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The common loss-of-function mutation R577X in the structural muscle protein ACTN3 emerged as a potential target of positive selection from early studies and has been the focus of insightful physiological work suggesting a significant impact on muscle metabolism. Adaptation to cold climates has been proposed as a key adaptive mechanism explaining its global allele frequency patterns. Here, we re-examine this hypothesis analyzing modern (n = 3,626) and ancient (n = 1,651) genomic data by using allele-frequency as well as haplotype homozygosity-based methods. The presented results are more consistent with genetic drift rather than selection in cold climates as the main driver of the ACTN3 R577X frequency distribution in human populations across the world. This Matters Arising paper is in response to Wyckelsma et al. (2021), 1 published in The American Journal of Human Genetics. See also the response by Wyckelsma et al. (2022), 2 published in this issue. [ABSTRACT FROM AUTHOR]

Additive Manufacturing (AM) is changing the manufacturing paradigm as it makes it possible to generate complex geometries that are impossible using conventional technologies. However, conventional GPS/GD&T practices are inadequate both at specifying and verifying geometric tolerances. In both cases, they lack the required flexibility. Applying volumetric instead of surface representations helps to solve the problem of specifying tolerances and coheres with topological optimization. The verification paradigm must be modified, too, as AM allows an increase in part complexity without a corresponding increase of cost. Among measurement techniques, only X-ray computed tomography (XCT), which is volumetric, is capable of easily measure complex parts. Leaving the discussion of volumetric tolerance specifications to the future, the aim of this work is exploring a part geometric accuracy verification by direct comparison between its nominal geometry and geometric tolerance volumetric representation, and an XCT volumetric image of it. Unlike the conventional use of XCT for geometric verification, this is a segmentation-free verification. The method is based on the "mutual information" of the two, i.e. information shared by the measured and nominal representations. The output is a conformance statement that does rely on a measurement but nor on a specific measured value not rely on a measurement result. This makes defining a decision rule considering consumer's and producer's risks difficult: uncertainty does not exist in this case. Statistic and simulation techniques make it possible to estimate these risks, defining a numerical model of the distribution of the gray values in a specific portion of the XCT image. Finally, an additive manufacturing case study validates the methodology. • Additive manufacturing (AM) requires design and verification paradigms renewal. • Volumetric representation flexibly describes AM parts, including tolerances. • X-ray CT is a flexible measuring technique for AM and measures volumetrically. • Direct verification of volumetric geometric tolerances is possible by volumetric measurement. • This paper analyzes the customer's and consumer's risks in volumetric verification of tolerances. [ABSTRACT FROM AUTHOR]

In this paper, a characterisation of diamond abrasive grains of grinding tools using industrial X-ray computed tomography (XCT) is carried out. One of the most challenge tasks in the characterisation is extracting the diamond abrasive grains from the XCT volume data. Methods that are able to extract the grains are then developed and introduced in this paper. The first step is to create a triangular mesh surface from the reconstructed volume file using a gradient anisotropic diffusion filter. The second step is to convert the measured greyscale volume into a signed distance field using a global threshold value and then a localised method for grain segmentation. To validate the proposed method, three different types of grinding tool specimens are measured and analysed. Each abrasive grain is segmented and the distributions of grains (with both random and designed patterns) are then calculated, plotted and analysed. The quantitative analysis clearly shows the deviations between the measured distribution and the designed pattern of the grinding tool, which indicates that the proposed method can provide an accurate and comprehensive characterisation of the grinding tools. [ABSTRACT FROM AUTHOR]

In the growing Industry 4.0 market, there is strong need to implement automatic inspection methods to support manufacturing processes. Tool wear in turning is one of the biggest concerns that most expert operators are able to indirectly infer through the analysis of the removed chips. Automatising this operation would enable developing more efficient cutting processes that turns in easier process planning management toward the Zero Defect Manufacturing paradigm. This paper presents a deep learning approach, based on image processing applied to turning chips for indirectly identifying tool wear levels. The procedure extracts different indicators from the RGB and HSV image channels and instructs a neural network for classifying the chips, based on tool state conditions. Images were collected with a high-resolution digital camera during an experimental cutting campaign involving tool wear analysis with direct microscope imaging. The sensitivity analysis confirmed that the most sensible image channels are the hue value H that were used to teach the network, leading to performances in the range of 95 of proper classification. The feasibility of the deep learning approach for indirectly understanding the tool wear from the chip colour characterisation is confirmed. However, due to the big effects on chip colours of variables as the workpiece material and cutting process parameters, the applicability is limited to stable production flows. An industrial implementation can be foreseen by populating proper large databases and by implementing real-time chip segmentation analysis. [ABSTRACT FROM AUTHOR]

With manufacturing shifting from traditional products to high value products, the complexity and accuracy of the products are increasing in order to reduce energy costs, create friendly environment and better health care. Structured surfaces, freeform surfaces, and other functional engineering surfaces are becoming the core part of high value manufacturing products. However, measurement of these surfaces is becoming very difficult due to instrumental limitations including measurement range, speed, resolution and accuracy. Multi-instruments/sensors measurement are now being developed for freeform and structured surface assessment, which requires the fusion of the data into a unified system to achieve larger dynamic measurements with greater reliability. This paper discusses the process of combining data from several information sources (instruments/sensors) into a common representational format and the surface topography can be reconstructed using Gaussian processes and B-spline techniques. In this paper the Gaussian process model is extended in order to take into account the uncertainty propagation and a new data fusion model based on least squares B-splines that drastically reduce the computational time are presented. The results are validated by two for freeform surface measurements. • A data fusion model based on least squares B-splines approximation is proposed. • The uncertainty propagation of the hierarchical fusion model is investigated. • A B-splines based model allow a fast and accurate surface reconstruction. [ABSTRACT FROM AUTHOR]

Automatic visual inspection methods for product quality checking are spreading more and more in the present 4.0 manufacturing industry. This paper addresses the automatic inspection of edge integrity in accurate holes obtained by direct drilling of cemented carbide with innovative diamond coated tools. These revolutionary cutting tools, recently appeared on the market, can process extremely hard carbide in the sintered state, with massive increase of productivity with respect to standard methodologies like electrical discharge machining (EDM). However, due to the brittleness of the materials, the mechanical cutting process becomes critical and sensitive to tool breakage and workpiece defects generation. In particular, chipping of the hole edges represents one of the most important issues to monitor and take under control. A software procedure, that analyses high-resolution images taken from optical microscopes, was then developed for that aim. Image processing algorithms were designed and applied to enable the automatic extraction of the holes profile, thus permitting the identification and quantification of the leading edge damage in the radial direction. The proposed approach is fully automatic and is based on a profile segmentation that exploits an edge detection algorithm followed by a contour extraction method based on the solution of a partial differential equation. Dedicated metrics were specifically developed to evaluate the extracted profiles. The approach was validated with a factorial plane involving 1.6 mm diameter holes generated with different cutting parameters and tools on tungsten-carbide (WC) material. The technique resulted suitable for the aim, enabling the automatic characterisation of the defects generation phenomenon throughout the entire tools life. This moves a step toward the implementation of both in-line hole inspection procedures and advanced drilling process control. • An automatic algorithm for chipping identification in small holes is proposed. • Innovative diamond drilling tools (φ 1.6 mm) are used on sintered WC. • The hole inspection procedure includes edge detection, extraction and classification. • Chipping phenomenon and connection with cutting process parameters are studied. • The method is compliant with in-process and process control implementations. [ABSTRACT FROM AUTHOR]

• A method to compute the hybrid and functional roughness parameter is presented. • Two surface reconstruction methods are investigated: Bezier surfaces and triangular meshes. • The comparison with the texture parameters defined in the ISO 25178-2 is analysed. • The method can be applied to meshes measured using computed tomography. • The proposed method is suitable for additive manufacturing parts. Characterisation of freeform surfaces is an increasingly importance area of metrology. Currently the characterisation of surfaces is performed using data that can be represented by a height map. Modern measurement devices allow the acquisition of surfaces with complex shapes that cannot properly be analysed using the current texture parameters definition. In this paper a method to characterise both freeform surfaces and surfaces with re-entrant features is proposed. Two surface approximation methods are investigated: triangular mesh and Bézier surface. The proposed method will be compared with a method able to extract the ISO 25178-2 areal texture parameters from a triangular mesh. [ABSTRACT FROM AUTHOR]

Abstract Intelligent sampling can be used to influence the efficiency of surface geometry measurement. With no design model information provided, reconstruction from prior sample points with a surrogate model has to be carried out iteratively, thus the next best sample point(s) can be intelligently selected. But, a lack of accurate and fast reconstruction models hinders the development of intelligent sampling techniques. In this paper, a smart surrogate model based on free-knot B-splines is used for intelligent surface sampling design with the aid of uncertainty modelling. By implementing intelligent sampling in a Cartesian, parametric or specific error space, the proposed method can be flexibly applied to reverse engineering and geometrical tolerance inspection, especially for high-dynamic-range structured surfaces with sparse and sharply edged features. Extensive numerical experiments on simulated and real surface data are presented. The results show that this parametric model-based method can achieve the same or higher sampling efficiency as some recent non-parametric methods but with far less computing time cost. Highlights • A free-knot B-spline (FKBS) modelling-based adaptive sampling strategy was developed. • This strategy efficiently works for the measurement of smooth and sharply-edged surfaces. • This strategy shows comparable sample saving performance to the latest techniques. • With far less computing time, this strategy meets practical requirement in industry. [ABSTRACT FROM AUTHOR]

Abstract In this paper a metrology-oriented specification schema is proposed to enrich the specification semantics with sufficient metrological information. It is designed particularly for applications where non-traditional measurement methods are applied; and it can also identify any redundancies, inconsistencies or incompletenesses of a specification. The proposed schema is based on category theoretical semantics which uses category theory as the foundation to model the semantics. A set of verification operations that derived from the measurement process was firstly formalised using the categorical semantics. Then a set of full faithful functors were constructed to map the set of verification operations to a set of specification operations. A set of simplification rules was then developed to deduce all of the necessary specification objects which are independent to each other. Then the residual specification objects provide a compact structure of the specification. Three test cases were conducted to validate the proposed schema. An industrial computed tomography (CT) measurement process for an impeller manufacturing using selective laser sintering (SLS) technique, was modelled and a set of independent specification elements was then deduced. The other two test cases for checking redundancy and incompleteness on general ISO specifications were carried out. The results show that the proposed schema works for proposing semantic enriched specification that are characterised by non-traditional measurement methods and for testing redundancy and incompleteness of specifications based on geometrical product specifications and verification (GPS) standards system. [ABSTRACT FROM AUTHOR]

Since the discovery of the first hominin fossils, East Africa has been in the spotlight of palaeo-anthropological investigation for its role as a potential cradle of humanity and as a gateway out of Africa. With the advent of the genomic era an ever increasing amount of information has started to complement this notion, and to place the area within a broader, Pan-African scenario. Here we examine the most recent genetic and fossil results that recapitulate the last hundreds of thousands of years of human evolution in the area, and point to a number of uncharted avenues that may complement the emerging scenario in the coming years. [ABSTRACT FROM AUTHOR]

Efficient sampling methods enable the reconstruction of a generic surface with a limited amount of points. The reconstructed surface can therefore be used for inspection purpose. In this paper a sampling method that enables the reconstruction of a curve or surface is proposed. The input of the proposed algorithm is the number of required samples. The method takes into account two factors: the regularity of the sampling and the complexity of the object. A higher density of samples is assigned where there are some significant features, described by the curvature. The analysed curves and surfaces are described through the B-splines spaces. The sampling of surfaces generated by two or more curves is also discussed. [ABSTRACT FROM AUTHOR]

Current definitions and computation of areal surface texture parameters are based on planar, measured or unwrapped, surface which is not applicable for non planar irregular meshes. In this paper an extension of areal surface texture parameters (height and hybrid parameters) for freeform surface is proposed. The proposed method can be used for both general and complex surfaces and it works well on surfaces where there are undercuts and non uniformly spaced points. The proposed method has been tested on six sets of different types of surfaces and the computed parameter results were compared with the values of the parameters defined in ISO 25178-2:2012. [ABSTRACT FROM AUTHOR]

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts [Cavalli-Sforza and Feldman (1981) Cultural Transmission and Evolution: A Quantitative Approach; Boyd and Richerson (1985) Culture and the Evolutionary Process]. The quantitative study of gene–culture coevolution has focused in particular on the mechanisms responsible for change in frequency and attributes of cultural traits, the spread of cultural information through demic and cultural diffusion, and detecting relationships between genetic and cultural lineages. Here, we make use of worldwide whole-genome sequences [Pagani et al. (2016) Nature 538:238–242] to assess the impact of processes involving population movement and replacement on cultural diversity, focusing on the variability observed in folktale traditions (n = 596) [Uther (2004) The Types of International Folktales: A Classification and Bibliography. Based on the System of Antti Aarne and Stith Thompson] in Eurasia. We find that a model of cultural diffusion predicted by isolation-by-distance alone is not sufficient to explain the observed patterns, especially at small spatial scales (up to ∼4,000 km). We also provide an empirical approach to infer presence and impact of ethnolinguistic barriers preventing the unbiased transmission of both genetic and cultural information. After correcting for the effect of ethnolinguistic boundaries, we show that, of the alternative models that we propose, the one entailing cultural diffusion biased by linguistic differences is the most plausible. Additionally, we identify 15 tales that are more likely to be predominantly transmitted through population movement and replacement and locate putative focal areas for a set of tales that are spread worldwide. [ABSTRACT FROM AUTHOR]

Geometrical accuracy of microfeatures in micromilling is strictly related with the choice of cutting parameters. Their correct selection is a challenging task in particular when the target feature geometry is a high aspect ratio feature with tight tolerance requirements. Metallic micromilled pins are adopted in many different industrial applications as in the micromold technology field, in the microelectromechanical systems, and in the biomedical devices and their geometrical accuracy represents a fundamental property for their functionality. This work outlines the connection between the achieved geometrical accuracy and the micromilling parameters and cutting strategies on pins with diameter = 100 µm and height=2 mm (i.e., aspect ratio=20). Pin geometrical error features are extracted from three-dimensional optical measurements and then correlated with cutting parameters to support machining process setup. A proper fitting based on Chebyshev functions is applied and a statistical analysis assesses the importance of each deviation component in relation to the imposed cutting conditions. The proposed methodology fills the specific lack in the literature domain about micropin machining and can easily extend to different types of geometrical microfeatures. Finally, correlation between part geometrical errors and machining forces is analyzed. Cutting force analysis is adopted in conventional machining for implementing online geometrical errors assessment or compensation methods. However, this study confirms that the applicability of this approach in high aspect ratio pin micromilling is prevented from the predominant scale-effects and the large part bending that generates a low direct correlation between forces and part geometrical errors. [ABSTRACT FROM AUTHOR]

Four types of weighted fusion methods, including pixel-level, least-squares, parametrical and non-parametrical, have been classified and theoretically analysed in this study. In particular, the uncertainty propagation of the weighted least-squares fusion was analysed and its relation to the Kalman filter was studied. In cooperation with different fitting models, these four weighted fusion methods can be applied to a range of measurement challenges. The experimental results of this study show that the four weighted fusion methods compose a computationally efficient and reliable system for multi-sensor measurement problems, especially for freeform surface measurement. A comparison of weighted fusion with residual approximation-based fusion has also been conducted by providing the input datasets with different noise levels and sample sizes. The results demonstrated that weighted fusion and residual approximation-based fusion are complementary approaches applicable to most fusion scenarios. [ABSTRACT FROM AUTHOR]

Traditionally, industrial sheet metal forming technologies use rigid metallic tools to plastically deform the blanks. In order to reduce the tooling costs, rubber or flexible tools can be used together with one rigid (metallic) die or punch, in order to enforce a predictable and repeatable geometry o f the stamped parts. If the complete tooling setup is built with deformable tools, the final part quality and geometry are hardly predictable and only a prototypal production is generally possible. The aim of this paper is to present the development o f an automatic tool design procedure, based on the explicit FEM simulation of a stamping process, coupled to a geometrical tool compensation algorithm. The FEM simulation model has been first validated by comparing the experiments done at different levels o f the process parameters. After the experimental validation of the FEM model, a compensation algorithm has been implemented for reducing the error between the simulated component and the designed one. The tooling setup is made o f machined thermoset polyurethane (PUR) punch, die, and blank holder, for the deep drawing of an aluminum part. With respect to conventional steel dies, the plastic tools used in the test case are significantly more economic. The proposed procedure is iterative. It allows, already after the first iteration, to reduce the geometrical deviation between the actual stamped part and the designed geometry. This methodology represents one step toward the transformation of the investigated process from a prototyping technique into an industrial process for small and medium batch sizes. [ABSTRACT FROM AUTHOR]

The predominantly African origin of all modern human populations is well established, but the route taken out of Africa is still unclear. Two alternative routes, via Egypt and Sinai or across the Bab el Mandeb strait into Arabia, have traditionally been proposed as feasible gateways in light of geographic, paleoclimatic, archaeological, and genetic evidence. Distinguishing among these alternatives has been difficult. We generated 225 whole-genome sequences (225 at 8× depth, of which 8 were increased to 30×; Illumina HiSeq 2000) from six modern Northeast African populations (100 Egyptians and five Ethiopian populations each represented by 25 individuals). West Eurasian components were masked out, and the remaining African haplotypes were compared with a panel of sub-Saharan African and non-African genomes. We showed that masked Northeast African haplotypes overall were more similar to non-African haplotypes and more frequently present outside Africa than were any sets of haplotypes derived from a West African population. Furthermore, the masked Egyptian haplotypes showed these properties more markedly than the masked Ethiopian haplotypes, pointing to Egypt as the more likely gateway in the exodus to the rest of the world. Using five Ethiopian and three Egyptian high-coverage masked genomes and the multiple sequentially Markovian coalescent (MSMC) approach, we estimated the genetic split times of Egyptians and Ethiopians from non-African populations at 55,000 and 65,000 years ago, respectively, whereas that of West Africans was estimated to be 75,000 years ago. Both the haplotype and MSMC analyses thus suggest a predominant northern route out of Africa via Egypt. [ABSTRACT FROM AUTHOR]

In this paper a fusion metamodeling approach is suggested as a method for reducing the experimental and computational effort generally required for calibrating the parameters of FEM simulations models. The metamodel is used inside an optimization routine for linking data coming from two different sources: simulations and experiments. The method is applied to a real problem: the optimal design of a metal foam filled tube to be used as an anti-intrusion bar in vehicles. The model is hierarchical, in the sense that one set of data (the experiments) is considered to be more reliable and it is labeled as 'high-fidelity' and the other set (the simulations) is labeled as 'low-fidelity'. In the proposed approach, Gaussian models are used to describe results of computer experiments because they are flexible and they can easily interpolate data coming from deterministic simulations. Since the results of experiments are obviously fully accurate, but aleatory, a second stage ('linkage') model is used, which adjusts the prediction provided by the first model to more accurately represent the real experimental data. In the paper, the modeling and prediction ability of the method is first demonstrated and explained by means of artificially generated data and then applied to the optimization of foam filled tubular structures. The fusion metamodel yields comparable predictions (and optimal solution) if built over calibrated simulations vs. non-calibrated FEM models. [ABSTRACT FROM AUTHOR]

Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels and increased blood pressure that have been attributed to adaptation to the extreme cold climate. In this study we introduce a dataset of 200 individuals from ten indigenous Siberian populations that were genotyped for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. A region on chromosome 11 (chr11:66–69 Mb) contained the largest amount of clustering of significant signals and also the strongest signals in all the different selection tests performed. We present a list of candidate cold adaption genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture. [ABSTRACT FROM AUTHOR]

Background: Many efforts have been made to detect signatures of positive selection in the human genome, especially those associated with expansion from Africa and subsequent colonization of all other continents. However, most approaches have not directly probed the relationship between the environment and patterns of variation among humans. We have designed a method to identify regions of the genome under selection based on Mantel tests conducted within a general linear model framework, which we call MAntel-GLM to Infer Clinal Selection (MAGICS). MAGICS explicitly incorporates population-specific and genome-wide patterns of background variation as well as information from environmental values to provide an improved picture of selection and its underlying causes in human populations. Results: Our results significantly overlap with those obtained by other published methodologies, but MAGICS has several advantages. These include improvements that: limit false positives by reducing the number of independent tests conducted and by correcting for geographic distance, which we found to be a major contributor to selection signals; yield absolute rather than relative estimates of significance; identify specific geographic regions linked most strongly to particular signals of selection; and detect recent balancing as well as directional selection. Conclusions: We find evidence of selection associated with climate (P < 10-5) in 354 genes, and among these observe a highly significant enrichment for directional positive selection. Two of our strongest 'hits’, however, ADRA2A and ADRA2C, implicated in vasoconstriction in response to cold and pain stimuli, show evidence of balancing selection. Our results clearly demonstrate evidence of climate-related signals of directional and balancing selection. [ABSTRACT FROM AUTHOR]

Humans and their ancestors have traversed the Ethiopian landscape for millions of years, and present-day Ethiopians show great cultural, linguistic, and historical diversity, which makes them essential for understanding African variability and human origins. We genotyped 235 individuals from ten Ethiopian and two neighboring (South Sudanese and Somali) populations on an Illumina Omni 1M chip. Genotypes were compared with published data from several African and non-African populations. Principal-component and STRUCTURE-like analyses confirmed substantial genetic diversity both within and between populations, and revealed a match between genetic data and linguistic affiliation. Using comparisons with African and non-African reference samples in 40-SNP genomic windows, we identified “African” and “non-African” haplotypic components for each Ethiopian individual. The non-African component, which includes the SLC24A5 allele associated with light skin pigmentation in Europeans, may represent gene flow into Africa, which we estimate to have occurred ∼3 thousand years ago (kya). The non-African component was found to be more similar to populations inhabiting the Levant rather than the Arabian Peninsula, but the principal route for the expansion out of Africa ∼60 kya remains unresolved. Linkage-disequilibrium decay with genomic distance was less rapid in both the whole genome and the African component than in southern African samples, suggesting a less ancient history for Ethiopian populations. [Copyright &y& Elsevier]

We have surveyed 15 high-altitude adaptation candidate genes for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform. 1,066 SNPs were called using false discovery and false negative thresholds of ~6%. The neutral regions provided an empirical null distribution to compare with the candidate genes for signals of selection. Two genes stood out. In Laks, a non-synonymous variant within HIF1A already known to be associated with improvement in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs located in a conserved intronic region within EGLN1 showing high population differentiation was found. These variants illustrate both the common pathways of adaptation to high altitude in different populations and features specific to the Daghestani populations, showing how even a mildly hypoxic environment can lead to genetic adaptation. [ABSTRACT FROM AUTHOR]

A wireless hand-held Webpad device was used to review a sample set of cranial computerized tomography (CT) studies to assess its diagnostic capabilities and its feasibility as a portable diagnostic workstation for radiology. The data-set consisted of 30 head CT studies of emergency cases. Two neuroradiologists and a senior radiologist participated in the evaluation of the portable workstation. They used a Web-based viewer that we developed, which provided all the major functionalities required for radiological image review. The reported radiological findings and diagnoses were compared with a gold standard, comprising a set of diagnoses previously formulated by a consensus panel of radiologists who had reviewed the original studies. The diagnoses made using the Webpad were correct (no major discrepancies) in 82 out of 90 interpretations (91%), which is comparable to the accuracy reported in image review with a conventional radiological workstation. The average total working time per diagnosis was 5 min 25 s (range 2–12 min). The simplicity of use of the system and its low cost make it suitable for distributing radiological studies within hospital facilities. [ABSTRACT FROM AUTHOR]

Before the end of the Last Glacial Maximum (LGM, ∼16.5 ka ago) 1 set in motion major shifts in human culture and population structure, 2 a consistent change in lithic technology, material culture, settlement pattern, and adaptive strategies is recorded in Southern Europe at ∼18–17 ka ago. In this time frame, the landscape of Northeastern Italy changed considerably, and the retreat of glaciers allowed hunter-gatherers to gradually recolonize the Alps. 3–6 Change within this renewed cultural frame (i.e., during the Late Epigravettian phase) is currently associated with migrations favored by warmer climate linked to the Bølling-Allerød onset (14.7 ka ago), 7–11 which replaced earlier genetic lineages with ancestry found in an individual who lived ∼14 ka ago at Riparo Villabruna, Italy, and shared among different contexts (Villabruna Cluster). 9 Nevertheless, these dynamics and their chronology are still far from being disentangled due to fragmentary evidence for long-distance interactions across Europe. 12 Here, we generate new genomic data from a human mandible uncovered at Riparo Tagliente (Veneto, Italy), which we directly dated to 16,980–16,510 cal BP (2σ). This individual, affected by focal osseous dysplasia, is genetically affine to the Villabruna Cluster. Our results therefore backdate by at least 3 ka the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød event. In light of the new genetic evidence, this population replacement chronologically coincides with the very emergence of major cultural transitions in Southern and Western Europe. • Genetic replacement in Southern European hunter-gatherers started at least 17 ka ago • The shift follows the LGM and precedes the onset of the Bølling/Allerød event • This process is chronologically associated with major cultural transitions in Europe Bortolini et al. generate genomic evidence and direct dating from an individual who lived ∼17 ka ago in northeastern Italy and backdate by about 3 ka the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia previously believed to have spread during later major warming shifts. [ABSTRACT FROM AUTHOR]

Background: In the process of adaptation of humans to their environment, positive or adaptive selection has played a main role. Positive selection has, however, been under-studied in African populations, despite their diversity and importance for understanding human history. Results: Here, we have used 119 available whole-genome sequences from five Ethiopian populations (Amhara, Oromo, Somali, Wolayta and Gumuz) to investigate the modes and targets of positive selection in this part of the world. The site frequency spectrum-based test SFselect was applied to idfentify a wide range of events of selection (old and recent), and the haplotype-based statistic integrated haplotype score to detect more recent events, in each case with evaluation of the significance of candidate signals by extensive simulations. Additional insights were provided by considering admixture proportions and functional categories of genes. We identified both individual loci that are likely targets of classic sweeps and groups of genes that may have experienced polygenic adaptation. We found population-specific as well as shared signals of selection, with folate metabolism and the related ultraviolet response and skin pigmentation standing out as a shared pathway, perhaps as a response to the high levels of ultraviolet irradiation, and in addition strong signals in genes such as IFNA, MRC1, immunoglobulins and T-cell receptors which contribute to defend against pathogens. Conclusions: Signals of positive selection were detected in Ethiopian populations revealing novel adaptations in East Africa, and abundant targets for functional follow-up. [ABSTRACT FROM AUTHOR]

Objectives: This paper starts from the unusual observation of the overrepresentation of females among adults in the cemetery of Bronze Age Shahr‐i Sokhta (Seistan, Iran) and explores the post marital residence pattern. By integrating taphonomical (skeletal preservation), anthropological (sex ratio [SR], sexual dimorphism, stress indicators, age at death), archeological (long distance trade indicators, habitation floor area, social role of women), and ancient DNA (heterozygosity levels in X chromosomes) data we test the hypothesis of post marital matrilocality in the site. Methods: We computed the SR (pelvis‐based sex determination) in a random unpublished adult sample from the cemetery of Shahr‐i Sokhta and in two samples previously published by other authors. We used comparative data on SR from: a large Supra Regional multi‐chronological sample of sites, n = 47, with 8808 adult sexed individuals, from Southern Europe, Egypt, Middle East, Southern Russia; a Regional Bronze Age sample of sites (n = 10) from Bactria Margiana and Indus Valley with 1324 adult sexed individuals. We estimated the heterozygosity levels in X chromosomes compared with the rest of the autosomes on the assumption that in a matrilocal society females should show lower variability than men. Results: Adult SR in a sample (n = 549) from Shahr‐i Sokhta is 70.5, the overrepresentation of females is shared with Regional Bronze Age sites from Bactria Margiana (SR = 72.09) and Indus Valley (SR = 67.54). On the contrary, in a larger Supra Regional multi‐chronological sample of sites, mean SR ranges between 112.7 (Bronze Age) and 163.1 (Middle Ages). Taphonomical and anthropological indicators do not explain the overrepresentation of female skeletons. Archeological indicators suggest a high social status of women and that the society was devoted to long range trade activities. heterozygosity levels in X chromosomes are in agreement with a matrilocal society. Conclusions: Indicators suggest that Bronze Age Shahr‐ì Sokhta was a matrilocal society and that long distance trade was an important economic factor producing an overrepresentation of adult female skeletons in the cemetery. [ABSTRACT FROM AUTHOR]

Most living organisms rely on double-stranded DNA (dsDNA) to store their genetic information and perpetuate themselves. This biological information has been considered as the main target of evolution. However, here we show that symmetries and patterns in the dsDNA sequence can emerge from the physical peculiarities of the dsDNA molecule itself and the maximum entropy principle alone, rather than from biological or environmental evolutionary pressure. The randomness justifies the human codon biases and context-dependent mutation patterns in human populations. Thus, the DNA 'exceptional symmetries,' emerged from the randomness, have to be taken into account when looking for the DNA encoded information. Our results suggest that the double helix energy constraints and, more generally, the physical properties of the dsDNA are the hard drivers of the overall DNA sequence architecture, whereas the selective biological processes act as soft drivers, which only under extraordinary circumstances overtake the overall entropy content of the genome. [ABSTRACT FROM AUTHOR]

Following the development of modern genome sequencing technologies, the investigation of museum osteological finds is increasingly informative and popular. Viable protocols to help preserve these collections from exceedingly invasive analyses, would allow greater access to the specimens for scientific research. The main aim of this work is to survey skeletal tissues, specifically petrous bones and roots of teeth, using infrared spectroscopy as a prescreening method to assess the bone quality for molecular analyses. This approach could overcome the major problem of identifying useful genetic material in archaeological bone collections without resorting to demanding, time consuming and expensive laboratory studies. A minimally invasive sampling of archaeological bones was developed and bone structural and compositional changes were examined, linking isotopic and genetic data to infrared spectra. The predictive model based on Infrared parameters is effective in determining the occurrence of ancient DNA (aDNA); however, the quality/quantity of aDNA cannot be determined because of the influence of environmental and local factors experienced by the examined bones during the burial period. [ABSTRACT FROM AUTHOR]

Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus' impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

This paper details a novel method to characterize and quantify edge wear patterns in ceramic-on-ceramic acetabular liners using a roundness measurement machine to measure the post-wear surface. A 3D surface map is produced which encompasses the measured surface covering the wear patch, the uncontrolled edge geometry and form of the bearing surface. The data is analysed to quantify linear penetration and volume. The developed method was applied in a blind study to a set of six 36 mm ceramic-on-ceramic acetabular cup liners that were measured and analysed to characterise the edge wear. The in-vitro linear wear penetration ranged from 10 μm to 30 μm. The computed volumetric wear results obtained from the blind roundness measurement study were compared against the measured gravimetric results indicating a strong correlation between the results (0.9846). This study has also highlighted that measured liners exhibited an area of localised edge wear locates above the bearing surface as well as a smearing effect on the bearing surface caused by debris from edge wear. A study was carried out to test the repeatability of the measurement method and the inter-operator variability of the analysis. The results of the study show a standard deviation for the entire measurement and analysis process of 0.009 mm 3 for first user and 0.003 mm 3 for second user over twenty datasets. Hence the method displays high repeatability of the measurement and analysis process between users. This method allows for the delineation of form and wear through the determination of local geometry changes on what is essentially a freeform surface. The edge geometry is only partially controlled from a GD&T perspective and its geometry relative to the bearing surface varies from part-to-part. This method whilst being subjective allows for the determination of wear in this area with a high level of repeatability. However the limitation of this method is that it can only measure 5mm wide band of the liner due to the limited gauge travel range of 2mm [ABSTRACT FROM AUTHOR]

The complex interplay between genetics, culture, and environment forms an individual’s biology, influencing their behavior, choices, and health. However, to what extent information derived from this intertwined network could be quantitatively summarized to provide a glance at an individual’s lifestyle is difficult to say. Here, we focused on dietary preferences as cultural proxies and genome-wide data of 543 individuals from six historical Silk Road countries: Georgia, Armenia, Azerbaijan, Uzbekistan, Kazakhstan, and Tajikistan. These lands favored the dispersal of innovations, foods, and DNA halfway across Eurasia, thus representing an ideal subject to explore interactions of cultural factors and genetic ancestry. We used discriminant analysis of principal components to infer cultural clusters, where mixed memberships are allowed. Five different clusters emerged. Of these, clusters 1 and 3, driven by aversion to pork and alcoholic beverages, mirrored genetic admixture patterns with the exception of Azerbaijan, which shares preferences supported by Islamic culture with Eastern countries. Cluster 3 was driven by protein-rich foods, whose preference was significantly related to steppe pastoralist ancestry. Sex and age were secondary clustering factors, with clusters formed by male and young individuals being related to alcohol preference and a reduced liking for vegetables. The soft clustering approach enabled us to model and summarize the individual’s dietary information in short and informative vectors, which show meaningful interaction with other nondietary attributes of the studied individuals. Encoding other cultural variables would help summarize an individual’s culture quantitatively, thus ultimately supporting its inclusion as a covariate in future association studies. [ABSTRACT FROM AUTHOR]

The population dynamics that followed the Out of Africa (OoA) expansion and the whereabouts of the early migrants before the differentiation that ultimately led to the formation of Oceanian, West and East Eurasian macropopulations have long been debated. Shedding light on these events may, in turn, provide clues to better understand the cultural evolution in Eurasia between 50 and 35 ka. Here, we analyze Eurasian Paleolithic DNA evidence to provide a comprehensive population model and validate it in light of available material culture. Leveraging on our integrated approach we propose the existence of a Eurasian population Hub, where Homo sapiens lived between the OoA and the broader colonization of Eurasia, which was characterized by multiple events of expansion and local extinction. A major population wave out of Hub, of which Ust'Ishim, Bacho Kiro, and Tianyuan are unadmixed representatives, is broadly associated with Initial Upper Paleolithic lithics and populated West and East Eurasia before or around 45 ka, before getting largely extinct in Europe. In this light, we suggest a parsimonious placement of Oase1 as an individual related to Bacho Kiro who experienced additional Neanderthal introgression. Another expansion, started before 38 ka, is broadly associated with Upper Paleolithic industries and repopulated Europe with sporadic admixtures with the previous wave (GoyetQ116-1) and more systematic ones, whereas moving through Siberia (Yana, Mal'ta). Before these events, we also confirm Zlatý Kůň as the most basal human lineage sequenced to date OoA, potentially representing an earlier wave of expansion out of the Hub. [ABSTRACT FROM AUTHOR]

During their migrations out of Africa, humans successfully colonised and adapted to a wide range of habitats, including extreme high altitude environments, where reduced atmospheric oxygen (hypoxia) imposes a number of physiological challenges. This study evaluates genetic and phenotypic variation in the Colla population living in the Argentinean Andes above 3500 m and compares it to the nearby lowland Wichí group in an attempt to pinpoint evolutionary mechanisms underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25 individuals from each population. In genome-wide scans of extended haplotype homozygosity Collas showed the strongest signal around VEGFB, which plays an essential role in the ischemic heart, and ELTD1, another gene crucial for heart development and prevention of cardiac hypertrophy. Moreover, pathway enrichment analysis showed an overrepresentation of pathways associated with cardiac morphology. Taken together, these findings suggest that Colla highlanders may have evolved a toolkit of adaptative mechanisms resulting in cardiac reinforcement, most likely to counteract the adverse effects of the permanently increased haematocrit and associated shear forces that characterise the Andean response to hypoxia. Regulation of cerebral vascular flow also appears to be part of the adaptive response in Collas. These findings are not only relevant to understand the evolution of hypoxia protection in high altitude populations but may also suggest new avenues for medical research into conditions where hypoxia constitutes a detrimental factor. [ABSTRACT FROM AUTHOR]

Linguistic and cultural evidence suggest that Madagascar was the final point of two major dispersals of Austronesian- and Bantu-speaking populations. Today, the Mikea are described as the last-known Malagasy population reported to be still practicing a hunter-gatherer lifestyle. It is unclear, however, whether the Mikea descend from a remnant population that existed before the arrival of Austronesian and Bantu agriculturalists or whether it is only their lifestyle that separates them from the other contemporary populations of South Madagascar. To address these questions we have performed a genome-wide analysis of >700,000 SNP markers on 21 Mikea, 24 Vezo, and 24 Temoro individuals, together with 50 individuals from Bajo and Lebbo populations from Indonesia. Our analyses of these data in the context of data available from other Southeast Asian and African populations reveal that all three Malagasy populations are derived from the same admixture event involving Austronesian and Bantu sources. In contrast to the fact that most of the vocabulary of the Malagasy speakers is derived from the Barito group of the Austronesian language family, we observe that only one-third of their genetic ancestry is related to the populations of the Java-Kalimantan-Sulawesi area. Because no additional ancestry components distinctive for the Mikea were found, it is likely that they have adopted their hunter-gatherer way of life through cultural reversion, and selection signals suggest a genetic adaptation to their new lifestyle. [ABSTRACT FROM AUTHOR]

Anatomically modern humans evolved around 300 thousand years ago in Africa. They started to appear in the fossil record outside of Africa as early as 100 thousand years ago, although other hominins existed throughout Eurasia much earlier. Recently, several studies argued in favor of a single out of Africa event for modern humans on the basis of whole-genome sequence analyses. However, the single out of Africa model is in contrast with some of the findings from fossil records, which support two out of Africa events, and uniparental data, which propose a back to Africa movement. Here, we used a deep-learning approach coupled with approximate Bayesian computation and sequential Monte Carlo to revisit these hypotheses from the whole-genome sequence perspective. Our results support the back to Africa model over other alternatives. We estimated that there are two sequential separations between Africa and out of African populations happening around 60-90 thousand years ago and separated by 13-15 thousand years. One of the populations resulting from the more recent split has replaced the older West African population to a large extent, while the other one has founded the out of Africa populations. [ABSTRACT FROM AUTHOR]

The Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of the human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area have been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However, many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern (1) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; (2) the role of Sicily and Sardinia before LGM; (3) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; (4) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples. [ABSTRACT FROM AUTHOR]

The Finnish population is a unique example of a genetic isolate affected by a recent founder event. Previous studies have suggested that the ancestors of Finnic-speaking Finns and Estonians reached the circum-Baltic region by the 1st millennium BC. However, high linguistic similarity points to a more recent split of their languages. To study genetic connectedness between Finns and Estonians directly, we first assessed the efficacy of imputation of low-coverage ancient genomes by sequencing a medieval Estonian genome to high depth (23×) and evaluated the performance of its down-sampled replicas. We find that ancient genomes imputed from >0.1× coverage can be reliably used in principal-component analyses without projection. By searching for long shared allele intervals (LSAIs; similar to identity-by-descent segments) in unphased data for >143,000 present-day Estonians, 99 Finns, and 14 imputed ancient genomes from Estonia, we find unexpectedly high levels of individual connectedness between Estonians and Finns for the last eight centuries in contrast to their clear differentiation by allele frequencies. High levels of sharing of these segments between Estonians and Finns predate the demographic expansion and late settlement process of Finland. One plausible source of this extensive sharing is the 8th–10th centuries AD migration event from North Estonia to Finland that has been proposed to explain uniquely shared linguistic features between the Finnish language and the northern dialect of Estonian and shared Christianity-related loanwords from Slavic. These results suggest that LSAI detection provides a computationally tractable way to detect fine-scale structure in large cohorts. [ABSTRACT FROM AUTHOR]

Detecting natural selection signals in admixed populations can be problematic since the source of the signal typically dates back prior to the admixture event. On one hand, it is now possible to study various source populations before a particular admixture thanks to the developments in ancient DNA (aDNA) in the last decade. However, aDNA availability is limited to certain geographical regions and the sample sizes and quality of the data might not be sufficient for selection analysis in many cases. In this study, we explore possible ways to improve detection of pre-admixture signals in admixed populations using a local ancestry inference approach. We used masked haplotypes for population branch statistic (PBS) and full haplotypes constructed following our approach from Yelmen et al. (2019) for cross-population extended haplotype homozygosity (XP-EHH), utilizing forward simulations to test the power of our analysis. The PBS results on simulated data showed that using masked haplotypes obtained from ancestry deconvolution instead of the admixed population might improve detection quality. On the other hand, XP-EHH results using the admixed population were better compared with the local ancestry method. We additionally report correlation for XP-EHH scores between source and admixed populations, suggesting that haplotype-based approaches must be used cautiously for recently admixed populations. Additionally, we performed PBS on real South Asian populations masked with local ancestry deconvolution and report here the first possible selection signals on the autochthonous South Asian component of contemporary South Asian populations. [ABSTRACT FROM AUTHOR]

Contemporary individuals are the combination of genetic fragments inherited from ancestors belonging to multiple populations, as the result of migration and admixture. Isolating and characterizing these layers are crucial to the understanding of the genetic history of a given population. Ancestry deconvolution approaches make use of a large amount of source individuals, therefore constraining the performance of Local Ancestry Inferences when only few genomes are available from a given population. Here we present WINC, a local ancestry framework derived from the combination of ChromoPainter and NNLS approaches, as a method to retrieve local genetic assignments when only a few reference individuals are available. The framework is aided by a score assignment based on source differentiation to maximize the amount of sequences retrieved and is capable of retrieving accurate ancestry assignments when only two individuals for source populations are used. [ABSTRACT FROM AUTHOR]

We consider the treatment of fermionic dark matter interacting with photons via dimension-5 and -6 effective operators, arguing that one should always use hypercharge gauge field form factors, instead of those of the photon. Beyond the simple observation that the electromagnetic form factor description breaks down at the electroweak scale, we show how the additional couplings to the Z boson predicted by the hypercharge form factors modify the relic density calculation and indirect detection limits for dark matter masses of a few tens of GeV and above. Furthermore, constraints from the invisible Z decay width can be competitive for masses below 10 GeV. We review the phenomenology of hypercharge form factors at the LHC as well as for direct and indirect detection experiments. We highlight where the electromagnetic and hypercharge descriptions lead to wildly different conclusions about the viable parameter space and the relative sensitivity of various probes, namely vector boson fusion versus mono-jet constraints from the LHC, and indirect versus direct searches, for larger dark matter masses. We find that the dimension-5 operators are strongly constrained by direct detection bounds, while for dimension-6 operators LHC mono-jet searches are competitive or better than the other probes we consider. [ABSTRACT FROM AUTHOR]

Generative models have shown breakthroughs in a wide spectrum of domains due to recent advancements in machine learning algorithms and increased computational power. Despite these impressive achievements, the ability of generative models to create realistic synthetic data is still under-exploited in genetics and absent from population genetics. Yet a known limitation in the field is the reduced access to many genetic databases due to concerns about violations of individual privacy, although they would provide a rich resource for data mining and integration towards advancing genetic studies. In this study, we demonstrated that deep generative adversarial networks (GANs) and restricted Boltzmann machines (RBMs) can be trained to learn the complex distributions of real genomic datasets and generate novel high-quality artificial genomes (AGs) with none to little privacy loss. We show that our generated AGs replicate characteristics of the source dataset such as allele frequencies, linkage disequilibrium, pairwise haplotype distances and population structure. Moreover, they can also inherit complex features such as signals of selection. To illustrate the promising outcomes of our method, we showed that imputation quality for low frequency alleles can be improved by data augmentation to reference panels with AGs and that the RBM latent space provides a relevant encoding of the data, hence allowing further exploration of the reference dataset and features for solving supervised tasks. Generative models and AGs have the potential to become valuable assets in genetic studies by providing a rich yet compact representation of existing genomes and high-quality, easy-access and anonymous alternatives for private databases. Author summary: Generative neural networks have been effectively used in many different domains in the last decade, including machine dreamt photo-realistic imagery. In our work, we apply a similar concept to genetic data to automatically learn its structure and, for the first time, produce high quality realistic genomes. These novel genomes are distinct from the original ones used for training the generative networks. We show that artificial genomes, as we name them, retain many complex characteristics of real genomes and the heterogeneous relationships between individuals. They can be used in intricate analyses such as imputation of missing data as we demonstrated. We believe they have a high potential to become alternatives for many genome databases which are not publicly available or require long application procedures or collaborations and remove an important accessibility barrier in genomic research in particular for underrepresented populations. [ABSTRACT FROM AUTHOR]

Bones and teeth from archaeological records are direct evidence of past individuals and they represent valuable archives for palaeo-anthropological and palaeoenvironmental studies. However, pristine information may be obliterated by the diagenetic alteration of bone specimens. Thus, defining in detail their preservation state is fundamental to assess the potential of extracting information about the past life of the individual, as well as to investigate the palaeo-environment at the burial site. For this reason, we have selected a set of archaeological samples (petrous bones and tooth roots) of different origin and chronology that have experienced diverse environmental and burial conditions, from arid and semi-arid to temperate regions in a time span from prehistoric to fresh bones. Thus, the selected samples underwent a variety of diagenetic processes, resulting in different types and extent of alteration patterns. Here we have applied a minimally-invasive sampling strategy and an analytical protocol based on Fourier transform infrared spectroscopy (FTIR) in order to ensure the investigation of a statistically significant set of samples. We provide a method to describe and quantify the changes in the physico-chemical properties of both the organic and inorganic constituents of bones, by establishing a set of parameters calculated from the FTIR spectra and evaluating their sensitivity in describing the alteration types and extent in bone specimens. Through FTIR spectral analysis, we have defined the most suitable parameters to effectively describe the alteration degree of bone specimens. Notably, the results have shown that, despite the complexity of multifactorial diagenetic processes, their measurable effects on differently altered bones can be described by a common mechanism. This indicates a progressive loss of collagen which is paralleled to the recrystallization of bioapatite and the loss of structural carbonate, regardless of the origin and chronology of the specimens. Thus, here we propose an FTIR-based model for bone diagenesis of general validity, highlighting that distinct diagenetic processes affecting the archaeological bones have acted according to common alteration mechanisms. • Bone diagenetic alterations were analysed on a large and diversified set of samples. • An alternative and minimally destructive sampling method was applied for FTIR analysis. • Suitable FTIR parameters were defined to effectively describe the diagenetic alterations. • Diagenesis affects bones at different extent through common alteration mechanisms. • We propose an FTIR-based model for bone diagenesis of general validity. [ABSTRACT FROM AUTHOR]

Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5 , SNX13 , TYRP1 , and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel. [ABSTRACT FROM AUTHOR]

The presence of genomic signatures of Eurasian origin in contemporary Ethiopians has been reported by several authors and estimated to have arrived in the area from 3000 years ago. Several studies reported plausible source populations for such a signature, using haplotype based methods on modern data or single-site methods on modern or ancient data. These studies did not reach a consensus and suggested an Anatolian or Sardinia-like proxy, broadly Levantine or Neolithic Levantine as possible sources. We demonstrate, however, that the deeply divergent, autochthonous African component which accounts for ~50% of most contemporary Ethiopian genomes, affects the overall allele frequency spectrum to an extent that makes it hard to control for it and, at once, to discern between subtly different, yet important, Eurasian sources (such as Anatolian or Levant Neolithic ones). Here we re-assess pattern of allele sharing between the Eurasian component of Ethiopians (here called "NAF" for Non African) and ancient and modern proxies. Our results unveil a genomic legacy that may connect the Eurasian genetic component of contemporary Ethiopians with Sea People and with population movements that affected the Mediterranean area and the Levant after the fall of the Minoan civilization. [ABSTRACT FROM AUTHOR]

A number of studies carried out since the early ‘70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,815 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as structured as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of inter-individual heterogeneity largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies. [ABSTRACT FROM AUTHOR]

In the U.S., more than 80% of African-American smokers use mentholated cigarettes, compared to less than 30% of Caucasian smokers. The reasons for these differences are not well understood. To determine if genetic variation contributes to mentholated cigarette smoking, we performed an exome-wide association analysis in a multiethnic population-based sample from Dallas, TX (N = 561). Findings were replicated in an independent cohort of African Americans from Washington, DC (N = 741). We identified a haplotype of MRGPRX4 (composed of rs7102322[G], encoding N245S, and rs61733596[G], T43T), that was associated with a 5-to-8 fold increase in the odds of menthol cigarette smoking. The variants are present solely in persons of African ancestry. Functional studies indicated that the variant G protein-coupled receptor encoded by MRGPRX4 displays reduced agonism in both arrestin-based and G protein-based assays, and alteration of agonism by menthol. These data indicate that genetic variation in MRGPRX4 contributes to inter-individual and inter-ethnic differences in the preference for mentholated cigarettes, and that the existence of genetic factors predisposing vulnerable populations to mentholated cigarette smoking can inform tobacco control and public health policies. [ABSTRACT FROM AUTHOR]

Rapidly Mutating Y-STRs (RM Y-STRs) were recently introduced in forensics in order to increase the differentiation of Y-chromosomal profiles even in case of close relatives. We estimate RM Y-STRs mutation rates and their power to discriminate between related individuals by using samples extracted from a wide set of paternal pedigrees and by comparing RM Y-STRs results with those obtained from the Y-filer set. In addition, we tested the ability of RM Y-STRs to discriminate between unrelated individuals carrying the same Y-filer haplotype, using the haplogroup R-M269 (reportedly characterised by a strong resemblance in Y-STR profiles) as a case study. Our results, despite confirming the high mutability of RM Y-STRs, show significantly lower mutation rates than reference germline ones. Consequently, their power to discriminate between related individuals, despite being higher than the one of Y-filer, does not seem to improve significantly the performance of the latter. On the contrary, when considering R-M269 unrelated individuals, RM Y-STRs reveal significant discriminatory power and retain some phylogenetic signal, allowing the correct classification of individuals for some R-M269-derived sub-lineages. These results have important implications not only for forensics, but also for molecular anthropology, suggesting that RM Y-STRs are useful tools for exploring subtle genetic variability within Y-chromosomal haplogroups. [ABSTRACT FROM AUTHOR]