Large-scale migration into Britain during the Middle to Late Bronze Age.

Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze Age1. To understand this, here we generated genome-wide data from 793 individuals, increasing data from the Middle to the Late Bronze Age and Iron Age in Britain by 12-fold, and western and central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of people of England and Wales from the Iron Age, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to the Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and the independent genetic trajectory in Britain is also reflected in the rise of the allele conferring lactase persistence to approximately 50% by this time compared to approximately 7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.

Grey wolf genomic history reveals a dual ancestry of dogs.

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1-8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.

A genetic history of the pre-contact Caribbean.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1-3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

Density separation of petrous bone powders for optimized ancient DNA yields.

Density separation is a process routinely used to segregate minerals, organic matter, and even microplastics, from soils and sediments. Here we apply density separation to archaeological bone powders before DNA extraction to increase endogenous DNA recovery relative to a standard control extraction of the same powders. Using nontoxic heavy liquid solutions, we separated powders from the petrous bones of 10 individuals of similar archaeological preservation into eight density intervals (2.15 to 2.45 g/cm3, in 0.05 increments). We found that the 2.30 to 2.35 g/cm3 and 2.35 to 2.40 g/cm3 intervals yielded up to 5.28-fold more endogenous unique DNA than the corresponding standard extraction (and up to 8.53-fold before duplicate read removal), while maintaining signals of ancient DNA authenticity and not reducing library complexity. Although small 0.05 g/cm3 intervals may maximally optimize yields, a single separation to remove materials with a density above 2.40 g/cm3 yielded up to 2.57-fold more endogenous DNA on average, which enables the simultaneous separation of samples that vary in preservation or in the type of material analyzed. While requiring no new ancient DNA laboratory equipment and fewer than 30 min of extra laboratory work, the implementation of density separation before DNA extraction can substantially boost endogenous DNA yields without decreasing library complexity. Although subsequent studies are required, we present theoretical and practical foundations that may prove useful when applied to other ancient DNA substrates such as teeth, other bones, and sediments.

The diverse genetic origins of a Classical period Greek army.

Trade and colonization caused an unprecedented increase in Mediterranean human mobility in the first millennium BCE. Often seen as a dividing force, warfare is in fact another catalyst of culture contact. We provide insight into the demographic dynamics of ancient warfare by reporting genome-wide data from fifth-century soldiers who fought for the army of the Greek Sicilian colony of Himera, along with representatives of the civilian population, nearby indigenous settlements, and 96 present-day individuals from Italy and Greece. Unlike the rest of the sample, many soldiers had ancestral origins in northern Europe, the Steppe, and the Caucasus. Integrating genetic, archaeological, isotopic, and historical data, these results illustrate the significant role mercenaries played in ancient Greek armies and highlight how participation in war contributed to continental-scale human mobility in the Classical world.

A minimally destructive protocol for DNA extraction from ancient teeth.

Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.

Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or µCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (µCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.

The genomic history of southeastern Europe.

Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12000 and 500 bc. We document a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern Europe, the early stages in the formation of Bronze Age steppe ancestry. We show that the first farmers of northern and western Europe dispersed through southeastern Europe with limited hunter-gatherer admixture, but that some early groups in the southeast mixed extensively with hunter-gatherers without the sex-biased admixture that prevailed later in the north and west. We also show that southeastern Europe continued to be a nexus between east and west after the arrival of farmers, with intermittent genetic contact with steppe populations occurring up to 2,000 years earlier than the migrations from the steppe that ultimately replaced much of the population of northern Europe.

The Beaker phenomenon and the genomic transformation of northwest Europe.

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

Erratum: The Beaker phenomenon and the genomic transformation of northwest Europe.

This corrects the article DOI: 10.1038/nature25738.

Diagnostic Capability of Intra-Articular Injections for Femoroacetabular Impingement Syndrome: A Systematic Review.

OBJECTIVE: To review and critically appraise available literature concerning the diagnostic capability of intra-articular injections for femoroacetabular impingement (FAI) syndrome. DESIGN: Systematic review. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Studies assessing pain relief following intra-articular injections for the diagnosis of FAI syndrome, compared with arthroscopy as diagnostic reference standard, were considered eligible. Searches were performed across 8 databases, and the risk of bias was evaluated through the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: From 489 articles identified, 4 were included for analysis. Intra-articular injections were composed of anesthetic agents (such as lidocaine, bupivacaine, and ropivacaine), combined or not with corticosteroids (triamcinolone and betamethasone). All studies were judged as "at risk of bias", and a substantial heterogeneity was found considering assessment methods and pain relief thresholds for a positive response to intra-articular injections. Overall, 2 studies reported that intra-articular injections presented a high accuracy in determining the presence of FAI syndrome. However, the remaining 2 studies indicated that intra-articular injections might present restricted diagnostic capability to discriminate FAI syndrome from healthy individuals or those with other hip pathologies. CONCLUSIONS: Based on limited evidence, the diagnostic capability of intra-articular injections for FAI syndrome cannot be supported. It remains unclear which pain relief thresholds are related to a higher diagnostic capability. The combination of anesthetics with corticosteroids should also be further explored, including multiple pain assessments for evaluation of prolonged effects.

Enhancing Methylene Blue Dye Removal using pyrolyzed Mytella falcata Shells: Characterization, Kinetics, Isotherm, and Regeneration through Photolysis and Peroxidation.

The potential of pyrolyzed Mytella falcata shells as an adsorbent for removing methylene blue dye molecules from aqueous solutions was investigated. The study found that the adsorbent produced at 600 °C of pyrolysis temperature, with an adsorbent mass of 0.5 g, particle diameter of 0.297-0.149 mm, and pH 12.0, demonstrated the highest dye molecule removal efficiency of 82.41%. The material's porosity was observed through scanning electron microscopy, which is favorable for adsorption, while Fourier-transform infrared spectroscopy and X-Ray diffraction analysis analyses confirmed the presence of calcium carbonate in the crystalline phases. The pseudo-second order model was found to be the best fit for the data, suggesting that the adsorption mechanism involves two steps: external diffusion and diffusion via the solid pores. The Redlich-Peterson isotherm model better represented the equilibrium data, and the methylene blue adsorption was found to be spontaneous, favorable, and endothermic. The hydrogen peroxide with UV oxidation was found to be the most efficient method of regeneration, with a regeneration percentage of 63% achieved using 600 mmol.L-1 of oxidizing agents. The results suggest that pyrolyzed Mytella falcata shells could serve as an ecologically viable adsorbent alternative, reducing the amount of waste produced in the local environment and at the same time removing pollutants from the water. The material's adsorption capacity remained almost constant in the first adsorption-oxidation cycles, indicating its potential for repeated use.

Amyloidosis: a rare cause of severe acute liver failure.

Gastrointestinal amyloidosis can be primary, more associated with monoclonal plasma cell dyscrasia, or secondary, usually secondary to a tissue-destructive, chronic inflammatory process (such as inflammatory bowel disease, for example) and long-term dialysis. The rare presentation of severe acute liver failure in systemic amyloidosis can make this diagnosis/ management more difficult. Hepatomegaly with signs of diffuse infiltrative disease and periportal involvement associated with thoracic and other abdominal radiological findings in the appropriate clinical context may constitute a diagnostic imaging clue in this challenge.

Hepatosplenic involvement of tuberculosis: an uncommon presentation that demands attention in specific scenarios.

Abdominal tuberculosis (TB), a potential differential diagnosis for acute and chronic abdomen, should be considered in specific situations, such as immunosuppressant or biological drug use, HIV, or in patients residing in endemic areas. Although the presence of thoracic tuberculosis may indicate abdominal TB, only 15% of patients with abdominal TB have evidence of pulmonary disease. Involvement of the liver and spleen is a common autopsy finding in patients with disseminated TB. However, the most common pattern is of fine miliary lesions. Hepatic involvement with a macronodular pattern, a rare occurrence, is linked to dissemination through the portal vein. The splenic macronodular form, an extremely rare presentation, can manifest as solitary or multiple nodules, oval or round, with a variable appearance reflecting different stages of the disease, adding to the uniqueness of this case.

Human auditory ossicles as an alternative optimal source of ancient DNA.

DNA recovery from ancient human remains has revolutionized our ability to reconstruct the genetic landscape of the past. Ancient DNA research has benefited from the identification of skeletal elements, such as the cochlear part of the osseous inner ear, that provides optimal contexts for DNA preservation; however, the rich genetic information obtained from the cochlea must be counterbalanced against the loss of morphological information caused by its sampling. Motivated by similarities in developmental processes and histological properties between the cochlea and auditory ossicles, we evaluate the ossicles as an alternative source of ancient DNA. We show that ossicles perform comparably to the cochlea in terms of DNA recovery, finding no substantial reduction in data quantity and minimal differences in data quality across preservation conditions. Ossicles can be sampled from intact skulls or disarticulated petrous bones without damage to surrounding bone, and we argue that they should be used when available to reduce damage to human remains. Our results identify another optimal skeletal element for ancient DNA analysis and add to a growing toolkit of sampling methods that help to better preserve skeletal remains for future research while maximizing the likelihood that ancient DNA analysis will produce useable results.

Local delivery of nitric oxide prevents endothelial dysfunction in periodontitis.

AIMS: Increased cardiovascular disease risk underlies elevated rates of mortality in individuals with periodontitis. A key characteristic of those with increased cardiovascular risk is endothelial dysfunction, a phenomenon synonymous with deficiencies of bioavailable nitric oxide (NO), and prominently expressed in patients with periodontitis. Also, inorganic nitrate can be reduced to NO in vivo to restore NO levels, leading us to hypothesise that its use may be beneficial in reducing periodontitis-associated endothelial dysfunction. Herein we sought to determine whether inorganic nitrate improves endothelial function in the setting of periodontitis and if so to determine the mechanisms underpinning any responses seen. METHODS AND RESULTS: Periodontitis was induced in mice by placement of a ligature for 14 days around the second molar. Treatment in vivo with potassium nitrate, either prior to or following establishment of experimental periodontitis, attenuated endothelial dysfunction, as determined by assessment of acetylcholine-induced relaxation of aortic rings, compared to control (potassium chloride treatment). These beneficial effects were associated with a suppression of vascular wall inflammatory pathways (assessed by quantitative-PCR), increases in the anti-inflammatory cytokine interleukin (IL)-10 and reduced tissue oxidative stress due to attenuation of xanthine oxidoreductase-dependent superoxide generation. In patients with periodontitis, plasma nitrite levels were not associated with endothelial function indicating dysfunction. CONCLUSION: Our results suggest that inorganic nitrate protects against, and can partially reverse pre-existing, periodontitis-induced endothelial dysfunction through restoration of nitrite and thus NO levels. This research highlights the potential of dietary nitrate as adjunct therapy to target the associated negative cardiovascular outcomes in patients with periodontitis.

When the adrenals alert us to a systemic fungal disease.

We present a patient referred for investigation of adrenal insufficiency, confirmed due to disseminated paracoccidioidomycosis (PCM), with abdominal and central nervous system (CNS) involvement. Establishing the pathogenesis and immunological processes involved in chronic or latent infections by PCM has been challenging. Medical doctors caring for patients with immunodeficiencies should learn about these fungal infections to properly guide travel planning and have this possibility in the diagnostic arsenal when the patient returns from endemic areas. After 13 months of treatment, the patient showed good clinical evolution, and we repeated imaging exams, showing partial improvement of the preview lesions. Diagnosis and treatment can prevent catastrophic events.

Applicability of machine learning techniques in food intake assessment: A systematic review.

The evaluation of food intake is important in scientific research and clinical practice to understand the relationship between diet and health conditions of an individual or a population. Large volumes of data are generated daily in the health sector. In this sense, Artificial Intelligence (AI) tools have been increasingly used, for example, the application of Machine Learning (ML) algorithms to extract useful information, find patterns, and predict diseases. This systematic review aimed to identify studies that used ML algorithms to assess food intake in different populations. A literature search was conducted using five electronic databases, and 36 studies met all criteria and were included. According to the results, there has been a growing interest in the use of ML algorithms in the area of nutrition in recent years. Also, supervised learning algorithms were the most used, and the most widely used method of nutritional assessment was the food frequency questionnaire. We observed a trend in using the data analysis programs, such as R and WEKA. The use of ML in nutrition is recent and challenging. Therefore, it is encouraged that more studies are carried out relating these themes for the development of food reeducation programs and public policies.

Genetic origins of the Minoans and Mycenaeans.

The origins of the Bronze Age Minoan and Mycenaean cultures have puzzled archaeologists for more than a century. We have assembled genome-wide data from 19 ancient individuals, including Minoans from Crete, Mycenaeans from mainland Greece, and their eastern neighbours from southwestern Anatolia. Here we show that Minoans and Mycenaeans were genetically similar, having at least three-quarters of their ancestry from the first Neolithic farmers of western Anatolia and the Aegean, and most of the remainder from ancient populations related to those of the Caucasus and Iran. However, the Mycenaeans differed from Minoans in deriving additional ancestry from an ultimate source related to the hunter-gatherers of eastern Europe and Siberia, introduced via a proximal source related to the inhabitants of either the Eurasian steppe or Armenia. Modern Greeks resemble the Mycenaeans, but with some additional dilution of the Early Neolithic ancestry. Our results support the idea of continuity but not isolation in the history of populations of the Aegean, before and after the time of its earliest civilizations.

Comparison Between Cardiorespiratory Fitness and Functions of Cognitive Control in Adolescents: A Tracking Study of 3 Years.

PURPOSE: Compare tracking groups with cognitive control functions and plasma brain-derived neurotrophic factors concentrations from childhood to adolescence. METHODS: This is a prospective study with 3 years of follow-up. At baseline, data from 394 individuals were collected (11.7 y), and data were obtained from 134 adolescents (14.9 y) at the 3-year follow-up. At both time points, anthropometric and maximal oxygen uptake data were collected. Cardiorespiratory fitness (CRF) groups were classified into high or low CRF. At follow-up, cognitive outcomes were collected via the Stroop and Corsi block test; plasma brain-derived neurotrophic factors concentrations were also analyzed. RESULTS: Comparisons demonstrated that maintaining high CRF over 3 years results in shorter reaction time, better inhibitory control, and higher working memory values. Likewise, the group that moved from low to high CRF over 3 years presented better reaction time. Plasma brain-derived neurotrophic factors concentrations were higher for the group that increased its CRF over the 3 years in relation to the low-low group (90.58 pg·mL-1; P = .004). However, after scaling by an allometric approach, differences were only found for reaction time and working memory between high-high and high-low groups. CONCLUSION: Maintaining high CRF over 3 years was positively related to reaction time and working memory in relation to adolescents that decreased their levels of CRF.