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1.
Nature ; 603(7900): 284-289, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35236981

RESUMEN

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.


Asunto(s)
Arqueología , Hominidae , Comportamiento del Uso de la Herramienta , Animales , Huesos , China , Historia Antigua , Humanos , Hombre de Neandertal
2.
Nature ; 593(7857): 95-100, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33953416

RESUMEN

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.


Asunto(s)
Entierro/historia , Fósiles , Esqueleto/anatomía & histología , Animales , Huesos/anatomía & histología , Preescolar , Evolución Cultural/historia , Dentición , Historia Antigua , Hominidae/anatomía & histología , Hominidae/clasificación , Humanos , Kenia
3.
Neurobiol Dis ; 192: 106413, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38253208

RESUMEN

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.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Serina/metabolismo , Dopamina/metabolismo , Levodopa/uso terapéutico , Aminoácidos , Ácido Glutámico , Envejecimiento
4.
Chemistry ; 30(12): e202303771, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38118132

RESUMEN

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.


Asunto(s)
Técnicas Biosensibles , Puntos Cuánticos , Puntos Cuánticos/química , Carbono/química , Dosímetros de Radiación , Nitrógeno/química , Colorantes Fluorescentes/química
5.
Nature ; 562(7725): 115-118, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30209394

RESUMEN

Depictive and abstract representations produced by drawing-known from Europe, Africa and Southeast Asia after 40,000 years ago-are a prime indicator of modern cognition and behaviour1. Here we report a cross-hatched pattern drawn with an ochre crayon on a ground silcrete flake recovered from approximately 73,000-year-old Middle Stone Age levels at Blombos Cave, South Africa. Our microscopic and chemical analyses of the pattern confirm that red ochre pigment was intentionally applied to the flake with an ochre crayon. The object comes from a level associated with stone tools of the Still Bay techno-complex that has previously yielded shell beads, cross-hatched engravings on ochre pieces and a variety of innovative technologies2-5. This notable discovery pre-dates the earliest previously known abstract and figurative drawings by at least 30,000 years. This drawing demonstrates the ability of early Homo sapiens in southern Africa to produce graphic designs on various media using different techniques.


Asunto(s)
Arte/historia , Cuevas , África Austral , Colorantes/análisis , Sedimentos Geológicos/química , Historia Antigua , Humanos
6.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34341069

RESUMEN

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.

7.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38928178

RESUMEN

Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain-including those involving serotonin and dopamine-exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in Tph2 knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in Tph2 knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.


Asunto(s)
Ritmo Circadiano , Dopamina , Ratones Noqueados , Serotonina , Triptófano Hidroxilasa , Tirosina 3-Monooxigenasa , Área Tegmental Ventral , Animales , Serotonina/metabolismo , Ratones , Ritmo Circadiano/fisiología , Dopamina/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Tirosina 3-Monooxigenasa/genética , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/metabolismo , Triptófano Hidroxilasa/deficiencia , Área Tegmental Ventral/metabolismo , Colecistoquinina/metabolismo , Colecistoquinina/genética , Neuronas Dopaminérgicas/metabolismo , Masculino , Sustancia Negra/metabolismo , Ratones Endogámicos C57BL , Trastorno Bipolar/metabolismo , Trastorno Bipolar/genética
8.
J Neurochem ; 166(3): 534-546, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37332201

RESUMEN

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.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Ratones , Animales , Encefalomielitis Autoinmune Experimental/metabolismo , Esclerosis Múltiple/metabolismo , Ácido Aspártico/líquido cefalorraquídeo , Ácido D-Aspártico/metabolismo , Médula Espinal/metabolismo , Encéfalo/metabolismo , Transmisión Sináptica , Aminoácidos Excitadores/metabolismo , Ácido Glutámico/metabolismo , Citocinas/metabolismo
9.
Neurobiol Dis ; 184: 106226, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37451474

RESUMEN

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.


Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Serina , Ratones , Animales , Serina/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Dopamina/metabolismo , Cuerpo Estriado/metabolismo , Mesencéfalo/metabolismo , Aminoácidos/metabolismo , Putamen/metabolismo , Homeostasis
10.
Neurobiol Dis ; 184: 106203, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37336364

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Esclerosis Amiotrófica Lateral , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Serina/metabolismo , Putamen/metabolismo , Enfermedad de Alzheimer/metabolismo , Aminoácidos , Receptores de N-Metil-D-Aspartato/metabolismo , N-Metilaspartato , Homeostasis
11.
J Hum Evol ; 184: 103438, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37742522

RESUMEN

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.

12.
Sensors (Basel) ; 22(3)2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35161824

RESUMEN

Since the Fukushima Daiichi Nuclear Power Plant accident in March 2011, the technology available for unmanned aerial vehicles (UAVs) for radiation monitoring has improved greatly. Remote access to radiation-contaminated areas not only eliminates unnecessary exposure of civilians or military personnel, but also allows workers to explore inaccessible places. Hazardous levels of radioactive contamination can be expected as a result of accidents in the nuclear power industry or as a result of the intentional release of radioactive materials for terrorist purposes (dirty bombs, building contamination, etc.). The possibility to detect, identify, and characterize radiation and nuclear material using mobile and remote sensing platforms is a common requirement in the radiation sensing community. The technology has applications in homeland security and law enforcement, customs and border protection, nuclear power plant safety and security, nuclear waste monitoring, environmental recovery, and the military. In this work, the authors have developed, implemented, and characterized a gamma-ray detection and spectroscopy system capable of operating on a UAV. The system was mainly developed using open-source software and affordable hardware components to reduce development and maintenance costs and provide satisfactory performance as a detection instrument. The designed platform can be used to perform mapping or localization tasks to improve the risk assessment process for first responders during the management of radiological and nuclear incidents. First, the design process of the system is described; the result of the characterization of the platform is then presented together with the use of the prototype installed on a UAV in an exercise simulating a radiological and nuclear contamination scenario.


Asunto(s)
Monitoreo de Radiación , Terrorismo , Humanos , Plantas de Energía Nuclear
13.
Int J Mol Sci ; 23(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35163460

RESUMEN

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 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post-mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non-psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson's and Alzheimer's disease. Interestingly, also in Parkinson's disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.


Asunto(s)
Proteína ADAM10/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Homólogo 1 de la Proteína Discs Large/genética , Proteínas de la Membrana/genética , Enfermedad de Parkinson/genética , Esquizofrenia/genética , Proteína ADAM10/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Autopsia , Estudios de Casos y Controles , Homólogo 1 de la Proteína Discs Large/metabolismo , Corteza Prefontal Dorsolateral/metabolismo , Femenino , Regulación de la Expresión Génica , Hipocampo/metabolismo , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Esquizofrenia/metabolismo
14.
J Proteome Res ; 20(1): 727-739, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33274941

RESUMEN

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.


Asunto(s)
Ácido Aspártico , Ácido D-Aspártico , Aminoácidos , Animales , Encéfalo/metabolismo , Ácido D-Aspártico/metabolismo , Metabolismo Energético , Femenino , Ratones , Embarazo , Receptores de N-Metil-D-Aspartato/metabolismo
15.
J Neurochem ; 159(5): 857-866, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34547109

RESUMEN

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1 year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS.


Asunto(s)
Ácido Glutámico/líquido cefalorraquídeo , Mediadores de Inflamación/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Adulto , Biomarcadores/líquido cefalorraquídeo , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico por imagen , Estrés Oxidativo/fisiología
16.
J Hum Evol ; 161: 103088, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34837740

RESUMEN

Personal ornaments have become a key cultural proxy to investigate cognitive evolution, modern human dispersal, and population dynamics. Here, we reassess personal ornaments found at Zhoukoudian Upper Cave and compare them with those from other Late Paleolithic Northern Chinese sites. We reappraise the information provided by Pei Wen Chung on Upper Cave personal ornaments lost during World War II and analyze casts of 17 of them, along with two unpublished objects displayed at the Zhoukoudian Site Museum and three original perforated teeth rediscovered at the Zhoukoudian Site Museum. We apply archeozoological, technological and use-wear analyses to document variation in ornamental practices and their change throughout the site stratigraphy. Badger, fox, red deer, sika deer, marten, and tiger teeth as well as carp bone, bird bone, Anadara shell, limestone beads, and perforated pebble appear to have been the preferred objects used as ornaments by Upper Cave visitors. Multivariate analysis of technological data highlights a correspondence between cultural layers and perforation techniques, with radial incising being typical of layer L2 and bidirectional incising of L4. The three rediscovered badger canines display features suggesting they were sewed on clothing rather than suspended from necklaces or bracelets. Elemental scanning electron microscopy coupled with energy dispersive X-ray spectromety and mineralogical (µ-Raman) analyses of red residues adhering to the rediscovered teeth indicate these objects were originally coated with ochre and identify variations that match differences in technology. The two ornaments exhibited at the Zhoukoudian Site Museum are ancient teeth that were recently perforated and should be excluded from the Upper Cave assemblage. A seriation of Late Paleolithic ornaments found at Northern Chinese sites identifies a clear-cut difference in preferred ornament types between western and eastern sites, interpreted as reflecting two long-lasting traditions in garment symbolic codes.


Asunto(s)
Ciervos , Animales , Arqueología , Cuevas , Museos , Dinámica Poblacional , Tecnología
17.
Amino Acids ; 53(3): 435-449, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33616735

RESUMEN

Altered glutamatergic neurotransmission is thought to play a crucial role in the progression of Alzheimer's disease (AD). Accordingly, the identification of peculiar biochemical patterns reflecting AD-related synaptopathy in blood and cerebrospinal fluid (CSF) could have relevant diagnostic and prognostic implications. In this study, we measured by High-Performance Liquid Chromatography the amount of glutamate, glutamine and glycine in post-mortem brain samples of AD patients, as well as in CSF and blood serum of drug-free subjects encompassing the whole AD clinical spectrum (pre-clinical AD, n = 18, mild cognitive impairment-AD, n = 29, dementia AD, n = 30). Interestingly, we found that glutamate and glycine levels, as well as total tau protein content, were significantly reduced in the superior frontal gyrus of patients with AD, compared with non-demented controls. No significant change was also found in glutamate, glutamine and glycine CSF concentrations between AD patients and neurological controls. Remarkably, serum glutamate levels were significantly higher in patients affected by early AD phases compared to controls, and were negatively correlated with CSF total tau levels. Conversely, serum glutamine concentration was significantly increased in AD patients, with a negative correlation with MMSE performances. Finally, we reported a significant correlation between serum L-glutamate concentrations and CDR score in female but not in male cohort of AD subjects. Overall, our results suggest that serum glutamate and glutamine levels in AD patients could vary across disease stages, potentially reflecting the progressive alteration of glutamatergic signaling during neurodegenerative processes.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Glicina/metabolismo , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Biomarcadores/análisis , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión , Femenino , Ácido Glutámico/análisis , Glutamina/análisis , Glicina/análisis , Humanos , Masculino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología
18.
Nature ; 518(7538): 228-31, 2015 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-25470048

RESUMEN

The manufacture of geometric engravings is generally interpreted as indicative of modern cognition and behaviour. Key questions in the debate on the origin of such behaviour are whether this innovation is restricted to Homo sapiens, and whether it has a uniquely African origin. Here we report on a fossil freshwater shell assemblage from the Hauptknochenschicht ('main bone layer') of Trinil (Java, Indonesia), the type locality of Homo erectus discovered by Eugène Dubois in 1891 (refs 2 and 3). In the Dubois collection (in the Naturalis museum, Leiden, The Netherlands) we found evidence for freshwater shellfish consumption by hominins, one unambiguous shell tool, and a shell with a geometric engraving. We dated sediment contained in the shells with (40)Ar/(39)Ar and luminescence dating methods, obtaining a maximum age of 0.54 ± 0.10 million years and a minimum age of 0.43 ± 0.05 million years. This implies that the Trinil Hauptknochenschicht is younger than previously estimated. Together, our data indicate that the engraving was made by Homo erectus, and that it is considerably older than the oldest geometric engravings described so far. Although it is at present not possible to assess the function or meaning of the engraved shell, this discovery suggests that engraving abstract patterns was in the realm of Asian Homo erectus cognition and neuromotor control.


Asunto(s)
Exoesqueleto , Grabado y Grabaciones/historia , Hominidae , Comportamiento del Uso de la Herramienta , Animales , Fósiles , Historia Antigua , Indonesia , Moluscos
19.
MAGMA ; 34(3): 451-467, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32785807

RESUMEN

OBJECTIVE: A method for Orthogonal Phase Encoding Reduction of Artifact (OPERA) was developed and tested. MATERIALS AND METHODS: Because the position of ghosts and aliasing artifacts is predictable along columns or rows, OPERA combines the intensity values of two images acquired using the same parameters, but with swapped phase-encoding directions, to correct the artifacts. Simulations and phantom experiments were conducted to define the efficacy, robustness, and reproducibility. Clinical validation was performed on a total of 1003 images by comparing the OPERA-corrected images and the corresponding image standard in terms of Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR). The method efficacy was also rated using a Likert-type scale response by two experienced independent radiologists using a single-blinded procedure. RESULTS: Simulations and phantom experiments demonstrated the robustness and effectiveness of OPERA in reducing artifacts strength. OPERA application did not significantly change the SNR [+ 4.16%; inter-quartile range (IQR): 2.72-5.01%] and CNR (+ 4.30%; IQR: 2.86-6.04%) values. The two radiologists observed a total of 893 original images with artifacts (89.03% of the total images), a reduction in the perceived artifacts of 82.0% and 83.9% (p < 0.0001), and an improvement in the perceived SNR (82.8% and 88.5%; K = 0.714) and perceived CNR (86.9-88.9%; K = 0.722). DISCUSSION: The study demonstrated that OPERA reduces MR artifacts and improves the perceived image quality.


Asunto(s)
Artefactos , Fantasmas de Imagen , Reproducibilidad de los Resultados , Relación Señal-Ruido
20.
Behav Brain Sci ; 44: e199, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34907875

RESUMEN

Clarke and Beck's defense of the theoretical construct "approximate number system" (ANS) is flawed in serious ways - from biological misconceptions to mathematical naïveté. The authors misunderstand behavioral/psychological technical concepts, such as numerosity and quantical cognition, which they disdain as "exotic." Additionally, their characterization of rational numbers is blind to the essential role of symbolic reference in the emergence of number.


Asunto(s)
Cognición , Lenguaje , Humanos , Matemática , Percepción
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