Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Free amino acids in Arctic salt-marsh coastal sites and plant nitrogen acquisition

The importance of free amino acids as a source of plant nitrogen was examined in an Arctic coastal salt-marsh. Concentrations of inorganic nitrogen in salt-marsh soils were low relative to those reported for most temperate soils, whereas soluble organic nitrogen concentrations of salt-marsh soils were relatively high; the median ratio of free amino acid nitrogen as a proportion of ammonium nitrogen was 0.36 and amino acid concentrations exceeded those of ammonium in 24% of samples. Growth of the salt-marsh grass 'Puccinellia phryganodes' on glycine in a continuous flow hydroponic medium was similar to growth on ammonium ions at an equivalent concentration of nitrogen. Furthermore, in short-term excised root uptake experiments, rates of glycine uptake were equal to rates of ammonium and nitrate uptake combined when roots were provided with all three nitrogen substrates at equal concentrations. Amino acid uptake relative to ammonium uptake was favoured at high temperatures, high salinity and low pH. Free amino acids turned over rapidly in the soil, with half-lives in the soil solution ranging from 8-23 h for glycine, compared with ranges of 6-15 h and 6-16 h for ammonium and nitrate ions, respectively. Plant incorporation of 15N tracer injected into soil cores was 56, 83, and 68% of incorporation by soil microorganisms for glycine, ammonium and nitrate ions, respectively. The simultaneous incorporation of 13C and 15N into plant roots following injection of 13C15N-glycine into soil cores indicated that at least a portion of this amino acid was absorbed intact. In a model of the dynamics of nitrogen movement in an Arctic salt-marsh grazed and grubbed by geese, the direct uptake of organic nitrogen by plant roots was required to obtain rates of mineralization consistent with empirical estimates. Overall, these results indicate that free amino acids are likely a substantial contribution to plant nitrogen nutrition in Arctic coastal marshes

Contrasting effects of freezing-stress memory on biomass production among herbaceous plant species

Prior exposure to freezing can increase the subsequent freezing tolerance of plants and reduce the severity of injury. However, it is unknown how freezing memory influences plant productivity. We investigated the effects of repeated freezing events over multiple seasons on the biomass of Bromus inermis, Lolium perenne, Festuca rubra, Plantago lanceolata, and Poa pratensis. The plants were exposed to different combinations of freezing in the early spring, late spring, or fall (2017), as well as the following spring (2018); control plants were frozen only once, along with all of the other treatments, during the spring of 2018. Bromus inermis that experienced every freeze, and the plants frozen in both the early and late spring, had higher biomass than the controls. Similarly, Poa pratensis plants frozen in both the early and late spring had higher biomass than the controls. In contrast, Festuca rubra plants frozen in early spring and fall had lower root biomass than the control plants, and Lolium perenne plants that experienced every freeze had lower root biomass than the controls. Variation among species in repeated freezing responses could have important consequences for the relative abundances of herbaceous species in northern temperate regions.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Development of Fertilizer Coatings from Polyglyoxylate-Polyester Blends Responsive to Root-Driven pH Change

Copyright © 2019 American Chemical Society. Many current controlled-release fertilizers (CRFs) are coated with nonbiodegradable polymers that can contribute to microplastic pollution. Here, coatings of self-immolative poly(ethyl glyoxylate) (PEtG) capped with a carbamate and blended with polycaprolactone (PCL) or poly(l-lactic acid) (PLA) were evaluated. They were designed to depolymerize and release fertilizers in the vicinity of plant roots, where the pH is lower than that in the surrounding environment. PEtG/PCL coatings exhibited significant temperature and pH effects, requiring 18 days at pH 5 and 30 °C, compared to 77 days at pH 7 and 22 °C, to reach 15% mass loss. Plant roots were also effective in triggering coating degradation. Spray-coating and melt-coating were explored, with the latter being more effective in providing pellets that retained urea prior to polymer degradation. Finally, PEtG/PCL-coated pellets promoted plant growth to a similar degree or better than currently available CRFs

Photoinduced Degradation of Polymer Films Using Polyglyoxylate-Polyester Blends and Copolymers

© 2018 American Chemical Society. Polymeric coatings are commonly employed to alter surface properties. While some coatings are designed to remain stable over a prolonged period, in applications such as pharmaceuticals or fertilizers, the coating is designed to erode and reveal or release the underlying material. Self-immolative polymers (SIPs) undergo depolymerization following the cleavage of stimuli-responsive end-caps from their termini, enabling controlled depolymerization in the solid state and in solution. Poly(ethyl glyoxylate) (PEtG) is a promising SIP because of its depolymerization to benign products, but its amorphous structure and low glass-transition temperature make it unsuitable alone for coating applications. This study explored the blending of PEtG with polyesters including polycaprolactone (PCL), poly(l-lactic acid), and poly(R-3-hydroxybutyrate). Block copolymers of PEtG with PCL were also synthesized and studied. It was found that the phase separation behavior and consequently the thermal and mechanical properties of the materials could be tuned according to the composition of the blend, while the stimuli-responsive degradation of PEtG was retained in the blends. This work therefore provides a framework for the application of PEtG-based coatings in applications ranging from pharmaceuticals to agricultural products