Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

Broadband Submillimeter Receivers Using Same Mechanical Block

International audienceWe present the performances of two sensitive submillimeter receivers operating in distinct bandwidth ranges: 330-540 GHz and 430-660 GHz, by using a unique robust, assembly-friendly, space-qualified fix-tuned mixer block. Only the corrugated horns and SIS devices have been swapped. The Fourier Transform Spectrometry measurements show 50% frequency bandwidth and the uncorrected measured DSB noise temperatures were less than 7 times the quantum limit in both cases. Index TermsFix-tuned mixer block, twin SIS junction, broad bandwidths

Broadband Submillimeter Receivers Using Same Mechanical Block

International audienceWe present the performances of two sensitive submillimeter receivers operating in distinct bandwidth ranges: 330-540 GHz and 430-660 GHz, by using a unique robust, assembly-friendly, space-qualified fix-tuned mixer block. Only the corrugated horns and SIS devices have been swapped. The Fourier Transform Spectrometry measurements show 50% frequency bandwidth and the uncorrected measured DSB noise temperatures were less than 7 times the quantum limit in both cases. Index TermsFix-tuned mixer block, twin SIS junction, broad bandwidths

Broadband Submillimeter Receivers Using Same Mechanical Block

International audienceWe present the performances of two sensitive submillimeter receivers operating in distinct bandwidth ranges: 330-540 GHz and 430-660 GHz, by using a unique robust, assembly-friendly, space-qualified fix-tuned mixer block. Only the corrugated horns and SIS devices have been swapped. The Fourier Transform Spectrometry measurements show 50% frequency bandwidth and the uncorrected measured DSB noise temperatures were less than 7 times the quantum limit in both cases. Index TermsFix-tuned mixer block, twin SIS junction, broad bandwidths

Zika virus cell tropism in the developing human brain and inhibition by azithromycin.

The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic

Zika virus cell tropism in the developing human brain and inhibition by azithromycin

The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone, such as calcifications in the cortical plate. Furthermore, we find that blocking the glia-enriched putative viral entry receptor AXL reduced ZIKV infection of astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection. Finally, we evaluate 2,177 compounds, focusing on drugs safe in pregnancy. We show that the macrolide antibiotic azithromycin reduced viral proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes. Our characterization of infection in the developing human brain clarifies the pathogenesis of congenital ZIKV infection and provides the basis for investigating possible therapeutic strategies to safely alleviate or prevent the most severe consequences of the epidemic

Nests of dividing neuroblasts sustain interneuron production for the developing human brain

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain

Precocious deposition of perineuronal nets on Parvalbumin inhibitory neurons transplanted into adult visual cortex

The end of the critical period for primary visual cortex (V1) coincides with the deposition of perineuronal nets (PNN) onto Parvalbumin (PV) inhibitory neurons. Recently, we found that transplantation of embryonic inhibitory neurons into adult V1 reinstates a new critical period. Here we used Wisteria Floribunda Agglutinin (WFA) staining to compare the deposition of PNNs onto neurons during normal development and following transplantation at equivalent cell ages. In accord with previous findings, PV and PNN expression increases from negligible levels at postnatal day 14 (P14) to mature levels by P70. In contrast to P14, PNNs are found on transplanted PV neurons by 21 days after transplantation and persist to 105 days after transplantation. This precocious deposition was specific to PV neurons and excluded transplanted neurons expressing Somatostatin. Notably, the onset of PV expression in transplanted inhibitory neurons follows the timing of PV expression in juvenile V1. Moreover, transplantation has no discernible effect on host PNNs. The precocious deposition of PNNs onto transplanted PV neurons suggests that PNN expression identified by WFA does not reflect neuronal maturity and may be an inaccurate marker for transplant-induced plasticity of cortical circuits