Evidence from personal ornaments suggest nine distinct cultural groups between 34,000 and 24,000 years ago in Europe.

Mechanisms governing the relationship between genetic and cultural evolution are the subject of debate, data analysis and modelling efforts. Here we present a new georeferenced dataset of personal ornaments worn by European hunter-gatherers during the so-called Gravettian technocomplex (34,000-24,000 years ago), analyse it with multivariate and geospatial statistics, model the impact of distance on cultural diversity and contrast the outcome of our analyses with up-to-date palaeogenetic data. We demonstrate that Gravettian ornament variability cannot be explained solely by isolation-by-distance. Analysis of Gravettian ornaments identified nine geographically discrete cultural entities across Europe. While broadly in agreement with palaeogenetic data, our results highlight a more complex pattern, with cultural entities located in areas not yet sampled by palaeogenetics and distinctive entities in regions inhabited by populations of similar genetic ancestry. Integrating personal ornament and biological data from other Palaeolithic cultures will elucidate the complex narrative of population dynamics of Upper Palaeolithic Europe.

Initial Upper Palaeolithic material culture by 45,000 years ago at Shiyu in northern China.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.

Blood D-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease.

We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D-/Total serine may represent a valuable biochemical signature of PD.

Carbon Dots based Tissue Equivalent Dosimeter as an Ionizing Radiation Sensor.

This work explores the potential of carbon dots as a fluorescent probe in the determination of heavy ions and as an electrochemical biosensor. It also discusses how carbon dots can be introduced into the Fricke solution to potentially serve as an ionizing radiation sensor. The study presents a novel tissue equivalent dosimeter carbon dots-based as an ionizing radiation sensor. The methodology for the synthesis of Nitrogen-doped Carbon Dots N-CDs and the characterization of the material are described. The results show that the N-CDs have a high sensitivity to ionizing radiation and can be used as a dosimeter for radiation detection. The study also discusses the limitations and challenges of using carbon dots as a dosimeter for ionizing radiation. Overall, this study provides valuable insights into the potential applications of carbon dots in different fields and highlights the importance of further research in this area.

SMN deficiency perturbs monoamine neurotransmitter metabolism in spinal muscular atrophy.

Beyond motor neuron degeneration, homozygous mutations in the survival motor neuron 1 (SMN1) gene cause multiorgan and metabolic defects in patients with spinal muscular atrophy (SMA). However, the precise biochemical features of these alterations and the age of onset in the brain and peripheral organs remain unclear. Using untargeted NMR-based metabolomics in SMA mice, we identify cerebral and hepatic abnormalities related to energy homeostasis pathways and amino acid metabolism, emerging already at postnatal day 3 (P3) in the liver. Through HPLC, we find that SMN deficiency induces a drop in cerebral norepinephrine levels in overt symptomatic SMA mice at P11, affecting the mRNA and protein expression of key genes regulating monoamine metabolism, including aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DßH) and monoamine oxidase A (MAO-A). In support of the translational value of our preclinical observations, we also discovered that SMN upregulation increases cerebrospinal fluid norepinephrine concentration in Nusinersen-treated SMA1 patients. Our findings highlight a previously unrecognized harmful influence of low SMN levels on the expression of critical enzymes involved in monoamine metabolism, suggesting that SMN-inducing therapies may modulate catecholamine neurotransmission. These results may also be relevant for setting therapeutic approaches to counteract peripheral metabolic defects in SMA.

Multiproxy analysis of Upper Palaeolithic lustrous gravels supports their anthropogenic use.

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, microscopic, and textural analyses. Our results indicate the lustrous gravels found at the five sites result from deliberate selection and suggest their shiny appearance is the consequence of human agency, possibly resulting from 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.

First identification of an evolving Middle Stone Age ochre culture at Porc-Epic Cave, Ethiopia.

The use of mineral pigments, in particular iron-rich rocks, holds significant importance in understanding the emergence and evolution of human cultures. However, sites that have yielded a number of pieces large enough to precisely identify how the use of this material changed through time are rare. In this study, we examine one of the largest known Middle Stone Age (MSA) ochre collections, from Porc-Epic Cave, Ethiopia, consisting of more than 40 kg of ochre (n = 4213 pieces), 21 ochre processing tools and two ochre-stained artefacts. By combining the analysis of the elemental and mineralogical composition of the archaeological material with that of natural ochre collected in the surroundings of the site, and correlating this information with shifts in ochre modification techniques over time, we unveil how MSA inhabitants of Porc-Epic Cave exploited mineral resources. We show that they could predict the properties of different ochre types accessible in their environment, and gradually adapted their technology to cope with changes in raw material availability. Furthermore, the analysis of ochre residues on a painted pebble, likely used to produce red dots on a surface, identifies an ochre type that was specifically employed for symbolic purposes.

New Blombos Cave evidence supports a multistep evolutionary scenario for the culturalization of the human body.

The emergence of technologies to culturally modify the appearance of the human body is a debated issue, with earliest evidence consisting of perforated marine shells dated between 140 and 60 ka at archaeological sites from Africa and western Asia. In this study, we submit unpublished marine and estuarine gastropods from Blombos Cave Middle Stone Age layers to taxonomic, taphonomic, technological, and use-wear analyses. We show that unperforated and naturally perforated eye-catching shells belonging to the species Semicassis zeylanica, Conus tinianus, and another Conus species, possibly Conus algoensis, were brought to the cave between 100 and 73 ka. At ca. 70 ka, a previously unrecorded marine gastropod, belonging to the species Tritia ovulata, was perforated by pecking and was worn as an ornamental object, isolated or in association with numerous intentionally perforated shells of the species Nassarius kraussianus. Fluctuations in sea level and consequent variations in the site-to-shoreline distances and landscape modifications during the Middle Stone Age have affected the availability of marine shells involved in symbolic practices. During the M3 and M2 Lower phases, with a sea level 50 m lower, the site was approximately 3.5 km away from the coast. In the later M2 Upper and M1 phases, with a sea level at -60 m, the distance increased to about 5.7 km. By the end of the M1 phase, when the site was abandoned, Blombos Cave was situated 18-30 km from the shoreline. We use the new Blombos evidence and a review of the latest findings from Africa and Eurasia to propose a testable ten-step evolutionary scenario for the culturalization of the human body with roots in the deep past.

Improvement of neutron sensitivity for lithium formate EPR dosemeters: a Monte Carlo analysis.

This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of predicting the increase in dose achievable by the addition of sensitizers inside the pellets. As expected, a larger amount of 6Li induces an increase of energy released because of the charged secondary particles (i.e. 3H ions and α-particles) produced after neutron capture. For small depths in water phantom and low-energy neutron spectra the dose increase due to 6Li enrichment is high (more than three orders of magnitude with respect to the case of with 7Li). In case of epithermal neutron beams the energy released in 6Li-enriched LFM compound is smaller but larger than in the case of fast neutron beams. On the other hand, the computational analysis evidenced that gadolinium is less effective than 6Li in improving neutron sensitivity of the LFM pellets. Discussion based on the features of MC transport code is provided. This result suggests that 6Li enrichment of LFM dosemeters would be more effective for neutron sensitivity improvement and these EPR dosemeters could be tested for dosimetric applications in Neutron Capture Therapy.

A 36,200-year-old carving from Grotte des Gorges, Amange, Jura, France.

The earliest European carvings, made of mammoth ivory, depict animals, humans, and anthropomorphs. They are found at Early Aurignacian sites of the Swabian Jura in Germany. Despite the wide geographical spread of the Aurignacian across Europe, these carvings have no contemporaneous counterparts. Here, we document a small, intriguing object, that sheds light on this uniqueness. Found at the Grotte des Gorges (Jura, France), in a layer sandwiched between Aurignacian contexts and dated to c. 36.2 ka, the object bears traces of anthropogenic modifications indicating intentional carving. Microtomographic, microscopic, three-dimensional roughness and residues analyses reveal the carving is a fragment of a large ammonite, which was modified to represent a caniformia head decorated with notches and probably transported for long time in a container stained with ochre. While achieving Swabian Jura-like miniaturization, the Grotte des Gorges specimen displays original features, indicating the craftsman emulated ivory carvings while introducing significant technical, thematic, and stylistic innovations. This finding suggests a low degree of cultural connectivity between Early Aurignacian hunter-gatherer groups in the production of their symbolic material culture. The pattern conforms to the existence of cultural boundaries limiting the transmission of symbolic practices while leaving space for the emergence of original regional expressions.

Perturbation of serine enantiomers homeostasis in the striatum of MPTP-lesioned monkeys and mice reflects the extent of dopaminergic midbrain degeneration.

Loss of dopaminergic midbrain neurons perturbs l-serine and d-serine homeostasis in the post-mortem caudate putamen (CPu) of Parkinson's disease (PD) patients. However, it is unclear whether the severity of dopaminergic nigrostriatal degeneration plays a role in deregulating serine enantiomers' metabolism. Here, through high-performance liquid chromatography (HPLC), we measured the levels of these amino acids in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and MPTP-plus-probenecid (MPTPp)-treated mice to determine whether and how dopaminergic midbrain degeneration affects the levels of serine enantiomers in various basal ganglia subregions. In addition, in the same brain regions, we measured the levels of key neuroactive amino acids modulating glutamatergic neurotransmission, including l-glutamate, glycine, l-aspartate, d-aspartate, and their precursors l-glutamine, l-asparagine. In monkeys, MPTP treatment produced severe denervation of nigrostriatal dopaminergic fibers (⁓75%) and increased the levels of serine enantiomers in the rostral putamen (rPut), but not in the subthalamic nucleus, and the lateral and medial portion of the globus pallidus. Moreover, this neurotoxin significantly reduced the protein expression of the astrocytic serine transporter ASCT1 and the glycolytic enzyme GAPDH in the rPut of monkeys. Conversely, concentrations of d-serine and l-serine, as well as ASCT1 and GAPDH expression were unaffected in the striatum of MPTPp-treated mice, which showed only mild dopaminergic degeneration (⁓30%). These findings unveil a link between the severity of dopaminergic nigrostriatal degeneration and striatal serine enantiomers concentration, ASCT1 and GAPDH expression. We hypothesize that the up-regulation of d-serine and l-serine levels occurs as a secondary response within a homeostatic loop to support the metabolic and neurotransmission demands imposed by the degeneration of dopaminergic neurons.

Cerebrospinal fluid, brain, and spinal cord levels of L-aspartate signal excitatory neurotransmission abnormalities in multiple sclerosis patients and experimental autoimmune encephalomyelitis mouse model.

The neuroinflammatory process characterizing multiple sclerosis (MS) is associated with changes in excitatory synaptic transmission and altered central concentrations of the primary excitatory amino acid, L-glutamate (L-Glu). Recent findings report that cerebrospinal fluid (CSF) levels of L-Glu positively correlate with pro-inflammatory cytokines in MS patients. However, to date, there is no evidence about the relationship between the other primary excitatory amino acid, L-aspartate (L-Asp), its derivative D-enantiomer, D-aspartate, and the levels of pro-inflammatory and anti-inflammatory cytokines in the CSF of MS. In the present study, we measured by HPLC the levels of these amino acids in the cortex, hippocampus, cerebellum, and spinal cord of mice affected by experimental autoimmune encephalomyelitis (EAE). Interestingly, in support of glutamatergic neurotransmission abnormalities in neuroinflammatory conditions, we showed reduced L-Asp levels in the cortex and spinal cord of EAE mice and increased D-aspartate/total aspartate ratio within the cerebellum and spinal cord of these animals. Additionally, we found significantly decreased CSF levels of L-Asp in both relapsing-remitting (n = 157) MS (RR-MS) and secondary progressive/primary progressive (n = 22) (SP/PP-MS) patients, compared to control subjects with other neurological diseases (n = 40). Importantly, in RR-MS patients, L-Asp levels were correlated with the CSF concentrations of the inflammatory biomarkers G-CSF, IL-1ra, MIP-1ß, and Eotaxin, indicating that the central content of this excitatory amino acid, as previously reported for L-Glu, reflects a neuroinflammatory environment in MS. In keeping with this, we revealed that CSF L-Asp levels were positively correlated with those of L-Glu, highlighting the convergent variation of these two excitatory amino acids under inflammatory synaptopathy occurring in MS.

Homeostasis of serine enantiomers is disrupted in the post-mortem caudate putamen and cerebrospinal fluid of living Parkinson's disease patients.

L-serine generated in astrocytes plays a pivotal role in modulating essential neurometabolic processes, while its enantiomer, D-serine, specifically regulates NMDA receptor (NMDAR) signalling. Despite their physiological relevance in modulating cerebral activity, serine enantiomers metabolism in Parkinson's disease (PD) remains elusive. Using High-Performance Liquid Chromatography (HPLC), we measured D- and L-serine levels along with other amino acids known to modulate NMDAR function, such as L-glutamate, L-aspartate, D-aspartate, and glycine, in the post-mortem caudate putamen (CPu) and superior frontal gyrus (SFG) of PD patients. Moreover, we examined these amino acids in the cerebrospinal fluid (CSF) of de novo living PD, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients versus subjects with other neurological disorders (OND), used as control. We found higher D-serine and L-serine levels in the CPu of PD patients but not in the SFG, a cerebral region that, in contrast to the CPu, is not innervated by nigral dopaminergic terminals. We also highlighted a significant elevation of both serine enantiomers in the CSF samples from PD but not in those of AD and ALS patients, compared with control subjects. By contrast, none or only minor changes were found in the amount of other NMDAR modulating amino acids. Our findings identify D-serine and L-serine level upregulation as a biochemical signature associated with nigrostriatal dopaminergic degeneration in PD.

D-Aspartate Depletion Perturbs Steroidogenesis and Spermatogenesis in Mice.

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 17ß-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.

A 39,600-year-old leather punch board from Canyars, Gavà, Spain.

Puncture alignments are found on Palaeolithic carvings, pendants, and other fully shaped osseous artifacts. These marks were interpreted as abstract decorations, system of notations, and features present on human and animal depictions. Here, we create an experimental framework for the analysis and interpretation of human-made punctures and apply it to a highly intriguing, punctured bone fragment found at Canyars, an Early Upper Palaeolithic coastal site from Catalonia, Spain. Changes of tool and variation in the arrangement and orientation of punctures are consistent with the interpretation of this object as the earliest-known leather work punch board recording six episodes of hide pricking, one of which was to produce a linear seam. Our results indicate that Aurignacian hunters-gatherers used this technology to produce leather works and probably tailored clothes well before the introduction of bone eyed needles in Europe 15,000 years later.

Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients.

BACKGROUND: Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, but has not been specifically investigated in patients affected by severe and milder forms of spinal muscular atrophy (SMA). METHODS: In this two-center retrospective study, we investigated signatures of neuroinflammation in forty-eight pediatric male and female SMA1 (n = 18), male and female SMA2 (n = 19), and female SMA3 (n = 11) patients, as well as in a limited number of male and female non-neurological control subjects (n = 4). We employed a Bio-Plex multiplex system based on xMAP technology and performed targeted quantitative analysis of a wide range of pro- and anti-inflammatory cytokines (chemokines, interferons, interleukins, lymphokines and tumor necrosis factors) and neurotrophic factors in the cerebrospinal fluid (CSF) of the study cohort before and after Nusinersen treatment at loading and maintenance stages. RESULTS: We find a significant increase in the levels of several pro-inflammatory cytokines (IL-6, IFN-γ, TNF-α, IL-2, IL-8, IL-12, IL-17, MIP-1α, MCP-1, and Eotaxin) and neurotrophic factors (PDGF-BB and VEGF) in the CSF of SMA1 patients relative to SMA2 and SMA3 individuals, who display levels in the range of controls. We also find that treatment with Nusinersen significantly reduces the CSF levels of some but not all of these neuroinflammatory molecules in SMA1 patients. Conversely, Nusinersen increases the CSF levels of proinflammatory G-CSF, IL-8, MCP-1, MIP-1α, and MIP-1ß in SMA2 patients and decreases those of anti-inflammatory IL-1ra in SMA3 patients. CONCLUSIONS: These findings highlight signatures of neuroinflammation that are specifically associated with severe SMA and the neuro-immunomodulatory effects of Nusinersen therapy.

Spinal muscular atrophy (SMA) is an inherited disorder which leads to muscle weakening. Three therapies have recently been developed, including Nusinersen. However, the effect of SMA on the immune system and how this could be affected by Nusinersen is unknown. The immune system protects the body from infection and, in some disorders, misfunctions and damages the body in the absence of infection. Here, we analyze components of the immune system in body fluids from SMA patients before and after treatment with Nusinersen. The immune system was found to be more active in patients with more severe disease. Treatment with Nusinersen reduced the levels of some, but not all of these, components of the immune system. Thus, treatments that impact the immune system might improve symptoms in patients with SMA.

Cytogenetic effects of ß-particles in Allium cepa cells used as a biological indicator for radiation damages.

Analysis of cytogenetics effects of ionizing radiation for flora and fauna is essential to determine the impact on these communities and may produce an efficient warning system to avoid harm to human health. Onion (Allium cepa) is a well-established in vivo standard model, and it is widely used in cytogenetics studies for different environmental pollutants. In this work, onion roots were exposed to 0.04-1.44 Gy of ß-particles from a 90Sr/90Y source. We investigated the capacity of brief external exposures to ß-particles on inducing cytogenetic damages in root meristematic cells of onion aiming to verify if onion can be used as a radiation-sensitive cytogenetic bioindicator. A nonlinear increase in the frequencies of chromosomal aberrations and cells with micronuclei was observed. Onion roots exposed to doses 0.13 Gy or higher of ß-particles showed a significant difference (p<0.05) in these frequencies when compared to the unirradiated group. The frequencies of these endpoints showed to be suitable to assess the difference in the dose of beta radiation received from 0.36 Gy. Our research shows the potential of using cytogenetic effects in Allium cepa cells as a biological indicator for a first screening of genotoxic damages induced by brief external exposures to ß-particles.

Nusinersen Induces Disease-Severity-Specific Neurometabolic Effects in Spinal Muscular Atrophy.

Intrathecal delivery of Nusinersen-an antisense oligonucleotide that promotes survival motor neuron (SMN) protein induction-is an approved therapy for spinal muscular atrophy (SMA). Here, we employed nuclear magnetic resonance (NMR) spectroscopy to longitudinally characterize the unknown metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of SMA patients across disease severity. Modulation of amino acid metabolism is a common denominator of biochemical changes induced by Nusinersen, with distinct downstream metabolic effects according to disease severity. In severe SMA1 patients, Nusinersen stimulates energy-related glucose metabolism. In intermediate SMA2 patients, Nusinersen effects are also related to energy homeostasis but involve ketone body and fatty acid biosynthesis. In milder SMA3 patients, Nusinersen mainly modulates amino acid metabolism. Moreover, Nusinersen modifies the CSF metabolome of a more severe clinical group towards the profile of untreated SMA patients with milder disease. These findings reveal disease severity-specific neurometabolic signatures of Nusinersen treatment, suggesting a selective modulation of peripheral organ metabolism by this CNS-directed therapy in severe SMA patients.

Technological and functional analysis of 80-60 ka bone wedges from Sibudu (KwaZulu-Natal, South Africa).

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.

Neural correlates of perceiving and interpreting engraved prehistoric patterns as human production: Effect of archaeological expertise.

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.