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Cloning and expression of interleukin-3 genes of chimpanzee and New World monkeys.

Interleukin-3 (IL-3) genes were cloned from chimpanzee (Pan troglodytes), tamarin (Saguinus oedipus) and marmoset (Callithrix jacchus) and expressed in COS cells. Although the IL-3 gene structure is well conserved in these primate species, sequence analysis revealed extensive base substitutions. The chimpanzee IL-3 protein, which is highly homologous (98.5% identity) to human IL-3, stimulated proliferation of human cells dependent on IL-3. In contrast, due to the numerous amino acid substitutions in the New World monkey IL-3 species, no stimulation of human cells was observed, illustrating the extensive evolutionary divergence of IL-3.

Amino Acid Sequence↗

Thermogenic capacity and brown adipose tissue activity in the common marmoset.

Resting oxygen consumption was measured in anaesthetized male and female common marmosets (Callithrix jacchus) at 29 degrees C. Injection of noradrenaline caused a marked increase in oxygen consumption (63%), but this response was lower in males. Large deposits (750 mg) of brown adipose tissue (BAT) were dissected from the cervical, subscapular, axillary and perirenal areas. High levels of guanosine diphosphate binding to isolated brown fat mitochondria were observed, indicating that the thermogenic proton conductance pathway is very active in brown fat from the marmoset. High levels of brown adipose tissue thermogenesis in these animals may be related to a requirement for diet-induced thermogenesis.

Adipose Tissue, Brown↗

An immunohistochemical study of the acute and long-term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset.

Administration of the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces a parkinsonian syndrome in primates. Intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the common marmoset (Callithrix jacchus) produced symptoms of rigidity, akinesia and tremor which persisted for at least one month. However, after this time, considerable behavioural recovery occurred, although animals were still severely bradykinetic compared with controls. Marmosets were allowed to survive for 1, 3 1/2 or 7 months prior to histological and immunocytochemical analysis. Detection of catecholaminergic neurons using antibodies directed against the enzyme tyrosine hydroxylase revealed a profound (80%) loss of dopaminergic cells from the substantia nigra one month after initiation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. This was accompanied by a severe gliosis. Fewer cells were lost from the adjacent ventral tegmental area (45%), but dopamine-containing cells in other brain areas were not obviously affected. At longer survival times the substantia nigra was less damaged, with a proliferation of glia in the pars compacta and a loss of approximately 20% of the dopaminergic perikarya. Using immunohistochemical techniques, the distribution of neuropeptides substance P, [Met]enkephalin and dynorphin 1-17-like immunoreactivity were examined and found to exhibit distinctive patterns in the marmoset substantia nigra. The integrity of these systems appeared intact at all times after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. These results support the hypothesis that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a clinical syndrome, indistinguishable from Parkinson's disease, via a selective destruction only of neurons with perikarya in the substantia nigra pars compacta and the ventral tegmental area. The findings that the peptidergic input to these cells together with most non-nigral dopaminergic cell groups are not damaged, indicate that the selectivity of the lesion produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine appears greater than that seen in idiopathic Parkinson's disease. The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset may not be permanent since both behavioural and biochemical recovery were observed after several months.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The immunoglobulin kappa locus of primates.

The immunoglobulin kappa genes of nonhuman primates were studied by using sequence information and hybridization probes derived from the human kappa gene regions. The following results were obtained: (1) V kappa gene probes of the three major human kappa subgroups hybridized to restriction nuclease digests of DNA from the chimpanzees Pan troglodytes (PTR) and Pan paniscus (PPA), the gorilla Gorilla gorilla (GGO), the orangutan Pongo pygmaeus (PPY), the macaque Macaca mulatta (MMU), the marmoset Callithrix geoffrei (CGE), and the bushbaby Galago demidovii (GDE), yielding patterns of decreasing similarity to the patterns of the human V kappa multigene family. (2) The C kappa gene segments of PTR, GGO, and PPY were 99.6, 97, and 93%, respectively, identical in sequence to the human C kappa gene. A V kappa gene in PTR, GGO, PPY, and MMU was 98, 96, 96, and 95%, respectively, identical to the most C kappa proximal V kappa gene, called B3. The other two J kappa-C kappa proximal V kappa genes in human, B1 and B2, hybridize to restriction fragments of sizes identical to that of DNA from humans and great apes. (3) The long-range restriction maps of the human (HSA), PTR, and GGO kappa loci as established by pulsed-field gel electrophoresis (PFGE) are quite homologous. According to the maps, however, and to hybridization studies with 11 duplication-differentiating probes, there is only one copy of the locus in PTR and GGO. This means that the duplication of large parts of the kappa locus as found in humans occurred after the branch-point of human and great ape evolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fall in coronary heart disease mortality in U.S.A. and Australia due to sudden death: evidence for the role of polyunsaturated fat.

Epidemiological studies have been reviewed which provide suggestive evidence of an association between the fall in coronary heart disease mortality in the U.S.A and Australia since 1967, characterized by a fall in sudden deaths, to the increase in polyunsaturate fat consumption that has occurred in both countries since 1960. This association led directly in the same institution to carefully designed experimental studies undertaken in the rat, and a non-human primate, the marmoset (Callithrix jacchus jacchus) with a heart and lipid metabolism more closely resembling that of man. In both animal species, a vegetable fat diet had a protective effect against the increase in contractility of isolated papillary muscles induced by age, the addition of animal fat, or by isoprenaline in vitro. Similar effects were observed following coronary artery ligation, where the extent of dysrhythmia was greatly reduced by supplementing the diet with a linoleic acid rich vegetable oil. It is concluded that the combination of epidemiological and experimental evidence indicates a protective effect of dietary polyunsaturates against sudden cardiac death. This work illustrates the value of the integration of epidemiological and experimental approaches to the aetiology of disease.

Animals↗

Locomotor mechanics of the slender loris (Loris tardigradus).

The quadrupedal walking gaits of most primates can be distinguished from those of most other mammals by the presence of diagonal-sequence (DS) footfall patterns and higher peak vertical forces on the hindlimbs compared to the forelimbs. The walking gait of the woolly opossum (Caluromys philander), a highly arboreal marsupial, is also characterized by diagonal-sequence footfalls and relatively low peak forelimb forces. Among primates, three species--Callithrix, Nycticebus, and Loris--have been reported to frequently use lateral-sequence (LS) gaits and experience relatively higher peak vertical forces on the forelimbs. These patterns among primates and other mammals suggest a strong association between footfall patterns and force distribution on the limbs. However, current data for lorises are limited and the frequency of DS vs. LS walking gaits in Loris is still ambiguous. To test the hypothesis that patterns of footfalls and force distribution on the limbs are functionally linked, kinematic and kinetic data were collected simultaneously for three adult slender lorises (Loris tardigradus) walking on a 1.25 cm horizontal pole. All subjects in this study consistently used diagonal-sequence walking gaits and always had higher peak vertical forces on their forelimbs relative to their hindlimbs. These results call into question the hypothesis that a functional link exists between the presence of diagonal-sequence walking gaits and relatively higher peak vertical forces on the hindlimbs. In addition, this study tested models that explain patterns of force distribution based on limb protraction angle or limb compliance. None of the Loris subjects examined showed kinematic patterns that would support current models proposing that weight distribution can be adjusted by actively shifting weight posteriorly or by changing limb stiffness. These data reveal the complexity of adaptations to arboreal locomotion in primates and indicate that diagonal-sequence walking gaits and relatively low forelimb forces could have evolved independently.

Adaptation, Physiological↗

Variation in maxillary sinus anatomy among platyrrhine monkeys.

Variations in the maxillary sinus anatomy of extant and fossil catarrhine primates have been extensively examined using computed tomography (CT), and have potential utility for phylogenetic analyses. This approach has also been used to demonstrate its anatomical variation in eight of the 16 extant genera of platyrrhines and the absence of the sinus in Saimiri and Cacajao. We used this approach to evaluate the three-dimensional anatomy of the maxillary sinus in all extant platyrrhine genera, and here argue the phylogenic implications of this variation. This study confirms, for the most part, previous CT studies and augments them with the six genera not studied previously: Ateles, Lagothrix, Callithrix, Cebuella, Pithecia and Chiropotes. The entire maxilla is pneumatized by the sinus in the atelines, Cebus, and Callicebus, whereas the sinus pneumatizes only the medial part of the maxilla in the callitrichines and Aotus. Pithecia has a unique conformation in which the maxillary sinus and the expanded inferior meatus pneumatize the posteromedial and anterolateral parts of the entire maxilla, respectively. Chiropotes has no sinus, and the inferior meatus possibly expands into the area between the middle meatus and medial surface of the maxilla to disturb sinus formation, as in the case of its close relative Cacajao. Finally, we argue that the sinus that pneumatizes the entire maxilla is a primitive feature in extant platyrrhines and was probably shared by the last common ancestor of the anthropoids.

Animals↗

Plasticity of human chromosome 3 during primate evolution.

Comparative mapping of more than 100 region-specific clones from human chromosome 3 in Bornean and Sumatran orangutans, siamang gibbon, and Old and New World monkeys allowed us to reconstruct ancestral simian and hominoid chromosomes. A single paracentric inversion derives chromosome 1 of the Old World monkey Presbytis cristata from the simian ancestor. In the New World monkey Callithrix geoffroyi and siamang, the ancestor diverged on multiple chromosomes, through utilizing different breakpoints. One shared and two independent inversions derive Bornean orangutan 2 and human 3, implying that neither Bornean orangutans nor humans have conserved the ancestral chromosome form. The inversions, fissions, and translocations in the five species analyzed involve at least 14 different evolutionary breakpoints along the entire length of human 3; however, particular regions appear to be more susceptible to chromosome reshuffling. The ancestral pericentromeric region has promoted both large-scale and micro-rearrangements. Small segments homologous to human 3q11.2 and 3q21.2 were repositioned intrachromosomally independent of the surrounding markers in the orangutan lineage. Breakage and rearrangement of the human 3p12.3 region were associated with extensive intragenomic duplications at multiple orangutan and gibbon subtelomeric sites. We propose that new chromosomes and genomes arise through large-scale rearrangements of evolutionarily conserved genomic building blocks and additional duplication, amplification, and/or repositioning of inherently unstable smaller DNA segments contained within them.

Animals↗

An ethogram of the common marmoset (Calithrix jacchus jacchus): general behavioural repertoire.

The behavioural repertoire of four captive breeding pairs of Callithrix jacchus jacchus is described. Social communication took the form of postures, facial expressions, vocalizations and piloerection displays. Detailed analyses were made of piloerection displays, adult play, copulatory, aggressive, and prey-catching behaviour. Aggressive behaviour was uncommon in adult mated pairs. Play between adults showed a degree of temporal of temporal organization. Vocalizations were the main methods of intragroup communication whilst piloerection displays were directed towards members of other groups and also to unfamiliar objects. The behavioural repertoire of C. jacchus jacchus is compared with that of other Primates.

Aggression↗

Expression of adhesion receptors on rat limb bud cells and results of treatment with a thalidomide derivative.

The expression of several adhesion surface receptors was studied on cells of early limb bud development of 58 Wistar rats treated orally with two daily doses of the thalidomide derivative EM12 (2 x 50 mg/kg body weight) from day 7 to 10 of pregnancy. EM12 is a more potent teratogen than thalidomide. Limb bud cells of 56 untreated animals served as controls. The studies revealed that the integrins CD11a, CD11b, CD18, CD49d, and CD61, as well as the additional adhesion receptors CD54, CD62L, and the transferrin receptor CD71 were expressed on day 11 of gestation to various degrees on these embryonic cells. In contrast to results of previous studies with a non-human primate (Callithrix jacchus) there was no down-regulation of any of these receptors on the surface of limb bud cells of the rat embryos after treatment with EM12. This result is in accordance with the lack of teratogenicity in this rodent species.

Animals↗

Primate embryonic stem cells.

Primate embryonic stem (ES) cells are derived from preimplantation embryos, have a normal karyotype, and are capable of indefinite, undifferentiated proliferation. Even after culture for more than a year, primate ES cells maintain the potential to differentiate to trophoblast and derivatives of embryonic endoderm, mesoderm, and ectoderm. In this review, we compare the characteristics of ES cell lines from two primate species, the rhesus monkey (Macaca mulatta) and the common marmoset (Callithrix jacchus), with the characteristics of mouse ES cells and human embryonal carcinoma cells. We also discuss the implications of using primate ES cells to understand early human development and discuss the practical and ethical implications for the understanding and treatment of human disease.

Animals↗

Structure, molecular evolution, and gene expression of primate superoxide dismutases.

Mn- and Cu,Zn-superoxide dismutase (SOD) cDNAs of eight primate species, Pan troglodytes, Pongo pygmaeus, Hylobates lar, Macaca fuscata, Macaca fascicularis, Macaca mulatta, Cebus apella, and Callithrix jacchus, were cloned. The whole protein-coding sequences were covered, comparing 198 and 153 (or 154) amino acids, for Mn- and Cu,Zn-SODs, respectively. Residues forming metal ligands were completely conserved in the two primate SODs and nucleotide/amino acid substitutions were more frequent in Cu,Zn-SODs than in Mn-SODs. Molecular evolutionary analyses showed Mn-SOD to have evolved at a constant rate and its phylogenetic tree well reflected primate phylogeny. Cu,Zn-SOD was shown to have evolved differently between primate lineages. The significant high ratio of a non-synonymous/synonymous rate was found in the lineage leading to great apes and humans, showing that this lineage underwent positive Darwinian selection. Southern hybridization suggested that the genes for primate Mn- and Cu,Zn-SOD exist as single copies. Northern analysis in various Japanese monkey tissues showed Mn- and Cu,Zn-SOD expression to be high in the liver, kidneys, and adrenal glands.

Amino Acid Sequence↗

Molecular cladistic markers in New World monkey phylogeny (Platyrrhini, Primates).

Transpositions of primate-specific Alu elements were applied as molecular cladistic markers in a phylogenetic analysis of South American primates. Seventy-four human and platyrrhine loci containing intronic Alu elements were PCR screened in various New World monkeys and the human outgroup to detect the presence of orthologous retrotransposons informative of New World monkey phylogeny. Six loci revealed size polymorphism in the amplification pattern, indicating a shared derived character state due to the presence of orthologous Alu elements confirmed by subsequent sequencing. Three markers corroborate (1) New World monkey monophyly and one marker supports each of the following callitrichine relationships: (2) Callithrix and Cebuella are more closely related to each other than to any other callitrichine, (3) the callitrichines form a monophyletic clade including Callimico, and (4) the next living relatives to the callitrichines are Cebus, Saimiri, and Aotus.

Alu Elements↗

An outbreak of shigellosis in laboratory marmosets and tamarins (Family: Callithricidae).

An outbreak of shigellosis due to Shigella sonnei, is reported in laboratory maintained marmosets (Callithrix jacchus) and tamarins (Saguinus nigricollis). The clinical signs and pathological lesions are described and the microbiological findings discussed. Control of the disease was based upon hygiene and antibiotic therapy and the consequences of this approach are described in detail.

Animals↗

An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2 1/2 years. Analysis of variance on data obtained from behavioral observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2 1/2 years after injection by automated activity monitoring. There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation. Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.

Animals↗

Chromosome painting comparison of Leontopithecus chrysomelas (Callitrichine, Platyrrhini) with man and its phylogenetic position.

Using human probes of whole chromosomes, the homoeologies between human and Leontopithecus chrysomelas (Platyrrhini) karyotypes were established. Thirty-three conserved segments were observed between the two species. Intrachromosomal rearrangements between the two species were identified using hybridization of chromosome arm probes of human chromosomes 1 and 3. We also used chromosomal data to investigate phylogenetic relationships of Callitrichines. These data were encoded using Cebus capucinus , a species which kept fairly ancestral chromosomes, as reference. Two equi-parsimonious trees, including reversion or convergence events, were obtained. The monophyly of Callitrichines is confirmed. They share nine chromosomal rearrangements at least. The Cebuella-Callithrix group forms a clade sharing five rearrangements at least. According to the tree considered, the Tamarins, Leontopithecus and Saguinus share two chromosomal rearrangements restricted to these two taxa or none. Callimico accumulated seven chromosomal rearrangements unshared with other taxa, at least. To avoid convergence and reversion events, we propose the hypothesis of a network (or populational) evolution. Six chromosomal rearrangements would have occurred during the period of this network evolution. Finally, the karyotype of the last common ancestor to all Callitrichines has been reconstructed. It possessed 48 chromosomes.

Animals↗

Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box binding protein gene: an evolutionary approach.

The variability and mutational changes of the CAG microsatellite in the TATA-box binding protein gene (TBP) were studied. We sequenced the microsatellite of the TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and 15 unaffected control individuals). In addition, the microsatellites were sequenced from individuals of 10 northern German families with at least one family member affected by SCA17. To study also the evolutionary history of this CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar, Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas, Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i) Patterns of synonymous CAA interruptions in the microsatellite are characteristic and likely to result from selection for stabilizing the repetitive region; (ii) Interspecific comparisons indicate that SCA17 is likely to be a human trait. The most common allele in humans (37 repeats) is close to the threshold value upon which neurodegenerative changes can occur and may act as a repository for expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17 expanded alleles can be attributed to unequal crossing over. This can explain the rare and sporadic de novo generation of SCA17 alleles.

Animals↗

Flow cytometric sorting of frozen-thawed spermatozoa in sheep and non-human primates.

Research was conducted in sheep to determine an effective preparation method for high-purity sorting of frozen-thawed spermatozoa. The efficacy of sorting frozen-thawed spermatozoa was then investigated in several non-human primate species. An aliquot of each ejaculate (three rams, three ejaculates per ram) was processed as a fresh control (FRESH). Frozen spermatozoa were thawed and prepared for sorting by no further processing (FT-NEAT), washing (FT-WASH) or gradient centrifugation (FT-GRADIENT) and evaluated for motility at 1 h post-staining and motility and acrosomal status at 0 and 4 h post-sorting. Samples were analysed using a high-speed cell sorter. High levels of purity for X- and Y-enriched samples were achieved for all treatments (85-92%). The percentage of motile spermatozoa before sorting was lower (P < 0.05) for frozen-thawed samples (FT-NEAT: 32.7 +/- 2.5%; FT-WASH: 32.2 +/- 3.3%; FT-GRADIENT: 73.9 +/- 3.7%) compared with FRESH (83.3 +/- 1.2%). Post-sorting, the percentage of motile spermatozoa before and after incubation for FT-NEAT (60.0 +/- 5.1% and 27.2 +/- 6.1% for 0 and 4 h, respectively) was lower than that for FRESH (87.8 +/- 0.9% and 83.3 +/- 1.2% for 0 and 4 h, respectively; P < 0.05), FT-WASH (80.0 +/- 2.4% and 71.7 +/- 3.6% for 0 and 4 h, respectively; P < 0.05) and FT-GRADIENT (84.4 +/- 1.3% and 77.2 +/- 1.7% for 0 and 4 h, respectively; P < 0.05). Vanguard sperm migration distance through artificial cervical mucus was lower (P < 0.05) for FT-NEAT (17.7 +/- 1.7 mm) compared with FT-WASH (29.1 +/- 3.8 mm) and FT-GRADIENT (28.4 +/- 2.0 mm) and similar (P < 0.05) to FRESH (23.7 +/- 1.8 mm). Sample preparation using a modified wash method enabled high-purity sorting (range 86-97% purity) of frozen-thawed epididymal spermatozoa in the baboon (Papio hamadryas), common marmoset (Callithrix jacchus) and common chimpanzee (Pan troglodytes). For all non-human primate species, sorted spermatozoa were progressively motile (marmoset: 20.5 +/- 5.5%; baboon: 37.5 +/- 2.5%; chimpanzee: 73.0 +/- 2.0%), acrosome intact (marmoset: 68.5 +/- 7.5%; baboon: 89.5 +/- 1.5%; chimpanzee: 84.0 +/- 1.0%) and able to penetrate an artificial cervical mucus. In summary, high-purity sorting of frozen-thawed ram and non-human primate spermatozoa with recovery of progressively motile, acrosome-intact spermatozoa was possible after processing to remove cryodiluent.

Animals↗