Mature oligodendrocytes bordering lesions limit demyelination and favor myelin repair via heparan sulphate production

International audienceMyelin destruction is followed by resident glia activation and mobilization of endogenous progenitors (OPC) which participate in myelin repair. Here we show that in response to demyelination, mature oligodendrocytes (OLG) bordering the lesion express Ndst1, a key enzyme for heparan sulfates (HS) synthesis. Ndst1+ OLG form a belt that demarcates lesioned from intact white matter. Mice with selective inactivation of Ndst1 in the OLG lineage display increased lesion size, sustained microglia and OPC reactivity. HS production around the lesion allows Sonic hedgehog (Shh) binding and favors the local enrichment of this morphogen involved in myelin regeneration. In MS patients, Ndst1 is also found overexpressed in oligodendroglia and the number of Ndst1-expressing oligodendroglia is inversely correlated with lesion size and positively correlated with remyelination potential. Our study suggests that mature OLG surrounding demyelinated lesions are not passive witnesses but contribute to protection and regeneration by producing HS

Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function

The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are often differentially affected in human neurodegenerative diseases across CNS region, age and sex. We hypothesize that this selective vulnerability is underpinned by physiological variation in white matter glia. Using single nucleus RNA sequencing of human post-mortem white matter samples from the brain, cerebellum and spinal cord and subsequent tissue-based validation we found substantial glial heterogeneity with tissue region: we identified region-specific oligodendrocyte precursor cells (OPCs) that retain developmental origin markers into adulthood, distinguishing them from mouse OPCs. Region-specific OPCs give rise to similar oligodendrocyte populations, however spinal cord oligodendrocytes exhibit markers such as SKAP2 which are associated with increased myelin production and we found a spinal cord selective population particularly equipped for producing long and thick myelin sheaths based on the expression of genes/proteins such as HCN2. Spinal cord microglia exhibit a more activated phenotype compared to brain microglia, suggesting that the spinal cord is a more pro-inflammatory environment, a difference that intensifies with age. Astrocyte gene expression correlates strongly with CNS region, however, astrocytes do not show a more activated state with region or age. Across all glia, sex differences are subtle but the consistent increased expression of protein-folding genes in male donors hints at pathways that may contribute to sex differences in disease susceptibility. These findings are essential to consider for understanding selective CNS pathologies and developing tailored therapeutic strategies

Generic Revision of the Holocystitidae of North America (Diploporita, Echinodermata) Based on Universal Elemental Homology

The Holocystites Fauna is an enigmatic group of North American diploporitans that presents a rare window into unusual middle Silurian echinoderm communities. Multiple systematic revisions have subdivided holocystitids on the basis of presumed differences in oral area plating and respiratory structures. However, these differences were based on a fundamental misunderstanding of the homologous elements of the oral area and the taphonomic process; taphonomic disarticulation of the oral area formed the basis for the erection of Pentacystis and Osgoodicystis as separate genera, and Osgoodicystis is interpreted as the junior synonym of Pentacystis. Holocystitids show a conservative peristomial bordering plate pattern that is shared among all described genera. The peristome is bordered by seven interradially positioned oral plates as is typical for oral plate–bearing blastozoans. A second open circlet of facetal plates lies distal to the oral plates; five of these facetal plates bear facets for feeding appendages (lost on the A ambulacrum in some taxa), while two lateral facets (present in all taxa except Pustulocystis) do not. Holocystitid taxa show minor modifications to this basic peristomial bordering plate pattern. As thecal morphologies are highly variable within populations, taxonomic revision of holocystitids is based on modifications of the plating of the oral area

Contextual risk and psychosocial profiles of opioid-using mothers:a mixed-methods study

Abstract Introduction: There is an increase in cases of mothers using opioids during pregnancy in the United States but research investigating mothers’ psychosocial environments along with individual variability among this high-risk group of women is scarce. Methods: This mixed-methods study aims to examine the complex interplay of contextual risks and experiences of opioid-using mothers. A sample of 50 opioid-using biological mothers of infants diagnosed with neonatal opioid withdrawal syndrome (NOWS) were studied using a set of standardized and open-ended questions, along with medical records extraction. Results: A high-risk subgroup of 36 mothers was identified using cluster analysis, characterized by a distinct profile of psychosocial risk. Thematic content analysis revealed four themes: (1) barriers to communication and mistrust of health professionals, (2) limitations of access to health care and the amplification of disadvantages related to COVID-19, (3) lifelong consequences of adverse childhood experiences (ACEs), and (4) intimate partner violence and its influence on drug use. Conclusion: Our findings highlight important information toward health services provision for opioid-using women of childbearing age. Efforts to reduce opioid usage in mothers need to consider psychosocial and contextual risks

Nature and origins of mathematics difficulties in very preterm children: A different etiology than Developmental Dyscalculia

Background. Children born very preterm (<32 weeks) are at high risk for mathematics learning difficulties that are out of proportion to other academic and cognitive deficits. However, the aetiology of mathematics difficulties in very preterm children is unknown. We sought to identify the nature and origins of preterm children’s mathematics difficulties. Methods. 115 very preterm children aged 8-10 years were assessed in school with a control group of 77 term-born classmates. Achievement in mathematics, working memory, visuospatial processing, inhibition and processing speed were assessed using standardised tests. Numerical representations and specific mathematics skills were assessed using experimental tests. Results. Very preterm children had significantly poorer mathematics achievement, working memory and visuo-spatial skills than term-born controls. Although preterm children had poorer performance in specific mathematics skills, there was no evidence of imprecise numerical representations. Difficulties in mathematics were associated with deficits in visuospatial processing and working memory. Conclusions. Mathematics difficulties in very preterm children are associated with deficits in working memory and visuo-spatial processing not numerical representations. Thus very preterm children’s mathematics difficulties are different in nature from those of children with developmental dyscalculia. Interventions targeting general cognitive problems, rather than numerical representations, are needed to improve very preterm children’s achievement

Search for Scalar Diphoton Resonances in the Mass Range 65−60065-600 GeV with the ATLAS Detector in pppp Collision Data at s\sqrt{s} = 8 TeVTeV

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65–600 GeV is performed using $20.3\text{}\text{}{\mathrm{fb}}^{-1}$ of $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$ $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95% confidence level on the production cross section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches