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Faithful replication of foraging techniques along cultural transmission chains by chimpanzees and children.

Observational studies of wild chimpanzees (Pan troglodytes) have revealed population-specific differences in behavior, thought to represent cultural variation. Field studies have also reported behaviors indicative of cultural learning, such as close observation of adult skills by infants, and the use of similar foraging techniques within a population over many generations. Although experimental studies have shown that chimpanzees are able to learn complex behaviors by observation, it is unclear how closely these studies simulate the learning environment found in the wild. In the present study we have used a diffusion chain paradigm, whereby a behavior is passed from one individual to the next in a linear sequence in an attempt to simulate intergenerational transmission of a foraging skill. Using a powerful three-group, two-action methodology, we found that alternative methods used to obtain food from a foraging device ("lift door" versus "slide door") were accurately transmitted along two chains of six and five chimpanzees, respectively, such that the last chimpanzee in the chain used the same method as the original trained model. The fidelity of transmission within each chain is remarkable given that several individuals in the no-model control group were able to discover either method by individual exploration. A comparative study with human children revealed similar results. This study is the first to experimentally demonstrate the linear transmission of alternative foraging techniques by non-human primates. Our results show that chimpanzees have a capacity to sustain local traditions across multiple simulated generations.

Animals↗

Determination of a wave function functional.

We propose expanding the space of variations in traditional variational calculations for the energy by considering the wave function psi to be a functional of a set of functions chi:psi=psi[chi], rather than a function. A constrained search in a subspace over all functions chi such that the functional psi[chi] satisfies a sum rule or leads to a physical observable is then performed. An upper bound to the energy is subsequently obtained by variational minimization. The rigorous construction of such a constrained-search-variational wave function functional is demonstrated.

Quantum Theory↗

[Comparison of hypervariable region gene of hepatitis C virus between an individual infected persistently and an individual recovered from infection].

OBJECTIVE: To explore the law of recovery from HCV infection. METHODS: Amplifiying, sequenceing and analyzing the gene of hypervariable region from an individual infected persistently and an individual recovered from infection. RESULTS: One base insertion (two clones, 10%) in the person recovered other than that infected persistently, but there is no difference between them in percentage of mumation, diversity of quasispecies and genetic distance among clones. CONCLUSION: The range of genetic variation at one time point did not seem to have obvious relationship with the HCV persistent infection or recovery from HCV infection. This study gave basic information for searching the relation of genetic variation and clinical status, and designing HCV vaccine.

Base Sequence↗

Genetic variation, nucleotide diversity, and linkage disequilibrium in seven telomere stability genes suggest that these genes may be under constraint.

To maintain chromosomal integrity and to protect the ends of chromosomes against recognition as damaged DNA, end-to-end fusion, or recombination, a coordinated set of genes is required to stabilize the telomere. We surveyed common genetic variation in seven genes that are vital to telomere stability (TERT, POT1, TNKS, TERF1, TINF2, TERF2, and TERF2IP) and validated single nucleotide polymorphisms (SNPs) in four different ethnic groups (n=118 total). Overall, our data show limited degrees of nucleotide diversity in comparison with data from other gene families. We observed that these genes are highly conserved in sequence between species, and that for nearly all of the coding SNPs the most common allele is ancestral (i.e., it is observed in primate sequences). Our findings support the hypothesis that genetic variation in a pathway that is critical for telomere stability may be under constraint. These data establish a foundation for further investigation of these genes in population-genetics, evolution, and disease-association studies.

Animals↗

Human-chimpanzee DNA sequence variation in the four major genes of the renin angiotensin system.

The renin angiotensin system (RAS) is involved in blood pressure control and water/sodium metabolism. The genes encoding the proteins of this system are candidate genes for essential hypertension. The RAS involves four main molecules: angiotensinogen, renin, angiotensin I-converting enzyme, and the angiotensin II type 1 receptor (encoded by the genes AGT, REN, DCP1, and AGTR1, respectively). We performed a molecular screening over 17,037 bp of the coding and 5' and 3' untranslated regions of these genes, from three to six common chimpanzees. We identified 44 single-nucleotide polymorphisms (SNPs) in chimpanzee samples, including 18 coding-region SNPs, 5 of which led to an amino acid replacement. We observed common and different features at various sites (synonymous, nonsynonymous, and noncoding) within and between the four chimpanzee genes: (1) the nucleotide diversity at noncoding sites was similar; (2) the nucleotide diversity at nonsynonymous sites was low, probably reflecting purifying selection, except for the AGT gene; (3) the nucleotide diversity at synonymous sites, which was dependent on the G+C content at the third position of the codon, was high, except for the AGTR1 gene. Comparison of the chimpanzee SNPs with those previously reported for humans identified 119 sites with fixed differences (including 62 coding sites, 17 of which resulted in amino acid differences between the species). Analysis of polymorphism within species and divergence between species shed light on the evolutionary constraints on these genes. In particular, comparison of the pattern of mutation at polymorphic and fixed sites between humans and chimpanzees suggested that the high G+C content of the DCP1 gene was maintained by positive selection at its silent sites. Finally, we propose 68 ancestral alleles for the human RAS genes and discuss the implications for their use in future hypertension-susceptibility association studies.

Angiotensinogen↗

The Werner syndrome gene and global sequence variation.

We have identified a dense set of markers useful in association studies involving the Werner syndrome (WRN) gene. The homozygotic disruption of the WRN gene is the cause of Werner disease. In addition, this gene is likely to be involved in many complex traits, such as aging, or at least some of the traits and diseases related to age. To investigate the genetic variation associated with the WRN gene, a sample of 93 individuals representing all the continents was analyzed by denaturing high-performance liquid chromatography. A systematic survey of all 35 exons and flanking regions identified 58 single-nucleotide polymorphisms, 15 of which fall in the coding region and cause 11 missense mutations. The resulting global nucleotide diversity was 5.226 x 10(-4), with a slight difference between coding and noncoding regions.

Alleles↗

Hepatitis C virus population dynamics during infection.

Hepatitis C virus (HCV) behaves as an evolving viral quasispecies in its continuously changing environment. The study of HCV quasispecies population dynamics in experimental models and infected patients can provide useful information on factors involved in the HCV life cycle and pathogenicity. HCV quasispecies variability also has therapeutic implications, as the continuous generation and selection of fitter or truly resistant variants can allow the virus to escape control by antiviral drugs.

Animals↗

Experimental vaccine activities of recombinant E1 and E2 glycoproteins and hypervariable region 1 peptides of hepatitis C virus in chimpanzees.

A chimpanzee was immunized with two recombinant envelope glycoproteins E1 and E2 of hepatitis C virus (HCV), strain HCV-N2, and the hypervariable region 1 (HVR1) peptides of a different isolate, HCV-#6, then received an intravenous inoculation of 10 chimpanzee infectious doses of HCV-#6. With high humoral immune response against E1 and E2 but a low response against HVR1, the vaccinee became infected with the HCV. However, after increasing the titer of anti-HVR1 against HCV-#6, the vaccinee showed protection. Neutralization of HCV-#6 with the antiserum from this protected vaccinee was achieved by inoculation of this mixture into another chimpanzee. These results suggest that vaccination with a peptide-vaccine of homologous HVR1 is effective in the chimpanzee.

Amino Acid Sequence↗

Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability.

Extensive variability in genomic sequence, especially at "hypervariable regions" within the NS1/E2 region of the long open reading frame, has been reported for RNA cloned from hepatitis C virus (HCV)-infected humans and chimpanzees. However, genetic changes of HCV occurring during the course of chronic infections in humans and animals have been evaluated only for partial sequences of the HCV genome. We compared two full-length cDNA sequences of HCV obtained from a chimpanzee that was experimentally infected with the HC-J4 strain of HCV: one during the early acute phase and another during a chronic phase 8.2 years afterward. Both isolates had 9412 nucleotides plus the 3' poly(U) tail with varying length organized as follows: 5'UTR (1-341); C (342-914); E (915-1490); NS1/E2 (1491-2528); NS2 (2529-3359); NS3 (3360-5186); NS4 (5187-6380); NS5 (6381-9371); and 3'UTR (9372-9412). We found that 111 (1.18%) of the 9412 nucleotides differed between the two isolates and estimated the mutation rate as approximately 1.44 x 10(-3) base substitutions per site per year. Changes in amino acid coding were associated with 42 mutations, 8 of which were clustered at 5' end of NS1/E2 coding region, so-called "HVR-1." We analyzed the HVR-1 and HVR-2 sequences during the course of infection and found that homologous populations were present at the beginning of infection, and sequence heterogeneity within the region had developed 3.5 years later. Two regions of the HCV genome were characterized by a high degree of conservation of nucleotide sequence: 5'UTR and the 3' half of the NS4 region. The possible secondary structure of the 5'UTR suggests a region for internal ribosomal entry. The 3' half of the NS4 region may also have some specific function which depends upon a strict conservation of nucleotide sequence.

Amino Acid Sequence↗

Display method can affect interobserver agreement: comparison of 'zoom-and-pan' and 'browse-and-paste' for primary CT interpretation.

Eight radiologists interpreted body CT images of 30 cases using a viewing station (six 17-in. monitors, 1024x1280). Using two different display methods, 'zoom-and-pan' and 'browse-and-paste', the readers described the presence or absence of liver tumors using a five-point rating scale and temporal changes between the current and previous studies using a seven-point rating scale. There was no significant difference in kappa values for tumor detection between the two display modes. However, in describing temporal changes, the kappa value of the browse-and-paste was significantly lower than that of zoom-and-pan (p<0.01). Browse-and-paste may have the disadvantage of greater interobserver variation.

Data Display↗

Virology of hepatitis C virus.

Advances in molecular biology techniques have allowed the cloning of HCV and the characterization of this virus. This article provides a short summary of our current knowledge on the genomic organization of HCV, the implications of its genetic heterogeneous nature, and the probable replication strategy of this virus.

Animals↗

Human genome sequence variation and the influence of gene history, mutation and recombination.

Variation in the human genome sequence is key to understanding susceptibility to disease in modern populations and the history of ancestral populations. Unlocking this information requires knowledge of the patterns and underlying causes of human sequence diversity. By applying a new population-genetic framework to two genome-wide polymorphism surveys, we find that the human genome contains sizeable regions (stretching over tens of thousands of base pairs) that have intrinsically high and low rates of sequence variation. We show that the primary determinant of these patterns is shared genealogical history. Only a fraction of the variation (at most 25%) is due to the local mutation rate. By measuring the average distance over which genealogical histories are typically preserved, these data provide the first genome-wide estimate of the average extent of correlation among variants (linkage disequilibrium). The results are best explained by extreme variability in the recombination rate at a fine scale, and provide the first empirical evidence that such recombination 'hot spots' are a general feature of the human genome and have a principal role in shaping genetic variation in the human population.

Animals↗

Assessment of the population structure of five Finnish dog breeds with microsatellites.

Genetic variabilities within and between Finnish populations of Golden Retrievers, German Shepherds, Wirehaired Dachshunds, Pembroke Welsh Corgis and Bedlington Terriers were quantified with microsatellite allele numbers, observed heterozygosities, expected heterozygosities, FIS estimates, FST estimates and DS distances. In a sample of 50 individuals from each, breed and ten polymorphic loci, the highest genetic diversity was exhibited in the Wirehaired Dachshunds and lowest in the Bedlington Terriers. Although statistically significant deviations from the Hardy-Weinberg (H-W) equilibrium were observed, they occurred at an unexpectedly low frequency. Most strikingly, the extremely small Bedlington Terrier population displayed genotypes in H-W proportions in all investigated loci. The H-W deviations always occurred with positive FIS estimates, which, on average, were not larger than values reported for free-living canids. Genetic differentiation between the breeds was very large. As a comparison, present estimates were, on average, over two times higher than previously observed between breeds of sheep, and over two times higher than the highest estimates reported between human populations. Moreover, the highest DS distances were only slightly lower than the lowest values inferred between humans and chimpanzees. Severe bottlenecks in the recent past of the examined breeds were not statistically supported. The presented data imply genetic isolation and intense artificial selection in the history of these breeds of dogs.

Alleles↗

Genetic organization and diversity of the hepatitis C virus.

The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there as little overall amino acid and nucleotide sequence homology with other viruses, the 5' HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5' termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N-linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5' structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.

Amino Acid Sequence↗

Variability of dopamine D4 receptor (DRD4) gene sequence within and among nonhuman primate species.

The dopamine D4 receptor is one of five receptors known to function in mammalian dopaminergic pathways. The DNA sequence of the human dopamine D4 receptor gene (DRD4) has previously been investigated in several populations and found to be highly polymorphic at both the DNA and amino acid levels, exhibiting at least 25 alleles. This variation results from differences in the number and DNA sequence of a 48-bp (16-amino acid) repeat unit in the coding region of DRD4. In the present study, DRD4 DNA sequence was examined in at least two individuals from each of five nonhuman primate species. All five species exhibit intraspecies variability, including both single nucleotide substitutions and variation in the number of 48-bp repeat units. No differences were found between the two alleles of one individual from a sixth nonhuman species. Within each species, all of the DRD4 alleles share species-specific features, indicating that while repeat-unit variation is nearly ubiquitous, ancestral variation has been lost and subsequently regenerated in each of the evolutionary lineages studied. Chimpanzees and gorillas share a unique 12-bp deletion in the coding region of DRD4, outside the repeat-unit segment of the gene. This suggest that the extant chimpanzee DRD4 is more closely related to the gorilla DRD4 than either is to the human DRD4.

Alleles↗