Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination

The contribution of oligodendrocytes to remyelination in functional recovery after spinal cord injury is not fully understood. Here, the authors show that oligodendrocyte progenitor cell differentiation is not required for functional recovery after spinal cord injury in mice

Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer

The folate derivatives folic acid (FA) and folinic acid (FNA) decrease the in vivo and in vitro activities of antifolate drugs in Plasmodium falciparum. However, the effects of 5-methyl-tetrahydrofolate (5-Me-THF) and tetrahydrofolate (THF), the two dominant circulating folate forms in humans, have not been explored yet. We have investigated the effects of FA, FNA, 5-Me-THF, and THF on the in vitro activity of the antimalarial antifolates pyrimethamine and chlorcycloguanil and the anticancer antifolates methotrexate (MTX), aminopterin, and trimetrexate (TMX), against P. falciparum. The results indicate that these anticancers are potent against P. falciparum, with IC50 < 50 nM. 5-Me-THF does not significantly decrease the activity of all tested drugs, and none of the tested folate derivatives significantly decrease the activity of these anticancers. Thus, malaria folate metabolism has features different from those in human, and the exploitation of this difference could lead to the discovery of new drugs to treat malaria. For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria

Structural and regulatory diversity shape HLA-C protein expression levels

Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression

Long-term changes in habitat and trophic level of Southern Ocean squid in relation to environmental conditions

Long-term studies of pelagic nekton in the Southern Ocean and their responses to ongoing environmental change are rare. Using stable isotope ratios measured in squid beaks recovered from diet samples of wandering albatrosses Diomedea exulans, we assessed decadal variation (from 1976 to 2016) in the habitat (δ13C) and trophic level (δ15N) of five important Southern Ocean squid species in relation to indices of environmental conditions—Southern Oscillation Index (SOI) and Southern Annular Mode (SAM). Based on δ13C values, corrected for the Suess effect, habitat had changed over the last 50 years for Taonius sp. B (Voss), Gonatus antarcticus, Galiteuthis glacialis and Histioteuthis atlantica but not Moroteuthopsis longimana. By comparison, mean δ15N values were similar across decades for all five species, suggesting minimal changes in trophic levels. Both SAM and SOI have increased in strength and frequency over the study period but, of the five species, only in Taonius sp. B (Voss) did these indices correlate with, δ13C and δ15N values, indicating direct relationships between environmental conditions, habitat and trophic level. The five cephalopod species therefore changed their habitats with changing environmental conditions over the last 50 years but maintained similar trophic levels. Hence, cephalopods are likely to remain important prey for top predators in Southern Ocean food webs, despite ongoing climate change

European Society of Endodontology position statement: Management of deep caries and the exposed pulp

This position statement on the management of deep caries and the exposed pulp represents the consensus of an expert committee, convened by the European Society of Endodontology (ESE). Preserving the pulp in a healthy state with sustained vitality, preventing apical periodontitis and developing minimally invasive biologically based therapies are key themes within contemporary clinical endodontics. The aim of this statement was to summarize current best evidence on the diagnosis and classification of deep caries and caries‐induced pulpal disease, as well as indicating appropriate clinical management strategies for avoiding and treating pulp exposure in permanent teeth with deep or extremely deep caries. In presenting these findings, areas of controversy, low‐quality evidence and uncertainties are highlighted, prior to recommendations for each area of interest. A recently published review article provides more detailed information and was the basis for this position statement (Bjørndal et al. 2019, International Endodontic Journal, doi:10.1111/iej.13128). The intention of this position statement is to provide the practitioner with relevant clinical guidance in this rapidly developing area. An update will be provided within 5 years as further evidence emerges

High proportion of cactus species threatened with extinction

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.Consejo Nacional de Ciencia y Tecnologí