α-Synuclein Oligomers Displace Monomeric α-Synuclein from Lipid Membranes.

Parkinson's disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder linked to the accumulation of α-synuclein (αS) protein aggregates in the nervous system. While αS binding to membranes in its monomeric state is correlated to its physiological role, αS oligomerization and subsequent aberrant interactions with lipid bilayers have emerged as key steps in PD-associated neurotoxicity. However, little is known of the mechanisms that govern the interactions of oligomeric αS (OαS) with lipid membranes and the factors that modulate such interactions. This is in large part due to experimental challenges underlying studies of OαS-membrane interactions due to their dynamic and transient nature. Here, we address this challenge by using a suite of microfluidics-based assays that enable in-solution quantification of OαS-membrane interactions. We find that OαS bind more strongly to highly curved, rather than flat, lipid membranes. By comparing the membrane-binding properties of OαS and monomeric αS (MαS), we further demonstrate that OαS bind to membranes with up to 150-fold higher affinity than their monomeric counterparts. Moreover, OαS compete with and displace bound MαS from the membrane surface, suggesting that disruption to the functional binding of MαS to membranes may provide an additional toxicity mechanism in PD. These findings present a binding mechanism of oligomers to model membranes, which can potentially be targeted to inhibit the progression of PD.

Effects of plant diversity on productivity strengthen over time due to trait-dependent shifts in species overyielding.

Plant diversity effects on community productivity often increase over time. Whether the strengthening of diversity effects is caused by temporal shifts in species-level overyielding (i.e., higher species-level productivity in diverse communities compared with monocultures) remains unclear. Here, using data from 65 grassland and forest biodiversity experiments, we show that the temporal strength of diversity effects at the community scale is underpinned by temporal changes in the species that yield. These temporal trends of species-level overyielding are shaped by plant ecological strategies, which can be quantitatively delimited by functional traits. In grasslands, the temporal strengthening of biodiversity effects on community productivity was associated with increasing biomass overyielding of resource-conservative species increasing over time, and with overyielding of species characterized by fast resource acquisition either decreasing or increasing. In forests, temporal trends in species overyielding differ when considering above- versus belowground resource acquisition strategies. Overyielding in stem growth decreased for species with high light capture capacity but increased for those with high soil resource acquisition capacity. Our results imply that a diversity of species with different, and potentially complementary, ecological strategies is beneficial for maintaining community productivity over time in both grassland and forest ecosystems.

Transformation scenarios towards multifunctional landscapes: A multi-criteria land-use allocation model applied to Jambi Province, Indonesia.

In tropical regions, shifting from forests and traditional agroforestry to intensive plantations generates conflicts between human welfare (farmers' demands and societal needs) and environmental protection. Achieving sustainability in this transformation will inevitably involve trade-offs between multiple ecological and socioeconomic functions. To address these trade-offs, our study used a new methodological approach allowing the identification of transformation scenarios, including theoretical landscape compositions that satisfy multiple ecological functions (i.e., structural complexity, microclimatic conditions, organic carbon in plant biomass, soil organic carbon and nutrient leaching losses), and farmers needs (i.e., labor and input requirements, total income to land, and return to land and labor) while accounting for the uncertain provision of these functions and having an actual potential for adoption by farmers. We combined a robust, multi-objective optimization approach with an iterative search algorithm allowing the identification of ecological and socioeconomic functions that best explain current land-use decisions. The model then optimized the theoretical land-use composition that satisfied multiple ecological and socioeconomic functions. Between these ends, we simulated transformation scenarios reflecting the transition from current land-use composition towards a normative multifunctional optimum. These transformation scenarios involve increasing the number of optimized socioeconomic or ecological functions, leading to higher functional richness (i.e., number of functions). We applied this method to smallholder farms in the Jambi Province, Indonesia, where traditional rubber agroforestry, rubber plantations, and oil palm plantations are the main land-use systems. Given the currently practiced land-use systems, our study revealed short-term returns to land as the principal factor in explaining current land-use decisions. Fostering an alternative composition that satisfies additional socioeconomic functions would require minor changes ("low-hanging fruits"). However, satisfying even a single ecological indicator (e.g., reduction of nutrient leaching losses) would demand substantial changes in the current land-use composition ("moonshot"). This would inevitably lead to a profit decline, underscoring the need for incentives if the societal goal is to establish multifunctional agricultural landscapes. With many oil palm plantations nearing the end of their production cycles in the Jambi province, there is a unique window of opportunity to transform agricultural landscapes.

Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2.

SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding of the protection against infection with SARS-CoV-2 is critical to ending the pandemic. Serological assays have been widely used to assess immune responses, but secretory antibodies, the essential first line of defense, have been studied to only a limited extent. Of particular interest and importance are neutralizing antibodies, which block the binding of the spike protein of SARS-CoV-2 to the human receptor angiotensin-converting enzyme-2 (ACE2) and thus are essential for immune defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, to characterize neutralizing antibody affinity to SARS-CoV-2 spike receptor-binding domain (RBD) and spike trimer in saliva. Affinity measurement was obtained through a contrived sample and buffer using recombinant SARS-CoV-2 RBD and monoclonal antibody. Limited saliva samples demonstrated that MDS applies to saliva neutralizing antibody measurement. The ability to disrupt a complex of ACE2-Fc and spike trimer is shown. Using a quantitative assay on the patient sample, we determined the affinity and binding site concentration of the neutralizing antibodies.