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Biology subjects

Nagel, S.

Publications and source records attributed to Nagel, S..

10 recordsLinked to original sources

A Method to Analyze Low-Quality Archaic Human Genomes and its Application to the Teshik-Tash 1 Neandertal

The Teshik-Tash 1 child whose remains were found in Uzbekistan represents the southeastern-most extent of the known Neandertal range, providing an important link with the better studied Caucasus and Altai Mountain ranges. However, due to poor DNA preservation, studying the genetics of Teshik Tash 1 has remained elusive. Here we present analyses of the nuclear DNA from the Teshik-Tash 1, from extracts that are highly contaminated with present-day human DNA. To achieve this, we developed a new computational method, admixslug, that jointly models contamination and population relationships, in order to infer the relationship of a target individual from which only low-quality nuclear DNA is available, to high-quality archaic human genomes. After validating admixslug, we show that Teshik-Tash 1 is genetically more similar to later Neandertals from Western Eurasia than to older Neandertals from the Altai Mountains. We estimate that Teshik-Tash 1 split from the Western Eurasian lineage between 80,000 and 100,000 years ago. Despite the geographical proximity of Teshik-Tash 1 to the Denisovan range, we find no evidence for Denisovan ancestry in his genome. Our results demonstrate that admixslug enables the study of archaic human specimens in cases where DNA preservation was previously considered too poor for population genetic analyses.

genetics↗

A high-coverage genome from a 200,000-year-old Denisovan

Denisovans, an extinct sister group of Neandertals who lived in Eastern Eurasia during the Middle and Late Pleistocene, are known only from a handful of skeletal remains and limited genetic data, including the high-coverage genome of a woman who lived [~]65,000 years ago. Here, we present a second high-quality Denisovan genome, reconstructed from a molar found at Denisova Cave. It belonged to a man who lived [~]200,000 years ago in a small Denisovan group. This group mixed with early Neandertals and was then replaced by Denisovans who had mixed with later Neandertals. We show that in addition Denisovans received gene flow from hominins that diverged before the split of the ancestors of Denisovans and modern humans. The two Denisovan genomes allow us to disentangle Denisovan ancestry in present-day humans revealing contributions from at least three distinct Denisovan groups. In particular, Oceanians and South Asians independently inherited DNA from a deeply diverged Denisovan population which was likely isolated in South Asia. This supports an early migration of the ancestors of Oceanians through South Asia followed by the later arrival of the ancestors of present-day South Asians. East Asians do not share this Denisovan component in their genomes, suggesting that their ancestors arrived independently, perhaps by a northerly route. Finally, the two high-quality Denisovan genomes allow us to refine the catalogue of genetic changes that arose on the Denisovan lineage, some of which were contributed to present-day humans.

genomics↗

Denisovan ancestry and population history of early East Asians

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in North East Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.

evolutionary biology↗

A systematic investigation of human DNA preservation in medieval skeletons

Ancient DNA (aDNA) analyses necessitate the destructive sampling of archaeological material. Currently the dense inner portion of the petrous pyramid, the location of the skull that houses the inner ear, is the most sought after skeletal element for molecular analyses of ancient humans as it has been shown to yield high amounts of endogenous DNA. Destructive sampling of the petrous pyramid, assuming its recovery, is often not recommended for highly valued specimens. To investigate alternatives, we present a survey of human aDNA preservation for each of ten skeletal elements in a skeletal collection from Medieval Germany. Through comparison of human DNA content and quality we confirm best performance of the petrous pyramid and identify seven additional sampling locations across four skeletal elements that yield adequate aDNA for most applications in human palaeogenetics. Our study provides a better perspective on DNA preservation across the human skeleton and takes a further step toward the more responsible use of ancient materials in human aDNA studies.

molecular biology↗

Genomic and dietary transitions during the Mesolithic and Early Neolithic in Sicily

Southern Italy is a key region for understanding the agricultural transition in the Mediterranean due to its central position. We present a genomic transect for 19 prehistoric Sicilians that covers the Early Mesolithic to Early Neolithic period. We find that the Early Mesolithic hunter-gatherers (HGs) are a highly drifted sister lineage to Early Holocene western European HGs, whereas a quarter of the Late Mesolithic HGs ancestry is related to HGs from eastern Europe and the Near East. This indicates substantial gene flow from (south-)eastern Europe between the Early and Late Mesolithic. The Early Neolithic farmers are genetically most similar to those from the Balkan and Greece, and carry only a maximum of [~]7% ancestry from Sicilian Mesolithic HGs. Ancestry changes match changes in dietary profile and material culture, except for two individuals who may provide tentative initial evidence that HGs adopted elements of farming in Sicily. One-sentence summaryGenome-wide and isotopic data from prehistoric Sicilians reveal a pre-farming connection to (south-) eastern Europe, and tentative initial evidence that hunter-gatherers adopted some Neolithic aspects prior to near-total replacement by early farmers.

genetics↗

Common Vetch: a drought tolerant, high protein neglected leguminous crop with potential as a sustainable food source.

Global demand for protein is predicted to increase by 50% by 2050. To meet the increasing demand whilst ensuring sustainability, protein sources that generate low-greenhouse gas emissions are required and protein-rich legume seeds have the potential to make a significant contribution. Legumes like common vetch (Vicia sativa) that grow in marginal cropping zones and are drought tolerant and resilient to changeable annual weather patterns, will be in high demand as the climate changes. In common vetch, the inability to eliminate the {gamma}-glutamyl-{beta}-cyano-alanine (GBCA) toxin present in the seed has hindered its utility as a human and animal food for many decades, leaving this highly resilient species an "orphan" legume. However, the availability of the vetch genome and transcriptome data together with the application of CRISPR-Cas genome editing technologies lay the foundations to eliminate the GBCA toxin constraint. In the near future, we anticipate that a zero-toxin vetch variety will become a significant contributor to global protein demand.

plant biology↗

Function of TRIP6 in brain-specific ciliogenesis

TRIP6, a member of the zyxin-family of LIM domain proteins, is a focal adhesion component. trip6 deletion in the mouse revealed, unexpectedly, in view of its ubiquitous expression, a function in the brain: ependymal and choroid plexus epithelial cells were poorly developed, carrying fewer and shorter cilia, and the mice developed hydrocephalus. TRIP6 disruption, via RNAi or inhibition of its homodimerization, in a choroid plexus epithelial cell line, confirmed its function in ciliogenesis. Zyxin-family members carry numerous protein interaction domains. In common with assembly of other multiprotein complexes, ciliogenesis may be facilitated by molecular assembly factors. Super-resolution microscopy demonstrated TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. This is the first discovery of a protein assembly factor essential for mammalian ciliogenesis.

cell biology↗

World's Fastest Brain-Computer Interface: Combining EEG2Code with Deep Learning

In this paper, we present a Brain-Computer Interface (BCI) that is able to reach an information transfer rate (ITR) of more than 1200 bit/min using non-invasively recorded EEG signals. By combining the EEG2Code method with deep learning, we present an extremely powerful approach for decoding visual information from EEG. This approach can either be used in a passive BCI setting to predict properties of a visual stimulus the person is viewing, or it can be used to actively control a BCI spelling application. The presented approach was tested in both scenarios and achieved an average ITR of 701 bit/min in the passive BCI approach with the best subject achieving an online ITR of 1237 bit/min. The presented BCI is more than three times faster than the previously fastest BCI and allows to discriminate 500,000 different visual stimuli based on 2 seconds of EEG data with an accuracy of up to 100 %. When using the approach in an asynchronous BCI for spelling, we achieved an average utility rate of 175 bit/min, which corresponds to an average of 35 error-free letters per minute. As we observe a ceiling effect where more powerful approaches for brain signal decoding do not translate into better BCI control anymore, we discuss if BCI research has reached a point where the performance of non-invasive BCI control cannot be substantially improved anymore.

neuroscience↗

Asynchronous non-invasive high-speed BCI speller with robust non-control state detection

Brain-Computer Interfaces (BCIs) enable users to control a computer by using pure brain activity. Recent BCIs based on visual evoked potentials (VEPs) have shown to be suitable for high-speed communication. However, all recent high-speed BCIs are synchronous, which means that the system works with fixed time slots so that the user is not able to select a command at his own convenience, which poses a problem in real-world applications. In this paper, we present the first asynchronous high-speed BCI with robust distinction between intentional control (IC) and non-control (NC), with a nearly perfect NC state detection of only 0.075 erroneous classifications per minute. The resulting asynchronous speller achieved an average information transfer rate (ITR) of 122.7 bit/min using a 32 target matrix-keyboard. Since the method is based on random stimulation patterns it allows to use an arbitrary number of targets for any application purpose, which was shown by using an 55 target German QWERTZ-keyboard layout which allowed the participants to write an average of 16.1 (up to 30.7) correct case-sensitive letters per minute. As the presented system is the first asynchronous high-speed BCI speller with a robust non-control state detection, it is an important step for moving BCI applications out of the lab and into real-life.

neuroscience↗

Modelling the brain response to arbitrary visual stimulation patterns for a flexible high-speed BCI

Visual evoked potentials (VEPs) can be measured in the EEG as response to a visual stimulus. Commonly, VEPs are displayed by averaging multiple responses to a certain stimulus or a classifier is trained to identify the response to a certain stimulus. While the traditional approach is limited to a set of predefined stimulation patterns, we present a method that models the general process of VEP generation and thereby can be used to predict arbitrary visual stimulation patterns from EEG and predict how the brain responds to arbitrary stimulation patterns. We demonstrate how this method can be used to model single-flash VEPs, steady state VEPs (SSVEPs) or VEPs to complex stimulation patterns. It is further shown that this method can also be used in a BCI to allow information transfer rates of more than 470 bit/min and lead to more flexible BCIs with a virtually unlimited amount of targets and any desired trial duration.

neuroscience↗