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Two Gravettian human deciduous teeth from Grub/Kranawetberg, lower Austria.

In this paper we present two heavily eroded tooth fragments found in Grub/Kranawetberg, a Gravettian excavation site near Stillfried, Lower Austria. Both fragments were found during wet screening of sediment taken from an area near a hearth. Overall, the cultural layer yielded a large number of stone tools and flakes as well as bony points and over sixty bone beads and bone bead fragments. They point to an absolute date of 24,400 to 25,400 BP. We present a description of the tooth fragments and identify them as remains of an early modern human. One of the fragments is a deciduous right first lower molar (84) and the other a deciduous left lateral upper incisor (62). Due to their characteristic shape and size, as well as the degree of attrition, both teeth could have belonged to one single individual--a possibility consistent with their position in the stratigraphic column. The incisor could be compared for its metrical dimensions to the few other contemporaneous Upper Palaeolithic findings showing an insignificantly smaller dimension in mesio-distal and bucco-lingual dimensions. Although the remains are limited they increase our very small sample of deciduous teeth for this time period, which is essential for a better understanding of possible evolutionary trends from the Upper Palaeolithic to the Mesolithic.

Anthropology, Physical↗

In vivo evolution of human immunodeficiency virus type 1 toward increased pathogenicity through CXCR4-mediated killing of uninfected CD4 T cells.

The destruction of the immune system by progressive loss of CD4 T cells is the hallmark of AIDS. CCR5-dependent (R5) human immunodeficiency virus type 1 (HIV-1) isolates predominate in the early, asymptomatic stages of HIV-1 infection, while CXCR4-dependent (X4) isolates typically emerge at later stages, frequently coinciding with a rapid decline in CD4 T cells. Lymphocyte killing in vivo primarily occurs through apoptosis, but the importance of apoptosis of HIV-1-infected cells relative to apoptosis of uninfected bystander cells is controversial. Here we show that in human lymphoid tissues ex vivo, apoptosis of uninfected bystander CD4 T cells is a major mechanism of lymphocyte depletion caused by X4 HIV-1 strains but is only a minor mechanism of depletion by R5 strains. Further, X4 HIV-1-induced bystander apoptosis requires the interaction of the viral envelope glycoprotein gp120 with the CXCR4 coreceptor on CD4 T cells. These results emphasize the contribution of bystander apoptosis to HIV-1 cytotoxicity and suggest that in association with a coreceptor switch in HIV disease, T-cell killing evolves from an infection-restricted stage to generalized toxicity that involves a high degree of bystander apoptosis.

Apoptosis↗

Intrinsic obstacles to human immunodeficiency virus type 1 coreceptor switching.

The natural evolution of human immunodeficiency virus type 1 infection often includes a switch in coreceptor preference late in infection from CCR5 to CXCR4, a change associated with expanded target cell range and worsened clinical prognosis. Why coreceptor switching takes so long is puzzling, since it requires as few as one to two mutations. Here we report three obstacles that impede the CCR5-to-CXCR4 switch. Coreceptor switch variants were selected by target cell replacement in vitro. Most switch variants showed diminished replication compared to their parental R5 isolate. Transitional intermediates were more sensitive to both CCR5 and CXCR4 inhibitors than either the parental R5 virus or the final R5X4 (or rare X4) variant. The small number of mutations in viruses selected for CXCR4 use were distinctly nonrandom, with a dominance of charged amino acid substitutions encoded by G-to-A transitions, changes in N-linked glycosylation sites, and isolate-specific mutation patterns. Diminished replication fitness, less-efficient coreceptor use, and unique mutational pathways may explain the long delay from primary infection until the emergence of CXCR4-using viruses.

Amino Acid Sequence↗

Dikaryons of the basidiomycete fungus Schizophyllum commune: evolution in long-term culture.

The impact of ploidy on adaptation is a central issue in evolutionary biology. While many eukaryotic organisms exist as diploids, with two sets of gametic genomes residing in the same nucleus, most basidiomycete fungi exist as dikaryons in which the two genomes exist in separate nuclei that are physically paired and that divide in a coordinated manner during hyphal extension. To determine if haploid monokaryotic and dikaryotic mycelia adapt to novel environments under natural selection, we serially transferred replicate populations of each ploidy state on minimal medium for 18 months (approximately 13,000 generations). Dikaryotic mycelia responded to selection with increases in growth rate, while haploid monokaryotic mycelia did not. To determine if the haploid components of the dikaryon adapt reciprocally to one another's presence over time, we recovered the intact haploid components of dikaryotic mycelia at different time points (without meiosis) and mated them with nuclei of different evolutionary histories. We found evidence for coadaptation between nuclei in one dikaryotic line, in which a dominant deleterious mutation in one nucleus was followed by a compensatory mutation in the other nucleus; the mutant nuclei that evolved together had the best overall fitness. In other lines, nuclei had equal or higher fitness when paired with nuclei of other histories, indicating a heterozygote advantage. To determine if genetic exchange occurs between the two nuclei of a dikaryon, we developed a 24-locus genotyping system based on single nucleotide polymorphisms to monitor somatic exchange. We observed genetic exchange and recombination between the nuclei of several different dikaryons, resulting in genotypic variation in these mitotic cell lineages.

Base Sequence↗

Sexually transmitted disease and the evolution of mating systems.

Sexually transmitted diseases (STDs) have been shown to increase the costs of multiple mating and therefore favor relatively monogamous mating strategies. We examine another way in which STDs can influence mating systems in species in which female choice is important. Because more popular males are more likely to become infected, STDs can counteract any selective pressure that generates strong mating skews. We build two models to investigate female mate choice when the sexual behavior of females determines the prevalence of infection in the population. The first model has no explicit social structure. The second model considers the spatial distribution of matings under social monogamy, when females mated to unattractive males seek extrapair fertilizations from attractive males. In both cases, the STD has the potential to drastically reduce the mating skew. However, this reduction does not always happen. If the per contact transmission probability is low, the disease dies out and is of no consequence. In contrast, if the transmission probability is very high, males are likely to be infected regardless of their attractiveness, and mating with the most attractive males imposes again no extra cost for the female. We also show that optimal female responses to the risk of STDs can buffer the prevalence of infection to remain constant, or even decrease, with increasing per contact transmission probabilities. In all cases considered, the feedback between mate choice strategies and STD prevalence creates frequency-dependent fitness benefits for the two alternative female phenotypes considered (choosy vs. randomly mating females or faithful vs. unfaithful females). This maintains mixed evolutionarily stable strategies or polymorphisms in female behavior. In this way, a sexually transmitted disease can stabilize the populationwide proportion of females that mate with the most attractive males or that seek extrapair copulations.

Choice Behavior↗

The protein burden of lac operon products.

A new approach to measuring the slowing of growth due to the manufacture of proteins not needed by a bacterium is presented. An entire single colony of Escherichia coli was used to start a chemostat culture that was then given a selective pressure by the addition of phenylgalactoside (phi-gal). This enriched the population for constitutive mutants that produced beta-galactosidase without induction and could split phi-gal, consume the galactose, and grow faster. When the phi-gal was removed, the constitutives grew slower than the parental strain and were gradually lost. This procedure allows competition experiments to be carried out with minimum effects due to genetic drift. Experiments with both strains having wild-type and mutant permease genes were conducted. With the former the selective disadvantage was initially much greater than expected from the simplest hypothesis that extra unused proteins would slow growth in proportion to their fraction of the total protein synthesis. This phase was followed by a second phase where the selective disadvantage was smaller than predicted by this simple hypothesis. With a very slowly reverting permease negative strain the selective disadvantage, and therefore the protein burden, was found to be much smaller and not statistically different from zero. Thus, while one would expect under carbon and energy limitation in the chemostat the protein burden to be larger than under unlimited conditions, it is so small that even the refined technique used here could not measure it accurately. It is certainly less than the fraction of 'waste' protein synthesis; but it could be between zero and the fraction of the cells' energy and carbon budget spent on manufacture of the proteins of the lac operon.

Bacterial Proteins↗

Organization and post-transcriptional processing of focal adhesion kinase gene.

BACKGROUND: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human. RESULTS: A single orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene duplication probably occurred in deuterostomes after the echinoderma embranchment, leading to the evolution of PYK2 with distinct properties. The amino acid sequence of FAK and PYK2 is conserved in their functional domains but not in their linker regions, with the absence of autophosphorylation site in C. elegans. Comparison of mouse and human FAK genes revealed the existence of multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK transcripts suggesting a complex regulation of their expression. Four alternatively spliced coding exons (13, 14, 16, and 31), previously described in rodents, are highly conserved in vertebrates. Cis-regulatory elements known to regulate alternative splicing were found in conserved alternative exons of FAK or in the flanking introns. In contrast, other reported human variant exons were restricted to Homo sapiens, and, in some cases, other primates. Several of these non-conserved exons may correspond to transposable elements. The inclusion of conserved alternative exons was examined by RT-PCR in mouse and human brain during development. Inclusion of exons 14 and 16 peaked at the end of embryonic life, whereas inclusion of exon 13 increased steadily until adulthood. Study of various tissues showed that inclusion of these exons also occurred, independently from each other, in a tissue-specific fashion. CONCLUSION: The alternative coding exons 13, 14, 16, and 31 are highly conserved in vertebrates and their inclusion in mRNA is tightly but independently regulated. These exons may therefore be crucial for FAK function in specific tissues or during development. Conversely pathological disturbance of the expression of FAK and of its isoforms could lead to abnormal cellular regulation.

5' Untranslated Regions↗

Gene conversion of ribosomal DNA in Nicotiana tabacum is associated with undermethylated, decondensed and probably active gene units.

We examined the structure, intranuclear distribution and activity of ribosomal DNA (rDNA) in Nicotiana sylvestris (2n = 2x = 24) and N. tomentosiformis (2n = 2x = 24) and compared these with patterns in N. tabacum (tobacco, 2n = 4x = 48). We also examined a long-established N. tabacum culture, TBY-2. Nicotiana tabacum is an allotetraploid thought to be derived from ancestors of N. sylvestris (S-genome donor) and N. tomentosiformis (T-genome donor). Nicotiana sylvestris has three rDNA loci, one locus each on chromosomes 10, 11, and 12. In root-tip meristematic interphase cells, the site on chromosome 12 remains condensed and inactive, while the sites on chromosomes 10 and 11 show activity at the proximal end of the locus only. Nicotiana tomentosiformis has one major locus on chromosome 3 showing activity and a minor, inactive locus on chromosome 11. In N. tabacum cv. 095-55, there are four rDNA loci on T3, S10, S11/t and S12 (S11/t carries a small T-genome translocation). The locus on S12 remains condensed and inactive in root-tip meristematic cells while the others show activity, including decondensation at interphase and secondary constrictions at metaphase. Nicotiana tabacum DNA digested with methylcytosine-sensitive enzymes revealed a hybridisation pattern for rDNA that resembled that of N. tomentosiformis and not N. sylvestris. The data indicate that active, undermethylated genes are of the N. tomentosiformis type. Since S-genome chromosomes of N. tabacum show rDNA expression, the result indicates rDNA gene conversion of the active rDNA units on these chromosomes. Gene conversion in N. tabacum is consistent with the results of previous work. However, using primers specific for the S-genome rDNA intergenic sequences (IGS) in the polymerase chain reaction (PCR) show that rDNA gene conversion has not gone to completion in N. tabacum. Furthermore, using methylation-insensitive restriction enzymes we demonstrate that about 8% of the rDNA units remain of the N. sylvestris type (from ca. 75% based on the sum of the rDNA copy numbers in the parents). Since the active genes are likely to be of an N. tomentosiformis type, the N. sylvestris type units are presumably contained within inactive loci (i.e. on chromosome S12). Nicotiana sylvestris has approximately three times as much rDNA as the other two species, resulting in much condensed rDNA at interphase. This species also has three classes of IGS, indicating gene conversion has not homogenised repeat length in this species. The results suggest that methylation and/or DNA condensation has reduced or prevented gene conversion from occurring at inactive genes at rDNA loci. Alternatively, active undermethylated units may be vulnerable to gene conversion, perhaps because they are decondensed and located in close proximity within the nucleolus at interphase. In TBY-2, restriction enzymes showed hybridisation patterns that were similar to, but different from, those of N. tabacum. In addition, TBY-2 has elevated rDNA copy number and variable numbers of rDNA loci, all indicating rDNA evolution in culture.

Blotting, Southern↗

The position of psychiatry in the understanding of human disease.

The article discusses psychiatry and the concept of disease. This is approached by first reviewing generic attributes of the concept and how it has come to be used in contemporary medicine. Psychiatry's time-honored concern with alterations in social behavior is analyzed in the light of the generic attributes of disease. A holistic and adaptational perspective toward disease is discussed, and in particular, how psychiatry stands in relation to such a perspective. Alternative paradigms for ordering behavioral changes that can be implicated in disease are suggested. In adopting such a perspective, and rigorously exploring how disease and behavior interrelate, psychiatry becomes one of the disciplines that examines fundamental questions about man and social adaptation.

Biological Evolution↗

Activation of Rb and decline in androgen receptor protein precede retinoic acid-induced apoptosis in androgen-dependent LNCaP cells and their androgen-independent derivative.

Androgen ablation-induced prostate cancer regression is transient and ends with the regrowth of androgen-independent (AI) tumors. To mimic this evolution in culture, we chronically deprived an androgen-dependent (AD) prostate cancer cell line (LNCaP) of androgen, generating an AI derivative which retained limited hormone proliferative responsiveness and a barely detectable prostate-specific antigen (PSA) mRNA level. While the cytokeratin 8 (CK8) level was low, the androgen receptor (AR) protein in AI cells was on average tenfold greater than in AD cells. When challenged for susceptibility to undergo apoptosis, the AI cells were more resistant than AD cells to all-trans retinoic acid (tRA) and two chemotherapeutic agents, Taxol and Adriamycin, requiring higher doses and longer periods of treatment to achieve similar effects. Compared to AD cells, the partially apoptosis-resistant AI cells expressed four times more Bcl-2 protein and undetectable levels of p21/WAF1. Induction of apoptosis by tRA in both cell types did not affect their expression but was preceded by the activation of Rb and a pronounced reduction of AR protein level. The kinetics of the Rb activation and AR downmodulation in both cell types matched their tRA sensitivity, suggesting that these events may be required for tRA-induced apoptosis. The results show that the apoptotic pathway in AI cells, although more difficult to induce, is not irrevocably lost and that targeted reduction of the AR protein level with retinoids in combination with androgen ablation therapy may prolong remissions in advanced prostate cancer patients.

Antigens, Surface↗

Comparison of population structure in Ohio's late archaic and late prehistoric periods.

Previous studies of population structure among prehistoric groups in the Ohio valley region have shown that hunting-gathering populations exhibited a different structure than horticultural populations. Among both Late Archaic hunter-gatherers and Late Prehistoric horticulturists, covariance structures for cranial metrics were found to be homogenous within the populations, but the Late Archaic subpopulations showed little differentiation while the Late Prehistoric subpopulations exhibited a marked differentiation. Biodistance based on cranial discrete trait frequency showed similar patterns, but in the Late Archaic discrete trait distance was associated significantly with the geographical distance separating populations. The present investigation is an extension of the previous studies increasing the Late Prehistoric sample (n = 8 samples and n = 341 individuals) and using the Harpending-Ward model, modified for use with multivariate quantitative data, to estimate the effects of differential gene flow and the amount of differentiation within populations. Results of the present analyses indicate that differentiation among subpopulations, measured by minimum F(ST), was greater in the Late Prehistoric compared to the Late Archaic period. However, for both periods the minimum F(ST) is comparable to values found for historic native populations of the northeast woodlands. Analysis of differential gene flow in the Late Archaic period indicates that geographically peripheral populations were affected more by external gene flow than more central populations. Late Prehistoric populations exhibit a very complex pattern of differential gene flow. We discuss the latter pattern in terms of proposed culture change in the Late Prehistoric period of Ohio.

Agriculture↗

Cultural expectations of muscularity in men: the evolution of playgirl centerfolds.

OBJECTIVE: We sought to assess whether cultural ideals of the male body, as illustrated by magazine models, have changed over the past 25 years. METHOD: We examined 115 male centerfold models in Playgirl magazine from 1973 to 1997. Using the models' heights and weights quoted by the magazine, together with visual estimates of body fat, we calculated the body mass index (BMI) and fat-free mass index (FFMI) of each model. RESULTS: The Playgirl centerfold models became increasingly "dense" and more muscular over time, as indicated by the significant correlations between BMI, FFMI, and year of publication. DISCUSSION: These observations, in combination with previous studies, suggest that cultural norms of the ideal male body are growing increasingly muscular.

Beauty↗

Cleavage stage versus blastocyst stage embryo transfer in assisted conception.

BACKGROUND: In the past decade, advances in the understanding of nutrient requirements of embryos, has led to the evolution of culture media designed to support extended culture of embryos in vitro from the standard procedure of 2 to 3 days (for early cleavage embryo transfer) to 5 to 6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Since the initial widespread introduction of blastocyst culture in 1998, there has been conflicting reports about the clinical benefits of this technique. OBJECTIVES: To determine if blastocyst stage embryo transfers (ETs) affects success rates compared with cleavage stage ETs and investigate what factors may influence this. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials. We also searched the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. Attempts were made to identify trials from the National Research Register, the Clinical Trials Register and the citation lists of review articles and included trials. The last search date was May 2005. The first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 45 trials that were identified, 16 trials met the inclusion criteria and were reviewed. Primary outcomes were rates of live birth, clinical pregnancy and multiple-pregnancy rates per couple. Secondary outcomes were rates of miscarriage, failure to transfer embryos, freezing, implantation and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using odds ratios (OR) for dichotomous outcomes and weighted mean differences for binary outcomes with 95% confidence intervals (CI). MAIN RESULTS: There was no evidence of a difference in live-birth rate per couple between the two treatment groups (7 RCTs; OR 1.16, 95% CI 0.74 to 1.44 [Day 2/3 34.3% vs. Day 5/6 35.4%]); in the clinical pregnancy rate per couple (15 RCTs; OR 1.05, 95% CI 0.88 to 1.26 [Day 2/3 38.8% vs. 40.3%]) even for good prognosis patients (6 RCTs: OR 96% 1.06 CI 0.83 to 1.34). There was also no difference in multiple-pregnancy rate per couple (12 RCTs; OR 0.85, 95% CI 0.63 to 1.13) particularly in trials where equal numbers of embryos were transferred in both groups (6 RCTs: OR 0.91, 95% CI 0.63 to 1.32). There was no evidence of a difference in high order multiple-pregnancy rates per couple (5 RCTs; OR 0.44, 95% CI 0.15 to 1.33) or miscarriage rate per couple between the two groups (9 RCTs; OR 1.33, 95% CI 0.89 to 2.01). Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.57). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (10 RCTs: OR 3.21, 95% CI 2.15 to 4.81[Day 2/3 3.5% vs D 5/6 10.1%]), but was not significantly different for good prognosis patients (7RCTs, OR 1.58 95% CI 0.65 to 3.82). AUTHORS' CONCLUSIONS: There is no evidence of a difference in live birth or pregnancy outcomes between Day 2 to 3 and Day 5 to 6 transfer of embryos. Blastocyst transfer was associated with an increase in failure to transfer any embryos in a cycle and a decrease in embryo freezing rates. In the absence of data on cumulative live birth rates resulting from fresh and thawed cycles, it is not possible to determine if this represents an advantage or disadvantage.

Blastocyst↗

Multicultural genetic counseling: then, now, and in the 21st century.

Scholars, educators, and practitioners have argued that racial-cultural issues are obstacles for those seeking genetic counseling. When available, cross-cultural genetic counseling has focused on simplistic knowledge of client health beliefs and cultural customs, professional cultures, and biased theoretical models as reasons for failure to create realistic knowledge of members of racial-cultural groups in the United States. Recognizing the importance of meeting the needs for all who seek genetic counseling services, genetic counselors have been providing direction in cross-cultural genetic counseling research, practice, training, and developing competency, ethical, and professional guidelines. However, emanating from a cultural pluralism perspective, cross-cultural genetic counseling has often resulted in homogenized group stereotypes without attention to intragroup variation and individual differences. A transition from cross-cultural towards multicultural genetics shifts from culture-specific group norms to an integrated social, historical, psychological, and political perspective. By valuing the process of personal and professional racial-cultural identity development, the evolution from cross-cultural to multicultural genetic counseling that has occurred within the past quarter century is discussed.

Clinical Competence↗

Genetic variation in North Africa and Eurasia: neolithic demic diffusion vs. Paleolithic colonisation.

The hypothesis that both genetic and linguistic similarities among Eurasian and North African populations are due to demic diffusion of neolithic farmers is tested against a wide database of allele frequencies. Demic diffusion of farming and languages from the Near East should have determined clines in areas defined by linguistic criteria; the alternative hypothesis of cultural transmission does not predict clines. Spatial autocorrelation analysis shows significant gradients in three of the four linguistic families supposedly affected by neolithic demic diffusion; the Afroasiatic family is the exception. Many such gradients are not observed when populations are jointly analyzed, regardless of linguistic classification. This is incompatible with the hypothesis that major cultural transformations in Eurasia (diffusion of related languages and spread of agriculture) took place without major demographic changes. The model of demic diffusion seems therefore to provide a mechanism explaining coevolution of linguistic and biological traits in much of the Old World. Archaeological, linguistic, and genetic evidence agree in suggesting a multidirectional process of gene flow from the Near East in the neolithic. However, the possibility should be envisaged that some allele frequency patterns can predate the neolithic and depend on the initial spread of Homo sapiens sapiens from Africa into Eurasia.

Agriculture↗

Late Chachapoya population structure prior to Inka conquest.

Archaeological and ethnohistorical documents suggest that the Chachapoya region was inhabited by a number of distinct sociopolitical groups that only united in the face of their common enemy, the Inka. The purpose of this research is to quantify the amount of internal genetic differentiation and levels of extraregional gene flow during the Late Chachapoya period, in order to obtain a better understanding of the genetic relationship between these presumed ethnic groups. Craniometric data were collected from three Late Chachapoya samples (Laguna Huayabamba, Kuelap, and Laguna de los Cóndores), in order to understand the genetic relationships between the groups and facilitate our understanding of Late Chachapoya population structure. Genetic differentiation among these series ranged from 0.047 (heritability = 1.0) to 0.090 (heritability = 0.55). The Relethford-Blangero residuals indicate that the Laguna Huayabamba and Laguna de los Cóndores populations were receiving greater than average external gene flow, while Kuelap was receiving less than average external gene flow. The correspondence between biological and archaeological data in the investigation of prehistoric ethnic identity is discussed.

Anthropology, Cultural↗