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Preeclampsia (PE), a multifactorial pregnancy-specific syndrome accounting for up to 8% of pregnancy complications, is a leading cause of maternal and fetal morbidity and mortality. PE is also associated with long-term risk of hypertension and stroke for both mother and fetus. Currently, the only “cure” is delivery of the baby and placenta, largely because the pathogenesis of PE is not yet fully understood. PE is associated with impaired vascular remodeling at the maternal-fetal interface and placental insufficiency; however, specific factors contributing to this impairment have not been identified. To identify molecular pathways involved in PE, we examined temporal transcriptomic changes occurring within the uterus, uterine implantation sites, and placentae from the Dahl salt-sensitive (Dahl S) rat model of superimposed PE compared with Sprague Dawley (SD) rats. We hypothesized that targeted gene analysis and whole transcriptome analysis would identify genetic factors that contribute to development of the preeclamptic phenotype in the Dahl S rat and unveil novel biomarkers, therapeutic targets, and mechanistic pathways in PE. Quantitative real-time PCR (qRT-PCR) and whole genome microarray analysis were performed on isolated total RNA from uterus ( day 0), uterine implantation sites ( days 7 and 10), and placenta ( days 14 and 20). We found 624, 332, 185, and 366 genes to be differentially expressed between Dahl S (PE) and SD (normal pregnancy) on days 0, 7, 10, and 14, respectively. Our data revealed numerous pathways that may play a role in the pathophysiology of spontaneous superimposed PE and allow for further investigation of novel therapeutic targets and biomarker development.

Epigenetics has enriched human disease studies by adding new interpretations to disease features that cannot be explained by genetic and environmental factors. However, identifying causal mechanisms of epigenetic origin has been challenging. New opportunities have risen from recent findings in intra-individual and cyclical epigenetic variation, which includes circadian epigenetic oscillations. Cytosine modifications display deterministic temporal rhythms, which may drive ageing and complex disease. Temporality in the epigenome, or the 'chrono' dimension, may help the integration of epigenetic, environmental and genetic disease studies, and reconcile several disparities stemming from the arbitrarily delimited research fields. The ultimate goal of chrono-epigenetics is to predict disease risk, age of onset and disease dynamics from within individual-specific temporal dynamics of epigenomes.

An extract of date (fruit of a palm tree) residue plus food-grade glutamate, acetic acid, and yeast extract (date residue extract mix, DREM) has been successfully fermented with using Lactobacillus brevis JCM 1059T to produce gamma-aminobutyric acid (GABA). Here, mouse splenocytes were found to be viable when supplemented with DREM and fermented DREM containing GABA (fDREM). The addition of DREM and fDREM resulted in the secretion of tumor necrosis factor (TNF)-α from the splenocytes, fDREM being more effective than DREM. The TNF-α secretion with DREM was elevated by exogenous addition of GABA and that with fDREM was in part mediated via A-type GABA receptors. Contrary to general understanding of the suppressive effects of GABA on various biological functions, our findings suggest that GABA-containing fDREM arguments the immune function as a food and pharmaceutical material.

The earliest dinosaurs (theropods and sauropodomorphs) are found in fossiliferous early Late Triassic strata dated to about 230 million years ago (Ma), mainly in northwestern Argentina and southern Brazil in the Southern Hemisphere temperate belt of what was Gondwana in Pangea. Sauropodomorphs, which are not known for the entire Triassic in then tropical North America, eventually appear 15 million years later in the Northern Hemi- sphere temperate belt of Laurasia. The Pangea supercontinent was traversable in principle by terrestrial vertebrates, so the main barrier to be surmounted for dispersal between hemispheres was likely to be climatic; in particular, the intense aridity of tropical desert belts and unstable climate in the equatorial humid belt accompanying high atmospheric pCO2 that characterized the Late Triassic. We revisited the chronostratigraphy of the dinosaur- bearing Fleming Fjord Group of central East Greenland and, with additional data, produced a correlation of a detailed magnetostra- tigraphy from more than 325 m of composite section from two field areas to the age-calibrated astrochronostratigraphic polarity time scale. This age model places the earliest occurrence of sauro- podomorphs (Plateosaurus) in their northernmost range to ∼214 Ma. The timing is within the 215 to 212 Ma (mid-Norian) window of a major, robust dip in atmospheric pCO2 of uncertain origin but which may have resulted in sufficiently lowered climate barriers that facilitated the initial major dispersal of the herbivorous sau- ropodomorphs to the temperate belt of the Northern Hemisphere. Indications are that carnivorous theropods may have had dis- persals that were less subject to the same climate constraints.

In archaeological research, changes in material culture and the evolution of styles are taken as major indicators for socio-cultural transformation. They form the basis for typo-chronological classification and the establishment of phases and periods. Central European Bronze Age material culture from burials reveals changes during the Bronze Age and represents a perfect case study for analyzing phenomena of cultural change and the adoption of innovation in the societies of prehistoric Europe. Our study focuses on the large-scale change in material culture which took place in the second millennium BC and the emergence at the same period of new burial rites: the shift from inhumation burials in flat graves to complex mounds and simple cremation burials. Paul Reinecke was the first to divide the European Bronze Age (EBA) into two phases, Bz A1 and A2. The shift from the first to the second phase has so far been ascribed to technical advances. Our study adopted an innovative approach to quantifying this phenomenon. Through regressive reciprocal averaging and Bayesian analysis of radiocarbon-dated grave contexts located in Switzerland and southern Germany, we modelled chronological changes in the material culture and changes in burial rites in these regions in a probabilistic way. We used kernel density models to summarize radiocarbon dates, with the aim of visualizing cultural changes in the third and second millennium BC. In 2015, Stockhammer et al. cast doubt on the chronological sequence of the Reinecke phases of the EBA on the basis of newly collected radiocarbon dates from southern Germany. Our intervention is a direct response to the results of that study. We fully agree with Stockhammer’s et al. dating of the start of EBA, but propose a markedly different dating of the EBA/MBA transition. Our modelling of radiocarbon data demonstrates a statistically significant typological sequence of phases Bz A1, Bz A2 and Bz B and disproves their postulated chronological overlap. The linking of the archaeological relative-chronological system with absolute dates is of major importance to understanding the temporal dimension of the EBA phases.

In this article, we investigate the dynamical robustness in a network of Van der Pol oscillators. In particular, we consider a network of diffusively coupled Van der Pol oscillators to explore the aging transition phenomena. Our investigation reveals that the route to aging transition in a network of Van der Pol oscillator is different from that of typical sinusoidal oscillators such as Stuart–Landau oscillators. Unlike sinusoidal oscillators, the order parameter does not follow smooth second-order phase transition. Rather, we observe an abnormal phase transition of the order parameter due to the sudden appearance of unbounded trajectories at a critical point. We provide detailed bifurcation analysis of such an abnormal phase transition. We show that the boundary crisis of a limit-cycle oscillator is at the helm of such an unusual discontinuous path of aging transition.

Mediterranean Early Iron Age chronology was mainly constructed by means of Greek Protogeometric and Geometric ceramic wares, which are widely used for chronological correlations with the Aegean. However, Greek Early Iron Age chronology that is exclusively based on historical evidence in the eastern Mediterranean as well as in the contexts of Greek colonisation in Sicily has not yet been tested by extended series of radiocarbon dates from well-dated stratified contexts in the Aegean. Due to the high chronological resolution that is only achievable by (metric-scale) stratigraphic 14C-age-depth modelling, the analysis of 21 14C-AMS dates on stratified animal bones from Sindos (northern Greece) shows results that immediately challenge the conventional Greek chronology. Based on pottery-style comparisons with other sites, the new dates for Sindos not only indicate a generally higher Aegean Early Iron Age chronology, but also imply the need for a revised understanding of the Greek periodisation system that will foreseeably have a major impact on our understanding of Greek and Mediterranean history.

Newly arrived species on young or remote islands are likely to encounter less predation and competition than source populations on continental landmasses. The associated ecological release might facilitate divergence and speciation as colonizing lineages fill previously unoccupied niche space. Characterizing the sequence and timing of colonization on islands represents the first step in determining the relative contributions of geographical isolation and ecological factors in lineage diversification. Herein, we use genome-scale data to estimate timing of colonization in Naesiotus snails to the Galápagos islands from mainland South America. We test inter-island patterns of colonization and within-island radiations to understand their contribution to community assembly. Partly contradicting previously published topologies, phylogenetic reconstructions suggest that most Naesiotus species form island-specific clades, with within-island speciation dominating cladogenesis. Galápagos Naesiotus also adhere to the island progression rule, with colonization proceeding from old to young islands and within-island diversification occurring earlier on older islands. Our work provides a framework for evaluating the contribution of colonization and in situ speciation to the diversity of other Galápagos lineages.

Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n = 99) and treated (n = 100) metastases. Treated metastases often harbored private ‘driver’ mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n = 17 out of 29, 59%) and distant metastases (n = 20 out of 70, 29%), but less frequent in treated distant metastases (n = 9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2–4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance. Analysis of whole-exome sequencing data from paired primary tumors and metastases from patients with breast, colorectal and lung cancer identifies clonal remodeling associated with therapy and few metastasis-private clonal mutations, consistent with early metastatic seeding.

Peatlands are globally important ecosystems where inorganic mercury is converted to bioaccumulating and highly toxic methylmercury, resulting in high risks of methylmercury exposure in adjacent aquatic ecosystems. Although biological mercury methylation has been known for decades, there is still a lack of knowledge about the organisms involved in mercury methylation and the drivers controlling their methylating capacity. In order to investigate the metabolisms responsible for mercury methylation and methylmercury degradation as well as the controls of both processes, we studied a chronosequence of boreal peatlands covering fundamentally different biogeochemical conditions. Potential mercury methylation rates decreased with peatland age, being up to 53 times higher in the youngest peatland compared to the oldest. Methylation in young mires was driven by sulfate reduction, while methanogenic and syntrophic metabolisms became more important in older systems. Demethylation rates were also highest in young wetlands, with a gradual shift from biotic to abiotic methylmercury degradation along the chronosequence. Our findings reveal how metabolic shifts drive mercury methylation and its ratio to demethylation as peatlands age.

In this study, Polyphenol oxidases (PPO) from royal dates fruit was purified and characterized. These procedures led to 8-fold purification with 14.72% recovery. Three isoenzymes of royal dates PPO exhibited a molecular weight of 20.,45 and 64 kDa. The royal date PPOs had maximum activity at pH 4.6 and 8, 3.6–5.6 and 5.6 with pyrogallol, 4-methylcatechol and pyrocatechol substrates, respectively. The enzyme showed high stability in the temperature range of 30–60 °C.4-Methylcatechol was the most suitable substrate, due to the lowest Km and the biggest Vmax/Km values. The kinetic of thermal inactivation were performed in a temperature range of 60–75 °C. A biphasic model provided a good description of dates PPO thermal inactivation. Indole-3acetic acid markedly inhibited Royal dates PPO activity. Its Anti-browning effect on dates was investigated. IAA-treatment reduced weight loss, pericarp decay, browning index and membrane electrolyte leakage. Thus, a higher total anthocyanins contents and total phenolic contents was correlated with higher DPPH scavenging activity and lower MDH contents Such effect was accredited to maintain of membrane integrity and inhibition of oxidative enzymes by IAA. In conclusion, IAA could be used as a potent inhibitor of fruits enzymatic browning reaction.

It is difficult to evaluate long-term ventilation and indoor-outdoor temperature variation on-site in the birth residence so as to investigate their associations with learning capacity from childhood through adolescence. Here, we conducted a questionnaire-based retrospective cohort study in ten schools from two northeast China cities with warm summers and severe cold winters when residences had very low air exchange rates. Scores for Chinese, Mathematics, and English in the final exams of the summer semester in June 2018 were collected to evaluate learning capacity. We surveyed 6238 students aged 14.7 (SD: 2.1) years old. Using the 2nd quarter (April-May-June) birth as reference, 4th quarter (October-November-December) birth consistently was significantly associated with lower scores in Chinese in bivariate (β, 95%CI: -3.2, -4.3 to -2.0) and multivariate (-1.8, -2.4 to -0.8) linear regression analyses. Stratified sub-analyses showed significant associations for male (-2.4, -3.7 to -1.1), urban (-2.4, -3.4 to -1.4), and primary students (-2.9, -4.5 to -1.4). Since household ventilation and indoor-outdoor temperature variation had great differences between the 2nd and 4th quarter of year, our results suggest that these two factors in the birth residence could be associated with learning capacity in childhood, especially for male and primary students in northeast China.

Background Psoriasis is a common inflammatory skin disease associated with several immune-mediated inflammatory diseases (IMIDs); however, little is known of the chronology of disease development. Objective To investigate the chronology of IMIDs relative to psoriasis. Methods We utilized routinely collected data from Danish nationwide administrative registries to examine the occurrence of IMIDs in patients with psoriasis (n = 10,923) and general population controls (n = 109,230). Results Approximately 20% of patients with psoriasis developed ≥1 IMID, with a 5-fold increased risk compared with the general population. Most IMIDs were diagnosed before psoriasis, except for psoriatic arthritis. Psoriasis was significantly associated with having multiple IMIDs (odds ratio 15.2, 95% confidence interval 11.6-20.0). Human leukocyte antigen B27 positivity was significantly more frequent among psoriasis patients. Limitations Clinical measurements were unavailable. Conclusion IMIDs occur frequently in patients with psoriasis and most are diagnosed before psoriasis. The observed chronology might represent important mechanisms of disease development.

Dendrochronology, the study of annual rings formed by trees and woody plants, has important applications in research of climate and environmental phenomena of the past. Since its inception in the late 19th century, dendrochronology has not had a way to quantify uncertainty about the years assigned to each ring (dating). There are, however, many woody species and sites where it is difficult or impossible to delimit annual ring boundaries and verify them with crossdating, especially in the lowland tropics. Rather than ignoring dating uncertainty or discarding such samples as useless, we present for the first time a probabilistic approach to assign expected ages with a confidence interval. It is proven that the cumulative age in a tree-ring time series advances by an amount equal to the probability that a putative growth boundary is truly annual. Confidence curves for the tree stem radius as a function of uncertain ages are determined. A sensitivity analysis shows the effect of uncertainty of the probability that a recognizable boundary is annual, as well as of the number of expected missing boundaries. Furthermore, we derive a probabilistic version of the mean sensitivity of a dendrochronological time series, which quantifies a tree's sensitivity to environmental variation over time, as well as probabilistic versions of the autocorrelation and process standard deviation. A computer code in Mathematica is provided, with sample input files, as supporting information. Further research is necessary to analyze frequency patterns of false and missing boundaries for different species and sites.

In the early 20th century, a political movement to secure access to euthanasia and assisted suicide began in the United States. The multitude of organizations associated with this effort has undergone an array of mergers, splits, and name changes, channeled through two progenitor organizations—the Euthanasia Society of America and the Hemlock Society. A few chronologies mapping the metamorphoses of these organizations are available, but they are not accessible in the medical literature. Moreover, they are not comprehensive, lack consistency, and are not rigorously validated. As debates about the legalization of euthanasia and assisted suicide continue, it is important to have a common understanding of the history behind these developments, including recognition of the factors driving these adaptations. In this paper, we offer a comprehensive and definitive history to aid those interested in knowing the roots of these organizations and those that are still active today.

The dingo is the only placental land mammal aside from murids and bats to have made the water crossings to reach Australia prior to European arrival. It is thought that they arrived as a commensal animal with people, some time in the mid Holocene. However, the timing of their arrival is still a subject of major debate with published age estimates varying widely. This is largely because the age estimates for dingo arrival are based on archaeological deposit dates and genetic divergence estimates, rather than on the dingo bones themselves. Currently, estimates vary from between 5000–4000 years ago, for finds from archaeological contexts, and as much as 18,000 based on DNA age estimates. The timing of dingo arrival is important as post arrival they transformed Indigenous societies across mainland Australia and have been implicated in the extinction of a number of animals including the Tasmanian tiger. Here we present the results of direct dating of dingo bones from their oldest known archaeological context, Madura Cave on the Nullarbor Plain. These dates demonstrate that dingoes were in southern Australia by between 3348 and 3081 years ago. We suggest that following their introduction the dingo may have spread extremely rapidly throughout mainland Australia.

Despite a significant decrease in acute hepatitis A in the last 2 decades in Italy, outbreaks were observed occurring mostly in southern Italy. In this study, Bayesian phylogenetic analysis was used to analyze the origin of these epidemics. With this aim, 5 different data sets of hepatitis A virus sequences were built to perform genotyping by the neighbor-joining method to estimate the evolutionary rates by using a Bayesian Markov chain Monte Carlo approach and to investigate the demographic history by independent Markov chain Monte Carlo runs enforcing both a strict and relaxed clock. The estimated mean value of the evolutionary rate, representing Ia and Ib strains, was 1.21 × 10-3 and 2.0 × 10-3 substitutions/site/year, respectively. The Bayesian maximum clade credibility tree of hepatitis A virus (HAV) Ia and Ib strains showed that Italian sequences mostly formed separate clusters. The root of the time for the most recent common ancestor (tMRCA) for HAV Ia and Ib strains dated back to 1981 and to 1988, respectively, showing in both cases different epidemic entrances. Phylodynamic analysis showed that genotype Ia increased in 1997, when the Apulia epidemic started, then suffered a bottleneck, probably consequent to vaccination and to the herd immunity, followed by a new increase in virus population in the years 2013-2014 consequent to the epidemic caused by the ingestion of mixed frozen berries. A similar trend without an evident bottleneck was observed also in the case of genotype Ib. In conclusion, the Bayesian phylogenetic analysis represents a good tool to measure the effectiveness of the public health plans used for HAV control.

In this paper we extend the previous work of Witten and her team on defining a classical physics-driven model of survival in aging populations (Eakin, Bull Math Biol 56(6):1121–1141, 1994; Eakin and Witten, Mech Aging Dev 78(2):85–101, 1995; Witten and Eakin, Exp Gerontol 32(2):259–285, 1997) by revisiting the concept of a force of aging and introducing the concepts of a momentum of aging, a kinetic energy and a potential energy of an aging population. We further extend the analysis beyond the deterministic Newtonian mechanics of a macroscopic population as a whole by considering the probabilistic nature of survival of individual population cohort members, thus producing new statistical physics-based concepts of entropy and of a gerontological “temperature”. These new concepts are then illustrated with application to the classic parametric Gompertz survival model, which is a commonly used empirical descriptor for survival dynamics of mammalian species, human populations in particular. As a function of chronological age the Gompertz Model force, momentum, and power are seen to have an asymmetric unimodal peak profile, while the potential energy has a descending sigmoidal profile similar to that of the survival fraction. The “temperature” is an exponential function of age and the entropy for a future age at a current census age can be represented as a topological surface with an asymmetric unimodal hump.

Found in 1968, the archaeological site of Anzick, Montana, contains the only known Clovis burial. Here, the partial remains of a male infant, Anzick-1, were found in association with a Clovis assemblage of over 100 lithic and osseous artifacts-all red-stained with ochre. The incomplete, unstained cranium of an unassociated, geologically younger individual, Anzick-2, was also recovered. Previous chronometric work has shown an age difference between Anzick-1 and the Clovis assemblage (represented by dates from two antler rod samples). This discrepancy has led to much speculation, with some discounting Anzick-1 as Clovis. To resolve this issue, we present the results of a comprehensive radiocarbon dating program that utilized different pretreatment methods on osseous material from the site. Through this comparative approach, we obtained a robust chronometric dataset that suggests that Anzick-1 is temporally coeval with the dated antler rods. This implies that the individual is indeed temporally associated with the Clovis assemblage.

Recent celebrity deaths have been widely reported in the media and turned the public attention to the coexistence of mood, psychiatric and substance-abuse disorders. These tragic and untimely deaths motivated us to examine the scientific and clinical data, including our own work in this area. The self-medication hypothesis states that individuals with psychiatric illness tend to use heroin to alleviate their symptoms. This study examined the correlations between heroin use, mood and psychiatric disorders, and their chronology in the context of dual diagnosis.Out of 506 dual diagnosed heroin addicts, 362 patients were implicated in heroin abuse with an onset of at least one year prior to the associated mental disorder (HER-PR), and 144 patients were diagnosed of mental illness at least one year prior to the associated onset of heroin use disorder (MI-PR). The retrospective cross-sectional analysis of the two groups compared their demographic, clinical and diagnostic characteristics at univariate and multivariate levels.Dual diagnosis heroin addicts whose heroin dependences existed one year prior to their diagnoses (HER-PR) reported more frequent somatic comorbidity (p≤0.001), less major problems at work (p=0.003), more legal problems (p=0.004) and more failed treatment for their heroin dependence (p0.001) in the past. More than 2/3 reached the third stage of heroin addiction (p=0.001). Their length of dependence was longer (p=0.004). HER-PR patients were diagnosed more frequently as affected by mood disorders and less frequently as affected by psychosis (p=0.004). At the multivariate level, HER-PR patients were characterized by having reached stage 3 of heroin dependence (OR=2.45), diagnosis of mood disorder (OR=2.25), unsuccessful treatment (OR=2.07) and low education (OR=1.79).The main limitation is its retrospective nature. Nonetheless, it does shed light on what needs to be done from a clinical and public health perspective and especially prevention.The data emerging from this study, does not allow us to determine a causal relation between heroin use and mental illness onset. However, this data, even if requiring longitudinal studies, suggest that self-medication theory, in these patients, can be applied only for chronic psychoses, but should not be applied to patients with mood disorders using heroin.

Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Here we review the historical genesis of the idea and assess anthropogenic signatures in the geological record against the formal requirements for the recognition of a new epoch. The evidence suggests that of the various proposed dates two do appear to conform to the criteria to mark the beginning of the Anthropocene: 1610 and 1964. The formal establishment of an Anthropocene Epoch would mark a fundamental change in the relationship between humans and the Earth system.

This study sought to estimate 1) the prevalence of the co-occurrence of, 2) the association between, and 3) the sequence of onset of chronic pain and mental disorders in adolescents. We used weighted data (N = 6,483) from the National Comorbidity Survey Replication Adolescent Supplement (participants' age, 13–18 years). Lifetime chronic pain was assessed by adolescent self-report; lifetime DSM-IV mental disorders were assessed by the WHO Composite International Diagnostic Interview, complemented by parent report. Among the participants in the study, 1,600 of 6,476 (25.93%) had experienced any type of chronic pain and any mental disorder in their lifetime. All types of pain were related to mental disorders. The most substantial temporal associations were those with onset of mental disorders preceding onset of chronic pain, including those between affective disorders and headaches and any chronic pain; between anxiety disorders and chronic back/neck pain, headaches, and any chronic pain; between behavior disorders and headaches and any chronic pain; and between any mental disorder and chronic back/neck pain, headaches, and any chronic pain. Perspective Findings indicate that affective, anxiety, and behavior disorders are early risk factors of chronic pain, thereby highlighting the relevance of child mental disorders for pain medicine. To improve prevention and interventions for chronic pain, integrative care should be considered.

International audience; The timing and location of the emergence of our species and of associated behavioural changes are crucial for our understanding of human evolution. The earliest fossil attributed to a modern form of Homo sapiens comes from eastern Africa and is approximately 195 thousand years old, therefore the emergence of modern human biology is commonly placed at around 200 thousand years ago. The earliest Middle Stone Age assemblages come from eastern and southern Africa but date much earlier. Here we report the ages, determined by thermoluminescence dating, of fire-heated flint artefacts obtained from new excavations at the Middle Stone Age site of Jebel Irhoud, Morocco, which are directly associated with newly discovered remains of H. sapiens. A weighted average age places these Middle Stone Age artefacts and fossils at 315 ± 34 thousand years ago. Support is obtained through the recalculated uranium series with electron spin resonance date of 286 ± 32 thousand years ago for a tooth from the Irhoud 3 hominin mandible. These ages are also consistent with the faunal and microfaunal assemblages and almost double the previous age estimates for the lower part of the deposits. The north African site of Jebel Irhoud contains one of the earliest directly dated Middle Stone Age assemblages, and its associated human remains are the oldest reported for H. sapiens. The emergence of our species and of the Middle Stone Age appear to be close in time, and these data suggest a larger scale, potentially pan-African, origin for both.

Tree rings have long been used to calibrate the net primary production (NPP) time-series predicted by process-based models, based on an implicit assumption that ring-width indices (RWI) can well reflect temporal NPP change. However, this assumption has seldom been tested systematically. In this study, 36 plots were set in three forest types from four sites along a latitudinal gradient in northeast China. For each plot, we constructed chronologies and stand NPP of the past 20 years to examine: is RWI a good proxy of inter-annual variation of forest NPP for different forest types under different climate? If it is, why? Our results indicate that RWI was closely related to stand NPP in most cases, and could be used as a good proxy of NPP in temperate forests. Standard and arstan chronologies were better related to NPP series than residual chronology. Stand NPP time-series were mainly determined by large trees, and the correlation between RWI and NPP was also higher for larger trees. We suggest that large trees and dominant species of canopy layer should be sampled for chronology construction. Large trees are major contributors of forest biomass and productivity, and should have priority in forest conservation in a rapid-warming world.

Fossil evidence points to an African origin of Homo sapiens from a group called either H. heidelbergensis or H. rhodesiensis. However, the exact place and time of emergence of H. sapiens remain obscure because the fossil record is scarce and the chronological age of many key specimens remains uncertain. In particular, it is unclear whether the present day ‘modern’ morphology rapidly emerged approximately 200 thousand years ago (ka) among earlier representatives of H. sapiens1 or evolved gradually over the last 400 thousand years2. Here we report newly discovered human fossils from Jebel Irhoud, Morocco, and interpret the affinities of the hominins from this site with other archaic and recent human groups. We identified a mosaic of features including facial, mandibular and dental morphology that aligns the Jebel Irhoud material with early or recent anatomically modern humans and more primitive neurocranial and endocranial morphology. In combination with an age of 315 ± 34 thousand years (as determined by thermoluminescence dating)3, this evidence makes Jebel Irhoud the oldest and richest African Middle Stone Age hominin site that documents early stages of the H. sapiens clade in which key features of modern morphology were established. Furthermore, it shows that the evolutionary processes behind the emergence of H. sapiens involved the whole African continent.

Knowledge on the Villafranchian faunas of Greece was limited for a long time, but over the past 3 decades several new fossiliferous sites have been discovered and new material has been unearthed. The carnivores constitute a remarkable part of this material and their study has provided useful information for the taxonomy, chronology and palaeoecology. The Villafranchian carnivoran guild includes numerous taxa belonging to various families. Some of them are interesting as they are differentiated from the other Eurasian families. They cover the entire Villafranchian but the mass is known from the Middle to the Epi-Villafranchian (EVC). Despite the discontinuous data, they provide useful biochronological results. The coexistence of Pliocrocuta perrieri and Pachycrocuta brevirostris in the locality of Gerakarou 1 is strong evidence for the Middle Villafranchian (MVC)/Late Villafranchian (LVC) boundary. The composition of the Villafranchian carnivores suggests that the canids predominate, while the felids, hyenids and mustelids are well represented; the ursids are represented by a single taxon, the well-known Ursus etruscus, which seems to be common during the entire Villafranchian. The carnivoran guild structure and the multivariate analysis of the Greek Villafranchian carnivoran assemblages (MVC, LVC and EVC) in comparison with modern assembalges from open and closed environments indicate a relatively open landscape, which is in agreement with previous results for the Villafranchian of Greece. During the EVC there is a faunal renewal that is related to a more open and dry environment, like savannah bushland/grassland.

A measured magnetozone sequence defined by 24 sampling sites with normal polarity and 28 sites with reverse polarity characteristic magnetizations was established for the heretofore poorly age-constrained Los Colorados Formation and its dinosaur-bearing vertebrate fauna in the Ischigualasto-Villa Union continental rift basin of Argentina. The polarity pattern in this ∼600-m-thick red-bed section can be correlated to Chrons E7r to E15n of the Newark astrochronological polarity time scale. This represents a time interval from 227 to 213 Ma, indicating that the Los Colorados Formation is predominantly Norian in age, ending more than 11 My before the onset of the Jurassic. The magnetochronology confirms that the underlying Ischigualasto Formation and its vertebrate assemblages including some of the earliest known dinosaurs are of Carnian age. The oldest dated occurrences of vertebrate assemblages with dinosaurs in North America (Chinle Formation) are younger (Norian), and thus the rise of dinosaurs was diachronous across the Americas. Paleogeography of the Ischigualasto and Los Colorados Formations indicates prolonged residence in the austral temperate humid belt where a provincial vertebrate fauna with early dinosaurs may have incubated. Faunal dispersal across the Pangean supercontinent in the development of more cosmopolitan vertebrate assemblages later in the Norian may have been in response to reduced contrasts between climate zones and lowered barriers resulting from decreasing atmospheric pCO2 levels.

The Bose (also Baise) Basin in Guangxi, southern China is well known for the presence of Paleolithic bifacially worked implements. The Bose Basin handaxes came to the attention of the international scientific community primarily for two reasons: 1) the age at 803 ka (thousands of years), places it at the Early to Middle Pleistocene transition; and 2) the presence of bifaces tests the validity of the Movius Line and whether it was time to simply discard the model. However, questions were almost immediately raised because the age was based on the supposed association of Australasian tektites that may or may not have been redeposited, and at the time of the initial publications all of the Bose Basin handaxes were surface collected. Thus, whether the Bose bifaces can necessarily be associated with the tektites and whether the tektites themselves were redeposited are important considerations. Here, we report the findings from recent excavations from the Fengshudao site located in the Bose Basin. The primary findings are: 1) the in situ excavation of tektites, which do not appear to have been redeposited, in association with bifaces from one stratigraphic level from one site indicates that the age of these stone tools should be around 803 ka; 2) the Fengshudao hominins were utilizing locally-available quartz, quartzite, and sandstone river cobbles; and 3) in a number of aspects, the Fengshudao handaxe morphology differs from the typical western Acheulean, and are quite large and thick compared with even the bifaces from other regions of eastern Asia (e.g., Luonan Basin, China; Imjin/Hantan River Basins, Korea). Although Fengshudao may be a case of western Acheulean hominins dispersing into the Bose Basin from nearby South Asia, it is quite possible that the Fengshudao bifaces can be considered an example of convergent evolution.

Since the late 1980s, northern Iberia has yielded some of the earliest radiocarbon dated Aurignacian assemblages in Western Europe, probably produced by anatomically modern humans (AMHs). This is at odds with its location furthest from the likely eastern entry point of AMHs, and has also suggested to some that the Châtelperronian resulted from cultural transfer from AMHs to Neanderthals. However, the accuracy of the early chronology has been extensively disputed, primarily because of the poor association between the dated samples and human activity. Here, we test the chronology of three sites in northern Iberia, L'Arbreda, Labeko Koba and La Viña, by radiocarbon dating ultrafiltered collagen from anthropogenically modified bones. The published dates from Labeko Koba are shown to be significant underestimates due to the insufficient removal of young contaminants. The early (c.44 ka cal BP [thousands of calibrated years before present]) Aurignacian chronology at L'Arbreda cannot be reproduced, but the reason for this is difficult to ascertain. The existing chronology of La Viña is found to be approximately correct. Together, the evidence suggests that major changes in technocomplexes occurred contemporaneously between the Mediterranean and Atlantic regions of northern Iberia, with the Aurignacian appearing around 42 ka cal BP, a date broadly consistent with the appearance of this industry elsewhere in Western Europe This research was funded by a NERC Standard grant (NE/D014077/1) as part of the project 'Dating of the Middle-Upper Palaeolithic transition in western Europe using ultrafiltration AMS radiocarbon' for which we are extremely grateful. R. Wood was funded by a tied studentship to this grant. A. Villaluenga was funded by the Basque Government Ph.D. funding program. Roger Jacobi, British Museum, is thanked for discussions, invaluable advice in sample selection and bone identification. Javier Fortea, Universidad de Oviedo, is thanked for help in sample selection and interpretation of results from La Villa. Both sadly passed away during the course of this project Maite Izquierdo, Heritage Preservation, Basque Government, is thanked for help sampling bone from Labeko Koba. Excavation and research at l'Arbreda is funded by the Culture Ministry of Catalonia and the ministerial projects HAR2010-19120 (The Middle Palaeolithic of the L'Arbreda Cave) and HAR2010-22013 (Cultural, Paleoenvironmental and Chronological History of the Last Neanderthals and Early Modern Humans in the North of the Iberian Peninsula)

Contrebandiers Cave preserves a Late Pleistocene sequence containing Middle Stone Age (MSA) so-called Maghrebian Mousterian and Aterian occupations, spanning from ∼126 to 95 ka (thousands of years ago), followed by spatially restricted Iberomaurusian industries. Micromorphological analyses, complemented by instrumental mineralogical identification and fabric orientation, allowed for the reconstruction of the main site formation processes at the site. Initial deposition is characterized by local reworking of marine shelly sands dating to Marine Isotopic Stage 5e (MIS5e). The subsequent stratification reveals sedimentary dynamics predominantly associated with gravity-driven inputs and contributions from weathering of the encasing bedrock, at the same time that anthropogenic sediments were being accumulated. The allochthonous components reflect soil degradation and vegetation changes around the cave during the last interglacial. Human occupations seems to be somewhat ephemeral in nature, with some stratigraphic units apparently lacking archaeological components, while in others the human-associated deposits (e.g., burned bones, charcoal, and ashes) can be substantial. Ephemeral breaks in sedimentation and/or erosion followed by stabilization are mainly discernible microscopically by the presence of phosphatic-rich laminae interpreted as short-lived surfaces, peaks of increased humidity and colonization by plants. More substantial erosion affects the uppermost Aterian layers, presumably due to localized reconfigurations of the cave's roof. The subsequent Iberomaurusian deposits are not in their primary position and are associated with well-sorted silts of aeolian origin. While the effects of chemical diagenesis are limited throughout the whole stratigraphic sequence, physical bioturbation (e.g., by wasps, rodents, and earthworms) is more pervasive and leads to localized movement of the original sedimentary particles.

The article presents a discussion of the mathematics behind improbable occurrences and situations, adapted from the book "The Improbability Principle: Why Coincidences, Miracles, and Rare Events Happen Every Day" by David J. Hand.

In 1986-1987, three human remains were unearthed from macro-unit II of San Bernardino Cave (Berici Hills, Veneto, Italy), a deposit containing a late Mousterian lithic assemblage. The human remains (a distal phalanx, a lower right third molar and a lower right second deciduous incisor) do not show diagnostic morphological features that could be used to determine whether they were from Homo neanderthalensis or Homo sapiens. Despite being of small size, and thus more similar to recent H. sapiens, the specimens were attributed to Neandertals, primarily because they were found in Mousterian layers. We carried out a taxonomic reassessment of the lower right third molar (LRM3; San Bernardino 4) using digital morphometric analysis of the root, ancient DNA analysis, carbon and nitrogen isotope analyses, and direct accelerator mass spectrometry (AMS) radiocarbon dating of dentine collagen. Mitochondria] DNA analysis and root morphology show that the molar belongs to a modern human and not to a Neandertal. Carbon 14 (C-14) dating of the molar attributes it to the end of the Middle Ages (1420 -1480 cal AD, 2 sigma). Carbon and nitrogen isotope analyses suggest that the individual in question had a diet similar to that of Medieval Italians. These results show that the molar, as well as the other two human remains, belong to recent H. sapiens and were introduced in the Mousterian levels post-depositionally. (C) 2013 Elsevier Ltd. All rights reserved.

The discovery and first dates of the paintings in Grotte Chauvet provoked a new debate on the origin and characteristics of the first figurative Palaeolithic art. Since then, other art ensembles in France and Italy (Aldène, Fumane, Arcy-sur-Cure and Castanet) have enlarged our knowledge of graphic activity in the early Upper Palaeolithic. This paper presents a chronological assessment of the Palaeolithic parietal ensemble in Altxerri B (northern Spain). When the study began in 2011, one of our main objectives was to determine the age of this pictorial phase in the cave. Archaeological, geological and stylistic evidence, together with radiometric dates, suggest an Aurignacian chronology for this art. The ensemble in Altxerri B can therefore be added to the small but growing number of sites dated in this period, corroborating the hypothesis of more complex and varied figurative art than had been supposed in the early Upper Palaeolithic.

Date syrup as a nutritional additive and safe alternative to added sugar is one of the best choices for milk flavoring. In this study, a flavored milk beverage was formulated using date syrup for flavoring the product and gum tragacanth to obtain an acceptable mouth feel. Steady shear and dynamic oscillatory rheological properties of the samples contained 3 concentrations (0, 0.1, 0.2, and 0.3%, wt/wt) of 2 types of gum tragacanth (Astragalus gossypinus and Astragalus rahensis) which at 3°C, were studied. Particle size distribution and colorimetric assays were determined by laser diffractometry and using reflection spectrometer, respectively. Sensory analysis was performed with 25 semitrained panelists, using a 5-point hedonic scale. The results showed that viscoelastic properties, flow behavior parameters, particle size, and color parameters (L*, a*, and b*, where L* represents lightness, a* represents the redness/greenness quality of the color, and b* represents the yellowness and blueness quality of the colors) were significantly affected by the concentration of the gum tragacanth and the severity of this effect was influenced by the type of gum. The use of appropriate type and concentration of gum tragacanth in date milk formulation can improve the texture and mouth feel by affecting on particle size and the flow behavior of this product.

Most researchers believe that anatomically modern humans (AMH) first appeared in Africa 160-190 ka ago, and would not have reached eastern Asia until ∼50 ka ago. However, the credibility of these scenarios might have been compromised by a largely inaccurate and compressed chronological framework previously established for hominin fossils found in China. Recently there has been a growing body of evidence indicating the possible presence of AMH in eastern Asia ca. 100 ka ago or even earlier. Here we report high-precision mass spectrometric U-series dating of intercalated flowstone samples from Huanglong Cave, a recently discovered Late Pleistocene hominin site in northern Hubei Province, central China. Systematic excavations there have led to the in situ discovery of seven hominin teeth and dozens of stone and bone artifacts. The U-series dates on localized thin flowstone formations bracket the hominin specimens between 81 and 101 ka, currently the most narrow time span for all AMH beyond 45 ka in China, if the assignment of the hominin teeth to modern Homo sapiens holds. Alternatively this study provides further evidence for the early presence of an AMH morphology in China, through either independent evolution of local archaic populations or their assimilation with incoming AMH. Along with recent dating results for hominin samples from Homo erectus to AMH, a new extended and continuous timeline for Chinese hominin fossils is taking shape, which warrants a reconstruction of human evolution, especially the origins of modern humans in eastern Asia.

The Acheulean to Middle Palaeolithic transition is one of the most important technological changes that occurs over the course of human evolution. Here we examine stone artefact assemblages from Patpara and two other excavated sites in the Middle Son Valley, India, which show a mosaic of attributes associated with Acheulean and Middle Palaeolithic industries. The bifaces from these sites are very refined and generally small, but also highly variable in size. A strong relationship between flake scar density and biface size indicates extensive differential resharpening. There are relatively low proportions of bifaces at these sites, with more emphasis on small flake tools struck from recurrent Levallois cores. The eventual demise of large bifaces may be attributed to the curation of small prepared cores from which sharper, or more task-specific flakes were struck. Levallois technology appears to have arisen out of adapting aspects of handaxe knapping, including shaping of surfaces, the utilization of two inter-dependent surfaces, and the striking of invasive thinning flakes. The generativity, hierarchical organization of action, and recursion evident in recurrent Levallois technology may be attributed to improvements in working memory.

Impact Dating The large mass extinction of terrestrial and marine life—most notably, non-avian dinosaurs—occurred around 66 million years ago, at the boundary between the Cretaceous and Paleogene periods. But attributing the cause to a large asteroid impact depends on precisely dating material from the impact with indicators of ecological stress and environmental change in the rock record. Renne et al. (p. 684 ; see the Perspective by Pälike ) acquired high-precision radiometric dates of stratigraphic layers surrounding the boundary, demonstrating that the impact occurred within 33,000 years of the mass extinction. The data also constrain the length of time in which the atmospheric carbon cycle was severely disrupted to less than 5000 years. Because the climate in the late Cretaceous was becoming unstable, the large-impact event appears to have triggered a state-shift in an already stressed global ecosystem.

Graphical displays of investigations are increasingly used in clinical care. Summaries of medical records for research or clinical review purposes can generate unmanageably large amounts of data, which may be helpfully summarised and displayed using timelines. During a prospective study of cancer care in primary care, care timelines were generated in Microsoft Visio, using data collected retrospectively from general practice records. Data from primary and secondary care consultations were included. Thirteen timelines were created, which proved valuable in summarising and analysing the data concerning the cases studied. Timelines provide a clear, concise way of displaying large amounts of diverse data, although some selectivity is required to facilitate interpretation. Generation of timelines in the software was time consuming: if they could be automatically generated within clinical IT systems, they would enable clinicians to generate useful summaries of care of complex cases, facilitating care reviews.

Central Asia has delivered significant paleoanthropological discoveries in the past few years. New genetic data indicate that at least two archaic human species met and interbred with anatomically modern humans as they arrived into northern Central Asia. However, data are limited: known archaeological sites with lithic assemblages generally lack human fossils, and consequently identifying the archaeological signatures of different human groups, and the timing of their occupation, remains elusive. Reliable chronologic data from sites in the region, crucial to our understanding of the timing and duration of interactions between different human species, are rare. Here we present chronologies for two open air Middle to Upper Palaeolithic (UP) sequences from the Tien Shan piedmont in southeast Kazakhstan, Maibulak and Valikhanova, which bridge southern and northern Central Asia. The chronologies, based on both quartz optically stimulated luminescence (OSL) and polymineral post-infrared infrared luminescence (pIR-IRSL) protocols, demonstrate that technological developments at the two sites differ substantially over the ∼47–19 ka time span. Some of the innovations typically associated with the earliest UP in the Altai or other parts of northeast Asia are also present in the Tien Shan piedmont. We caution against making assumptions about the directionality of spread of these technologies until a larger, better defined database of transitional sites in the region is available. Connections between the timing of occupation of regions, living area setting and paleoenvironmental conditions, while providing hypotheses worth exploring, remain inconclusive. We cautiously suggest a trend towards increasing occupation of open air sites across the Central Asian piedmont after ∼40 ka, corresponding to more humid climatic conditions which nevertheless included pulses of dust deposition. Human occupation persisted into the Last Glacial Maximum, despite cooler, and possibly drier, conditions. Our results thus provide additional data to substantiate arguments for occupation of Central Asia.

Sentence-initial temporal clauses headed by before, as in "Before the scientist submitted the paper, the journal changed its policy", have been shown to elicit sustained negative-going brain potentials compared to maximally similar clauses headed by after, as in "After the scientist submitted the paper, the journal changed its policy". Such effects may be due to either one of two potential causes: before clauses may be more difficult than after clauses because they cause the two events in the sentence to be mentioned in an order opposite the order in which they actually occurred, or they may be more difficult because they are ambiguous with regard to whether the event described in the clause actually happened. The present study examined the effect of before and after clauses on sentence processing in both sentence-initial contexts, like those above, and in sentence-final contexts ("The journal changed its policy before/after the scientist submitted the paper"), where an order-of-mention account of the sustained negativity predicts a negativity for after relative to before. There was indeed such a reversal, with before eliciting more negative brain potentials than after in sentence-initial clauses but more positive in sentence-final clauses. The results suggest that the sustained negativity indexes processing costs related to comprehending events that were mentioned out of order.

Researchers must consider human impacts on entire Earth systems and not get trapped in discipline-specific definitions, says Clive Hamilton.