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Human wild-type Superoxide dismutase-1 (wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic lateral sclerosis (FALS), in double transgenic models of FALS, and in cell culture systems, but the structural determinants of this process are unclear. Here we molecularly dissect the effects of intracellular and cell-free obligately misfolded SOD1 mutant proteins on natively structured wild-type SOD1. Expression of the enzymatically inactive, natural familial ALS SOD1 mutations G127X and G85R in human mesenchymal and neural cell lines induces misfolding of wild-type natively structured SOD1, as indicated by: acquisition of immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly enhanced protease sensitivity suggestive of structural loosening; and nonnative disulfide-linked oligomer and multimer formation. Expression of G127X and G85R in mouse cell lines did not induce misfolding of murine wtSOD1, and a species restriction element for human wtSODI conversion was mapped to a region of sequence divergence in loop II and β-strand 3 of the SOD1 β-barrel (residues 24-36), then further refined surprisingly to a single tryptophan residue at codon 32 (W32) in human SOD1. Time course experiments enabled by W32 restriction revealed that G127X and misfolded wtSOD1 can induce misfolding of cell-endogenous wtSOD1. Finally, aggregated recombinant G127X is capable of inducing misfolding and protease sensitivity of recombinant human wtSOD1 in a cell-free system containing reducing and chelating agents; cell-free wtSOD1 conversion was also restricted by W32. These observations demonstrate that misfolded SOD1 can induce misfolding of natively structured wtSOD1 in a physiological intracellular milieu, consistent with a direct protein-protein interaction.

Satellite observations of Amazon forests show seasonal and interannual variations, but the underlying biological processes remain debated. Here we combined radiative transfer models (RTMs) with field observations of Amazon forest leaf and canopy characteristics to test three hypotheses for satellite-observed canopy reflectance seasonality: seasonal changes in leaf area index, in canopy-surface leafless crown fraction and/or in leaf demography. Canopy RTMs (PROSAIL and FLiES), driven by these three factors combined, simulated satellite-observed seasonal patterns well, explaining c. 70% of the variability in a key reflectance-based vegetation index (MAIAC EVI, which removes artifacts that would otherwise arise from clouds/aerosols and sun–sensor geometry). Leaf area index, leafless crown fraction and leaf demography independently accounted for 1, 33 and 66% of FLiES-simulated EVI seasonality, respectively. These factors also strongly influenced modeled near-infrared (NIR) reflectance, explaining why both modeled and observed EVI, which is especially sensitive to NIR, captures canopy seasonal dynamics well. Our improved analysis of canopy-scale biophysics rules out satellite artifacts as significant causes of satellite-observed seasonal patterns at this site, implying that aggregated phenology explains the larger scale remotely observed patterns. This work significantly reconciles current controversies about satellite-detected Amazon phenology, and improves our use of satellite observations to study climate–phenology relationships in the tropics.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis . This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M .  fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs. A large-scale single-cell transcriptomic atlas of the non-human primate Macaca fascicularis encompasses over 1 million cells from 45 adult tissues.

The observed cooperation on the level of genes, cells, tissues, and individuals has been the object of intense study by evolutionary biologists, mainly because cooperation often flourishes in biological systems in apparent contradiction to the selfish goal of survival inherent in Darwinian evolution. In order to resolve this paradox, evolutionary game theory has focused on the Prisoner's Dilemma (PD), which incorporates the essence of this conflict. Here, we encode strategies for the iterated Prisoner's Dilemma (IPD) in terms of conditional probabilities that represent the response of decision pathways given previous plays. We find that if these stochastic strategies are encoded as genes that undergo Darwinian evolution, the environmental conditions that the strategies are adapting to determine the fixed point of the evolutionary trajectory, which could be either cooperation or defection. A transition between cooperative and defective attractors occurs as a function of different parameters such as mutation rate, replacement rate, and memory, all of which affect a player's ability to predict an opponent's behavior. These results imply that in populations of players that can use previous decisions to plan future ones, cooperation depends critically on whether the players can rely on facing the same strategies that they have adapted to. Defection, on the other hand, is the optimal adaptive response in environments that change so quickly that the information gathered from previous plays cannot usefully be integrated for a response.

Ribonuclease mitochondrial RNA processing, a site-specific endoribonuclease involved in primer RNA metabolism in mammalian mitochondria, requires an RNA component for its activity. On the basis of copurification and selective inactivation with complementary oligonucleotides, a 135-nucleotide RNA species, not encoded in the mitochondrial genome, is identified as the RNA moiety of the endoribonuclease. This finding implies transport of a nucleus-encoded RNA, essential for organelle DNA replication, to the mitochondrial matrix.