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High levels of free D-aspartate (D-Asp) are present in vertebrate testis during post-natal development, coinciding with the onset of testosterone production, which suggests that this atypical amino acid might participate in the regulation of hormone biosynthesis. To elucidate the unknown role of D-Asp on testicular function, we investigated steroidogenesis and spermatogenesis in a one-month-old knockin mouse model with the constitutive depletion of D-Asp levels due to the targeted overexpression of D-aspartate oxidase (DDO), which catalyzes the deaminative oxidation of D-Asp to generate the corresponding α-keto acid, oxaloacetate, hydrogen peroxide, and ammonium ions. In the Ddo knockin mice, we found a dramatic reduction in testicular D-Asp levels, accompanied by a significant decrease in the serum testosterone levels and testicular 17β-HSD, the enzyme involved in testosterone biosynthesis. Additionally, in the testes of these Ddo knockin mice, the expression of PCNA and SYCP3 proteins decreased, suggesting alterations in spermatogenesis-related processes, as well as an increase in the cytosolic cytochrome c protein levels and TUNEL-positive cell number, which indicate an increase in apoptosis. To further investigate the histological and morphometric testicular alterations in Ddo knockin mice, we analyzed the expression and localization of prolyl endopeptidase (PREP) and disheveled-associated activator of morphogenesis 1 (DAAM1), two proteins involved in cytoskeletal organization. Our results showed that the testicular levels of DAAM1 and PREP in Ddo knockin mice were different from those in wild-type animals, suggesting that the deficiency of D-Asp is associated with overall cytoskeletal disorganization. Our findings confirmed that physiological D-Asp influences testosterone biosynthesis and plays a crucial role in germ cell proliferation and differentiation, which are required for successful reproduction.

PURPOSE Automatizing the scoring of the cytokinesis-blocked micronucleus assay spares a lot of valuable time. The dose-effect relationship can be applied reliably for dose estimation if the quality of the slides is the same from the perspective of the used image processing algorithm. This aspect brings in additional requirements against the quality of the slides compared to the conventional visual scoring. MATERIALS AND METHODS An add-in software was created to the non-fluorescent RS-MN automatic MN scoring system which is capable of measuring quantitatively the degree of typical anomalies. The image processing is less reliable when the presence of these anomalies is more frequent. The behavior of the designed sample quality parameters (SQPs) was tested on in vitro irradiated peripheral blood samples (0, 1, and 2 Gy) obtained from a healthy donor and also on samples from patients undergoing low dose-rate brachytherapy. RESULTS We examined 20 different SQPs and identified two that are independent and correlate significantly with the error of the fully automatic MN frequency. One is related to the size of the cells and the other reflects the homogeneity of the environment. An equation was established which presents a connection between the error of the auto MN frequency and the SQPs. By adding a fourth cleaning step to the conventional sample preparation and changing the pre-dripping temperature of the slide, the SQP can be modified, and consequently, the sample quality can be improved. The gain in accuracy is 54 ± 10 MN per 1000 binucleated cells, which corresponds to the effects of 0.5 Gy. Around the lowest limit of detection (

Fully shaped, morphologically standardized bone tools are generally considered reliable indicators of the emergence of modern behavior. We report the discovery of 23 double-beveled bone tools from ~ 80,000–60,000-year-old archaeological layers at Sibudu Cave in KwaZulu-Natal, South Africa. We analyzed the texture of use-wear on the archaeological bone tools, and on bone tool replicas experimentally used in debarking trees, processing rabbit pelts with and without an ochre compound, digging in sediment in and outside a cave, and on ethnographic artefacts. Debarking trees and digging in humus-rich soil produce use-wear patterns closely matching those observed on most Sibudu tools. This tool type is associated with three different Middle Stone Age cultural traditions at Sibudu that span 20,000 years, yet they are absent at contemporaneous sites. Our results support a scenario in which some southern African early modern human groups developed and locally maintained specific, highly standardized cultural traits while sharing others at a sub-continental scale. We demonstrate that technological and texture analyses are effective means by which to infer past behaviors and assess the significance of prehistoric cultural innovations.

This chapter highlights methodological challenges for an understanding of acculturation and creolization in early prehistory. The authors note that this is especially evident in situations such as the Châtelperronian where there is little chronological definition. In reference to the Châtelperronian, it is recognized as remarkable how such a restricted spectrum of evidence proves to be so incredibly agile, producing such outwardly conflicting and occasionally paradoxical models. It is also noted that concepts such as acculturation and creolization flounder when confronted with the period’s temporal resolution and lack of direct evidence for individual and group-level interactions. The authors recognize that the satisfactory furtherance of this research depends upon a thorough archaeological and taphonomic analysis of key sites.

The detailed dose analysis at the extremities remains a challenge, without affecting operators’ mobility and their tactile sense. Using films loaded with optically stimulated luminescence (OSL) crystals have been studied in order to overcome some of these challenges in 2D dosimetry. In this work, we investigated flexible polymeric films loaded with MgB4O7:Ce,Li to acquire a better understanding of the dependence of the dosimetric signal characteristics on the production process and the influence of using different powder grain sizes. In film production, five different solvents were used: acetone–benzene, dichloromethane, chloroform, tetrahydrofuran and formic acid. Our results indicate that acetone–benzene is the solvent mixture that less influences the signal emitted by treated crystals, in comparison with the signal emitted by the pristine crystal powder. Conversely, by using formic acid, the crystalline structure of the sample was most severely modified, leading to a drastic reduction of the emitted OSL signal. We found that the extent of the grain surface in contact with the solvent in the process is important and should be taken into consideration when choosing the proper grain size to be used. Highlights Polymeric films loaded with MgB4O7:Ce,Li crystals were produced using different solvents.Different effect on the OSL signal was found depending on the used solvent.Among the evaluated solvents, acetone–benzene was the one that less affected the OSL signal.

The formation of the coastal plain of the Brazilian sea is mainly due to the fluctuation of relative sea level in the past. Armacao dos Buzios or simply Buzios is a municipality in the microregion of lakes, in the state of Rio de Janeiro. In this region there is a lowland area about two meters above current sea level. This lowland area is also known as coastal plain of Una River. It is expected that during the Holocene period the sea level reached a maximum about 2.5 meters above the current level. During that time billions of mollusks lived and proliferated in the shallow waters around the coastal plain of the Una River. As they died their shells formed a layer in the soil including Malhada Marsh that belongs to the Una River plain. In this study, shells were collected from this region and dated using the techniques of Electronic Paramagnetic Resonance (EPR). Ages from 2480±130 to 4490±270 years were obtained. Radiocarbon dating were performed at the Beta Analytic Lab, USA for comparison with the EPR results. Shells ages obtained are compatible with geological data from the Holocene period relative to past sea level fluctuations.

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene.

Schizophrenia is a disorder of synaptic plasticity and aberrant connectivity in which a major dysfunction in glutamate synapse has been suggested. However, a multi-level approach tackling diverse clusters of interacting molecules of the glutamate signaling in schizophrenia is still lacking. We investigated in the post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus of schizophrenia patients and non-psychiatric controls, the levels of neuroactive d- and l-amino acids (l-glutamate, d-serine, glycine, l-aspartate, d-aspartate) by HPLC. Moreover, by quantitative RT-PCR and western blotting we analyzed, respectively, the mRNA and protein levels of pre- and post-synaptic key molecules involved in the glutamatergic synapse functioning, including glutamate receptors (NMDA, AMPA, metabotropic), their interacting scaffolding proteins (PSD-95, Homer1b/c), plasma membrane and vesicular glutamate transporters (EAAT1, EAAT2, VGluT1, VGluT2), enzymes involved either in glutamate-dependent GABA neurotransmitter synthesis (GAD65 and 67), or in post-synaptic NMDA receptor-mediated signaling (CAMKIIα) and the pre-synaptic marker Synapsin-1. Univariable analyses revealed that none of the investigated molecules was differently represented in the post-mortem DLPFC and hippocampus of schizophrenia patients, compared with controls. Nonetheless, multivariable hypothesis-driven analyses revealed that the presence of schizophrenia was significantly affected by variations in neuroactive amino acid levels and glutamate-related synaptic elements. Furthermore, a Machine Learning hypothesis-free unveiled other discriminative clusters of molecules, one in the DLPFC and another in the hippocampus. Overall, while confirming a key role of glutamatergic synapse in the molecular pathophysiology of schizophrenia, we reported molecular signatures encompassing elements of the glutamate synapse able to discriminate patients with schizophrenia and normal individuals.

The PVA-GTA Fricke Gel is a three-dimensional tissue-equivalent dosimeter that can be analyzed with optical imaging techniques. In this work we demonstrate that the addition of silver nanoparticles to the gel reduces the diffusion effect.

This contribution focuses on the recently excavated lithic assemblage from Border Cave Members 1 RGBS, 3 BS, 2 WA and 2 BS. These members were attributed by Beaumont to the Howiesons Poort and post-Howiesons Poort Industries of the southern African Middle Stone Age. Here we consider lithics as indicators of cultural behaviour, site formation processes, and occupation intensity. As such, the assemblage is explored in depth through lithic technology attribute analysis, particle size distribution, and spatial analysis. These lines of inquiry follow the new allostratigraphic divisions proposed for the deposits by Stratford and colleagues. Results show that the lower members share a degree of similarity in terms of flaking strategies and raw material selection, whereas the upper members record a dissimilar set of features, with differentiation between them. The technological and spatial analyses suggest the sporadic presence of different groups at the site, each characterized by distinct sets of knapping techniques and methods but employing related knapping strategies and using similar raw materials. The interpretation of these members as a palimpsest of sporadic occupation is supported by the low number of archaeological finds by sediment volume. The evidence at hand does not support a Howiesons Poort attribution for the lowest members. The data show that lithics from part of Member 2 WA and 2 BS are in accordance with those of the recently defined Sibudan technocomplex.

Upper Palaeolithic sites in southwestern France attributed to the Upper Gravettian and the Solutrean yielded sub spherical gravels with a highly shiny appearance that have intrigued researchers since the 1930s. In this work, we analyze specimens from five sites, including the recently excavated Solutrean site of Landry, to establish whether their presence in archaeological layers and peculiar aspect are due to natural processes or human agency. We study the spatial distribution of gravels at Landry and submit archaeological gravels from the five sites, natural formations, Landry sediment sieving, and polishing experiments with a rotary tumbling machine to morphometric, colorimetric and textural analyses. Our results suggest that the lustrous gravels found at the five sites result from deliberate selection and their shiny appearance is the probable consequence of prolonged contact with a soft material such as animal skin. Ethnographic accounts indicate that these gravels may have been used for magico-religious ritual purposes (charms, sorcery, divination etc.), in games, as elements of musical instruments, and as items serving other social and personal purposes. We argue that these objects reflect a cultural innovation emerged during the Gravettian and continued into the Solutrean.

It has been suggested that engraved abstract patterns dating from the Middle and Lower Palaeolithic served as means of representation and communication. Identifying the brain regions involved in visual processing of these engravings can provide insights into their function. In this study, brain activity was measured during perception of the earliest known Palaeolithic engraved patterns and compared to natural patterns mimicking human-made engravings. Participants were asked to categorise marks as being intentionally made by humans or due to natural processes (e.g. erosion, root etching). To simulate the putative familiarity of our ancestors with the marks, the responses of expert archaeologists and control participants were compared, allowing characterisation of the effect of previous knowledge on both behaviour and brain activity in perception of the marks. Besides a set of regions common to both groups and involved in visual analysis and decision-making, the experts exhibited greater activity in the inferior part of the lateral occipital cortex, ventral occipitotemporal cortex, and medial thalamic regions. These results are consistent with those reported in visual expertise studies, and confirm the importance of the integrative visual areas in the perception of the earliest abstract engravings. The attribution of a natural rather than human origin to the marks elicited greater activity in the salience network in both groups, reflecting the uncertainty and ambiguity in the perception of, and decision-making for, natural patterns. The activation of the salience network might also be related to the process at work in the attribution of an intention to the marks. The primary visual area was not specifically involved in the visual processing of engravings, which argued against its central role in the emergence of engraving production.

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin-binding protein cyclase-associated protein 2 (

Lithic assemblages immediately following the Howiesons Poort, often loosely referred to as the ‘post- Howiesons Poort’ or MSA III, have attracted relatively little attention when compared to other wellknown phases of the South African Middle Stone Age (MSA) sequence. Current evidence from sites occurring in widely-differing environments suggests that these assemblages are marked by temporal and technological variability, with few features in common other than the presence of unifacial points. Here we present a technological and geometric morphometric analysis of ‘points’ from the new excavations of Members 2 BS, 2WA and the top of 3 BS members at Border Cave, KwaZulu-Natal, one of the key sites for studying modern human cultural evolution. Our complementary methodologies demonstrate that, at this site, hominins adopted a knapping strategy that primarily produced non-standardised unretouched points. Triangular morphologies were manufactured using a variety of reduction strategies, of which the discoidal and Levallois recurrent centripetal methods produced distinctive morphologies. We find technological and morphological variability increases throughout the post-Howiesons Poort sequence, with clear differences between and within chrono-stratigraphic groups. Finally, we assess the suitability of the ‘Sibudan’ cultural-technological typology proposed for post-Howiesons Poort assemblages at Sibhudu, another KwaZulu-Natal site, and find similarities in the morphological axes characterising the samples, despite differences in the shaping strategies adopted. Overall, our work contributes to the growing body of research that is helping to address historical research biases that have slanted our understanding of cultural evolution during the MSA of southern Africa towards the Still Bay and Howiesons Poort technocomplexes., UK Research & Innovation (UKRI), Arts & Humanities Research Council (AHRC) NGS-54810R-19, Wenner Gren Foundation CEOOP2020-1, Poroulis grant through Cambridge University, Spanish FEDER/Ministry of Science and Innovation 262618, National Geographic Explorer grant ANR-10-LABX-52, DSI- NRF Centre of Excellence in Palaeosciences grant 191022_001, Research Council of Norway through its Centres of Excellence funding scheme, LaScArBx research programme, Grand Programme de Recherche 'Human Past' of the Initiative d'Excellence (IdEx) of the Bordeaux University, Leakey Foundation (Movement, interaction, and structure: modelling population networks and cultural diversity in the African Middle Stone Age), Lithic Studies Society (Jacobi Bursary Awardee, 2020), SFF Centre for Early Sapiens Behaviour (SapienCE), Talents Programme AH/R012792/1 Gr. 10157 PID2019-1049449 GB-I00

Cueva de Ardales in Málaga, Spain, is one of the richest and best-preserved Paleolithic painted caves of southwestern Europe, containing over a thousand graphic representations. Here, we study the red pigment in panel II.A.3 of “Sala de las Estrellas,” dated by U-Th to the Middle Paleolithic, to determine its composition, verify its anthropogenic nature, infer the associated behaviors, and discuss their implications. Using optical microscopy, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, and X-ray diffraction, we analyzed a set of samples from the panel and compared them to natural coloring materials collected from the floor and walls of the cave. The conspicuously different texture and composition of the geological samples indicates that the pigments used in the paintings do not come from the outcrops of colorant material known in the cave. We confirm that the paintings are not the result of natural processes and show that the composition of the paint is consistent with the artistic activity being recurrent. Our results strengthen the hypothesis that Neanderthals symbolically used these paintings and the large stalagmitic dome harboring them over an extended time span.

L- α -alanine has aroused considerable interest for use in radiation EPR dosimetry and has been formally accepted as a secondary standard for high-dose (kGy) and transfer dosimetry of high-energy photons and electrons. In this work, we extended the investigation of the energy response of alanine EPR films in the low energy range for X-photons (1–30 keV). Electron Paramagnetic Resonance (EPR) measurements were performed on Kodak BioMax alanine films exposed to low-energy X-rays from a Cu-, W- and Mo-targets tube operating at voltages up to 30 kV. Films were chosen because of the low penetration of the soft X-rays used. The response of alanine to low-energy X-rays was characterized experimentally and the relative response (with respect to high energy photons) was found to be between 0.8 and 0.9 for Cu- and W-tube X-rays, and 1.0 for Mo-tube X-rays. The attenuation profiles were investigated and it was found that 1 mm of film material reduces the intensity of the X-ray-beam by about 70%, 50% and 40% for Cu-, W- and Mo-tube X-rays, respectively. Monte Carlo simulations were performed to model the energy release as well as the depth dose profiles for the various radiation beams used. These data are considered relevant for dosimetric applications in low energy beams such the high-gradient treatment fields used in monoenergetic microbeam radiation therapy (MRT) with synchrotron radiation as well as in brachytherapy with low energy sources, for instance 169Yb.

In 2015, which marked 35 years since Beaumont had worked at the site, we renewed excavations at Border Cave. Our primary aims were to reassess the stratigraphic context of the sedimentary and cultural sequence, gain insight into site formation processes, make a detailed study of organic remains, identify long term cultural trends, and characterize expressions of complex behaviour and innovation. This contribution serves as an update on activities conducted in 2018 and 2019 and provides an overview of our research findings to date, placing them in the broader context of the Middle Stone Age in southern Africa. New luminescence ages based on feldspar grains in the sedimentary sequence are in broad agreement with the previous chronology established for the site. Geoarchaeology and faunal taphonomy have started to elucidate site formation processes, showing that the members should not be considered as homogeneous units, and that associated formation interpretations established by Beaumont are simplifications that are not representative of the diverse site formation processes active in the shelter. This finding is supported by lithic analysis of the Member 2 WA assemblage that shows differences in technology between artefacts from the top, middle, and lower part of the same member. In addition, the lithic artefacts from the middle and lower part of Member 2 WA show continuities with the lithics from the underlying Members 3 BS and 1 RGBS, which were attributed by Beaumont to a different industry. Grass mats/bedding layers are preserved throughout the sequence, the oldest of which dates to ∼200 ka. The use of ash and leaves with insecticidal properties in the bedding construction reflects complex cognition, as does the cooking of starchy rhizomes that come from layers dated to 170 ka. In addition to a rich mammal fauna found in all of the deposits, the remains of a new individual, a 3–4-year-old child, were recovered from Member 1 BS.LR C that has an ESR date of 42.6 ka.

Effective provisions of preparedness and response are necessary to protect human life, health, property, and the environment in any nuclear and radiological emergency. Recently, the International Commission on Radiological Protection recognized the need to provide more quantitative guidance on environmental radiation protection to integrate these analyses. A required assessment is a correlation between dose and its effects in non-human biota. Plants are highly sensitive environmental monitors for the assessment of potentially genotoxic agents and avoid the controversial use of animal models. The Allium test is commonly used to assess genotoxicity for a wide variety of chemical and physical factors, as it allows for estimates of possible DNA damage in eukaryotes in general, including humans. In this work, onion (Allium cepa) seedlings were exposed to 20–200 mGy of $$\alpha$$ -radiation. We studied the possibility of using cytogenetic analyses of irradiated onion cells to determine the biological dose. It was observed that the increase in the frequencies of chromosomal aberrations, mitotic abnormalities, and micronuclei occurred proportional to the radiation dose, but a reduction in cytological damage was observed from 100 mGy, suggesting the onset of cytotoxic activity. Our research shows the potential of Allium cepa as a sensitive support system for dosimetry, detection, and screening of cellular effects produced by low doses of environmental radiation.

d-Amino acids were believed to occur only in bacteria and invertebrates. Today, it is well known that d-amino acids are also present in mammalian tissues in a considerable amount. In particular, high levels of free d-serine (d-Ser) and d-aspartate (d-Asp) are found in the brain. While the functions of d-Ser are well known, many questions remain unanswered regarding the role of d-Asp in the central nervous system. d-Asp is very abundant at the embryonic stage, while it strongly decreases after birth because of the expression of d-aspartate oxidase (Ddo) enzyme, which catalyzes the oxidation of this d-amino acid into oxaloacetate, ammonium, and hydrogen peroxide. Pharmacologically, d-Asp acts as an endogenous agonist of N-methyl d-aspartate and mGlu5 receptors, which are known to control fundamental brain processes, including brain development, synaptic plasticity, and cognition. In this work, we studied a recently generated knockin mouse model (R26ddo/ddo), which was designed to express DDO beginning at the zygotic stage. This strategy enables d-Asp to be almost eliminated in both prenatal and postnatal lives. To understand which biochemical pathways are affected by depletion of d-Asp, in this study, we carried out a metabolomic and lipidomic study of ddo knockin brains at different stages of embryonic and postnatal development, combining nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) techniques. Our study shows that d-Asp deficiency in the brain influences amino acid pathways such as threonine, glycine, alanine, valine, and glutamate. Interestingly, d-Asp is also correlated with metabolites involved in brain development and functions such as choline, creatine, phosphocholine (PCho), glycerophosphocholine (GPCho), sphingolipids, and glycerophospholipids, as well as metabolites involved in brain energy metabolism, such as GPCho, glucose, and lactate.

Classical sensor security relies on cryptographic algorithms executed on trusted hardware. This approach has significant shortcomings, however. Hardware can be manipulated, including below transistor level, and cryptographic keys are at risk of extraction attacks. A further weakness is that sensor media themselves are assumed to be trusted, and any authentication and encryption is done ex situ and a posteriori. Here we propose and demonstrate a different approach to sensor security that does not rely on classical cryptography and trusted electronics. We designed passive sensor media that inherently produce secure and trustworthy data, and whose honest and non-malicious nature can be easily established. As a proof-of-concept, we manufactured and characterized the properties of non-electronic, physical unclonable, optically complex media sensitive to neutrons for use in a high-security scenario: the inspection of a military facility to confirm the absence or presence of nuclear weapons and fissile materials.

The irradiation facility of the University of Pisa (UNIPI) is a neutron and gamma irradiation facility of the University of Pisa used for calibration purposes and to evaluate detectors and dosemeters for mixed neutron and gamma fields. The facility consists of a fairly large room (5.0 × 7.8 × 2.5 m3) with concrete walls and roof designed to minimise radiation scattering. Sealed neutron and gamma radionuclide sources are stored in the facility for calibration and test purposes. In order to perform accurate response measurements, this study applied a methodology of general validity to assess the neutron and gamma room scatter contributions (albedo) to the fluence and to the ambient dose equivalent rates. The assessment was done for the standard irradiation points of the facility, using detailed Monte Carlo simulations and considering several source-to-wall and source-to-detector distances.

The advent of bone technology in Africa is often associated with behavioral modernity that began sometime in the Middle Stone Age. Yet, small numbers of bone tools are known from Early Pleistocene sites in East and South Africa, complicating our understanding of the evolutionary significance of osseous technologies. These early bone tools vary geographically, with those in South Africa indicating use in foraging activities such as termite extraction and those in East Africa intentionally shaped in a manner similar to lithic tool manufacture, leading some to infer multiple hominin species were responsible for bone technology in these regions, with Paranthropus robustus assumed to be the maker of South African bone tools and Homo erectus responsible for those in East Africa. Here we present on a largely unknown assemblage of 52 supposed bone tools primarily from Beds III and IV, Olduvai Gorge, Tanzania, that was excavated by Mary Leakey in the late 1960s and early 1970s. The majority of the sites from which the tools were recovered were deposited when only Homo erectus is known to have existed in the region, potentially allowing a direct link between this fossil hominin and bone technology. Our analysis confirms at least six bone tools in the assemblage, the majority of which are intentionally flaked large mammal bones and one of which is a preform of the oldest barbed bone point known to exist anywhere in the world pushing back the origins for this technology by 700 kyr., This research was funded by Wenner-Gren Foundation for Anthropological Research (grant numbers 7640 and 9245); the European Research Council (European Union's Seventh Framework Programme [FP7/2007-2013]/ERC grant agreement no 283366 [ORACEAF]), and the Rutgers University Center for Human Evolutionary Studies. I.d.l.T. is currently funded by a European Research Council-Advanced Grant (BICAEHFID; grant agreement no. 832980). F.d'E.'s work was partially funded by the Research Council of Norway through its Centre of Excellence funding scheme (SFF Centre for Early Sapiens Behaviour – SapienCE – project number 262618), and the Talents program of the University of Bordeaux ‘Initiative d’Excellence.’

Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication.

Radiophotoluminescence (RPL) properties of Sm-doped CaSO4 for radiation dosimetry applications are reported. The samples with varying Sm concentrations are prepared via the solid-state reaction process. The as-prepared samples show photoluminescence due to typical 4f–f transitions of Sm3+ whereas, after X-ray irradiation, additional emission features appear with a broad band peaking at 630 nm as well as a set of multiple sharp lines across 680–820 nm, which are attributed to the 5d–4f and 4f–4f transitions of Sm2+, respectively. Therefore, the RPL in the present material system relies on the generation of Sm2+ centers. The sensitivity is about 3 times lower than that of Ag-doped phosphate glass, but no fading and build-up of signal are evident even immediately after the irradiation. The signal is reversible by heat-treatment at 500 °C, and is reproducible even after the thermal erasure, especially when the differential signal between pre- and post-irradiation is taken into account.

The chelator eriochrome cyanine R (ECR) in aqueous solutions forms metal complexes with Fe(III) ions with 1:1 (metal:ligand) stoichiometry. Because ECR absorbs light in the visible spectrum at different wavelengths for its free and complexed forms, this ligand may behave as a dose marker in a Fricke gel (FG) dosimeter. This is the first investigation of the influence of the organic ligand ECR in Fricke gels produced with a polyvinyl alcohol matrix cross-linked with glutaraldehyde (FGECR). The concentrations of sulfuric acid, ECR, and Fe(II) ions were varied in the FG synthesis in order to optimize the detector sensitivity to ionizing radiation. For comparison sake, FG synthesized with xylenol orange (FGXO) was also produced. The formation of the Fe(III)-ECR complex after irradiation has two absorption bands in the visible region. The absorbance intensities vary linearly with the absorbed dose in the range of 0.0–40.0 Gy. The FGECR and FGXO showed similar properties: sensitivity of (0.072 ± 0.001) Gy-1 and (0.079 ± 0.001) Gy-1; and diffusion of (0.192 ± 0.006) mm2 h-1 and (0.184 ± 0.022) mm2 h-1, respectively. FGECR has some advantages for application in radiotherapy, as it presented sensitivity for low doses, whose minimum detectable dose was 0.67 Gy, with maximum optical absorption at low energy wavelengths, ideal for measuring radiation dose by optical tomography, and it has a high saturation dose. Therefore, FGECR has the potential for dosimetric studies in radiotherapy, including flash radiotherapy, which deposits high doses in extremely short times.

Extraordinary preservation of plant remains provides an insight into the construction and materials of bedding at Border Cave, South Africa. Towards the back of the cave there are particularly thick layers of desiccated and charred grass and our botanical study is from bulk samples of these approximately 60,000 to 40,000 year-old layers (Members 3 BS, 2 WA, 2 BS and 1 BS Lower C). More than one type of panicoid grass was identified, sedge nutlets were present in the older layers and in Member 2 WA particularly, eudicotyledon leaves were preserved. Plant bedding construction may have altered slightly over time with the use of sedges decreasing in favour of grass. A small item that appears to be woven monocotyledon leaf blades was recovered from Member 1 BS Lower C (42,600 years old), potentially making it the oldest evidence of simple weaving. The bedding is generally desiccated rather than burned, and often lies on an ash base. It is possible that the site's occupants burned old bedding to provide an ash base for fresh bedding. The unique preservation of desiccated plant material from as early as 60,000 years ago may in part be due to these ashy surfaces.

The detection of low-intensity light is a crucial issue in many aspects of science and technology. So far, the solution has involved extremely delicate and somewhat bulky devices, the photomultiplier tubes, providing high sensitivity but suffering from fragility and susceptibility to interference. The silicon photomultiplier (SiPM) is a solid-state photon detector that provides a new solution for a wide range of photometry applications in fields as diverse as medicine, biology, environmental science, chemistry, physics, and nuclear physics. SiPMs are on a par with conventional photomultiplier tubes (PMT) in terms of internal gain and photon detection efficiency, while they are undoubtedly superior in terms of mechanical robustness, compact size, electronic stability, low power consumption, and affordability. Our group has long been involved in ionizing radiation measurements based on light emitting sensors both for industrial nuclear technology applications and for hybrid diagnostic imaging techniques. In both cases, SiPMs offer the unquestionable advantages described in this review.

On the basis of recent advancements in both neuroscience and archaeology, we propose a plausible biocultural mechanism at the basis of cultural evolution. The proposed mechanism, which relies on the notions of cultural exaptation and cultural neural reuse, may account for the asynchronous, discontinuous, and patchy emergence of innovations around the globe. Cultural exaptation refers to the reuse of previously devised cultural features for new purposes. Cultural neural reuse refers to cases in which exposure to cultural practices induces the formation, activation, and stabilization of new functional and/or structural brain networks during the individual lifespan. The invention of writing is interpreted as a case of cultural exaptation of previous devices to record information, in use since at least the Early Later Stone Age and the beginning of the Upper Paleolithic (44,000 years before present). The measurable changes in brain structure and functioning caused by learning to read are proposed as an exemplar case of cultural neural reuse. It is argued that repeated cycles of cultural exaptation, development of appropriate strategies of cultural transmission, and ensuing cultural neural reuse represent the fundamental mechanism that has regulated the cultural evolution of our lineage. A general predictive model of when and under which circumstances the proposed mechanism should be expected to occur is proposed, and the relationship of our mechanism with gene-culture coevolutionary models is discussed.

This study analyzed the optically simulated luminescence (OSL) of borate glasses containing lithium carbonate and potassium carbonate. Borate glasses present desirable characteristics for dosimetry and have been extensively analyzed in relation to thermoluminescence (TL). Five formulations containing 20% of Li2CO3 and different amounts of B2O3 and K2CO3 were produced. Their OSL signal was analyzed following exposure to beta particles. The decay pattern typical of continuous wave stimulation (CW-OSL) was observed for all compositions. Depending on the parameter chosen to normalize the dose-response curve, the sensitivity range changed. If the initial OSL intensity was chosen as reference, the composition containing 65% B2O3 and 15% K2CO3 (named L15KB) presented the most intense signal. However, if the total area below the curve was considered, the composition containing 70% B2O3 and 10% K2CO3 (named L10KB) was the most sensitive. A comparison of the OSL decay for the two quoted compositions, after pre-heating to 200 °C for 10 s prior to the OSL readout, showed a slight change in the decay pattern compared to the absence of pre-heating. The pre-heating treatments also showed the correlation between the shallow traps and the fast component of the OSL decay for L15KB. For all compositions, an increase in dose implied an increase in emitted signal, and no saturation was observed between 0.1 Gy and 7 Gy.

Polysulphone films are the only type of UV passive dosimeters that are widely adopted for research and personal monitoring. Even though many studies concentrated on the development and characterization of these films, they still present some shortcomings. The more important limitations of them are that they can measure only UVB radiations and that they change color at 330 nm, requiring special equipment to read them. To overcome these limitations we developed an aqueous dosimeter that is sensitive to UVA, UVB and X-rays named Redox-Phen solution. This dosimeter is inexpensive and water equivalent, being made of more than 99 wt% of water. It changes color in the visible region upon irradiation, thus it can be measured via simple optical method, and an evaluation of the exposition can be made also by naked eyes.

Lumps of mineral pigments are the more widespread archaeological remains found at Mousterian sites that may have been used by Neanderthals for symbolic activities. The characterisation of their chemical composition is essential to identify behavioural consistencies in their selection, transformation, and use, reconstruct changes through time in Neanderthals cultural practices, and discuss the emergence of symbolic cultures. In the Dordogne department of France, hundreds of black lumps, often bearing traces of intentional modification, were recovered at Middle (MP) and Upper Palaeolithic (UP) sites. In this paper we apply particle-induced X-ray emission (PIXE) to a representative sample of black lumps recovered at three MP and four UP sites as well as eight geological outcrops from this region with the aim of using major, minor, and trace elements content to identify potential sources and explore intra- and inter-site variability in the use of black colouring matter. Results suggest that MP and UP communities systematically searched for and surveyed Mn-rich formations to collect Mn-rich lumps. Differences in composition indicate that archaeological lumps were collected at a number of different outcrops, not sampled in the present study. A higher compositional variability is observed at UP compared to MP sites with single cultural layers. This suggests that UP modern humans may have, in some cases, exploited a wider range of Mn-rich sources than Mousterian Neanderthals.

The Middle Stone Age in Africa The Olorgesailie basin in the southern Kenya rift valley contains sediments dating back to 1.2 million years ago, preserving a long archaeological record of human activity and environmental conditions. Three papers present the oldest East African evidence of the Middle Stone Age (MSA) and elucidate the system of technology and behavior associated with the origin of Homo sapiens . Potts et al. present evidence for the demise of Acheulean technology that preceded the MSA and describe variations in late Acheulean hominin behavior that anticipate MSA characteristics. The transition to the MSA was accompanied by turnover of large mammals and large-scale landscape change. Brooks et al. establish that ∼320,000 to 305,000 years ago, the populations in eastern Africa underwent a technological shift upon procurement of distantly sourced obsidian for toolmaking, indicating the early development of social exchange. Deino et al. provide the chronological underpinning for these discoveries. Science , this issue p. 86 , p. 90 , p. 95

The bowand arrowis thought to be a unique development of our species, signalling higherlevel cognitive functioning. How this technology originated and how we identify archaeological evidence for it are subjects of ongoing debate. Recent analysis of the putative bone arrow point from Sibudu Cave in South Africa, dated to 61.7±1.5kya, has provided important new insights. High-resolution CT scanning revealed heat and impactdamage in both the Sibudu point and in experimentally produced arrow points. Thesefeatures suggest that the Sibudu point was first used as an arrowhead for hunting, andafterwards was deposited in a hearth. Our results support the claim that bone weapon tips were used in South African hunting long before the Eurasian Upper Palaeolithic. Fil: Backwell, Lucinda Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; Argentina Fil: Bradfield, Justin. University of the Witwatersrand; Sudáfrica Fil: Carlson, Kristian J.. University of Southern California; Estados Unidos Fil: Jashashvili, Tea. University of Southern California; Estados Unidos Fil: Wadley, Lyn. University of the Witwatersrand; Sudáfrica Fil: D'Errico, Francesco. Universite de Bordeaux; Francia

Fricke gel dosimeters produced with a matrix of Poly-vinyl alcohol (PVA) cross-linked with glutaraldehyde (GTA) were analyzed with magnetic resonance imaging (MRI). Previous studies based on spectrophotometry showed valuable dosimetric features of these gels in terms of X-ray sensitivity and diffusion of the ferric ions produced after irradiation. In this study, MRI was performed on the gels at 1.5 T with a clinical scanner in order to optimize the acquisition parameters and obtain high contrast between irradiated and non-irradiated samples. The PVA gels were found to offer good linearity in the range of 0–10 Gy and a stable signal for several hours after irradiation. The sensitivity was about 40% higher compared to gels produced with agarose as gelling agent. The effect of xylenol orange (XO) on the MRI signal was also investigated: gel dosimeters made without XO show higher sensitivity to x-rays than those made with XO. The dosimetric accuracy of the 3D gels was investigated by comparing their MRI response to percentage depth dose and transversal dose profile measurements made with an ionization chamber in a water phantom. The comparison of PVA-GTA gels with and without XO showed that the chelating agent reduces the MRI sensitivity of the gels. Depth-dose and transversal dose profiles acquired by PVA-GTA gels without XO are more accurate and consistent with the ionization chamber data. However, diffusion effects hinder accurate measurements in the steep dose gradient regions and they should be further reduced by modifying the gel matrix and/or by minimizing the delay between irradiation and imaging.

International audience; Bone tool-use by Early Pleistocene hominins is at the center of debates in human evolution. It is especially the case in South Africa, where bone tools have been described from four Early Stone Age (ESA) archaeological sites, which have yielded Oldowan and possibly Acheulean artefacts, as well as Paranthropus robustus and early Homo remains. Here we describe a bone tool from Cooper's D. The deposit, dated between 1.4 and 1.0 Ma, has yielded seven P. robustus remains and 50 stone artefacts. Our results highlight similarities in morphology and use-wear patterns between the Cooper's D bone tool and those previously identified at nearby Sterkfontein, Swartkrans, Kromdraai and Drimolen. Our findings increase the number of Early Stone Age bone tools and provide further evidence of their association with P. robustus. They suggest P. robustus had the cognitive capacities to develop this cultural adaptation and the manipulative abilities to implement it.

Beads are a communication technology used by humans to transmit information on the wearer identity to members of the same or neighbouring groups by means of a shared symbolic language. Here we focus on the earliest evidence from Eastern Asia of a communication technology – the production of artificially coloured beads – that has allowed humans to further complexify the messages conveyed by personal ornaments, and associate, to some extent, the performance characteristics of beads and pigment. We study six ochred ostrich eggshell beads (OESB) from Shuidonggou Locality 2 (SDG2), Cultural Layer (CL) 2, China, dated to c. 31 kyr cal BP. Analysis of the beads manufacturing technique, size, and wear, combined with SEM-EDS and µ-Raman spectroscopy (µ-RS) study of well-preserved red residues sampled on the beads and sediment from CL2 indicate that these beads come from body ornaments and that red residues are the remnant of a pigmented compound coating the beads at the time they were worn by the SDG Palaeolithic visitors. SDG2-CL2 red stained OESBs thus represent, with the red stained bone disk from Xiaogushan, the earliest consistent evidence of pigment use for symbolic activities from China. Results also identify variations in the composition of the pigmental compound used to colour the beads that closely match differences in bead technology, size, and style. We argue that such a hitherto unknown consistency in bead production and decoration may reflect technological, morphological, and pigment coating standardisation at the individual level, standardisation in technology associated with variation in morphology and pigment at the group level, and substantial differences in these three domains at inter-group level.