After bilateral superior to the lesion-only group. Visualized by Nissl staining, foetal grafts formed clumps of pyramidal-like N-methyl-D-aspartate (0.12 M) lesions through the cornu ammonis-1 (CA1) field (7 µl in five sites), marmosets cells within the denervated CA1 field, or jutted into the lateral ventricles. MHP36 cells, identified by βshowed profound impairment in recall of CDs but not SDs, and were assigned to lesion only, lesion plus CA1 galactosidase staining and autoradiography, showed neuronal and astrocytic morphology, and were distributed grafts and lesion plus Maudsley hippocampal cell line, clone 36 (MHP36) grafts groups matched for lesion-evenly throughout the CA1 region. The results indicate that MHP36 cell grafts are as functionally effective as induced impairment. Cell suspension grafts (4 µl, 15-25 000 cells/µl) of cells dissected from the CA1 region of foetal grafts and appear to integrate into the host brain in a structurally appropriate manner, showing the foetal brain at embryonic day 94-96, or of conditionally immortalized MHP36 cells, derived from the H-2K bcapacity to differentiate into both mature neurons and glia, and to develop morphologies appropriate to the site tsA58 transgenic mouse neuroepithelium and labelled with [ 3 H]thymidine, were infused at the lesion sites. The of migration. These findings, which parallel the facilitative effects of foetal and MHP36 grafts in rats with ischaemic lesion plus MHP36 grafts group was injected five times per week with cyclosporin A (10 mg/kg) throughout CA1 damage, offer encouragement for the development of conditionally immortal neuroepithelial stem cell lines testing. Lesion, grafted and intact control marmosets (n ⍧ 4-5/group) were tested on recall of SDs and CDs for grafting in conditions of severe amnesia and hippocampal damage following recovery from cardiac learned before lesioning and on acquisition of four new CDs over a 6-month period. Lesioned animals were highly arrest or other global ischaemic episodes.

PURPOSE. The authors recently used topical endoscopy to image the mouse eye fundus. Here, they widened the field of application for this ophthalmologic tool, imaging both the posterior and the anterior eye segments in larger animals... more

PURPOSE. The authors recently used topical endoscopy to image the mouse eye fundus. Here, they widened the field of application for this ophthalmologic tool, imaging both the posterior and the anterior eye segments in larger animals commonly encountered in research laboratories and veterinary clinics. METHODS. Pupils were dilated, and local anesthetic and gel were applied to the animal cornea. The endoscopic probe was placed in contact with the cornea of conscious rats, sedated cats and dogs, anesthetized sheep, and nonhuman primates. RESULTS. High-resolution digital images of the eye fundus were obtained in all investigated animals using the endoscopic probe along the eye axis. Arteriovenous filling time was monitored with fluorescein angiography in pigmented rats. The retinal periphery and ciliary bodies could be visualized with the probe placed at an oblique angle. The probe was inclined further to observe the iridocorneal angle such that the pectinate ligaments could be seen at high resolution in cats. The authors used the probe on eyes with retinal detachment, luxation of a cataractous lens, and pigment infiltration in the iridocorneal angle, demonstrating its potential use in eye diseases. CONCLUSIONS. This topical endoscopic technique provides a unique tool for single eye examinations. The authors obtained a circular view of the anterior (iridocorneal angle) and the posterior (fundus) eye segments from all animal species studied. This technique is inexpensive and easy to use. It can be easily moved to the eye of the patient who cannot move to stand in front of classic apparatus, offering new opportunities in ophthalmology. (Invest Ophthalmol Vis Sci. 2008;49: 5168 -5174)

Oxidative-stress, in response to the activation of the superoxide-producing enzyme Nox2, has been implicated in the schizophrenia-like behavioral dysfunction that develops in animals that were subject to either neonatal NMDA... more

Oxidative-stress, in response to the activation of the superoxide-producing enzyme Nox2, has been implicated in the schizophrenia-like behavioral dysfunction that develops in animals that were subject to either neonatal NMDA receptor-antagonist treatment or social isolation. In both of these animal models of schizophrenia, an environmental insult occurring during the period of active maturation of the fast-spiking parvalbumin-positive (PV+) interneuronal circuit leads to a diminished expression of parvalbumin in GABA-inhibitory neurons when animals reach adulthood. The loss of PV+ interneurons in animal models had been tentatively attributed to the death of these neurons. However, present results show that for the perinatal NMDA-R antagonist model these interneurons are still alive when animals are 5-6 weeks of age even though they have lost their phenotype and no longer express parvalbumin. Alterations in parvalbumin expression and sensory-evoked gamma oscillatory activity, regulated by PV+ interneurons, are consistently observed in schizophrenia. We propose that cortical networks consisting of faulty PV+ interneurons interacting with pyramidal neurons may be responsible for the aberrant oscillatory activity observed in schizophrenia. Thus, oxidative stress during the maturation window for PV+ interneurons may, by alteration of normal brain development, lead to the emergence of schizophrenia-like behavioral dysfunctions when subjects reach early adulthood.

Bifocal contact lenses were used to impose hyperopic and myopic defocus on the peripheral retina of marmosets. Eye growth and refractive state were compared with untreated animals and those treated with single-vision or multizone contact... more

Bifocal contact lenses were used to impose hyperopic and myopic defocus on the peripheral retina of marmosets. Eye growth and refractive state were compared with untreated animals and those treated with single-vision or multizone contact lenses from earlier studies. Thirty juvenile marmosets wore one of three experimental annular bifocal contact lens designs on their right eyes and a plano contact lens on the left eye as a control for 10 weeks from 70 days of age (10 marmosets/group). The experimental designs had plano center zones (1.5 or 3 mm) and +5 diopters [D] or -5 D in the periphery (referred to as +5 D/1.5 mm, +5 D/3 mm and -5 D/3 mm). We measured the central and peripheral mean spherical refractive error (MSE), vitreous chamber depth (VC), pupil diameter (PD), calculated eye growth, and myopia progression rates prior to and during treatment. The results were compared with age-matched untreated (N=25), single-vision positive (N=19), negative (N=16), and +5/-5 D multizone len...

The acquisition by spermatozoa of the capacity for movement upon liberation from the epididymal duct into buffer is one of the obvious changes associated with sperm maturation and, hence, studies of sperm kinematics might provide good... more

The acquisition by spermatozoa of the capacity for movement upon liberation from the epididymal duct into buffer is one of the obvious changes associated with sperm maturation and, hence, studies of sperm kinematics might provide good indices for sperm maturation. Profiles of development in the movement pattern of spermatozoa taken from six regions of the epididymis were established in marmoset and cynomolgus monkeys using computer-assisted sperm analysis. Motion of spermatozoa from initial regions was sluggish and irregular, then developed in the more distal region into erratic movement effected by an increase in the vigour of flagellation as reflected by curvilinear velocity. The tendency of immature spermatozoa to display circular motion was more common in the marmoset than in the cynomolgus monkey. In the marmoset the most drastic changes in percentage motility and kinematic parameters of spermatozoa occurred between the distal caput and the proximal corpus; maximal values for these parameters were found around the distal corpus epididymis. For the cynomolgus spermatozoa the sharpest gain in percentage motility was also achieved between the caput and proximal corpus epididymis, but with full kinematic development in the proximal cauda epididymis. These maturational changes were not synchronous among spermatozoa from the same site as they moved along the epididymis, as reflected in the heterogeneity of each sample in the kinematic properties of individual spermatozoa, especially those from the proximal corpus epididymis. The maturational profiles in the monkeys are comparable to the situation in the human, for which they may provide a useful model.

Developmental and reproductive toxicology testing in nonhuman primates (NHPs) has become more common due to the increasing number of biopharmaceuticals in drug development, since NHPs are frequently the only species to express... more

Developmental and reproductive toxicology testing in nonhuman primates (NHPs) has become more common due to the increasing number of biopharmaceuticals in drug development, since NHPs are frequently the only species to express pharmacologic responses similar to humans. NHPs may also be used to help resolve issues associated with smallmolecule reproductive toxicology in traditional species (rodents and rabbits). Adequate designs in NHP are presented for developmental toxicity (embryo-fetal development, pre-postnatal development, enhanced pre-postnatal development), reproductive toxicity (male and female), and juvenile toxicity studies. Optional parameters that may be included in these studies are discussed, as are new study designs that consolidate multiple aspects of the reproductive assessment and thereby conserve the limited supply of sexually mature NHPs available for testing. The details described will assist scientists in pharmaceutical, regulatory, and contract research organizations who are involved in conducting these unique studies to optimize their design based on case-by-case considerations. Birth Defects Res (Part B) 86: 446-462, 2009.

Studies of social learning and tradition formation under field conditions have recently gained momentum, but suffer from the limited control of socio-ecological factors thought to be responsible for transmission patterns. The use of... more

Studies of social learning and tradition formation under field conditions have recently gained momentum, but suffer from the limited control of socio-ecological factors thought to be responsible for transmission patterns. The use of artificial visual stimuli is a potentially powerful tool to overcome some of these problems. Here, in a field experiment, we used video images of unfamiliar conspecifics performing virtual demonstrations of foraging techniques. We tested 12 family groups of wild common marmosets. Six groups received video demonstrations (footage of conspecifics either pulling a drawer open or pushing a lid upwards, in an 'artificial fruit'); the other six groups served as controls (exposed to a static image of a conspecific next to the fruit). Subjects in video groups were more manipulative and successful in opening the fruit than controls; they were also more likely to use the technique they had witnessed and thus could serve as live models for other family members. To our knowledge, this is the first study that used video demonstrations in the wild and demonstrated the potent force of social learning, even from unfamiliar conspecifics, under field conditions.

For 30 years Gallup's (Science 167:86-87, 1970) mark test, which consists of confronting a mirrorexperienced test animal with its own previously altered mirror image, usually a color mark on forehead, eyebrow or ear, has delivered... more

For 30 years Gallup's (Science 167:86-87, 1970) mark test, which consists of confronting a mirrorexperienced test animal with its own previously altered mirror image, usually a color mark on forehead, eyebrow or ear, has delivered valuable results about the distribution of visual self-recognition in non-human primates. Chimpanzees, bonobos, orangutans and, less frequently, gorillas can learn to correctly understand the reflection of their body in a mirror. However, the standard version of the mark test is good only for positively proving the existence of self-recognition. Conclusive statements about the lack of self-recognition are more difficult because of the methodological constraints of the test. This situation has led to a persistent controversy about the power of Gallup's original technique. We devised a new variant of the test which permits more unequivocal decisions about both the presence and absence of self-recognition. This new procedure was tested with marmoset monkeys (Callithrix jacchus), following extensive training with mirror-related tasks to facilitate performance in the standard mark test. The results show that a slightly altered mark test with a new marking substance (chocolate cream) can help to reliably discriminate between true negative results, indicating a real lack of ability to recognize oneself in a mirror, from false negative results that are due to methodological particularities of the standard test. Finally, an evolutionary hypothesis is put forward as to why many primates can use a mirror instrumentally -i.e. know how to use it for grasping at hidden objects -while failing in the decisive mark test.

The aim of this research was to describe two fatal cases of Yersinia enterocolitica bioserotype 4/O:3 infection in non-human primates and to characterise the isolates by PCR and PFGE. In July 2004, two marmosets (Callitrix jacchuss) born... more

The aim of this research was to describe two fatal cases of Yersinia enterocolitica bioserotype 4/O:3 infection in non-human primates and to characterise the isolates by PCR and PFGE. In July 2004, two marmosets (Callitrix jacchuss) born in captivity in Zagreb Zoo, died following a few days of intermittent diarrhoea in intervals of 2 weeks. The pathomorphological diagnosis of the female (born in 1997) and the male (born in 1995) marmoset, was disseminated miliary necrosis of the liver. Y. enterocolitica 4/O:3 was isolated from both livers showing that monkeys are susceptible to this bioserotype. The ail gene, which is an essential chromosomal virulence factor in pathogenic Y. enterocolitica isolates, was present in the marmoset isolates. Two different PFGE patterns were obtained from the isolates of the male liver with NotI enzyme. One genotype of the male marmoset isolate was indistinguishable from the genotype of the female marmoset isolate when NotI, ApaI and XhoI enzymes were used indicating a common infection source for the marmosets. The genotypes of the marmoset isolates differed only slightly from one human (of seven Croatian isolates) and from one pig isolate (representing a common genotype found among human and porcine isolates in Germany) suggesting that raw pork fed to the marmoset could have been the infection source.

Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of... more

Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl 2 ·H 2 0 in the tail vein using T 1 -weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 hours apart and we imaged the animals 48 hours after the final dose. We find that marmosets have significantly larger T 1 -weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (χ 1 ) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humans.

We developed and validated a method to measure steroid hormones with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in faecal samples of white-faced capuchins. The method includes the measurement of adrenal and gonadal hormones... more

We developed and validated a method to measure steroid hormones with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in faecal samples of white-faced capuchins. The method includes the measurement of adrenal and gonadal hormones such as cortisol, testosterone, estrone, progesterone and a number of their faecal metabolites. This method can be used for simultaneous routine measurements of steroids in faecal samples and provides a reference method for the validation of new immunoassays in this matrix. The optimised method consists of an extraction of the dried faecal samples with 80% methanol followed by purification of the extracts by solid phase extraction, solvolytic cleavage of conjugates and liquid-liquid extraction. Extracts were measured by LC-MS/MS with an electrospray interface in positive ionisation mode. Out of 19 steroids spiked into methanol extracts, 14 showed a recovery of 79.8-118.5% with an intra-day precision of 2.5-13.0% and an inter-day precision of 7.2-15.1%. Detection limits for these steroids ranged from 0.3 to 27.0 ng/mL of extract. Five steroids did not fulfil our requirements concerning precision and accuracy and we therefore considered these to not be reliably measurable with this method. While there was no indication of considerable amounts of conjugated forms for most metabolites, 87% of the testosterone was found in the solvolysis fraction, which indicates that the majority of testosterone was conjugated. Therefore, solvolysis turned out to be crucial, especially for the quantification of the total amount of testosterone. The physiological validation of this LC-MS/MS method confirmed known physiologically caused differences in faecal steroid concentrations. This indicates the usefulness of the method in investigating variation in the levels of major steroid hormones in faeces of white-faced capuchins. The possibility to simultaneously measure hormones of the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis makes this method suitable for dealing with questions concerning the cross talk between those axes.

The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on... more

The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on the wavefront aberrations of the marmoset eye, measured with a clinical Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days. Twenty-one of the subjects were members of studies of emmetropization and accommodation, and two were untreated normal subjects. Eleven of the 21 experimental subjects had worn monocular diffusers and 10 had worn binocular spectacle lenses of equal power. Monocular deprivation or lens rearing began at about 45 days of age and ended at about 108 days of age. All refractions and aberration measures were performed while the eyes were cyclopleged; most aberration measures were made while subjects were awake, but some control measurements were performed under anesthesia. Wavefront error was expressed as a seventh-order Zernike polynomial expansion, using the Optical Society of America's naming convention. Aberrations in young marmosets decreased up to about 100 days of age, after which the higher-order RMS aberration leveled off to about 0.10 lm over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times greater when the subjects were under general anesthesia than when they were awake. Young marmoset eyes were characterized by negative spherical aberration. Form-deprived eyes of the monocular deprivation animals had greater wavefront aberrations than their fellow untreated eyes, particularly for asymmetric aberrations in the odd-numbered Zernike orders. Both lens-treated and form-deprived eyes showed similar significant increases in Z À3 3 trefoil aberration, suggesting the increase in trefoil may be related to factors that do not involve visual feedback.

PURPOSE. We evaluated the effect of imposing negative and positive defocus simultaneously on the eye growth and refractive state of the common marmoset, a New World primate that compensates for either negative and positive defocus when... more

PURPOSE. We evaluated the effect of imposing negative and positive defocus simultaneously on the eye growth and refractive state of the common marmoset, a New World primate that compensates for either negative and positive defocus when they are imposed individually.

Several recent studies suggested a role for neuronal major histocompatibility complex class I (MHCI) molecules in certain forms of synaptic plasticity in the hippocampus of rodents. Here, we report for the first time on the expression... more

Several recent studies suggested a role for neuronal major histocompatibility complex class I (MHCI) molecules in certain forms of synaptic plasticity in the hippocampus of rodents. Here, we report for the first time on the expression pattern and functional properties of MHCI molecules in the hippocampus of a nonhuman primate, the common marmoset monkey (Callithrix jacchus). We detected a presynaptic, mossy fiber-specific localization of MHCI proteins within the marmoset hippocampus. MHCI molecules were present in the large, VGlut1-positive, mossy fiber terminals, which provide input to CA3 pyramidal neurons. Furthermore, whole-cell recordings of CA3 pyramidal neurons in acute hippocampal slices of the common marmoset demonstrated that application of antibodies which specifically block MHCI proteins caused a significant decrease in the frequency, and a transient increase in the amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in CA3 pyramidal neurons. These findings add to previous studies on neuronal MHCI molecules by describing their expression and localization in the primate hippocampus and by implicating them in plasticity-related processes at the mossy fiber-CA3 synapses. In addition, our results suggest significant interspecies differences in the localization of neuronal MHCI molecules in the hippocampus of mice and marmosets, as well as in their potential function in these species.

Central glutamate neurotransmission is modulated by an upregulatory cholinergic influence and an inhibitory serotonergic influence. In Alzheimer's disease, cognitive decline is associated with loss of both glutamatergic and cholinergic... more

Central glutamate neurotransmission is modulated by an upregulatory cholinergic influence and an inhibitory serotonergic influence. In Alzheimer's disease, cognitive decline is associated with loss of both glutamatergic and cholinergic neurones (Francis et al., 1992, Progress in Neurobiology 39, 517-545). While therapeutic strategies for alleviating this cognitive decline have concentrated on restoring cholinergic tone, we suggest that 5-HT 1A antagonists also have the potential to alleviate the cognitive symptoms of Alzheimer's disease. Previous studies have shown that dizocilpine (MK-801), a glutamatergic antagonist acting at the NMDA receptor, produces learning impairments in the common marmoset, a non-human primate. Specifically, it impairs the acquisition of shape discrimination and visuospatial conditional tasks, at doses that do not affect locomotor behaviour or coordination , Society for Neuroscience Abstracts 23(1), 219). In the present study we investigated the effects of WAY 100 635, a 5-HT 1A antagonist, on the cognitive deficits induced by dizocilpine. The number of trials required to learn each type of task under combined treatment with dizocilpine and WAY 100 635 was significantly lower than under dizocilpine treatment alone, and did not differ significantly from the number of trials required under saline, demonstrating that the cognitive effects of glutamatergic blockade can be overcome by treatment with a 5-HT 1A antagonist.

Melanopsin is a photopigment expressed in retinal ganglion cells, which are intrinsically photosensitive and are also involved in retinal circuits arising from rod and cone photoreceptors. This circuitry, however, is poorly understood.... more

Melanopsin is a photopigment expressed in retinal ganglion cells, which are intrinsically photosensitive and are also involved in retinal circuits arising from rod and cone photoreceptors. This circuitry, however, is poorly understood. Here, we studied the morphology, distribution and synaptic input to melanopsin-containing ganglion cells in a New World monkey, the common marmoset (Callithrix jacchus). The dendrites of melanopsin-containing cells in marmoset stratify either close to the inner nuclear layer (outer stratifying), or close to the ganglion cell layer (inner stratifying). The dendritic fields of outer-stratifying cells tile the retina, with little overlap. However, the dendritic fields of outer-stratifying cells largely overlap with the dendritic fields of inner-stratifying cells. Thus, innerstratifying and outer-stratifying cells may form functionally independent populations. The synaptic input to melanopsin-containing cells was determined using synaptic markers (antibodies to C-terminal binding protein 2, CtBP2, for presumed bipolar synapses, and antibodies to gephyrin for presumed amacrine synapses). Both outer-stratifying and inner-stratifying cells show colocalized immunoreactive puncta across their entire dendritic tree for both markers. The density of CtBP2 puncta on inner dendrites was about 50% higher than that on outer dendrites. The density of gephyrin puncta was comparable for outer and inner dendrites but higher than the density of CtBP2 puncta. The inner-stratifying cells may receive their input from a type of diffuse bipolar cell (DB6). Our results are consistent with the idea that both outer and inner melanopsin cells receive bipolar and amacrine input across their dendritic tree.

Zoonotic orthopoxvirus (OPV) can induce severe disease in man and the virus has potential for use in bioterrorism. New vaccines and therapeutics against OPV infections must be tested in animal models. The aim of this study was to... more

Zoonotic orthopoxvirus (OPV) can induce severe disease in man and the virus has potential for use in bioterrorism. New vaccines and therapeutics against OPV infections must be tested in animal models. The aim of this study was to characterize the clinical course and pathology of a new OPV isolate, calpox virus, which is infectious in marmosets. Infection experiments were performed with 28 common marmosets (Callithrix jacchus) exposed to different challenge doses of calpox virus by the intravenous, oropharyngeal and intranasal (IN) routes. The median marmoset IN infectious dose corresponded to 8.3 Â 10 2 plaque forming units of calpox virus. Infected animals developed reproducible clinical signs and died within 4e15 days post infection. Characteristic pox-like lesions developed in affected organs, particularly in the skin, mucous membranes, lymph nodes, liver and spleen. Calpox virus disease progression and pathological findings in the common marmoset appear to be consistent with lethal OPV infections in man and in other non-human primate (NHP) models. IN inoculation with low virus doses mimics the natural route of the human variola virus infection. Thus, the marmoset model of calpox virus infection can be considered to be relevant to investigation of the mechanisms of OPV pathogenesis and pathology and for the evaluation of new vaccines and antiviral therapies.

In this work a polyphenol oxidase (PPO) from Solanum lycocarpum ripe and unripe fruits was studied. The unripe fruits presented higher activity than ripe for both fresh fruits and dried pulp flours. The purification procedure was based on... more

In this work a polyphenol oxidase (PPO) from Solanum lycocarpum ripe and unripe fruits was studied. The unripe fruits presented higher activity than ripe for both fresh fruits and dried pulp flours. The purification procedure was based on freezing precipitation and a sixfold purification factor was obtained. The SDS-PAGE of the partially purified PPO showed two bands around 47 and 68 kDa. Optimal conditions for enzymatic studies were determined to be pH 6.0-6.5 and 28 • C. The partially purified PPO presented high activity toward catechol (V max 3.42 U mL −1 and K m 6.47 mM) and 4-methylcatechol (V max 3.01 U mL −1 and K m 0.15 mM) and low activity toward phenol being classified as a catecholase type polyphenol oxidase. S. lycocarpum PPO was sensitive to inhibitors such as l-cysteine, sodium metabisulfite, ascorbic acid, thiourea and citric acid. l-Cysteine was the most effective inhibitor, presenting a competitive inhibition. The results from kinetic and thermodynamic parameters for the thermal inactivation evidenced that the partially purified PPO is a biocatalyst, whose inactivation process is related to aggregation of partially unfolded enzyme molecules.

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits... more

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.

Deferasirox (Exjade, ICL670) is an orally active iron chelator. Two molecules of deferasirox can form a complex with ferric iron (Fe-[ICL670] 2 ) that can be excreted, reducing body iron overload. The blood binding parameters across... more

Deferasirox (Exjade, ICL670) is an orally active iron chelator. Two molecules of deferasirox can form a complex with ferric iron (Fe-[ICL670] 2 ) that can be excreted, reducing body iron overload. The blood binding parameters across species and the interaction with human serum albumin were analyzed for deferasirox and its iron complex. Both molecules were very highly bound to plasma proteins in all the tested species with unbound fractions in plasma in the range of 0.4 to 1.8% and 0.2 to 1.2% for deferasirox and Fe-[ICL670] 2 , respectively; binding of the iron complex was either similar or higher in all the species. The high plasma protein binding was in line with a distribution mainly into the plasma fraction of blood; the fraction in plasma was around 100% for Fe-[ICL670] 2 in all the species and 65 to 95% for deferasirox depending on the species. Investigations with isolated proteins pointed to serum albumin as the principal binding protein for deferasirox and its iron complex in human plasma. Competition binding experiments indicated that deferasirox at high concentrations displaced markers from the two main drug binding sites of human albumin, whereas Fe-[ICL670] 2 displaced only warfarin. In the context of the pharmacokinetic properties of deferasirox and Fe-[ICL670] 2 , the data indicate the importance of plasma protein binding for their disposition and support a comparison of the pharmacokinetics of deferasirox and its iron complex across species. The low likelihood of clinically relevant drug displacement by deferasirox in plasma is discussed.

Background Vitamin D is a secosteroid hormone with important roles in the control of bone and mineral metabolism of vertebrates and in the maintenance of systemic homeostasis. This study aimed (i) to evaluate the serum concentrations of... more

Background Vitamin D is a secosteroid hormone with important roles in the control of bone and mineral metabolism of vertebrates and in the maintenance of systemic homeostasis. This study aimed (i) to evaluate the serum concentrations of 25-hydroxy-vitamin D levels [25(OH)D], parathyroid hormone (PTH) and ionized calcium (iCa) of wild Callithrix penicillata (blacktufted marmosets) and (ii) to propose reference ranges for those analytes for free-living marmosets. Methods Blood samples were collected from 15 wild animals and analyzed for 25(OH)D, PTH and iCa. Reference values were calculated following standard analytical criteria. Results The observed mean serum levels (±standard deviation) were 25(OH) D, 61.7 (±20.8) ng/ml; PTH, 275.2 (±34.1) pg/ml; iCai 4.0 (±0.6) mg/dl. Conclusions For free-living marmosets, the proposed physiological range for 25(OH)D is 20.1-103.3 ng/ml and for PTH is 207.0-343.3 pg/dl, with a confidence interval of 95%.

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a... more

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a nonhuman primate model (Callithrix jacchus), using an objective computer analysis system and principal component analysis (PCA) methods to establish the relationship between the subpopulation distribution observed and among-donor variation. The PCA method revealed a stable number of principal components in all donors studied, that represented more than 85% of the cumulative variance in all cases. After cluster analysis, a variable number (from three to seven) sperm morphometric subpopulations were identified with defined sperm dimensions and shapes. There were differences in the distribution of the sperm morphometric subpopulations (P Ͻ 0.001) in all ejaculates among the four donors analyzed. In conclusion, in this study, computerized sperm analysis methods combined with PCA cluster analyses were useful to identify, classify, and characterize various head sperm morphometric subpopulations in nonhuman primates, yielding considerable biological information. In addition, because all individuals were kept in the same conditions, differences in the distribution of these subpopulations were not attributed to external or management factors. Finally, the substantial information derived from subpopulation analyses provided new and relevant biological knowledge which may have a practical use for future studies in human and nonhuman primate ejaculates, including identifying individuals more suitable for assisted reproductive technologies.

equally to this paper To understand the relationship between the structure and function of primate neocortical areas at a molecular level, we have been screening for genes differentially expressed across macaque neocortical areas by... more

equally to this paper To understand the relationship between the structure and function of primate neocortical areas at a molecular level, we have been screening for genes differentially expressed across macaque neocortical areas by restriction landmark cDNA scanning (RLCS). Here, we report enriched expression of the paraneoplastic antigenlike 5 gene (PNMA5) in association areas but not in primary sensory areas, with the lowest expression level in primary visual cortex. In situ hybridization in the primary sensory areas revealed PNMA5 mRNA expression restricted to layer II. Along the ventral visual pathway, the expression gradually increased in the excitatory neurons from the primary to higher visual areas. This differential expression pattern was very similar to that of retinol-binding protein (RBP) mRNA, another association-area-enriched gene that we reported previously. Additional expression analysis for comparison of other genes in the PNMA gene family, PNMA1, PNMA2, PNMA3, and MOAP1 (PNMA4), showed that they were widely expressed across areas and layers but without the differentiated pattern of PNMA5. In mouse brains, PNMA1 was only faintly expressed and PNMA5 was not detected. Sequence analysis showed divergence of PNMA5 sequences among mammals. These findings suggest that PNMA5 acquired a certain specialized role in the association areas of the neocortex during primate evolution. Figure 4. Double ISH of PNMA5 and VGLUT1 or GAD67 mRNAs in area TE. (A) PNMA5 mRNA (left, red) was expressed in most of the VGLUT1-mRNA-positive cells (middle, green) in layer II (bottom: higher magnification). (B) PNMA5 mRNA was barely expressed in GAD67-mRNA-positive cells (middle, green).

In this study, we investigated the reciprocal exchanges of grooming, tolerance and reduced aggression in common marmosets (Callithrix jacchus), a cooperatively breeding primate whose groups are typically characterized by uniformly high... more

In this study, we investigated the reciprocal exchanges of grooming, tolerance and reduced aggression in common marmosets (Callithrix jacchus), a cooperatively breeding primate whose groups are typically characterized by uniformly high genetic relatedness and high interdependency between group members. Both partner control and partner choice processes played a role in the reciprocal exchanges of grooming. In contrast, we did not find any evidence of reciprocity between grooming and tolerance over a preferred food source or between grooming and reduced aggression. Thus, reciprocity seems to play a variable role in the exchange of cooperative behaviors in marmosets.

Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketolase-positive bacterial strains with a peculiar morphology were isolated from faecal samples of baby common marmosets (Callithrix jacchus).... more

Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketolase-positive bacterial strains with a peculiar morphology were isolated from faecal samples of baby common marmosets (Callithrix jacchus). Cells of these strains showed a morphology not reported previously for a bifidobacterial species, which resembled a coiled snake, always coiled or ring shaped or forming a 'Y' shape. Strains MRM 3/1(T) and MRM 4/2 were chosen as representative strains and characterized further. The bacteria utilized a wide range of carbohydrates and produced urease. Glucose was fermented to acetate and lactate. Strain MRM 3/1(T) showed a peptidoglycan type unique among members of the genus Bifidobacterium. The DNA base composition was 64.7 mol% G+C. Almost-complete 16S rRNA, hsp60, clpC and rpoB gene sequences were obtained and phylogenetic relationships were determined. Comparative analysis of 16S rRNA gene sequences showed that strains MRM 3/1(T) and MRM 4/2...

Abbreviations: DIG = digoxigenin; EK = enterokinase; GFAP = glial ®brillary acidic protein; GFP = green¯uorescent protein; MMP = matrix metalloproteinases; MSP = myelencephalon-speci®c protease; MSP-IR = MSP immunoreactivity; PLP =... more

Abbreviations: DIG = digoxigenin; EK = enterokinase; GFAP = glial ®brillary acidic protein; GFP = green¯uorescent protein; MMP = matrix metalloproteinases; MSP = myelencephalon-speci®c protease; MSP-IR = MSP immunoreactivity; PLP = proteolipid protein; r-MSP = recombinant MSP; SNK = Student±Newman±Keuls; TMEV = Theiler's murine encephalomyelitis virus

The aim of the experiments was to assess the toxicity of minoxidil, a potent vasodilator, in marmosets. The animals were treated either at escalating doses from 2 to 40 mg/kg, escalating doses from 40 to 200 mg/kg or single doses of 150... more

The aim of the experiments was to assess the toxicity of minoxidil, a potent vasodilator, in marmosets. The animals were treated either at escalating doses from 2 to 40 mg/kg, escalating doses from 40 to 200 mg/kg or single doses of 150 mg/kg or 200 mg/kg. ECG recording and echocardiographic examination were conducted before and 1 h after treatment. Necropsy and histopathology were performed 24 h after the last dose. The treatment with minoxidil induced myocardial necrosis, coronary arteriopathy and degeneration of renal tubules in animals treated with 150 mg/kg or 200 mg/kg. Myocardial necrosis associated with fibrosis in some animals was located mainly in the left and right ventricles (including papillary muscles), but also in the right atrium, left atrium and/or interventricular septum. Arteriopathy was observed in small coronary arteries of the right or left atrium. ECG and echocardiographic examinations showed that in animals treated with 150 mg/kg or 200 mg/kg, there were positive chronotropic and inotropic effects that compensated for the hypotensive effect of the drug and were considered to have played a key role in the pathogenesis of the cardiovascular lesions. The cardiotoxicity of minoxidil in marmosets was similar to that described in dogs, but occurred at much higher doses. In conclusion minoxidil produced cardiovascular toxicity in the marmoset, which was probably due to the marked changes in the cardiac function associated with exaggerated pharmacological effects of the compound. The marmosets were found to be less sensitive than dogs to the cardiotoxicity of minoxidil.

Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks... more

Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameter...

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits... more

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.

Follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI-8) is a novel octapeptide purified from human ovarian follicular fluid. In vitro, it inhibits the binding of FSH to granulosa cells and in vivo, it induces atresia in... more

Follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI-8) is a novel octapeptide purified from human ovarian follicular fluid. In vitro, it inhibits the binding of FSH to granulosa cells and in vivo, it induces atresia in developing follicles in rodents. This peptide, when administered to marmosets and bonnet monkeys, altered the circulating progesterone levels. This study was carried out to elucidate structure of the FRBI-8 and understand its mechanism of inhibiting interaction of FSH to its receptors. Homology modeling predicted that the FRBI-8 adopts a turn and random coil. This is further confirmed by circular dichroism and NMR. Docking studies of the FRBI-8 with reported FSH-FSHR hormone binding (FSHR HB ) domain complex using ZDOCK algorithm revealed that the FRBI-8 binds to FSHbL2-FSHR HB binding interface which is otherwise known to be crucial for activation of signal transduction cascade. FRBI-8 analogs were designed by replacing the acidic amino acid residues at positions 2, 5 and 6 with Ala, individually. Docking studies revealed that D6A mutant (FRBI-8 D6A ) had a higher binding affinity than the native FRBI-8. In vitro radioreceptor assay with FRBI-8 D6A showed 50% lower IC 50 compared with the FRBI-8, confirming the in silico observations. Thus, the study reveals that both FRBI-8 and FRBI-8 D6A interfered with the binding of FSH to its receptor.

An ELISA was developed for measuring serum antibodies against the arenavirus lymphocytic choriomeningitis virus (LCMV) and a closely related isolate termed callitrichid hepatitis virus (CHV). The ELISA was used to test sera from healthy... more

An ELISA was developed for measuring serum antibodies against the arenavirus lymphocytic choriomeningitis virus (LCMV) and a closely related isolate termed callitrichid hepatitis virus (CHV). The ELISA was used to test sera from healthy adults and from hepatitis patients. In Birmingham, Alabama, the seropositivity rate for healthy black women was 5.1% (7/138), and the rate for patients with all types of hepatitis or cirrhosis was 4.3% (2/46). In San Antonio, Texas, the seropositivity rate among a clinical series of patients with non-A, non-B hepatitis was 0 (0/20), and the rate among persons rejected from blood donation because of high serum alanine aminotransferase levels was 2.4% (2/82). These results indicate that infection with LCMV or CHV is common in Birmingham but that infection is not associated with hepatitis. 0 1992 Witey-Liss, inc.

Previous studies of macaque and human cortices identified cytoarchitectonically distinct germinal zones; the ventricular zone, inner subventricular zone (ISVZ), and outer subventricular zone (OSVZ). To date, the OSVZ has only been... more

Previous studies of macaque and human cortices identified cytoarchitectonically distinct germinal zones; the ventricular zone, inner subventricular zone (ISVZ), and outer subventricular zone (OSVZ). To date, the OSVZ has only been described in gyrencephalic brains, separated from the ISVZ by an inner fiber layer and considered a milestone that triggered increased neocortical neurogenesis. However, this observation has only been assessed in a handful of species without the identification of the different progenitor populations. We examined the Amazonian rodent agouti (Dasyprocta agouti) and the marmoset monkey (Callithrix jacchus) to further understand relationships among progenitor compartmentalization, proportions of various cortical progenitors, and degree of cortical folding. We identified a similar cytoarchitectonic distinction between the OSVZ and ISVZ at midgestation in both species. In the marmoset, we quantified the ventricular and abventricular divisions and observed similar proportions as previously described for the human and ferret brains. The proportions of radial glia, intermediate progenitors, and outer radial glial cell (oRG) populations were similar in midgestation lissencephalic marmoset as in gyrencephalic human or ferret. Our findings suggest that cytoarchitectonic subdivisions of SVZ are an evolutionary trend and not a primate specific feature, and a large population of oRG can be seen regardless of cortical folding.

Central to many emotional responses is the accompanying peripheral somatic and autonomic arousal, feedback from which has been hypothesized to enhance emotional memory and to contribute to appraisal processes and decision making, and... more

Central to many emotional responses is the accompanying peripheral somatic and autonomic arousal, feedback from which has been hypothesized to enhance emotional memory and to contribute to appraisal processes and decision making, and dysfunction of which may contribute to antisocial behaviour. Whilst peripheral arousal may accompany both positive and negative emotional contexts, its relationship with the former is poorly understood, as are the neural mechanisms underlying such a relationship. The purpose of the present study was to determine the autonomic correlates of anticipation, as well as consumption, of high incentive food, in the freely moving common marmoset and to investigate the contribution of the amygdala to such effects. Blood pressure (BP) and heart rate (HR) were measured remotely by a telemetric device implanted into the descending aorta and behavioural responses were monitored whilst marmosets viewed preferred or non-preferred foods and were then allowed access to eat those foods. A marked rise in blood pressure in unrestrained marmosets was observed in response both to the sight of highly preferred foods (anticipatory period) as well as during the actual consumption of those foods (consummatory period). Excitotoxic lesions of the amygdala abolished the autonomic arousal in the anticipatory period, but spared both the behavioural arousal in the anticipatory period and the autonomic arousal in the consummatory period. Together these data serve as an important step towards understanding the role of autonomic arousal in emotion and its neural underpinnings.