Single-Cell Transcriptional Analysis of Neuronal Progenitors

AbstractThe extraordinary cellular heterogeneity of the mammalian nervous system has largely hindered the molecular analysis of neuronal identity and diversity. In order to uncover mechanisms involved in neuronal differentiation and diversification, we have monitored the expression profiles of individual neurons and progenitor cells collected from dissociated tissue or captured from intact slices. We demonstrate that this technique provides a sensitive and reproducible representation of the single-cell transcriptome. In the olfactory system, hundreds of transcriptional differences were identified between olfactory progenitors and mature sensory neurons, enabling us to define the large variety of signaling pathways expressed by individual progenitors at a precise developmental stage. Finally, we show that regional differences in gene expression can be predicted from transcriptional analysis of single neuronal precursors isolated by laser capture from defined areas of the developing brain

Absorption properties of Mediterranean aerosols obtained from multi-year ground-based remote sensing observations.

International audienceAerosol absorption properties are of high importance to assess aerosol impact on regional climate. This study presents an analysis of aerosol absorption products obtained over the Mediterranean basin or land stations in the region from multi-year ground-based AERONET observations with a focus on the Absorbing Aerosol Optical Depth (AAOD), Single Scattering Albedo (SSA) and their spectral dependence. The AAOD and Absorption Angström Exponent (AAE) dataset is composed of daily averaged AERONET level 2 data from a total of 22 Mediterranean stations having long time series, mainly under the influence of urban-industrial aerosols and/or soil dust. This dataset covers the 17-yr period 1996-2012 with most data being from 2003-2011 (~89% of level-2 AAOD data). Since AERONET level-2 absorption products require a high aerosol load (AOD at 440 nm > 0.4), which is most often related to the presence of desert dust, we also consider level-1.5 SSA data, despite their higher uncertainty, and filter out data with an Angström exponent < 1.0 in order to study absorption by carbonaceous aerosols. The SSA dataset includes AERONET level-2 products. Sun-photometer observations show that values of AAOD at 440 nm vary between 0.024 ± 0.01 (resp. 0.040 ± 0.01) and 0.050 ± 0.01 (0.055 ± 0.01) for urban (dusty) sites. Analysis shows that the Mediterranean urban-industrial aerosols appear "moderately" absorbing with values of SSA close to ~0.94-0.95 ± 0.04 (at 440 nm) in most cases except over the large cities of Rome and Athens, where aerosol appears more absorbing (SSA ~0.89-0.90 ± 0.04). The aerosol Absorption Angström Exponent (AAE, estimated using 440 and 870 nm) is found to be larger than 1 for most sites over the Mediterranean, a manifestation of mineral dust (iron) and/or brown carbon producing the observed absorption. AERONET level-2 sun-photometer data indicate a possible East-West gradient, with higher values over the eastern basin (AAEEast = 1.39/AAEWest = 1.33). The North-South AAE gradient is more pronounced, especially over the western basin. Our additional analysis of AERONET level-1.5 data also shows that organic absorbing aerosols significantly affect some Mediterranean sites. These results indicate that current climate models treating organics as nonabsorbing over the Mediterranean certainly underestimate the warming effect due to carbonaceous aerosols

Unusual consequences of status epilepticus in Dravet syndrome

AbstractAlthough status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected

Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: A European consensus statement

Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patient

Specific Mesenchymal/Epithelial Induction of Olfactory Receptor, Vomeronasal, and Gonadotropin-Releasing Hormone (GnRH) Neurons

We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs), and gonadotropin-releasing hormone (GnRH) neurons, the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions specify the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons.Molecular and Cellular Biolog

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Three-dimensional coherent X-ray diffraction imaging of a ceramic nanofoam: determination of structural deformation mechanisms

Ultra-low density polymers, metals, and ceramic nanofoams are valued for their high strength-to-weight ratio, high surface area and insulating properties ascribed to their structural geometry. We obtain the labrynthine internal structure of a tantalum oxide nanofoam by X-ray diffractive imaging. Finite element analysis from the structure reveals mechanical properties consistent with bulk samples and with a diffusion limited cluster aggregation model, while excess mass on the nodes discounts the dangling fragments hypothesis of percolation theory.Comment: 8 pages, 5 figures, 30 reference

Electricity savings and greenhouse gas emission reductions from global phase-down of hydrofluorocarbons

Hydrofluorocarbons (HFCs) are widely used as cooling agents in refrigeration and air conditioning, as solvents in industrial processes, as fire-extinguishing agents, for foam blowing, and as aerosol propellants. They have been used in large quantities as the primary substitutes for ozone-depleting substances regulated under the Montreal Protocol. However, many HFCs are potent greenhouse gases (GHGs) and as such subject to global phase-down under the Kigali Amendment (KA) to the Montreal Protocol. In this study, we develop a range of long-term scenarios for HFC emissions under varying degrees of stringency in climate policy and assess co-benefits in the form of electricity savings and associated reductions in GHG and air pollutant emissions. Due to technical opportunities to improve energy efficiency in cooling technologies, there exist potentials for significant electricity savings under a well-managed phase-down of HFCs. Our results reveal that the opportunity to simultaneously improve energy efficiency in stationary cooling technologies could bring additional climate benefits of about the same magnitude as that attributed to the HFCs phase-down. If technical energy efficiency improvements are fully implemented, the resulting electricity savings could exceed 20 % of future global electricity consumption, while the corresponding figure for economic energy efficiency improvements would be about 15 %. The combined effect of HFC phase-down, energy efficiency improvement of the stationary cooling technologies, and future changes in the electricity generation fuel mix would prevent between 411 and 631 Pg CO2 equivalent of GHG emissions between 2018 and 2100, thereby making a significant contribution towards keeping the global temperature rise below 2 ∘C. Reduced electricity consumption also means lower air pollution emissions in the power sector, estimated at about 5 %–10 % for sulfur dioxide (SO2), 8 %–16 % for nitrogen oxides (NOx), and 4 %–9 % for fine particulate matter (PM2.5) emissions compared with a pre-Kigali baseline