Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration

Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration.     

Key Ecological Function Peaks at the Land–Ocean Transition Zone When Vertebrate Scavengers Concentrate on Ocean Beaches

Ecosystems - Ecotones can form hot spots of biodiversity by containing species from multiple ecosystems. Because biodiversity is often linked to ecological function, we posit that rates of key...     

Increased high‐latitude photosynthetic carbon gain offset by respiration carbon loss during an anomalous warm winter to spring transition

Arctic and boreal ecosystems play an important role in the global carbon (C) budget, and whether they act as a future net C sink or source depends on climate and environmental change. Here, we used complementary in situ measurements, model simulations, and satellite observations to investigate the net carbon dioxide (CO₂) seasonal cycle and its climatic and environmental controls across Alaska and northwestern Canada during the anomalously warm winter to spring conditions of 2015 and 2016 (relative to 2010–2014). In the warm spring, we found that photosynthesis was enhanced more than respiration, leading to greater CO₂ uptake. However, photosynthetic enhancement from spring warming was partially offset by greater ecosystem respiration during the preceding anomalously warm winter, resulting in nearly neutral effects on the annual net CO₂ balance. Eddy covariance CO₂ flux measurements showed that air temperature has a primary influence on net CO₂ exchange in winter and spring, while soil moisture has a primary control on net CO₂ exchange in the fall. The net CO₂ exchange was generally more moisture limited in the boreal region than in the Arctic tundra. Our analysis indicates complex seasonal interactions of underlying C cycle processes in response to changing climate and hydrology that may not manifest in changes in net annual CO₂ exchange. Therefore, a better understanding of the seasonal response of C cycle processes may provide important insights for predicting future carbon–climate feedbacks and their consequences on atmospheric CO₂ dynamics in the northern high latitudes.     

Projected climate and land use change alter western blacklegged tick phenology,seasonal host‐seeking suitability and human encounter risk in California

Global environmental change is having profound effects on the ecology of infectious disease systems, which are widely anticipated to become more pronounced under future climate and land use change. Arthropod vectors of disease are particularly sensitive to changes in abiotic conditions such as temperature and moisture availability. Recent research has focused on shifting environmental suitability for, and geographic distribution of, vector species under projected climate change scenarios. However, shifts in seasonal activity patterns, or phenology, may also have dramatic consequences for human exposure risk, local vector abundance and pathogen transmission dynamics. Moreover, changes in land use are likely to alter human–vector contact rates in ways that models of changing climate suitability are unlikely to capture. Here we used climate and land use projections for California coupled with seasonal species distribution models to explore the response of the western blacklegged tick (Ixodes pacificus), the primary Lyme disease vector in western North America, to projected climate and land use change. Specifically, we investigated how environmental suitability for tick host‐seeking changes seasonally, how the magnitude and direction of changing seasonal suitability differs regionally across California, and how land use change shifts human tick‐encounter risk across the state. We found vector responses to changing climate and land use vary regionally within California under different future scenarios. Under a hotter, drier scenario and more extreme land use change, the duration and extent of seasonal host‐seeking activity increases in northern California, but declines in the south. In contrast, under a hotter, wetter scenario seasonal host‐seeking declines in northern California, but increases in the south. Notably, regardless of future scenario, projected increases in developed land adjacent to current human population centers substantially increase potential human–vector encounter risk across the state. These results highlight regional variability and potential nonlinearity in the response of disease vectors to environmental change.     

MMS2plot: An R Package for Visualizing Multiple MS/MS Spectra for Groups of Modified and Non‐Modified Peptides

A large number of post‐translational modifications (PTMs) in proteins are buried in the unassigned mass spectrometric (MS) spectra in shot‐gun proteomics datasets. Because the modified peptide fragments are low in abundance relative to the corresponding non‐modified versions, it is critical to develop tools that allow facile evaluation of assignment of PTMs based on the MS/MS spectra. Such tools will preferably have the ability to allow comparison of fragment ion spectra and retention time between the modified and unmodified peptide pairs or group. Herein, MMS2plot, an R package for visualizing peptide‐spectrum matches (PSMs) for multiple peptides, is described. MMS2plot features a batch mode and generates the output images in vector graphics file format that facilitate evaluation and publication of the PSM assignment. MMS2plot is expected to play an important role in PTM discovery from large‐scale proteomics datasets generated by liquid chromatography‐MS/MS. The MMS2plot package is freely available at https://github.com/lileir/MMS2plot under the GPL‐3 license.