Poster: the macaque genome

The rhesus macaque (Macaca mulatta) facilitates an extraordinary range of biomedical and basic research, and the publication of the genome only makes it a more powerful model for studies of human disease; moreover, the macaque's position relative to humans and chimpanzees affords the opportunity to learn about the processes that have shaped the last 25 million years of primate evolution. To allow users to explore these themes of the macaque genome, Science has created a special interactive version of the poster published in the print edition of the 13 April 2007 issue. The interactive version includes additional text and exploration, as well as embedded video featuring seven scientists discussing the importance of the macaque and its genome sequence in studies of biomedicine and evolution. We have also created an accompanying teaching resource, including a lesson plan aimed at teachers of advanced high school life science students, for exploring what a comparison of the macaque and human genomes can tell us about human biology and evolution. These items are free to all site visitors.     

Morphine: conditioned increases in self-administration in rhesus monkeys

Operant responding in three monkeys was maintained by intravenous presentations of morphine. Nalorphine produced reliable increases in morphine-reinforced responding. With successive daily nalorphine injections there was a decreased latency of self-administration responding for morphine, and substituted saline injections produced conditioned increases in morphine-reinforced responding.     

Aging in rhesus monkeys: relevance to human health interventions

Progress in gerontological research has been promoted through the use of numerous animal models, which have helped identify possible mechanisms of aging and age-related chronic diseases and evaluate possible interventions with potential relevance to human aging and disease. Further development of nonhuman primate models, particularly rhesus monkeys, could accelerate this progress, because their closer genetic relationship to humans produces a highly similar aging phenotype. Because the relatively long lives of primates increase the administrative and economic demands on research involving them, new emphasis has emerged on increasing the efficient use of these valuable resources through cooperative, interdisciplinary research.     

Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination

With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.     

Calcification of the permanent first mandibular molar in rhesus monkeys

Evidence suggests that in rhesus monkeys calcification in the mandibular permanent first molar commences much earlier than has been previously reported. This tooth is the first secondary dental element to calcify, as it is in man.     

Free-ranging rhesus monkeys: age and sex differences in individual activity patterns

Two hundred thirty of the feral rhesus monkeys on Cayo Santiago were observed individually for postural adjustments, locomotor behavior, manipulation, and other nonsocial activities. Both form and frequency of activity were influenced strongly by age; sex differences were minimal. Most activities decreased with age, but head movements, presumably reflecting visual scanning, were more frequent in adults.     

Defensive behaviors in infant rhesus monkeys: environmental cues and neurochemical regulation

To survive, primates must detect danger in time to activate appropriate defensive behaviors. In this study, the defensive behaviors of infant rhesus monkeys exposed to humans were characterized. It was observed that the direction of the human's gaze is a potent cue for the infant. Infants separated from their mothers were active and emitted frequent distress vocalizations. When a human entered the room but did not look at the infant, it became silent and froze in one position. If the human stared at the infant, it responded with aggressive barking. Alterations of the opiate system affected the frequency of the infant's distress calls without affecting barking and freezing, whereas benzodiazepine administration selectively reduced barking and freezing. This suggests that opiate and benzodiazepine systems regulate specific defensive behaviors in primates and that these systems work together to mediate behavioral responses important for survival.     

Redirection of filial attachments in rhesus monkeys: dogs as mother surrogates

Rhesus infants raised from birth with their mothers, age-mates, or cloth surrogates for periods varying fronm 1 to 10 months were separated from these objects and placed with dogs. Contrary to previous suggestions that were consistent with the notions of a critical period for attachment formation and irreversibility of filial bonds, the monkeys formed strong and specific attachments to their canine surrogates.     

Ross sea region in the middle miocene: a glimpse into the past

Fossil diatoms and pollen from sea-floor sediments beneath the Ross Ice Shelf indicate that a permanent ice cover was not present in the Ross Sea and that vegetation including angiosperms, gymnosperms, and ferns existed on at least some parts of the largely glaciated Antarctic mainland in the late middle Miocene.     

Interferon-beta-related DNA is dispersed in the human genome

Interferon-beta 1 (IFN-beta 1) complementary DNA was used as a hybridization probe to isolate human genomic DNA clones lambda B3 and lambda B4 from a human genomic DNA library. Blot-hybridization procedures and partial nucleotide sequencing revealed that lambda B3 is related to IFN-beta 1 (and more distantly to IFN-alpha 1). Analyses of DNA obtained from a panel of human-rodent somatic cell hybrids that were probed with DNA derived from lambda B3 showed that lambda B3 is on human chromosome 2. Similar experiments indicated that lambda B4 is not on human chromosomes 2, 5, or 9. The finding that DNA related to the IFN-beta 1 gene (and IFN-alpha 1 gene) is dispersed in the human genome raises new questions about the origins of the interferon genes.     

Stable RNA/DNA hybrids in the mammalian genome: inducible intermediates in immunoglobulin class switch recombination

Although it is well established that mammalian class switch recombination is responsible for altering the class of immunoglobulins, the mechanistic details of the process have remained unclear. Here, we show that stable RNA/DNA hybrids form at class switch sequences in the mouse genome upon cytokine-specific stimulation of class switch in primary splenic B cells. The RNA hybridized to the switch DNA is transcribed in the physiological orientation. Mice that constitutively express an Escherichia coli ribonuclease H transgene show a marked reduction in RNA/DNA hybrid formation, an impaired ability to generate serum immunoglobulin G antibodies, and significant inhibition of class switch recombination in their splenic B cells. These data provide evidence that stable RNA/DNA hybrids exist in the mammalian nuclear genome, can serve as intermediates for physiologic processes, and are mechanistically important for efficient class switching in vivo.     

Domestication of Pulses in the Old World: Legumes were companions of wheat and barley when agriculture began in the Near East

This article reviews the available information on the place of origin and time of domestication of the cultivated pea (Pisum sativum), lentil (Lens culinaris), broad bean (Vicia faba), bitter vetch (V. ervilia), and chickpea (Cicer arietinum). On the basis of (i) an examination and evaluation of archeological remains and (ii) an identification of the wild progenitors and delimitation of their geographic distribution, it was concluded that pea and lentil should be regarded as founder crops of Old World Neolithic agriculture. Most probably they were domesticated, in the Near East, simultaneously with wheats and barley (certainly not later than the sixth millennium B.C.). Bitter vetch shows a similar mode of origin. The evidence on the broad bean and the chickpea is much more fragmentary and the wild progenitors of these legumes are yet not satisfactorily identified. But also these two pulses emerge as important food elements in Bronze Age cultures of the Near East and Europe.     

Patches with links: a unified system for processing faces in the macaque temporal lobe

The brain processes objects through a series of regions along the ventral visual pathway, but the circuitry subserving the analysis of specific complex forms remains unknown. One complex form category, faces, selectively activates six patches of cortex in the macaque ventral pathway. To identify the connectivity of these face patches, we used electrical microstimulation combined with simultaneous functional magnetic resonance imaging. Stimulation of each of four targeted face patches produced strong activation, specifically within a subset of the other face patches. Stimulation outside the face patches produced an activation pattern that spared the face patches. These results suggest that the face patches form a strongly and specifically interconnected hierarchical network.     

Extensive DNA inversions in the B. fragilis genome control variable gene expression

The obligately anaerobic bacterium Bacteroides fragilis, an opportunistic pathogen and inhabitant of the normal human colonic microbiota, exhibits considerable within-strain phase and antigenic variation of surface components. The complete genome sequence has revealed an unusual breadth (in number and in effect) of DNA inversion events that potentially control expression of many different components, including surface and secreted components, regulatory molecules, and restriction-modification proteins. Invertible promoters of two different types (12 group 1 and 11 group 2) were identified. One group has inversion crossover (fix) sites similar to the hix sites of Salmonella typhimurium. There are also four independent intergenic shufflons that potentially alter the expression and function of varied genes. The composition of the 10 different polysaccharide biosynthesis gene clusters identified (7 with associated invertible promoters) suggests a mechanism of synthesis similar to the O-antigen capsules of Escherichia coli.     

Aflatoxin P-1: a new aflatoxin metabolite in monkeys

A new phenolic derivative of aflatoxin B(1), appearing mainly in conjugated form, was identified as the principal urinary metabolite of aflatoxin B(1) in rhesus monkeys. Its identification in human urine might facilitate estimation of aflatoxin exposure in human populations.     

Thalidomide: effect upon pregnancy in the rhesus monkey

Thalidomide was administered to 44 female rhesus monkeys immediately after they had mated. There were no live births from these animals, whereas there were 11 live births in 57 untreated monkeys. The results are statistically significant. The hypothesis is advanced that thalidomide killed the embryo prior to implantation.