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PubMed1994

Electromyography of back muscles during quadrupedal and bipedal walking in primates.

Despite the extensive electromyographic research that has addressed limb muscle function during primate quadrupedalism, the role of the back muscles in this locomotor behavior has remained undocumented. We report here the results of an electromyographic (EMG) analysis of three intrinsic back muscles (multifidus, longissimus, and iliocostalis) in the baboon (Papio anubis), chimpanzee (Pan troglodytes), and orangutan (Pongo pygmaeus) during quadrupedal walking. The recruitment patterns of these three back muscles are compared to those reported for the same muscles during nonprimate quadrupedalism. In addition, the function of the back muscles during quadrupedalism and bipedalism in the two hominoids is compared. Results indicate that the back muscles restrict trunk movements during quadrupedalism by contracting with the touchdown of one or both feet, with more consistent activity associated with touchdown of the contralateral foot. Moreover, despite reported differences in their gait preferences and forelimb muscle EMG patterns, primates and nonprimate mammals recruit their back muscles in an essentially similar fashion during quadrupedal walking. These quadrupedal EMG patterns also resemble those reported for chimpanzees, gibbons and humans (but not orangutans) walking bipedally. The fundamental similarity in back muscle function across species and locomotor behaviors is consistent with other data pointing to conservatism in the evolution of the neural control of tetrapod limb movement, but does not preclude the suggestion (based on forelimb muscle EMG and spinal lesion studies) that some aspects of primate neural circuitry are unique.

Animals↗
PubMed1994

Ontogenetic correlates of diet in anthropoid primates.

This study assesses ontogenetic correlates of diet in anthropoid primates. Associations between body weight growth, adult size, and diet are evaluated for a sample of 42 primate species, of which 8 are classifiable as "folivores." The hypothesis that folivores show a pattern of growth that differs from "nonfolivores" is tested. Ontogenetic variation is summarized through use of parametric and nonparametric regression analysis. Several analytical techniques, including broad interspecific and detailed comparisons among species of similar adult size, are applied. This investigation indicates a clear association between body weight ontogeny and diet: folivorous species grow more rapidly over a shorter duration than comprably sized nonfolivorus species. A positive correlation between adult size and diet is not unambiguously established in this sample. A threshold (at around 1 kg) below which insectivory is very common may adequately characterize the association between adult size and diet in anthropoid primates. Above this threshold, adult size does not appear to covary predictably with diet. Evolutionary correlates of the ontogenetic pattern seen in folivores may include a variety of factors. The distinctive pattern of development in folivores may relate to the profile of ecological and social risks that these species face. Morphophysiological advantages to rapid growth may relate to a need for accelerated alimentary (dental and gut) development. The implications of ontogenetic variation in folivores are discussed.

Age Factors↗
PubMed1994

Patterns of ingestive behavior and anterior tooth use differences in sympatric anthropoid primates.

Little research has been directed towards the examination of ingestive behaviors in wild primates. This paper describes a naturalistic study of anterior tooth use in four sympatric anthropoid species: Hylobates lar, Macaca fascicularis, Pongo pygmaeus, and Presbytis thomasi. Instantaneous group scan data were collected during nearly 1,800 hours of observation between August 1990 and July 1991 at the Ketambe Research Station in the Gunung Leuser National Park, Sumatra, Indonesia. Ingestive behaviors are documented for specific food items and compared among the primate taxa. Results indicate significant differences among the species in preferred methods of food ingestion. These differences are related in part to dietary differences, and in part to other aspects of each primate's biology and ecology.

Animals↗
PubMed1995

Socioecology and the ontogeny of sexual size dimorphism in anthropoid primates.

This study examines statistical correlations between socioecological variables (including measures of group composition, intermale competition, and habitat preference) and the ontogeny of body size sexual dimorphism in anthropoid primates. A regression-based multivariate measure of dimorphism in body weight ontogeny is derived from a sample of 37 species. Quantitative estimates of covariation between socioecological variables and this multivariate measure are evaluated. Statistically significant covariation between the ontogeny of dimorphism and socioecological variables, with the possible exception of habitat preference, is observed. Sex differences in ontogeny are lacking in species that exhibit low levels of intermale competition and are classifiable as species with monogamous/polyandrous mating systems. Among dimorphic species, two modes of dimorphic growth are apparent, which seem to be related to different kinds of group compositions. Multimale/multifemale species tend to become dimorphic through bimaturism (sex differences in duration of growth) with minimal sex differences in growth rate. Single-male/multifemale species tend to attain dimorphism through differences in rate of growth, often with limited bimaturism. Measures of intermale competition may also covary with these modes of dimorphic growth, but the relations among these variables are sometimes ambiguous. Correlations between dimorphic growth and behavioral variables may reflect alternative life history strategies in primates. Specifically, the ways in which risks faced by subadult males are distributed and the relations of these risks to growth rates seem to influence the evolution of size ontogenies. The absence of dimorphic ontogeny in some species can be tied to similar distributions of risk in each sex. In taxa that become dimorphic primarily through rate differences in growth, the lifetime distribution of risks for males may change rapidly. In contrast, males may face a pattern of uniformly changing or stable risk in species that become dimorphic through bimaturism. Finally, much variation recorded by this study remains unexplained, providing additional evidence of the need to specially examine female ontogeny before primate body size dimorphism can be satisfactorily explained.

Analysis of Variance↗
PubMed2006

Chromosome painting between human and lorisiform prosimians: evidence for the HSA 7/16 synteny in the primate ancestral karyotype.

Multidirectional chromosome painting with probes derived from flow-sorted chromosomes of humans (Homo sapiens, HSA, 2n = 46) and galagos (Galago moholi, GMO, 2n = 38) allowed us to map evolutionarily conserved chromosomal segments among humans, galagos, and slow lorises (Nycticebus coucang, NCO, 2n = 50). In total, the 22 human autosomal painting probes detected 40 homologous chromosomal segments in the slow loris genome. The genome of the slow loris contains 16 sytenic associations of human homologues. The ancient syntenic associations of human chromosomes such as HSA 3/21, 7/16, 12/22 (twice), and 14/15, reported in most mammalian species, were also present in the slow loris genome. Six associations (HSA 1a/19a, 2a/12a, 6a/14b, 7a/12c, 9/15b, and 10a/19b) were shared by the slow loris and galago. Five associations (HSA 1b/6b, 4a/5a, 11b/15a, 12b/19b, and 15b/16b) were unique to the slow loris. In contrast, 30 homologous chromosome segments were identified in the slow loris genome when using galago chromosome painting probes. The data showed that the karyotypic differences between these two species were mainly due to Robertsonian translocations. Reverse painting, using galago painting probes onto human chromosomes, confirmed most of the chromosome homologies between humans and galagos established previously, and documented the HSA 7/16 association in galagos, which was not reported previously. The presence of the HSA 7/16 association in the slow loris and galago suggests that the 7/16 association is an ancestral synteny for primates. Based on our results and the published homology maps between humans and other primate species, we propose an ancestral karyotype (2n = 60) for lorisiform primates.

Animals↗
PubMed2007

On the time scale of New World primate diversification.

New World primates comprise a diverse group of neotropical mammals that suddenly appeared in the Late Oligocene deposits of South America at around 26 million years ago (MYA). Platyrrhines seem to have separated from Old World anthropoids ca. 35 MYA, and their subsequent diversfication is not well documented in the fossil record. Therefore, molecular clock studies were conducted to unveil the temporal scenario for the evolution of the group. In this study, divergence times of all splits within platyrrhines until the generic level were investigated, using two different gene data sets under relaxed molecular clocks. Special attention was paid to the basal diversification of living platyrrhines and to the basal split of the modern Cebidae family, since these nodes were reported to be phylogenetically difficult to resolve. The results showed that analyses from various genomic regions are similar to estimates obtained by early single-gene studies. Living New World primates are descendants of ancestors that lived in the Early Miocene, at around 20 MYA, and modern Cebidae and Pitheciidae appeared ca. 16.9 and 15.6 MYA, respectively. The last common ancestor of living Atelidae is 12.4 million years old, making this clade the youngest New World primate family; at approximately the same time, modern Callitrichinae was evolving (11.8 MYA). The gap between the Platyrrhini/Catarrhini separation and the last common ancestor of living Platyrrhini may be as big as 20 million years. Paleontological and geoclimatological evidence corroborates that the sudden appearance of modern families may be a consequence of environmental changes during the Miocene.

Animal Migration↗
PubMed1982

Femoral mechanics in the lesser bushbaby (Galago senegalensis): structural adaptations to leaping in primates.

One method used to examine the relationship between behavioral strategies and anatomical adaptation is to study the results of mechanical stress associated with a given behavior and compare this with skeletal adaptations to other behaviors. This comparative approach is appropriate for highlighting combinations of features that are specializations to specific types of behavior. The purpose of this paper is to compare femoral mechanics in Galago senegalensis with previously collected data for macaques and humans as a basis for discussing structural adaptations in the primate hindlimb to leaping. The stiffness and load carrying capabilities of the femoral diaphyses of 27 G. senegalensis were analyzed using the SCADS computer program. The data suggest that the galago femur is well adapted to sustain large sagittal plane compressive loads rather than large bending loads. The straightness of the femoral shaft and large midshaft area moments of inertia prevent buckling from these large compressive loads. Calculations indicate that the ratio of critical buckling load to body weight in galago is 31 times that in macaques and 55 times that in humans. The femur of this saltatory primate is morphologically adapted to resist buckling when subjected to large compressive loads, while those of macaques and humans are better adapted to resist bending moments caused by ground reaction forces acting on the extended limb. The differences between galago on the one hand and macaques and humans on the other suggest that relatively smaller moments about the hip and relatively larger moments about the knee accompany more quadrupedal and bipedal walking, while habitual leaping is associated with relatively larger moments about the hip. These data reinforce the apparent similarity of the mechanical effects of quadrupedal and bipedal locomotion on the femur and dissimilarity with femoral mechanics in habitually saltatory primates.

Adaptation, Physiological↗
PubMed1992

Morphogenetic and functional activity of type II cells in early fetal rhesus monkey lungs. A comparison between primates and rodents.

To evaluate further the role of type II alveolar epithelial cells in primate lung development, lungs of fetal (46 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys were investigated with antibodies against surfactant protein A (SP-A), Alcian blue (AB) staining, and periodic acid-Schiff (PAS) staining with/without alpha-amylase pre-treatment. In adult and postnatal lungs, type II cells (cuboid shape; large, roundish nucleus) displayed a unique cytoplasmic staining for SP-A. In prenatal lungs, a low-columnar to cuboid type of cell with a large, roundish nucleus was first detectable by 62 DGA. It was the only cell type to line the distalmost tubules or buds of the prospective respiratory tract. It exhibited (initially partial) cytoplasmic staining for SP-A. AB and PAS stainings showed the presence of acid glycoconjugates and large apical and/or basal glycogen fields. After 95 DGA, the lining of the distal respiratory tract additionally displayed flatter cells with immunoreactivity for SP-A and non-reactive zones. Columnar epithelium (pseudostratified or simple) never stained for SP-A. We conclude that morphologically identifiable type II cells first appear in fetal rhesus monkey lungs by 62 DGA (pseudoglandular period). The cells may already synthesize surfactant and extracellular matrix components. They generate type I cells, and thus the entire pulmonary acinus lining. These conclusions for the rhesus monkey fully agree with our earlier conclusions for another primate, the human, and for rodents. However, as presently shown, primates differ greatly from rodents with respect to the timing of type II cell differentiation (at 29-38% versus 73-75% of gestation or at 22-25% versus 48-49% of prenatal lung development).

Animals↗
PubMed2003

Glutamate receptors at bipolar synapses in the inner plexiform layer of primate retina: light microscopic analysis.

At least 10 different types of bipolar cells have been distinguished in the primate retina. The axon terminals of these cells stratify in distinct strata in the inner plexiform layer and are involved in parallel pathways to distinct types of ganglion cells. Ionotropic glutamate receptor (GluR) subunits also show a stratified distribution in the inner plexiform layer. Here, we investigated whether different types of bipolar cells are associated with different types of ionotropic glutamate receptors in the inner retina of a New World primate, the common marmoset Callithrix jacchus. Vertical cryostat sections through central retina were double labeled with immunohistochemical markers for bipolar cell types and with antibodies to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1 to 4, kainate receptor subunits GluR6/7, and the NR1C2' subunit of the N-methyl-D-aspartate (NMDA) receptor. The axon terminals of bipolar cell types were reconstructed from confocal sections, and the colocalized immunoreactive puncta were quantified. For all bipolar cell types, immunoreactive puncta for the AMPA receptor subunits GluR2, 2/3, and 4 were colocalized at highest densities, whereas GluR1-immunoreactive puncta were expressed at very low densities. The kainate receptor subunits GluR6/7 were predominantly associated with diffuse bipolar (DB6) and rod bipolar cells. The NMDA receptor subunit NR1C2' was specifically colocalized with flat midget and DB3 axons. These findings suggest that rod and cone bipolar cell types contribute to multiple but distinct glutamate receptor pathways in primate retina.

Animals↗
PubMed1978

Patterns of retinal terminations and laminar organization of the lateral geniculate nucleus of primates.

Autoradiographic tracing procedures have been used to study the organization of retinogeniculate axons in seven primates, i.e., four species of New World monkeys, one species of Old World monkeys and two species of prosimians. These data suggest that the basic primate pattern of geniculate lamination consists of two parvocellular layers, two magnocellular layers, and two poorly developed and highly variable superficial (S) layers which are ventrally located. Ocular input to each member of each of the three pairs differs. In the macaque, the squirrel, and the saki monkey, the parvocellular layers subdivide and interdigitate into four leaflets so as to give the appearance of four parvocellular "layers." These leaflets are much less extensive in the owl and marmoset monkeys. In some individual macaque monkeys, there is further splitting of the parvocellular leaflets into subleaflets, giving the appearance of six parvocellular "layers." The prosimians (galago and slow loris) have two additional layers that are not found in pithecoid primates, and only one superficial layer is apparent. The two additional layers are termed "koniocellular" since they consist of very small cells. Finally, New and Old World monkeys have both ipsilateral and contralateral retinal input to the interlaminar zones. We conclude that the basic pattern of lateral geniculate organization is six layers, but not the traditional six. Prosimians have evolved two additional layers, the koniocellular layers, and have possibly lost one superficial layer. Both New World and Old World monkeys have elaborated the parvocellular layers by forming leaflets to varying extents. With the possible exception of the single S layer in prosimians, layers form pairs that are similar in cell types, but different in ocular input.

Animals↗
PubMed1980

The primate cochlear nuclei: loss of lamination as a phylogenetic process.

In primates from prosimians to hominoids (lorisoid prosimians, marmoset and ceboid monkeys, cercopithecoid monkeys, and gibbon), there are differences in the location, depth, and extent of the granular layer of the cochlear nuclei. In the prosimians, the deep granular layer of the DCN is similar to that of other mammals, but there is, in addition, a superficial or subependymal layer of granule cells in the DCN. In ceboid and cercopithecoid monkeys, only a superficial or external granular layer is present in the DCN, and the granular layer over the VCN is much reduced. In the gibbon, there is no granular layer in either of the cochlear muclei. In conjunction with the progressive reduction of the cochlear granular layer in primates, fusiform cells lose their position as a radially oriented peripheral cell layer in the DCN and become located in the central region of the nucleus. These changes in primates are interpreted as resulting from failure of inward migration and increasing cell death in the ontogeny of the cochlear external granular layer, with concomitant changes occurring in the position and orientation of their target neurons, the fusiform cells.

Animals↗
PubMed1986

Studies on the evolution of multiple somatosensory representations in primates: the organization of anterior parietal cortex in the New World Callitrichid, Saguinus.

Because members of the New World family, Callithricidae, are generally regarded as the most primitive of monkeys, we studied the organization of somatosensory cortex in the tamarin (Saguinus) in hopes of better understanding differences in the organization of anterior parietal cortex in primates and how these differences relate to phylogeny. In most prosimian primates only one complete representation of cutaneous receptors has been found in the region of primary cortex, S-I, while in all Old and New World monkeys studied to date, two cutaneous representations exist in distinct architectonic fields, areas 3b and 1. In detailed microelectrode mapping studies in anesthetized tamarins, only one complete representation responsive to low-threshold cutaneous stimulation was evident in the S-I region. This topographic representation was in a parietal koniocortical field that architectonically resembles area 3b of other monkeys, and the general somatotopic organization of the field was similar to that of area 3b of other monkeys. Cortex rostral to the single representation was generally unresponsive to somatosensory stimuli, or required more intense stimulation for neural activation. Cortex caudal to the representation, in the region of area 1 of other monkeys, was generally either unresponsive or responded to only high-threshold stimulation, although some recording sites were activated by low-threshold tactile stimulation. The present evidence, together with that from previous studies, suggests that the single, complete body surface representation in Saguinus is homologous to the S-I representation found in some prosimians (Galago, Perodicticus) and the area 3b cutaneous representation found in New World Cebidae (Aotus, Saimiri, and Cebus) and Old World Macaca. Cortex rostral to S-I in Saguinus has the appearance of areas 3a and 4 of other primates. The cortex caudal to S-I in Saguinus, while resembling area 1 in some ways, does not have all of the features of area 1 of other monkeys. In particular, the field was not easily activated by low-threshold cutaneous stimuli, as area 1 is in other monkeys, and therefore a second cutaneous representation of all body parts was not demonstrated. Thus, cortex in the expected location of area 1 of Saguinus was not as responsive as area 1 of other monkeys, and it somewhat resembled the high-threshold fringe zones found caudal to S-I in anesthetized prosimians and some nonprimates. The results raise the possibility that the area 1 cutaneous representation that is characteristic of other New World monkeys and Old World monkeys evolved from a less responsive precursor along the caudal border of S-I in early monkeys.

Animals↗
PubMed1989

Extrinsic determinants of retinal ganglion cell development in primates.

As in all mammals studied to date, primate retina contains morphologically distinct classes of retinal ganglion cells (Polyak: The Retina. Chicago: University of Chicago Press, '41; Boycott and Dowling: Philos. Trans. R. Soc. Lond. [Biol.] 225:109-184, '69; Leventhal et al.: Science 213:1139-1142, '81; Perry et al.: Neuroscience 12:1101-1123, '84; Rodieck et al.: J. Comp. Neurol. 233:115-132, '85; Rodieck: In H.D. Steklis and J. Erwin (eds): Comparative Primate Biology, Volume 4: Neurosciences. New York: Alan R. Liss, Inc., pp. 203-278, '88). We have now studied the morphologies, central projections, and retinal distributions of the major morphological classes of ganglion cells in the normal adult monkey, the newborn monkey, and the adult monkey in which restricted regions of retina were depleted of ganglion cells at birth as a result of small lesions made around the perimeter of the optic disc. Both old-world (Macaca fascicularis) and new-world (Saimiri sciureus) monkeys were studied. Our results indicate that, at birth, the major morphological classes of monkey retinal ganglion cells are recognizable; cells in central regions are close to adult size whereas cells in peripheral regions are much smaller than in the adult. As in the adult (Stone et al.: J. Comp. Neurol. 150:333-348, '73), in newborn monkeys there is a very sharp division between ipsilaterally and contralaterally projecting retinal ganglion cells (nasotemporal division). Consistent with earlier work (Hendrickson and Kupfer: Invest. Ophthalmol. 15:746-756, '76) we find that the foveal pit in the neonate is immature and contains many more ganglion cells than in the adult. In the adult monkey in which the density of retinal ganglion cells in the central retina was reduced experimentally at birth, the fovea appeared immature, and an abnormally large number of retinal ganglion cells were distributed throughout the foveal pit. The cell bodies and dendritic fields of ganglion cells that developed within cell-poor regions of the central retina were nearly ten times larger than normal. In peripheral regions the effects were smaller. The dendrites of the abnormally toward the foveal pit. They did not extend preferentially into the cell-poor region as do the abnormally large cells on the borders of experimentally induced cell-poor regions of cat central retina (Leventhal et al.: J. Neurosci. 8:1485-1499, '88) or, as we found here, in paracentral regions of primate retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1994

Synaptic terminal coverage of primate triceps surae motoneurons.

This study examined the synaptic terminal coverage of primate triceps surae (TS) motoneurons at the electron microscopic level. In three male pigtail macaques, motoneurons were labeled by retrograde transport of cholera toxin-horseradish peroxidase that was injected into TS muscles bilaterally and visualized with tetramethylbenzidine stabilized with diaminobenzidine. Somatic, proximal dendritic, and distal dendritic synaptic terminals were classified by standard criteria and measured. Overall and type-specific synaptic terminal coverages and frequencies were determined. Labeled cells were located in caudal L5 to rostral S1 ventral horn and ranged from 40 to 74 microns in diameter (average, 54 microns). The range and unimodal distribution of diameters, the label used, and the presence of C terminals on almost all cells indicated that the 15 cell bodies and associated proximal dendrites analyzed here probably belonged to alpha-motoneurons. Synaptic terminals covered 39% of the cell body membrane, 60% of the proximal dendritic membrane, and 40% of the distal dendritic membrane. At each of these three sites, F terminals (flattened or pleomorphic vesicles, usually symmetric active zones, average contact length 1.6 microns) were most common, averaging 52%, 56%, and 58% of total coverage and 56%, 57%, and 58% of total number of cell bodies, proximal dendrites, and distal dendrites respectively. S terminals (round vesicles, usually asymmetric active zones, average contact length 1.3 microns) averaged 24%, 29%, and 33% of coverage and 33%, 35%, and 36% of number at these three sites, respectively. Thus, S terminals were slightly more prominent relative to F terminals on distal dendrites than on cell bodies. C terminals (spherical vesicles, subsynaptic cisterns associated with rough endoplasmic reticulum, average contact length 3.5 microns) constituted 24% and 11% of total terminal coverage on cell bodies and proximal dendrites, respectively, and averaged 11% and 6% of terminal number at these two locations. M terminals (spherical vesicles, postsynaptic Taxi bodies, some with presynaptic terminals, average contact length 2.7 microns) were absent on cell bodies and averaged 3% and 7% of total coverage and 2% and 5% of terminals on proximal and distal dendrites, respectively. Except for M terminals, which tended to be smaller distally, terminal contact length was not correlated with location. Total and type-specific coverages and frequencies were not correlated with cell body diameter. Primate TS motoneurons are similar to cat TS motoneurons in synaptic terminal morphology, frequency, and distribution. However, primate terminals appear to be smaller, so that the fraction of membrane covered by them is lower.

Animals↗
PubMed2004

Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H.

Although the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4+ CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4+ T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4+ CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse peptide-sensitized Patr-DR7+ cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.

Amino Acid Sequence↗
PubMed1979

Prevention of the mutagenic activation of an antischistosomal isothiocyanate in primates by an antibiotic.

Administration of 4 nitro-4' isothiocyano-diphenylamine (CGP 4540, amoscanate) to two nonhuman primates, Macaca mulatta and Cebus apella, resulted in the appearance of mutagenic material in the urines of these animals. Mutagenic metabolites of this drug could also be detected in the urines when the drug was administered to primates infected with Schistosoma mansoni and Schistosoma japonicum. As observed previously in mice, the mutagenic activation of amoscanate can be prevented in primates by coadministration of a single oral dose of erythromycin with no concomitant reduction in antischistosomal activity. The protective effect of erythromycin was confirmed in several crossover experiments. This dissociation of mutagenic from chemotherapeutic effects provides an opportunity to reduce serious potential long-term risks of this antischistosomal drug.

Aniline Compounds↗
PubMed2003

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates.

Because of the paucity of primate experimental models, the precise molecular mechanism of ischemic neuronal death remains unknown in humans. This study focused on nonhuman primates to determine which cascade necrosis or apoptosis is predominantly involved in the development of delayed (day 5) neuronal death in the hippocampal CA1 sector undergoing 20 min ischemia. We investigated expression, activation, and/or translocation of micro-calpain, lysosome-associated membrane protein-1 (LAMP-1), caspase-3, and caspase-activated DNase (CAD), as well as morphology of the postischemic CA1 neurons and DNA electrophoresis pattern. Immunoblotting showed sustained (immediately after ischemia until day 5) and maximal (day 3) activation of micro-calpain. The immunoreactivity of activated micro-calpain became remarkable as coarse granules at lysosomes on day 2, while it translocated throughout the perikarya on day 3. The immunoreactivity of LAMP-1 also showed a dynamic and concomitant translocation that was maximal on days 2-3, indicating calpain-mediated disruption of the lysosomal membrane after ischemia. In contrast, immunoblotting demonstrated essentially no increase in the activated caspase-3 at any time points after ischemia, despite upregulation of pro-caspase-3. Although expression of CAD was slightly upregulated on day 1 or 2, or both, it was much less compared with lymph node or intestine tissues. Furthermore, light and electron microscopy showed eosinophilic coagulation necrosis and membrane disruption without apoptotic body formation, while DNA electrophoresis did not show a ladder pattern, but rather a smear pattern. Sustained calpain activation and the resultant lysosomal rupture, rather than CAD-mediated apoptosis, may cause ischemic neuronal necrosis in primates.

Animals↗
PubMed2005

Conservation of the RB1 gene in human and primates.

Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence variation in diverse human populations and primates. Therefore, we analyzed the coding (2,787 bp) and adjacent intronic and untranslated (7,313 bp) sequences of RB1 in 137 individuals from a wide range of ethnicities, including 19 Asian Indian hereditary retinoblastoma cases, and five primate species. Aside from nine apparently disease-associated mutations, 52 variants were identified. They included six singleton, coding variants that comprised five amino acid replacements and one silent site. Nucleotide diversity of the coding region (pi=0.0763+/-1.35 x 10(-4)) was 52 times lower than that of the noncoding regions (pi=3.93+/-5.26 x 10(-4)), indicative of significant sequence conservation. The occurrence of purifying selection was corroborated by phylogeny-based maximum likelihood analysis of the RB1 sequences of human and five primates, which yielded an estimated ratio of replacement to silent substitutions (omega) of 0.095 across all lineages. RB1 displayed extensive linkage disequilibrium over 174 kb, and only four unique recombination events, two in Africa and one each in Europe and Southwest Asia, were observed. Using a parsimony approach, 15 haplotypes could be inferred. Ten were found in Africa, though only 12.4% of the 274 chromosomes screened were of African origin. In non-Africans, a single haplotype accounted for from 63 to 84% of all chromosomes, most likely the consequence of natural selection and a significant bottleneck in effective population size during the colonization of the non-African continents.

Animals↗