206 research outputs found
Operation of a Stark decelerator with optimum acceptance
With a Stark decelerator, beams of neutral polar molecules can be
accelerated, guided at a constant velocity, or decelerated. The effectiveness
of this process is determined by the 6D volume in phase space from which
molecules are accepted by the Stark decelerator. Couplings between the
longitudinal and transverse motion of the molecules in the decelerator can
reduce this acceptance. These couplings are nearly absent when the decelerator
operates such that only every third electric field stage is used for
deceleration, while extra transverse focusing is provided by the intermediate
stages. For many applications, the acceptance of a Stark decelerator in this
so-called mode significantly exceeds that of a decelerator in the
conventionally used () mode. This has been experimentally verified by
passing a beam of OH radicals through a 2.6 meter long Stark decelerator. The
experiments are in quantitative agreement with the results of trajectory
calculations, and can qualitatively be explained with a simple model for the 6D
acceptance. These results imply that the 6D acceptance of a Stark decelerator
in the mode of operation approaches the optimum value, i.e. the value
that is obtained when any couplings are neglected.Comment: 13 pages, 11 figure
A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis
The quest for novel therapeutic targets in acute myeloid leukemia (AML) is still ongoing. One of such targets, cyclin A1, was shown to be overexpressed in AML including AML stem cells. However, the function of cyclin A1 in AML is largely unknown, and the data on its impact on patientsŽ survival remain controversial. Therefore, we developed a transgenic mouse model of stem cell-directed inducible cyclin A1 overexpression and crossed these mice with PML-RARα-knockin mice, which develop an AML M3-like phenotype. To observe the effects of cyclin A1 loss-of-function, we also crossed PML-RARα-knockin mice to cyclin A1-knockout mice. Neither overexpression nor loss of cyclin A1 significantly altered leukemogenesis in PML-RARα-knockin mice. These findings imply that upregulation of cyclin A1 is not essential for leukemogenesis. Our data suggest that cyclin A1 does not represent a suitable target for AML therapy
Massive migration from the steppe is a source for Indo-European languages in Europe
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000
years ago by enriching ancient DNA libraries for a target set of almost four
hundred thousand polymorphisms. Enrichment of these positions decreases the
sequencing required for genome-wide ancient DNA analysis by a median of around
250-fold, allowing us to study an order of magnitude more individuals than
previous studies and to obtain new insights about the past. We show that the
populations of western and far eastern Europe followed opposite trajectories
between 8,000-5,000 years ago. At the beginning of the Neolithic period in
Europe, ~8,000-7,000 years ago, closely related groups of early farmers
appeared in Germany, Hungary, and Spain, different from indigenous
hunter-gatherers, whereas Russia was inhabited by a distinctive population of
hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By
~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred
throughout much of Europe, but in Russia, the Yamnaya steppe herders of this
time were descended not only from the preceding eastern European
hunter-gatherers, but from a population of Near Eastern ancestry. Western and
Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded
Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya,
documenting a massive migration into the heartland of Europe from its eastern
periphery. This steppe ancestry persisted in all sampled central Europeans
until at least ~3,000 years ago, and is ubiquitous in present-day Europeans.
These results provide support for the theory of a steppe origin of at least
some of the Indo-European languages of Europe
From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes
Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users.
Results: Here we present an âA to Zâ protocol for obtaining complete human mitochondrial (mtDNA) genomes â from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling).
Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual âmodulesâ can be swapped out to suit available resources
Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland
Genetic studies of Neolithic and Bronze Age skeletons from Europe have provided evidence for strong population genetic changes at the beginning and the end of the Neolithic period. To further understand the implications of these in Southern Central Europe, we analyze 96 ancient genomes from Switzerland, Southern Germany, and the Alsace region in France, covering the Middle/Late Neolithic to Early Bronze Age. Similar to previously described genetic changes in other parts of Europe from the early 3rd millennium BCE, we detect an arrival of ancestry related to Late Neolithic pastoralists from the Pontic-Caspian steppe in Switzerland as early as 2860-2460 calBCE. Our analyses suggest that this genetic turnover was a complex process lasting almost 1000 years and involved highly genetically structured populations in this region
The genetic prehistory of the Baltic Sea region
Correction: Nature communications 9 (2018), art. no. 1494 doi:10.1038/s41467-018-03872-yWhile the series of events that shaped the transition between foraging societies and food producers are well described for Central and Southern Europe, genetic evidence from Northern Europe surrounding the Baltic Sea is still sparse. Here, we report genome-wide DNA data from 38 ancient North Europeans ranging from similar to 9500 to 2200 years before present. Our analysis provides genetic evidence that hunter-gatherers settled Scandinavia via two routes. We reveal that the first Scandinavian farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Mesolithic Western hunter-gatherers extended to the east of the Baltic Sea, where these populations persisted without gene-flow from Central European farmers during the Early and Middle Neolithic. The arrival of steppe pastoralists in the Late Neolithic introduced a major shift in economy and mediated the spread of a new ancestry associated with the Corded Ware Complex in Northern Europe.Peer reviewe
Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities
The first farmers from Central Europe reveal a genetic affinity to modern-day populations from the Near East and Anatolia, which suggests a significant demographic input from this area during the early Neolithic
Les individus du dĂ©pĂŽt multiple nĂ©olithique du site de Pontcharaud, Clermont-Ferrand (fouilles 1986) : guerriers ou morts dâaccompagnement ?
Le site de Pontcharaud 2 (4300-3900 cal. BCE), fouillĂ© en 1986, a livrĂ© 68 individus issus de 56 structures parmi lesquelles un dĂ©pĂŽt multiple exceptionnel de par le nombre de sujets qui le compose (5 adultes et 2 immatures) et la prĂ©sence dâune pointe de flĂšche dans la vertĂšbre de lâun dâentre eux. Cette dĂ©couverte a Ă©tĂ© abordĂ©e dans plusieurs publications sans quâil y ait consensus quant Ă lâinterprĂ©tation qui peut en ĂȘtre donnĂ©e. Or, la sĂ©rie ostĂ©ologique de Pontcharaud 2 bĂ©nĂ©ficie depuis..
Survival of Late Pleisticene Hunter-gatherer ancestry in the Iberian Peninsula
The Iberian Peninsula in southwestern Europe represents an important test case for the study of human population movements during prehistoric periods. During the Last Glacial Maximum (LGM), the peninsula formed a periglacial refugium for hunter-gatherers (HGs) and thus served as a potential source for the re-peopling of northern latitudes. The post-LGM genetic signature was previously described as a cline from Western HG (WHG) to Eastern HG (EHG), further shaped by later Holocene expansions from the Near East and the North Pontic steppes. Western and central Europe were dominated by ancestry associated with the 14,000-year-old individual from Villabruna, Italy, which had largely replaced earlier genetic ancestry, represented by 19,000-15,000-year-old individuals associated with the Magdalenian culture. However, little is known about the genetic diversity in southern European refugia, the presence of distinct genetic clusters, and correspondence with geography. Here, we report new genome-wide data from 11 HGs and Neolithic individuals that highlight the late survival of Paleolithic ancestry in Iberia, reported previously in Magdalenian-associated individuals. We show that all Iberian HGs, including the oldest, a 19,000-year-old individual from El MirĂłn in Spain, carry dual ancestry from both Villabruna and the Magdalenian-related individuals. Thus, our results suggest an early connection between two potential refugia, resulting in a genetic ancestry that survived in later Iberian HGs. Our new genomic data from Iberian Early and Middle Neolithic individuals show that the dual Iberian HG genomic legacy pertains in the peninsula, suggesting that expanding farmers mixed with local HGs
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