Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease. The potential for cell transfer of AA using the C3H/HeJ mouse model was examined. Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal C3H/HeJ recipients. Within 5 wk, all CD8(+) cell-injected mice exhibited localized hair loss exclusively at the site of injection that persisted until necropsy. In contrast, some CD4(+) and CD4(+)/CD25(-) cell-injected mice developed extensive, systemic AA, and a combination of CD8(+) and CD4(+)/CD25(-) cells injected yielded the highest frequency of systemic AA induction. CD4(+)/CD25(+) cells were less able to transfer the disease phenotype, partially blockaded systemic AA induction by CD4(+)/CD25(-) cells, and prevented CD8(+) cell-induced, injection site-localized hair loss. CD11c(+) and CD19(+) cells failed to promote significant phenotype changes. Increases in co-stimulatory ligands CD40 and CD80, plus increased leukocyte apoptosis resistance with reduced CD95, CD95L, and CD120b expression, were associated with successful alopecia induction. The results suggest that CD8(+) cells may be the primary instigators of the hair loss phenotype. However, systemic disease expression fate is, apparently determined by CD4(+)/CD25(-) cells, while CD4(+)/CD25(+) lymphocytes may play a predominantly regulatory role.

To determine the effect of environmental factors on the preservation of DNA, archeological teeth of approximately similar age but greatly differing site milieu were examined for DNA content. The complex relational system of locational milieu of the samples was reduced to its essential and, at the same time, easily measurable factors. These are temperature, humidity, pH value, the geochemical properties of the soil, the amount of postmortal organic substances and the general degree of microbial infestation in the respective soil. The relative DNA content in the samples was established by determining the rate of successful polymerase chain reaction (PCR) amplifications. Differences in quantity and quality of the results are attributed to the respective prevailing environmental factor or to the respective storage conditions. Dryness, low temperature and absence of microorganisms favors the preservation of DNA. The bioapatite of bones and teeth, like the DNA, are preserved under neutral or slightly alkaline conditions. Brief storage at room temperature does not affect the amount of amplifiable DNA but does affect the reproducibility of the results. Long storage outside a lab freezer reduces the amount and the reproducibility of DNA amplifications in ancient specimens.

A mutant allele of the chemokine receptor CCR5 gene (CCR5-D32), which confers resistance to HIV-1 infection, is believed to have originated from a single mutation event in historic times, and rapidly expanded in Caucasian populations, owing to an unknown selective advantage. Among other candidates, the plague bacillus Yersinia pestis was implicated as a potential source of strong selective pressure on European populations during medieval times. Here, we report amplifications of the CCR5-D32 DNA sequence from up to 2900-year-old skeletal remains from different burial sites in central Germany and southern Italy. Furthermore, the allele frequency of CCR5-D32 in victims of the 14th century plague pandemic in Lü beck/ northern Germany was not different from a historic control group. Our findings indicate that this mutation was prevalent already among prehistoric Europeans. The results also argue against the possibility of plague representing a major selective force that caused rapid increase in CCR5-D32 gene frequencies within these populations. Genes and Immunity (2005) The human chemokine receptor CCR5 serves, together with CD4, as the principal coreceptor for macrophagetropic (R5) human immunodeficiency virus type 1 (HIV-1) strains. 1 A large number of genetic variants in the coding or the promotor region of the CCR5 gene have been identified in different ethnic groups. 2,3 Several of these naturally occurring mutations result in alterations of the receptor's amino-acid sequence and affect the ability of CCR5 to act as a chemokine receptor or HIV coreceptor. 4,5 The finding that nonfunctional receptor alleles are relatively frequent among different human populations has led to the hypothesis that a selective advantage might be associated with the loss of CCR5 function.The CCR5-D32 mutant, which is characterized by a 32-bp deletion in the gene segment encoding the second extracellular loop of the receptor, provides an instructive example of how host genetic variation may contribute to HIV-related pathology. Individuals homozygous for CCR5-D32 are almost completely protected against HIV-1 infection due to the absence of functional receptors from the cell surface. 6-8 Population surveys revealed a north to south gradient of CCR5-D32 allele frequencies of 16 to 3% across Europe and its absence in individuals of nonCaucasian descent. 9-11 Determination of the intrahaplotypic variation of flanking microsatellite loci in strong linkage disequilibrium with CCR5-D32 allowed calculation of the approximate age of the CCR5-D32 containing ancestral haplotype. Two different studies that analyzed separate microsatellite markers concluded that the CCR5-D32 allele originated from a single mutation event that took place in historic times approximately 700 years (95% confidence interval (CI): 275-1800) 11 to 3500 years (CI 400-13 000) 10 ago in northeastern Europe. Both studies assumed a heterozygote advantage of the CCR5-D32 mutant. The European locale and timing of the bubonic plague of the 14th century coincide with the calculat...

No abstract

Alternative models have been proposed to explain the formation and decline of the south Peruvian Nasca culture, ranging from migration or invasion to autochthonous development and ecological crisis. To reveal to what extent population dynamic processes accounted for cultural development in the Nasca mainland, or were influenced by them, we analyzed ancient mitochondrial DNA of 218 individuals, originating from chronologically successive archaeological sites in the Palpa region, the Paracas Peninsula, and the Andean highlands in southern Peru. The sampling strategy allowed a diachronic analysis in a time frame from approximately 800 BC to 800 AD. Mitochondrial coding region polymorphisms were successfully analyzed and replicated for 130 individuals and control region sequences (np 16021-16408) for 104 individuals to determine Native American mitochondrial DNA haplogroups and haplotypes. The results were compared with ancient and contemporary Peruvian populations to reveal genetic relations of the archaeological samples. Frequency data and statistics show clear proximity of the Nasca populations to the populations of the preceding Paracas culture from Palpa and the Peninsula, and suggest, along with archaeological data, that the Nasca culture developed autochthonously in the Rio Grande drainage. Furthermore, the influence of changes in socioeconomic complexity in the Palpa area on the genetic diversity of the local population could be observed. In all, a strong genetic affinity between pre-Columbian coastal populations from southern Peru could be determined, together with a significant differentiation from ancient highland and all present-day Peruvian reference populations, best shown in the differential distribution of mitochondrial haplogroups.

SummaryThis study examines the reciprocal effects of cultural evolution, and population dynamics in pre-Columbian southern Peru by the analysis of DNA from pre-Columbian populations that lived in the fringe area between the Andean highlands and the Pacific coast. The main objective is to reveal whether the transition from the Middle Horizon (MH: 650-1000 AD) to the Late Intermediate Period (LIP: 1000-1400 AD) was accompanied or influenced by population dynamic processes. Tooth samples from 90 individuals from several archaeological sites, dating to the MH and LIP, in the research area were collected to analyse mitochodrial, and Y-chromosomal genetic markers. Coding region polymorphisms were successfully analysed and replicated for 72 individuals, as were control region sequences for 65 individuals and Ychromosomal single nucleotide polymorphisms (SNPs) for 19 individuals, and these were compared to a large set of ancient and modern indigenous South American populations. The diachronic comparison of the upper valley samples from both time periods reveals no genetic discontinuities accompanying the cultural dynamic processes. A high genetic affinity for other ancient and modern highland populations can be observed, suggesting genetic continuity in the Andean highlands at the latest from the MH. A significant matrilineal differentiation to ancient Peruvian coastal populations can be observed suggesting a differential population history.

A few decades after the collapse of the Avar Khaganate (c. 822 AD), Hungarian invaders conquered the Carpathian Basin (c. 862-895 AD). The first Hungarian ruling dynasty, the Árpáds played an important role in European history during the Middle Ages. King Béla III (1172-1196) was one of the most significant rulers of the dynasty. He also consolidated Hungarian dominance over the Northern Balkans. The provostry church of the Virgin Mary (commonly known as the Royal Basilica of Székesfehérvár) played a prominent role as a coronation church and burial place of medieval Hungarian kings. The basilica's building and graves had been destroyed over the centuries. The only royal graves that remained intact were those of King Béla III and his first spouse, Anna of Antioch. These graves were discovered in 1848. We defined the autosomal STR (short tandem repeat) fingerprints of the royal couple and eight additional individuals (two females and six males) found in the Royal Basilica. These results revealed no evidence of first-degree relationship between any of the investigated individuals. Y-chromosomal STR profiles were also established for all the male skeletons. Based upon the Y-chromosomal data, one male skeleton showed an obvious patrilineal relationship to King Béla III. A database search uncovered an existing Y-chromosomal haplotype, which had a single-repeat difference compared to that of King Béla. It was discovered in a person living in an area close to Hungary. This current male line is probably related paternally to the Árpád Dynasty. The control region of the mitochondrial DNA was determined in the royal couple and in the remains of the inferred relative. The mitochondrial results excluded sibling relationship between the King and the patrilineal relative. In summary, we successfully defined a Y-chromosomal profile of King Béla III, which can serve as a reference for the identification of further remains and disputed living descendants of the Árpád Dynasty. Among the examined skeletons, we discovered an Árpád member, whose exact affiliation, however, has not yet been established.

No abstract