Biology subjects

Tagliabue, A.

Publications and source records attributed to Tagliabue, A..

6 recordsLinked to original sources

bioRxiv2026

The monomeric conformational ensembles of Aβ40 and Aβ42 encode their differential amyloid aggregation propensity

A{beta}40 and A{beta}42 peptides differ by just two C-terminal residues, yet they display strikingly different aggregation and toxicity profiles. Whether this distinction is already encoded at the monomer level is still under debate. Here, we combine extensive all-atom simulations in explicit solvent, well-tempered metadynamics, and a tailored consensus cluster analysis to compare the monomeric ensembles of the two isoforms under identical conditions. Both peptides populate broad, coil-like conformational distributions; however, A{beta}42 shows systematically higher {beta}-structure propensity, especially in the C-terminal region, and samples more extended conformations with higher hydrophobic exposure compared to A{beta}40. These results support a mechanistic link between sequence-encoded monomer conformational preferences and the differential amyloidogenicity of the two isoforms, highlighting monomer-level determinants of A{beta}42s distinct aggregation behavior.

biophysics↗

bioRxiv2023

Human monoclonal antibodies reveal subdominant gonococcal and meningococcal cross-protective antigens

Gonococcus (Gc), a bacterium resistant to most antibiotics causing more than 80 million cases of gonorrhea annually, is a WHO high priority pathogen. Recently, vaccine development prospects were boosted by reports that licensed meningococcus serogroup B (MenB) vaccines provided partial protection against Gc infection. To determine antigens responsible for cross-protection, memory B cells from 4CMenB vaccinated volunteers were single-cell sorted to identify antibodies that kill Gc in a bactericidal assay. Nine different antibodies, all deriving from the IGHV4-34 germline carrying unusually long HCDR3s, recognized the PorB protein, four recognized the lipooligosaccharide (LOS), and four unknown antigens. One of the PorB antibodies, tested in vivo, provided protection from Gc infection. The identification of PorB and LOS as key antigens of gonococcal and meningococcal immunity provides a mechanistic explanation of the cross-protection observed in the clinic and shows that isolating human monoclonal antibodies from vaccinees can be instrumental for bacterial antigen discovery.

immunology↗

bioRxiv2023

Towards modeling genome-scale knowledge in the global ocean

Earth System Models (ESMs) highly simplify their representation of biological processes, leading to major uncertainty in climate change impacts. Despite a growing understanding of molecular networks from genomic data, describing how changing phytoplankton physiology affects the production of key metabolites remains elusive. Here we embed a genome-scale model within a state-of-the-art ESM to deliver an integrated understanding of how gradients of nutritional constraints modulate metabolic reactions and molecular physiology. Applied to the prevalent marine cyanobacteria Prochlorococcus, we find that glycogen and lipid storage can be understood as a consequence of acclimation to environmental gradients. Given the pressing need to assess how biological diversity influences biogeochemical functions, genome-enabled ESMs allow the quantification of the contribution of modeled organisms to the production of dissolved organic carbon and its molecular composition.

bioinformatics↗

bioRxiv2023

Microbial siderophore production is tightly coupled to iron in hydrothermal plumes

Hydrothermal vents have emerged as an important source of iron to seawater, yet only a subset of iron is soluble and persists long enough to be available for surface biological uptake. The longevity and solubility of iron in seawater is governed by strong organic ligands, like siderophores, that are produced by marine microorganisms and are a part of the oceans dissolved iron-binding ligand pool. These ligands have been hypothesized to aid in the persistence of dissolved iron in hydrothermal environments. To explore this hypothesis, we measured iron, iron-binding ligands, and siderophores from 11 geochemically distinct sites along a 1,700 km section of the Mid-Atlantic Ridge. Siderophores were found in hydrothermal plumes at all sites, with proximity to the vent playing an important role in dictating siderophore types and diversity. The notable presence of amphiphilic siderophores may point to microbial utilization of siderophores to access particulate hydrothermal iron, and the exchange of dissolved and particulate iron. The tight coupling between strong ligands and dissolved iron within neutrally buoyant plumes across six distinct hydrothermal environments, and the presence of dissolved siderophores with siderophore-producing microbial genera, suggests that biological production of siderophores exerts a key control on hydrothermal dissolved iron concentrations.

biochemistry↗

bioRxiv2022

Synechococcus nitrogen gene loss in iron-limited ocean regions

Synechococcus are the most abundant cyanobacteria in high latitude regions and are responsible for an estimated 17% of annual marine primary productivity. Despite their biogeochemical importance, Synechococcus populations have been unevenly sampled across the ocean, with most studies focused on low-latitude strains. In particular, the near absence of Synechococcus genomes from high-latitude, High Nutrient Low Chlorophyll (HNLC) regions leaves a gap in our knowledge of picocyanobacterial adaptation to iron limitation and their influence on carbon, nitrogen, and iron cycles. We examined Synechococcus populations from the subarctic North Pacific, a well-characterized HNLC region, with quantitative metagenomics. Assembly with short and long reads produced two near complete Synechococcus metagenome-assembled genomes (MAGs). Quantitative metagenome-derived abundances of these populations matched well with flow cytometry counts, and the Synechococcus MAGs were estimated to comprise >99% of the Synechococcus at Station P. Whereas the Station P Synechococcus MAGs contained multiple genes for adaptation to iron limitation, both genomes lacked genes for uptake and assimilation of nitrate and nitrite, suggesting a dependence on ammonium, urea, and other forms of recycled nitrogen leading to reduced iron requirements. A global analysis of Synechococcus nitrate reductase abundance in the TARA Oceans dataset found nitrate assimilation genes are also lower in other HNLC regions. We propose nitrate and nitrite assimilation gene loss in Synechococcus represents an adaptation to severe iron limitation in high-latitude regions where ammonium availability is higher. Our findings have implications for models that quantify the contribution of cyanobacteria to primary production and subsequent carbon export. SignificanceThe cyanobacterium Synechococcus is a major contributor to ocean primary production and biogeochemistry. Here, we used quantitative metagenomics to assemble and enumerate two Synechococcus genomes from an iron-limited, High Nutrient Low Chlorophyll region. We show these genomes represent the majority of Synechococcus cells at the site and are the first known Synechococcus unable to assimilate either nitrate or nitrite. This gene loss is likely due to the high iron quota of these proteins and predominant availability of recycled forms of nitrogen. Synechococcus loss of nitrate assimilation affects their role in elemental cycles (e.g., carbon, nitrogen, and iron), limits their potential for carbon export, and enhances our understanding of Synechococcus evolution in response to nutrient limitation and competition.

ecology↗

bioRxiv2021

Timing and magnitude of climate driven range shifts in transboundary fish stocks challenge their management

Climate change is shifting the distribution of shared fish stocks between neighboring countries Exclusive Economic Zones (EEZ) and the high seas. The timescale of these transboundary shifts determines how climate change will affect international fisheries governance. Coupling a large ensemble simulation of an Earth system model to a species distribution model, we show that by 2030, 23% of transboundary stocks would have shifted and 78% of the world EEZs will experience at least one shifting stock under a high emission climate change scenario. By the end of this century, 81% of EEZ waters will see at least one shifting stock with a total of 45% of stocks shifting globally, under a high emissions scenario. Importantly, many countries that are highly dependent on fisheries for income, food and nutrition security, as well as livelihoods emerge as hotspots for transboundary shifts showing early, and sometimes past shifts. Existing fisheries agreements need to be assessed for their capacity in addressing transboundary shifts, and strengthened where necessary to limit conflict over these fish stocks while new agreements are urged to considere this problematic in order to be resilient to global change.

ecology↗