Dinamismo vital, el dogma de la medicina homeopática / Vital dynamism, the dogma of homeopathic medicine

El dinamismo vital ha tenido diversas interpretaciones a lo largo del tiempo. El maestro Samuel Hahnemann ha sido pionero al dar una primera concepción a la fuerza y al sistema que controlan el equilibrio en el organismo. Visionario para su tiempo y sin las herramientas que ahora acompañan a la biología molecular, élsupo conjeturar que existía un procesamiento complejo en cada una de las células que nos conforman como seres vivos y que, gracias al avance tecnológico, hoy recibe el nombre de dogma central de la biología molecular, mismo que se encuentra compuesto por la replicación del ADN, la transcripción del ARN y la traducciónde las proteínas, asegurando así la ejecución de la vida mediante un mecanismo siempre dinámico. (AU)

The vital dynamism has undergone various interpretations over time. The teacher Samuel Hahnemann pioneered the first notion about both the strength and the system that control the body balance. Visionary for his time and without the tools now accompanying the molecular biology, he envisioned that there existed a complex processing in every cell making us up as living beings, and that thanks to technological breakthroughs, today it is called the central dogma of molecular biology, which is composed of the replication of DNA, RNA transcription and protein translation, thus ensuring the realization of life through an ever dynamic mechanism. (AU)

Twenty-five thousand years of fluctuating selection on leopard complex spotting and congenital night blindness in horses.

Leopard complex spotting is inherited by the incompletely dominant locus, LP, which also causes congenital stationary night blindness in homozygous horses. We investigated an associated single nucleotide polymorphism in the TRPM1 gene in 96 archaeological bones from 31 localities from Late Pleistocene (approx. 17 000 YBP) to medieval times. The first genetic evidence of LP spotting in Europe dates back to the Pleistocene. We tested for temporal changes in the LP associated allele frequency and estimated coefficients of selection by means of approximate Bayesian computation analyses. Our results show that at least some of the observed frequency changes are congruent with shifts in artificial selection pressure for the leopard complex spotting phenotype. In early domestic horses from Kirklareli-Kanligecit (Turkey) dating to 2700-2200 BC, a remarkably high number of leopard spotted horses (six of 10 individuals) was detected including one adult homozygote. However, LP seems to have largely disappeared during the late Bronze Age, suggesting selection against this phenotype in early domestic horses. During the Iron Age, LP reappeared, probably by reintroduction into the domestic gene pool from wild animals. This picture of alternating selective regimes might explain how genetic diversity was maintained in domestic animals despite selection for specific traits at different times.

Unravelling the complexity of domestication: a case study using morphometrics and ancient DNA analyses of archaeological pigs from Romania.

Current evidence suggests that pigs were first domesticated in Eastern Anatolia during the ninth millennium cal BC before dispersing into Europe with Early Neolithic farmers from the beginning of the seventh millennium. Recent ancient DNA (aDNA) research also indicates the incorporation of European wild boar into domestic stock during the Neolithization process. In order to establish the timing of the arrival of domestic pigs into Europe, and to test hypotheses regarding the role European wild boar played in the domestication process, we combined a geometric morphometric analysis (allowing us to combine tooth size and shape) of 449 Romanian ancient teeth with aDNA analysis. Our results firstly substantiate claims that the first domestic pigs in Romania possessed the same mtDNA signatures found in Neolithic pigs in west and central Anatolia. Second, we identified a significant proportion of individuals with large molars whose tooth shape matched that of archaeological (likely) domestic pigs. These large 'domestic shape' specimens were present from the outset of the Romanian Neolithic (6100-5500 cal BC) through to later prehistory, suggesting a long history of admixture between introduced domestic pigs and local wild boar. Finally, we confirmed a turnover in mitochondrial lineages found in domestic pigs, possibly coincident with human migration into Anatolia and the Levant that occurred in later prehistory.

Paleogenomics. Genomic structure in Europeans dating back at least 36,200 years.

The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from central Siberia, European Mesolithic hunter-gatherers, some contemporary western Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki 14 genome shows evidence of shared ancestry with a population basal to all Eurasians that also relates to later European Neolithic farmers. We find that Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than present Europeans. Our findings reveal the timing of divergence of western Eurasians and East Asians to be more than 36,200 years ago and that European genomic structure today dates back to the Upper Paleolithic and derives from a metapopulation that at times stretched from Europe to central Asia.

Establishing the validity of domestication genes using DNA from ancient chickens.

Modern domestic plants and animals are subject to human-driven selection for desired phenotypic traits and behavior. Large-scale genetic studies of modern domestic populations and their wild relatives have revealed not only the genetic mechanisms underlying specific phenotypic traits, but also allowed for the identification of candidate domestication genes. Our understanding of the importance of these genes during the initial stages of the domestication process traditionally rests on the assumption that robust inferences about the past can be made on the basis of modern genetic datasets. A growing body of evidence from ancient DNA studies, however, has revealed that ancient and even historic populations often bear little resemblance to their modern counterparts. Here, we test the temporal context of selection on specific genetic loci known to differentiate modern domestic chickens from their extant wild ancestors. We extracted DNA from 80 ancient chickens excavated from 12 European archaeological sites, dated from ∼ 280 B.C. to the 18th century A.D. We targeted three unlinked genetic loci: the mitochondrial control region, a gene associated with yellow skin color (ß-carotene dioxygenase 2), and a putative domestication gene thought to be linked to photoperiod and reproduction (thyroid-stimulating hormone receptor, TSHR). Our results reveal significant variability in both nuclear genes, suggesting that the commonality of yellow skin in Western breeds and the near fixation of TSHR in all modern chickens took place only in the past 500 y. In addition, mitochondrial variation has increased as a result of recent admixture with exotic breeds. We conclude by emphasizing the perils of inferring the past from modern genetic data alone.

High levels of Paleolithic Y-chromosome lineages characterize Serbia.

Whether present-day European genetic variation and its distribution patterns can be attributed primarily to the initial peopling of Europe by anatomically modern humans during the Paleolithic, or to latter Near Eastern Neolithic input is still the subject of debate. Southeastern Europe has been a crossroads for several cultures since Paleolithic times and the Balkans, specifically, would have been part of the route used by Neolithic farmers to enter Europe. Given its geographic location in the heart of the Balkan Peninsula at the intersection of Central and Southeastern Europe, Serbia represents a key geographical location that may provide insight to elucidate the interactions between indigenous Paleolithic people and agricultural colonists from the Fertile Crescent. In this study, we examine, for the first time, the Y-chromosome constitution of the general Serbian population. A total of 103 individuals were sampled and their DNA analyzed for 104 Y-chromosome bi-allelic markers and 17 associated STR loci. Our results indicate that approximately 58% of Serbian Y-chromosomes (I1-M253, I2a-P37.2 and R1a1a-M198) belong to lineages believed to be pre-Neolithic. On the other hand, the signature of putative Near Eastern Neolithic lineages, including E1b1b1a1-M78, G2a-P15, J1-M267, J2-M172 and R1b1a2-M269 accounts for 39% of the Y-chromosome. Haplogroup frequency distributions in Western and Eastern Europe reveal a spotted landscape of paleolithic Y chromosomes, undermining continental-wide generalizations. Furthermore, an examination of the distribution of Y-chromosome filiations in Europe indicates extreme levels of Paleolithic lineages in a region encompassing Serbia, Bosnia-Herzegovina and Croatia, possibly the result of Neolithic migrations encroaching on Paleolithic populations against the Adriatic Sea.

On how Watson and Crick discovered what Watson and Crick had suggested: the "folk" concept of discovery rediscovered.

This article opens with general and historical remarks on philosophy of science's problems with the concept of discovery. Then, drawing upon simple examples of Watson's and Crick's non-philosophical usage, I characterize phrases of the type "x discovers y" semantically. It will subsequently be shown how widespread philosophical discussion on discovery violates the semantic constraints of phrases of the type "x discovers y." Then I provide a philosophical reconstruction of "x discovers y" that is in keeping with the "folk" notion of discovery. The philosophical ingredients of this approach are taken from a certain aspect of action theory and from epistemological reliabilism. The approach draws upon the concept of superior action and connects this concept to progressive research. In contrast to normal actions, superior actions are primarily explained by competencies. This perspective includes reminders of what some nineteenth-century philosopher-scientists had advocated as a competence-oriented view on scientific research. Finally, this approach is applied to the case of Watson's and Crick's discovery.

Ancient biomolecules from deep ice cores reveal a forested southern Greenland.

It is difficult to obtain fossil data from the 10% of Earth's terrestrial surface that is covered by thick glaciers and ice sheets, and hence, knowledge of the paleoenvironments of these regions has remained limited. We show that DNA and amino acids from buried organisms can be recovered from the basal sections of deep ice cores, enabling reconstructions of past flora and fauna. We show that high-altitude southern Greenland, currently lying below more than 2 kilometers of ice, was inhabited by a diverse array of conifer trees and insects within the past million years. The results provide direct evidence in support of a forested southern Greenland and suggest that many deep ice cores may contain genetic records of paleoenvironments in their basal sections.

Y chromosomes of prehistoric people along the Yangtze River.

The ability to extract mitochondrial and nuclear DNA from ancient remains has enabled the study of ancient DNA, a legitimate field for over 20 years now. Recently, Y chromosome genotyping has begun to be applied to ancient DNA. The Y chromosome haplogroup in East Asia has since caught the attention of molecular anthropologists, as it is one of the most ethnic-related genetic markers of the region. In this paper, the Y chromosome haplogroup of DNA from ancient East Asians was examined, in order to genetically link them to modern populations. Fifty-six human remains were sampled from five archaeological sites, primarily along the Yangtze River. Strict criteria were followed to eliminate potential contamination. Five SNPs from the Y chromosome were successfully amplified from most of the samples, with at least 62.5% of the samples belonging to the O haplogroup, similar to the frequency for modern East Asian populations. A high frequency of O1 was found in Liangzhu Culture sites around the mouth of the Yangtze River, linking this culture to modern Austronesian and Daic populations. A rare haplogroup, O3d, was found at the Daxi site in the middle reaches of the Yangtze River, indicating that the Daxi people might be the ancestors of modern Hmong-Mien populations, which show only small traces of O3d today. Noticeable genetic segregation was observed among the prehistoric cultures, demonstrating the genetic foundation of the multiple origins of the Chinese Civilization.

Molecular genetic analysis of remains from Lamadong cemetery, Liaoning, China.

The Xianbei existed as a remarkable nomadic tribe in northeastern China for three dynasties: the Han, Jin, and Northern-Southern dynasties (206 BC to 581 AD) in Chinese history. A very important subtribe of the Xianbei is the Murong Xianbei. To investigate the genetic structure of the Murong Xianbei population and to address its genetic relationships with other nomadic tribes at a molecular level, we analyzed the control region sequences and coding-region single nucleotide polymorphism markers of mtDNA from the remains of the Lamadong cemetery of the Three-Yan Culture of the Murong Xianbei population, which is dated to 1,600-1,700 years ago. By combining polymorphisms of the control region with those from the code region, we assigned 17 individuals to haplogroups B, C, D, F, G2a, Z, M, and J1b1. The frequencies of these haplogroups were compared with those of Asian populations and a multidimensional scaling graph was constructed to investigate relationships with other Asian populations. The results indicate that the genetic structure of the Lamadong population is very intricate; it has haplogroups prevalent in both the Eastern Asian and the Siberian populations, showing more affinity with the Eastern Asian populations. The present study also shows that the ancient nomadic tribes of Huns, Tuoba Xianbei, and Murong Xianbei have different maternal genetic structures and that there could have been some genetic exchange among them.

Comparison of maternal lineage and biogeographic analyses of ancient and modern Hungarian populations.

The Hungarian language belongs to the Finno-Ugric branch of the Uralic family, but Hungarian speakers have been living in Central Europe for more than 1000 years, surrounded by speakers of unrelated Indo-European languages. In order to study the continuity in maternal lineage between ancient and modern Hungarian populations, polymorphisms in the HVSI and protein coding regions of mitochondrial DNA sequences of 27 ancient samples (10th-11th centuries), 101 modern Hungarian, and 76 modern Hungarian-speaking Sekler samples from Transylvania were analyzed. The data were compared with sequences derived from 57 European and Asian populations, including Finno-Ugric populations, and statistical analyses were performed to investigate their genetic relationships. Only 2 of 27 ancient Hungarian samples are unambiguously Asian: the rest belong to one of the western Eurasian haplogroups, but some Asian affinities, and the genetic effect of populations who came into contact with ancient Hungarians during their migrations are seen. Strong differences appear when the ancient Hungarian samples are analyzed according to apparent social status, as judged by grave goods. Commoners show a predominance of mtDNA haplotypes and haplogroups (H, R, T), common in west Eurasia, while high-status individuals, presumably conquering Hungarians, show a more heterogeneous haplogroup distribution, with haplogroups (N1a, X) which are present at very low frequencies in modern worldwide populations and are absent in recent Hungarian and Sekler populations. Modern Hungarian-speaking populations seem to be specifically European. Our findings demonstrate that significant genetic differences exist between the ancient and recent Hungarian-speaking populations, and no genetic continuity is seen.

Genetic analysis of modern and historical burned human remains.

Burning of corpses is a well-known funeral procedure that has been performed for a long time in many cultures. Nowadays more and more corpses are burned in crematories and buried in urns, often for practical and financial reasons. In some scientific, criminal or civil cases even after cremation there is the need of genetic investigations for identification or paternity testing. Furthermore, burned remains are the only remains left in North Europe from 1200 BC to 500 AD. This makes genetic investigation of those materials interesting for anthropological reasons. We present on one hand a systematic investigation of 10 corpses before and after the cremation and on the other hand the analysis of seven historical remains representing the bronze age. We chose the ground bone powder and the less destroyed bone parts respectively and employed a slightly modified commercially available DNA extraction method. The presence of human nuclear and mitochondrial DNA was tested by a simple but highly sensitive Duplex-PCR. DNA quantification was done using real time PCR, and genetic typing was tried out using the AmpFISTR Identifiler Multiplex Kit, followed by an automatic analysis on an AbiPrism310.

Detection of a single nucleotide polymorphism in the IL-6 promoter region of ancient nuclear DNA.

In the current study a method was developed to examine the G/C single nucleotide polymorphism (SNP) at position -174 in the IL-6 promoter from nuclear DNA samples isolated from human skeletal remains from Manitoba, Canada, dating to as early as 3500 years ago. The IL-6 (-174) SNP was detected in three ancient samples and determined, as expected, in three out of three to be homozygous G/G. The analysis of cytokine SNPs of ancient nuclear DNA may provide novel insights into the genetic basis of autoimmune diseases and the susceptibility/resistance to infectious agents.

[Ancient DNA studies: from paleopathology to population genetics]. / Medicina molecolare e storia della medicina: dalla paleopatologia alla genetica delle popolazioni.

We discuss the relevance of ancient DNA studies for novel approaches to a variety of fields of scientific inquiry, including population and evolutionary genetics, prehistoric archaeology, paleopathology and history of human diseases. To exemplify the potential of ancient DNA research, we provide accounts of studies currently conducted at our laboratories in four different areas: 1) origins of the dog and phylogeny of prehistoric Italian canids; 2) paleogenetics of ancient Roma; 3) antiquity for variant alleles implicated in disease predisposition; 4) molecular investigation of pathologic lesions in Italian mummies of Renaissance age. The implications of the results obtained are briefly outlined.

Reconstruction of kinship by fecal DNA analysis of orangutans.

Genetic analysis is a useful tool for assigning biological relationships. Thus, it will improve genetic management of wild animal populations and breeding colonies. Kinship analysis will give new insights into the behavior, sociobiology and genetic management of orangutans. In this study, chromosomal DNA from orangutan (Pongo pygmaeus ssp.) was extracted from excrements. Feces samples were screened for up to nine microsatellite markers from related zoo populations of orangutans (Pongo pygmaeus ssp.) kept at the Zoological Garden Berlin and the Zoological Garden Heidelberg, Germany. Family structures are documented in the "International Studybook of the Orangutan" (Perkins 1995) and the "Europäisches Erhaltungszucht Programm 1998" (Becker 1998). To examine whether human short tandem repeat loci (STR) are suitable for the reconstruction of kinship in orangutans, nine STRs, commonly used in forensic studies and the amelogenin system, were amplified in a multiplex-PCR approach (AmpFlSTR Profiler Plus). We were able to show that five of the nine human autosomal STRs in question amplified successfully in orangutans. Thus, we could reconstruct kinship structures of the Berlin and Heidelberg populations.

Repair of degraded duplex DNA from prehistoric samples using Escherichia coli DNA polymerase I and T4 DNA ligase.

The most notable feature of DNA extracted from prehistoric material is that it is of poor quality. Amplification of PCR products from such DNA is consequently an exception. Here we present a simple method for the repair of degraded duplex DNA using the enzymes Escherichia coli DNA polymerase I and T4 DNA ligase. Adjacent sequences separated by nicks do not split up into intact strands during the denaturation step of PCR. Thus the target DNA is refractory to amplification. The proposed repair of nicked, fragmented ancient DNA results in an increase of amplification efficiency, such that the correct base order of the respective nuclear DNA segment can be obtained.