Italian burials from the Upper Palaeolithic. Inventory and anthropological observations

The Upper Paleolithic burials currently known in Italy represent a rich and important group which constitutes the major part of the European sample. Among these burials, those attributed to the Gravettian are concentrated in two regions, Liguria and Puglia. Epigravettian burials were found in most parts of the peninsula and in Sicily. Grave goods are often very rich, especially in Gravettian burials. With regard to the anthropological characteristics of the buried, research has focused mainly on postcranial skeleton and on the information it can give us about weight, stature and somatic proportions. Among the Gravettians, Ligurian males reach the highest stature. The average height decreases from Gravettian to Epigravettian, as already observed in the European sample

Functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp

Peripheral nerve researchers frequently use the rat sciatic nerve crush as a model for axonotmesis.Unfortunately, studies from various research groups report results from different crush techniquesand by using a variety of evaluation tools, making comparisons between studies difficult. The pur-pose of this investigation was to determine the sequence of functional and morphologic changes af-ter an acute sciatic nerve crush injury with a non-serrated clamp, giving a final standardized pres-sure of p9 MPa. Functional recovery was evaluated using the sciatic functional index (SFI), theextensor postural thrust (EPT) and the withdrawal reflex latency (WRL), before injury, and thenat weekly intervals until week 8 postoperatively. The rats were also evaluated preoperatively andat weeks 2, 4, and 8 by ankle kinematics, toe out angle (TOA), and gait-stance duration. In addi-tion, the motor nerve conduction velocity (MNCV) and the gastrocnemius-soleus weight parameterswere measured just before euthanasia. Finally, structural, ultrastructural and histomorphometricanalyses were carried out on regenerated nerve fibers. At 8 weeks after the crush injury, a full func-tional recovery was predicted by SFI, EPT, TOA, and gait-stance duration, while all the other pa-rameters were still recovering their original values. On the other hand, only two of the histomor-phometric parameters of regenerated nerve fibers, namely myelin thickness/axon diameter ratio andfiber/axon diameter ratio, returned to normal values while all other parameters were significantlydifferent from normal values. The employment of traditional methods of functional evaluation inconjunction with the modern techniques of computerized analysis of gait and histomorphometricanalysis should thus be recommended for an overall assessment of recovery in the rat sciatic nervecrush model

Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system

Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li+ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K+-distribution of neurons and glial cells. In view of the therapeutic action of Li+ in manicdepressive disease, a special effort was made to determine the threshold concentration for the actions of Li+ on the parameters described above. It was observed that Li+ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li+ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li+ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li+ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li+ may be an interaction with the transport-function of the Na+/K+ pump

Taxon ordering in phylogenetic trees by means of evolutionary algorithms

<p>Abstract</p> <p>Background</p> <p>In in a typical "left-to-right" phylogenetic tree, the vertical order of taxa is meaningless, as only the branch path between them reflects their degree of similarity. To make unresolved trees more informative, here we propose an innovative Evolutionary Algorithm (EA) method to search the best graphical representation of unresolved trees, in order to give a biological meaning to the vertical order of taxa.</p> <p>Methods</p> <p>Starting from a West Nile virus phylogenetic tree, in a (1 + 1)-EA we evolved it by randomly rotating the internal nodes and selecting the tree with better fitness every generation. The fitness is a sum of genetic distances between the considered taxon and the <it>r </it>(radius) next taxa. After having set the radius to the best performance, we evolved the trees with (<it>λ </it>+ <it>μ</it>)-EAs to study the influence of population on the algorithm.</p> <p>Results</p> <p>The (1 + 1)-EA consistently outperformed a random search, and better results were obtained setting the radius to 8. The (<it>λ </it>+ <it>μ</it>)-EAs performed as well as the (1 + 1), except the larger population (1000 + 1000).</p> <p>Conclusions</p> <p>The trees after the evolution showed an improvement both of the fitness (based on a genetic distance matrix, then close taxa are actually genetically close), and of the biological interpretation. Samples collected in the same state or year moved close each other, making the tree easier to interpret. Biological relationships between samples are also easier to observe.</p

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)

Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease

BACKGROUND: The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Yokukansan Inhibits Neuronal Death during ER Stress by Regulating the Unfolded Protein Response

Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD