Variations of blood D-serine and D-aspartate homeostasis track psychosis stages.

Schizophrenia (SCZ) is a severe psychotic disorder characterized by a disruption in glutamatergic NMDA receptor (NMDAR)-mediated neurotransmission. Compelling evidence has revealed that NMDAR activation is not limited to L-glutamate, L-aspartate, and glycine since other free amino acids (AAs) in the atypical D-configuration, such as D-aspartate and D-serine, also modulate this class of glutamatergic receptors. Although dysregulation of AAs modulating NMDARs has been previously reported in SCZ, it remains unclear whether distinct variations of these biomolecules occur during illness progression from at-risk premorbid to clinically manifest stage.

Dysregulated balance of D- and L-amino acids modulating glutamatergic neurotransmission in severe spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. In addition to motor neuron survival, SMN deficiency affects the integrity and function of afferent synapses that provide glutamatergic excitatory drive essential for motor neuron firing and muscle contraction. However, it is unknown whether deficits in the metabolism of excitatory amino acids and their precursors contribute to neuronal dysfunction in SMA.

Diffusion Correction in Fricke Hydrogel Dosimeters: A Deep Learning Approach with 2D and 3D Physics-Informed Neural Network Models.

In this work an innovative approach was developed to address a significant challenge in the field of radiation dosimetry: the accurate measurement of spatial dose distributions using Fricke gel dosimeters. Hydrogels are widely used in radiation dosimetry due to their ability to simulate the tissue-equivalent properties of human tissue, making them ideal for measuring and mapping radiation dose distributions. Among the various gel dosimeters, Fricke gels exploit the radiation-induced oxidation of ferrous ions to ferric ions and are particularly notable due to their sensitivity.

Decreased free D-aspartate levels in the blood serum of patients with schizophrenia.

Introduction: Schizophrenia (SCZ) and autism spectrum disorder (ASD) are neurodevelopmental diseases characterized by different psychopathological manifestations and divergent clinical trajectories. Various alterations at glutamatergic synapses have been reported in both disorders, including abnormal NMDA and metabotropic receptor signaling.

Methods: We conducted a bicentric study to assess the blood serum levels of NMDA receptors-related glutamatergic amino acids and their precursors, including L-glutamate, L-glutamine, D-aspartate, L-aspartate, L-asparagine, D-serine, L-serine and glycine, in ASD, SCZ patients and their respective control subjects.

Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes.

Paleolithic eyed needles and the evolution of dress.

Eyed needles are among the most iconic of Paleolithic artifacts, traditionally seen as rare indicators of prehistoric clothing, particularly tailoring. However, recent finds across Africa and Eurasia show that other technologies like bone awls also facilitated the creation of fitted garments. Nonetheless, the advent of delicate eyed needles suggests a demand for more refined, efficient sewing.

Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.