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Alpha‐Synuclein Demonstrates Varying Binding Affinities With Different Tau Isoforms
No full textABSTRACT The hallmark of various neurodegenerative diseases is the accumulation and aggregation of amyloidogenic proteins, such as amyloid‐beta (Aβ) and tau in Alzheimer's disease ( AD ) and alpha‐synuclein (aSyn) in synucleinopathies. Many neurodegenerative diseases express mixed pathology. For instance, Lewy bodies are reported in tauopathies and neurofibrillary tau‐tangles are detected in synucleinopathies, suggesting a potential co‐existence or crosstalk of misfolded aSyn and tau. In the present study, we investigated the binding characteristics of monomeric aSyn with different tau isoforms by using surface plasmon resonance (SPR) spectroscopy allowing monitoring direct protein–protein interactions and their potential co‐localization using SH‐SY5Y cells. The calculation of the binding parameters (association and dissociation rate constants) indicated the strongest binding affinity between aSyn and tau isoform 1N3R followed by tau 2N3R and tau 2N4R. Co‐localization studies in SH‐SY5Y cells, treated with aSyn and all six tau isoforms revealed an intracellular co‐localization of aSyn with different isoforms of tau. Subcellular fractionation confirmed the cellular uptake and colocalization of tau and aSyn in the same compartment, showing their expression in membrane, nuclear, and cytoskeletal fractions. Understanding the intricate interplay between aSyn and tau is crucial for unraveling the pathophysiology of PD, AD , and related neurodegenerative disorders, ultimately paving the way for the development of effective treatments targeting this interaction. In conclusion, our data indicate that aSyn and tau are direct interaction partners with varying binding affinities depending on the tau isoform. This interaction may be significant for understanding the pathophysiology of dementia with mixed pathologies. imageAlzheimer Forschung Initiative https://doi.org/10.13039/10001014
Proteorhodopsin insights into the molecular mechanism of vectorial proton transport
No full textBacterial proton pumps, proteorhodopsins (PRs), are a major group of light-driven membrane proteins found in marine bacteria. They are functionally and structurally distinct from archaeal and eukaryotic proton pumps. To elucidate the proton transfer mechanism by PRs and understand the differences to nonbacterial pumps on a molecular level, high-resolution structures of PRs’ functional states are needed. In this work, we have determined atomic-resolution structures of MAR, a PR from marine actinobacteria, in various functional states, notably the challenging late O intermediate state. These data and information from recent atomic-resolution structures on an archaeal outward proton pump bacteriorhodopsin and bacterial inward proton pump xenorhodopsin allow for deducing key universal elements for light-driven proton pumping. First, long hydrogen-bonded chains characterize proton pathways. Second, short hydrogen bonds allow proton storage and inhibit their backflow. Last, the retinal Schiff base is the active proton donor and acceptor to and from hydrogen-bonded chains.Bacteria aptly use fundamental mechanisms for light-driven proton transfer across a membrane.Bacterial proton pumps, proteorhodopsins (PRs), are a major group of light-driven membrane proteins found in marine bacteria. They are functionally and structurally distinct from archaeal and eukaryotic proton pumps. To elucidate the proton transfer mechanism by PRs and understand the differences to nonbacterial pumps on a molecular level, high-resolution structures of PRs’ functional states are needed. In this work, we have determined atomic-resolution structures of MAR, a PR from marine actinobacteria, in various functional states, notably the challenging late O intermediate state. These data and information from recent atomic-resolution structures on an archaeal outward proton pump bacteriorhodopsin and bacterial inward proton pump xenorhodopsin allow for deducing key universal elements for light-driven proton pumping. First, long hydrogen-bonded chains characterize proton pathways. Second, short hydrogen bonds allow proton storage and inhibit their backflow. Last, the retinal Schiff base is the active proton donor and acceptor to and from hydrogen-bonded chains.Bacteria aptly use fundamental mechanisms for light-driven proton transfer across a membrane
Microbial life-history strategies and genomic traits between pristine and cropland soils
No full textABSTRACT Microbial life-history strategies [inferred from ribosomal RNA operon ( rrn ) gene copy numbers] and associated genomic traits and metabolism potentials in soil significantly influence ecosystem properties and functions globally. Yet, the differences in microbial strategies and traits between disturbed (cropland) and pristine soils, along with their dominant driving factors, remain underexplored. Our large-scale survey of 153 sites, including 84 croplands and 69 pristine soils, combined with long-term field experiments demonstrates that cropland soils support microbial communities with more candidate r-strategies characterized by higher rrn copy numbers and genomic traits conducive to rapid resource utilization. Conversely, pristine soils tend to host communities aligned with more candidate K-strategies marked by high resource use potentials. Elevated nitrogen (N) and phosphorus (P) levels in cropland soils emerge as key factors promoting these candidate r-strategies, overshadowing the influence of organic carbon content, soil structure, or climatic conditions. Results from four long-term field experiments also corroborate that sustained N and P inputs significantly elevate rrn copy numbers, favoring these candidate r-strategists. Our findings highlight that land use and fertilization practices critically shape microbial life-history strategies, with nutrient availability being a decisive factor in increasing the r-strategists in cropland soils. IMPORTANCE Microbial life-history strategies and genomic traits are key determinants shaping the response of populations to environmental impacts. In this paper, 84 cropland and 69 pristine soil samples were studied, and microorganisms in two ecosystems were categorized into two types of ecological groups using the classical copiotroph–oligotroph dichotomy, promoting a general understanding of the ecological roles of microorganisms. This study is the first to investigate the microbial life-history strategies under different land uses across five climatic zones in China. The results showed that the microbes in cropland soils are more copiotrophic than pristine soils. It also demonstrates that elevated levels of nitrogen and phosphorus in cropland soils are the key factors promoting these r-strategies. This observation emphasizes the critical role of nutrient management in shaping microbial community dynamics and ecosystem functioning and lays the foundation for predicting the response of microbial community composition under resource perturbation.Microbial life-history strategies and genomic traits are key determinants shaping the response of populations to environmental impacts. In this paper, 84 cropland and 69 pristine soil samples were studied, and microorganisms in two ecosystems were categorized into two types of ecological groups using the classical copiotroph–oligotroph dichotomy, promoting a general understanding of the ecological roles of microorganisms. This study is the first to investigate the microbial life-history strategies under different land uses across five climatic zones in China. The results showed that the microbes in cropland soils are more copiotrophic than pristine soils. It also demonstrates that elevated levels of nitrogen and phosphorus in cropland soils are the key factors promoting these r-strategies. This observation emphasizes the critical role of nutrient management in shaping microbial community dynamics and ecosystem functioning and lays the foundation for predicting the response of microbial community composition under resource perturbation.ABSTRACT Microbial life-history strategies [inferred from ribosomal RNA operon ( rrn ) gene copy numbers] and associated genomic traits and metabolism potentials in soil significantly influence ecosystem properties and functions globally. Yet, the differences in microbial strategies and traits between disturbed (cropland) and pristine soils, along with their dominant driving factors, remain underexplored. Our large-scale survey of 153 sites, including 84 croplands and 69 pristine soils, combined with long-term field experiments demonstrates that cropland soils support microbial communities with more candidate r-strategies characterized by higher rrn copy numbers and genomic traits conducive to rapid resource utilization. Conversely, pristine soils tend to host communities aligned with more candidate K-strategies marked by high resource use potentials. Elevated nitrogen (N) and phosphorus (P) levels in cropland soils emerge as key factors promoting these candidate r-strategies, overshadowing the influence of organic carbon content, soil structure, or climatic conditions. Results from four long-term field experiments also corroborate that sustained N and P inputs significantly elevate rrn copy numbers, favoring these candidate r-strategists. Our findings highlight that land use and fertilization practices critically shape microbial life-history strategies, with nutrient availability being a decisive factor in increasing the r-strategists in cropland soils. IMPORTANCE Microbial life-history strategies and genomic traits are key determinants shaping the response of populations to environmental impacts. In this paper, 84 cropland and 69 pristine soil samples were studied, and microorganisms in two ecosystems were categorized into two types of ecological groups using the classical copiotroph–oligotroph dichotomy, promoting a general understanding of the ecological roles of microorganisms. This study is the first to investigate the microbial life-history strategies under different land uses across five climatic zones in China. The results showed that the microbes in cropland soils are more copiotrophic than pristine soils. It also demonstrates that elevated levels of nitrogen and phosphorus in cropland soils are the key factors promoting these r-strategies. This observation emphasizes the critical role of nutrient management in shaping microbial community dynamics and ecosystem functioning and lays the foundation for predicting the response of microbial community composition under resource perturbation.Microbial life-history strategies and genomic traits are key determinants shaping the response of populations to environmental impacts. In this paper, 84 cropland and 69 pristine soil samples were studied, and microorganisms in two ecosystems were categorized into two types of ecological groups using the classical copiotroph–oligotroph dichotomy, promoting a general understanding of the ecological roles of microorganisms. This study is the first to investigate the microbial life-history strategies under different land uses across five climatic zones in China. The results showed that the microbes in cropland soils are more copiotrophic than pristine soils. It also demonstrates that elevated levels of nitrogen and phosphorus in cropland soils are the key factors promoting these r-strategies. This observation emphasizes the critical role of nutrient management in shaping microbial community dynamics and ecosystem functioning and lays the foundation for predicting the response of microbial community composition under resource perturbation
Modeling Heterogeneity in the Long-Term Trajectories of Individuals’ Well-Being
No full textVery little is known about how long-term well-being trajectories vary across populations. Using data from 45,160 adults in New Zealand (62% women, M age = 41 years) surveyed annually over 13 years, we identified latent trajectories for belongingness, social support, self-esteem, and life satisfaction. Through a group-based trajectory modeling approach, we found five trajectory groups: low (3%–5%), moderate (11%–17%), moderate-high (29%–32%), high (35%–45%), and very high (11%–20%) well-being. While most individuals showed minimal changes, those with initially low well-being experienced the greatest change, in the direction of decreasing well-being over time. Individuals with higher education were more likely to follow higher well-being trajectories. Similarly, women were more likely to follow higher well-being trajectories, except for self-esteem, where men tended to score higher over time. Lastly, age and ethnicity demonstrated more complex patterns. These findings highlight the importance of acknowledging long-term heterogeneity in well-being trajectories and emphasize the need for targeted preventive mental health interventions, particularly for individuals who begin with lower well-being levels
Cooperativity of Electron Transfer Coupled Spin Transitions in a Tetranuclear Fe/Co Prussian Blue Analogue Revealed by Ultrafast Spectroscopy
No full textCooperative intermolecular interactions, usually observed in solid state, can confer useful properties to stimuli‐responsive spin transition materials. Here we evidence for the first time intramolecular cooperativity between the two Fe‐Co subunits of a molecular cyanido‐bridged square Fe2Co2 Prussian blue analog (PBA) in solution, which upon single photon excitation sequentially undergo electron transfer coupled spin transition (ETCST) from a diamagnetic low‐spin (LS) to a paramagnetic high‐spin (HS) state. Ultrafast UV/vs and IR pump‐probe spectroscopies show that irradiation into the IVCT band of the LS state induces electron transfer within one Fe‐Co subunit followed by fast (360 fs) SCO to an intermediate HS/LS species, and a further ETCST event in the other Fe‐Co subunit then occurs on a ns timescale. Kinetic analysis reveals that this cooperative switching of the two Fe‐Co subunits is caused by two coupled equilibria favouring the second ETCST step, and the free energy landscape for the square Fe2Co2 system is determined experimentally
Highly‐Selective Electrochemical Decarboxylative Late‐Stage Functionalization of Amino Acids
No full textAbstract A unified electrochemical decarboxylative strategy for the site‐selective construction of carbon‐heteroatom bonds is disclosed herein. The metal‐ and catalyst‐free decarboxylation provides access to the functionalization of C‐ and N‐terminus from the simple amino acid feedstock. A wide variety of primary, secondary, and tertiary acids or alcohols were well tolerated. Late‐stage functionalization using α ‐D‐galactopyranose, di‐peptide, steroid derivatives, and bio‐active drug molecules established the robustness and synthesis potential of our approach.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Alexander von Humboldt-Stiftung https://doi.org/10.13039/10000515
Climate and biodiversity perceptions amid the European energy crisis: shifting social media narratives
No full textAbstract Public support for addressing the sustainability crisis is crucial for mainstreaming environmental issues into policymaking. Recently, escalating impacts of an energy crisis have sparked debates over European energy governance, influencing policymaking on climate and biodiversity goals. Understanding how public attention towards climate and biodiversity is mediated by social media during crises can provide insights into the processes of public opinion formation. We investigated the attention patterns, narrative shifts, and sentiment regarding climate and biodiversity concerning European energy governance on X (formerly Twitter), between 2021 and 2023. We employed the issue–attention cycle framework and combined quantitative methods with qualitative thematic analysis. We found limited attention on climate and biodiversity in European energy governance, suggesting low engagement with the interconnected dimensions of the crisis. Climate and biodiversity issues were mainly linked to energy governance in relation to the transition from fossil fuels to renewables. Attention fluctuated over time following three waves of salient themes: the unfolding energy crisis, geopolitical instability, and socio-economic concerns. Geopolitical events elicited a sense of urgency for accelerating the energy transition. However, socio-economic events (high energy prices) aroused critical views towards the transition, reflecting emerging discourses against decarbonization in the EU. Limited attention to climate and biodiversity on social media may reinforce the perception that these issues are unrelated to energy governance, driving public support towards uncoordinated, even contradictory, sectorial policies. The construction of saliency around polarized framing on social media may push opinions against environmental policies on energy governance, challenging the reconciliation of environmental, economic, and social imperatives of sustainability.Maj ja Tor Nesslingin Säätiö http://dx.doi.org/10.13039/501100004157University of Jyväskylä http://dx.doi.org/10.13039/50110000522
Tree Architecture and Structural Complexity in Mountain Forests of the Annapurna Region, Himalaya
No full textABSTRACT Mountain ranges comprise heterogeneous environments and high plant diversity, but little is known about the architecture and structural complexity of trees in mountain forests. We studied the relationship between tree architecture, environmental conditions, and tree structural complexity in forests of the Annapurna region in the Himalaya. We further asked whether and how tree structural complexity translates into forest stand structural complexity. The study covers 546 trees on 14 undisturbed study plots across wide ranges of elevation (1300 to 3400 m asl.) and annual precipitation (1180 to 3600 mm yr. −1 ). They were assessed by ground‐based mobile laser scanning. We found that tree structural complexity, expressed as box‐dimension ( D b ), was lowest for the needle‐leaved Pinus wallichiana and highest for the broad‐leaved Daphniphyllum himalense . A high share of the variation in D b was explained by tree architecture. In multivariate models, tree height, crown radius, and crown length explained more than 60% of the observed variation in D b . Stem density of the plot accounted for 19% of the variation in D b , and there was no influence of tree diversity. Precipitation explained l3% of the observed variation in tree D b , but elevation and slope did not have significant influences. As expected, tree height decreased with increasing elevation, but small trees often had relatively high D b values. The standard deviation of tree‐level D b within a plot explained 47% of the variation in stand‐level structural complexity among plots, surpassing the maximum tree‐level D b . This suggests that both the sole removal of small or large trees would reduce the stand‐level complexity by 36%. We conclude that in the Himalayan forests, species identity and tree architecture play a significant role in determining tree structural complexity, while environmental factors have a smaller role. Furthermore, structural variation among the trees within a plot plays a crucial role for the structural complexity at the stand level.Deutscher Akademischer Austauschdienst https://doi.org/10.13039/50110000165
SNARE complex assembly and disassembly dynamics in response to Ca2+ current activation in live cells
No full texthttp://dx.doi.org/10.13039/100011199 FP7 Ideas: European Research Councilhttp://dx.doi.org/10.13039/100000002 National Institutes of Healthhttp://dx.doi.org/10.13039/501100000781 European Research Councilhttp://dx.doi.org/10.13039/100000057 NIH National Institute of General Medical Science
BenchXAI: Comprehensive benchmarking of post-hoc explainable AI methods on multi-modal biomedical data
No full texthttp://dx.doi.org/10.13039/501100002347 Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100004189 Max-Planck-Gesellschafthttp://dx.doi.org/10.13039/501100014840 Gemeinsame Bundesausschusshttp://dx.doi.org/10.13039/501100003385 Georg-August-Universität Göttingenhttp://dx.doi.org/10.13039/501100001659 German Research Foundatio