331 research outputs found
The contribution of Neanderthals to phenotypic variation in modern humans
Assessing the genetic contribution of Neanderthals to non-disease phenotypes in modern humans has been difficult because of the absence of large cohorts for which common phenotype information is available. Using baseline phenotypes collected for 112,000 individuals by the UK Biobank, we can now elaborate on previous findings that identified associations between signatures of positive selection on Neanderthal DNA and various modern human traits but not any specific phenotypic consequences. Here, we show that Neanderthal DNA affects skin tone and hair color, height, sleeping patterns, mood, and smoking status in present-day Europeans. Interestingly, multiple Neanderthal alleles at different loci contribute to skin and hair color in present-day Europeans, and these Neanderthal alleles contribute to both lighter and darker skin tones and hair color, suggesting that Neanderthals themselves were most likely variable in these traits
ABAEnrichment: An R package to test for gene set expression enrichment in the adult and developing human brain
Summary: We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. Availability and Implementation: ABAEnrichment was implemented as an R package and is available under GPL (≥ 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). Contacts: [email protected], [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics online
Drift estimation in sparse sequential dynamic imaging, with application to nanoscale fluorescence microscopy.
A major challenge in many modern superresolution fluorescence microscopy techniques at the nanoscale lies in the correct alignment of long sequences of sparse but spatially and temporally highly resolved images. This is caused by the temporal drift of the protein structure, e.g. due to temporal thermal inhomogeneity of the object of interest or its supporting area during the observation process. We develop a simple semiparametric model for drift correction in single-marker switching microscopy. Then we propose an M-estimator for the drift and show its asymptotic normality. This is used to correct the final image and it is shown that this purely statistical method is competitive with state of the art calibration techniques which require the incorporation of fiducial markers in the specimen. Moreover, a simple bootstrap algorithm allows us to quantify the precision of the drift estimate and its effect on the final image estimation. We argue that purely statistical drift correction is even more robust than fiducial tracking, rendering the latter superfluous in many applications. The practicability of our method is demonstrated by a simulation study and by a single-marker switching application. This serves as a prototype for many other typical imaging techniques where sparse observations with high temporal resolution are blurred by motion of the object to be reconstructed
Genetic evidence of human adaptation to a cooked diet
Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but not by caloric intake or consumer energy balance. Genes affected by cooking were highly correlated with genes known to be differentially expressed in liver between humans and other primates, and more genes in this overlap set show signals of positive selection in humans than would be expected by chance. Sequence changes in the genes under selection appear before the split between modern humans and two archaic human groups, Neandertals and Denisovans, supporting the idea that human adaptation to a cooked diet had begun by at least 275,000 years ago
Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets
Measurement of the diffractive structure function in deep inelastic scattering at HERA
This paper presents an analysis of the inclusive properties of diffractive
deep inelastic scattering events produced in interactions at HERA. The
events are characterised by a rapidity gap between the outgoing proton system
and the remaining hadronic system. Inclusive distributions are presented and
compared with Monte Carlo models for diffractive processes. The data are
consistent with models where the pomeron structure function has a hard and a
soft contribution. The diffractive structure function is measured as a function
of \xpom, the momentum fraction lost by the proton, of , the momentum
fraction of the struck quark with respect to \xpom, and of . The \xpom
dependence is consistent with the form \xpoma where
in all bins of and
. In the measured range, the diffractive structure function
approximately scales with at fixed . In an Ingelman-Schlein type
model, where commonly used pomeron flux factor normalisations are assumed, it
is found that the quarks within the pomeron do not saturate the momentum sum
rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil
Observation of hard scattering in photoproduction events with a large rapidity gap at HERA
Events with a large rapidity gap and total transverse energy greater than 5
GeV have been observed in quasi-real photoproduction at HERA with the ZEUS
detector. The distribution of these events as a function of the
centre of mass energy is consistent with diffractive scattering. For total
transverse energies above 12 GeV, the hadronic final states show predominantly
a two-jet structure with each jet having a transverse energy greater than 4
GeV. For the two-jet events, little energy flow is found outside the jets. This
observation is consistent with the hard scattering of a quasi-real photon with
a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil
Determination of the mechanical properties of amorphous materials through instrumented nanoindentation
A novel methodology based on instrumented indentation is developed to determine the mechanical properties of amorphous materials which present cohesive-frictional behaviour. The approach is based on the concept of a universal hardness equation, which results from
the assumption of a characteristic indentation pressure proportional to the hardness. The actual universal hardness equation is obtained from a detailed finite element analysis of the process of sharp indentation for a very wide range of material properties, and the inverse
problem (i.e. how to extract the elastic modulus, the compressive yield strength and the friction angle) from instrumented indentation is solved. The applicability and limitations of the novel approach are highlighted. Finally, the model is validated against experimental data
in metallic and ceramic glasses as well as polymers, covering a wide range of amorphous materials in terms of elastic modulus, yield strength and friction angle
Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans.
Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans
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