Our findings demonstrate a folded protein system in which spontaneously formed intermolecular disulfide bonds initiate amyloid fibril formation by recruitment of monomers. This dimer-induced aggregation mechanism may be of relevance for human amyloid diseases in which oxidative stress is often an associated hallmark.Land-use intensification can increase provisioning ecosystem services, such as food and timber production, but it also drives changes in ecosystem functioning and biodiversity loss, which may ultimately compromise human wellbeing. To understand how changes in land-use intensity affect the relationships between biodiversity, ecosystem functions, and services, we built networks from correlations between the species richness of 16 trophic groups, 10 ecosystem functions, and 15 ecosystem services. We evaluated how the properties of these networks varied across land-use intensity gradients for 150 forests and 150 grasslands. Land-use intensity significantly affected network structure in both habitats. Changes in connectance were larger in forests, while changes in modularity and evenness were more evident in grasslands. Our results show that increasing land-use intensity leads to more homogeneous networks with less integration within modules in both habitats, driven by the belowground compartment in grasslands, while forest responses to land management were more complex. Land-use intensity strongly altered hub identity and module composition in both habitats, showing that the positive correlations of provisioning services with biodiversity and ecosystem functions found at low land-use intensity levels, decline at higher intensity levels. Our approach provides a comprehensive view of the relationships between multiple components of biodiversity, ecosystem functions, and ecosystem services and how they respond to land use. This can be used to identify overall changes in the ecosystem, to derive mechanistic hypotheses, and it can be readily applied to further global change drivers.An essential mechanism for severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2).  https://www.selleckchem.com/products/zeocin.html  Here, we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest-affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human immunoglobulin crystallizable fragment (Fc) domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2-pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50s) in the 10- to 100-ng/mL range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-using coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be predesigned for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated from convalescent patients.The periplasmic chaperone network ensures the biogenesis of bacterial outer membrane proteins (OMPs) and has recently been identified as a promising target for antibiotics. SurA is the most important member of this network, both due to its genetic interaction with the β-barrel assembly machinery complex as well as its ability to prevent unfolded OMP (uOMP) aggregation. Using only binding energy, the mechanism by which SurA carries out these two functions is not well-understood. Here, we use a combination of photo-crosslinking, mass spectrometry, solution scattering, and molecular modeling techniques to elucidate the key structural features that define how SurA solubilizes uOMPs. Our experimental data support a model in which SurA binds uOMPs in a groove formed between the core and P1 domains. This binding event results in a drastic expansion of the rest of the uOMP, which has many biological implications. Using these experimental data as restraints, we adopted an integrative modeling approach to create a sparse ensemble of models of a SurA•uOMP complex. We validated key structural features of the SurA•uOMP ensemble using independent scattering and chemical crosslinking data. Our data suggest that SurA utilizes three distinct binding modes to interact with uOMPs and that more than one SurA can bind a uOMP at a time. This work demonstrates that SurA operates in a distinct fashion compared to other chaperones in the OMP biogenesis network.Resting-state functional connectivity is used throughout neuroscience to study brain organization and to generate biomarkers of development, disease, and cognition. The processes that give rise to correlated activity are, however, poorly understood. Here we decompose resting-state functional connectivity using a temporal unwrapping procedure to assess the contributions of moment-to-moment activity cofluctuations to the overall connectivity pattern. This approach temporally resolves functional connectivity at a timescale of single frames, which enables us to make direct comparisons of cofluctuations of network organization with fluctuations in the blood oxygen level-dependent (BOLD) time series. We show that surprisingly, only a small fraction of frames exhibiting the strongest cofluctuation amplitude are required to explain a significant fraction of variance in the overall pattern of connection weights as well as the network's modular structure. These frames coincide with frames of high BOLD activity amplitude, corresponding to activity patterns that are remarkably consistent across individuals and identify fluctuations in default mode and control network activity as the primary driver of resting-state functional connectivity.