Structural Dynamics Research Articles

Ice plate deformation and cracking revealed by an in situ-distributed acoustic sensing array

Abstract. Studying seismic sources and wave propagation in ice plates can provide valuable insights into understanding various processes, such as ice structure dynamics, migration, fracture mechanics and mass balance. However, the harsh environment makes it difficult to conduct in situ dense seismic observations. Consequently, our understanding of the dynamic changes within the ice sheet remains insufficient. We conducted a seismic experiment using a distributed acoustic sensing (DAS) array on a frozen lake, exciting water vibrations through underwater airgun shots. By employing an artificial intelligence method, we were able to detect seismic events that include both high-frequency icequakes and low-frequency events. The icequakes clustered along ice fractures and their activity correlated with local temperature variations. The waveforms of low-frequency events exhibit characteristics of flexural-gravity waves, which offers insights into the properties of the ice plate. Our study demonstrates the effectiveness of an DAS array as an in situ dense seismic network for investigating the internal failure process and dynamic deformation of ice plates such as the ice shelf, which may contribute to an enhanced comprehension and prediction of ice shelf disintegration.

Occupancy Analysis of Water Molecules inside Channels within 25 Å Radius of the Oxygen-Evolving Center of Photosystem II in Molecular Dynamics Simulations.

At room temperature and neutral pH, the oxygen-evolving center (OEC) of photosystem II (PSII) catalyzes water oxidation. During this process, oxygen is released from the OEC, while substrate waters are delivered to the OEC and protons are passed from the OEC to the lumen through water channels known as the narrow or the O4 channel, broad or the Cl1 channel, and large or the O1 channel. Protein residues lining the surfaces of these channels play a critical role in stabilizing the hydrogen-bonding networks that assist in the process. We carried out an occupancy analysis to better understand the structural and possible substrate water dynamics in full PSII monomer molecular dynamics (MD) trajectories in both the S1 and S2 states. We find that the equilibrated positions of water molecules derived from MD-derived electron density maps largely match the experimentally observed positions in crystallography. Furthermore, the occupancy reduction in MD simulations of some water molecules inside the single-filed narrow channel also correlates well with the crystallographic data during a structural transition when the S1 state of the OEC advances to the S2 state. The overall reduced occupancies of water molecules are the source of their "vacancy-hopping" dynamic nature inside these channels, unlike water molecules inside an ice lattice where all water molecules have a fixed unit occupancy. We propose on the basis of findings in our structural and molecular dynamics analysis that the water molecule occupying a pocket formed by D1-D61, D1-S169, and O4 of the OEC could be the last steppingstone to enter into the OEC and that the broad channel may be favored for proton transfer.

Binding site prediction between lysozyme and glucose-regulated protein 78, a hope to fight amyloidosis

Amyloidosis is an extraordinarily vigorous and heterogeneous group of disorders that causes numerous organ failures due to the precipitation of misfolded proteins. Many of these damaged proteins are discarded before causing any fatal diseases due to the contribution of the protein quality control (PQC) system and its chaperons, including glucose-regulated protein (GRP78). One of the most important enzymatic proteins inside the body is lysozyme, which is reported to have many mutated variants that may cause amyloid fibrils. This study used structural bioinformatics and molecular dynamics simulations to test and suggest binding sites for the human lysozyme protein with GRP78. Multiple sequence alignment (MSA) shows that part of the lysozyme envelope protein (C65–C81 cyclic region) has high similarities (30.77% identity) with the cyclic Pep42. Additionally, the binding between the lysozyme cyclic region (C65–C81) and GRP78 substrate binding domain (SBD) is found favorable. The number and types of interactions vary between each of the mutant isoforms of lysozyme. The more significant the conformational changes in the mutation, the greater its probability of aggregation and the formation of amyloid fibrils. Each mutation leads to different interactions and binding patterns with GRP78. The present computational study suggests a lysozyme-GRP78 binding site, thus paving the way for drug designers to construct suitable carriers that can collect misfolded lysozyme proteins and eliminate them from the body, preventing their aggregation and amyloidogenesis. Communicated by Ramaswamy H. Sarma

Some remarks on load modeling in nonlinear structural analysis–Statics with large deformations–Consistent treatment of follower load effects and load control

AbstractLoad modeling in nonlinear statics, particularly incorporating large deformations differs significantly from the treatment in linear analysis. As in structural dynamics masses in a gravity field generate the loading, their location, and their modifications within the deformation process must be considered in a nonlinear simulation. A specific view besides loading by masses is on gas and fluid interaction with structures. In addition, load control using specifically designed algorithms is evaluated with respect to realistic applications. Within the load modeling an unavoidable, however side aspect, is the general discussion about the so‐called follower forces and non‐conservative loading. As an example of real‐world applications, the specifics of inflated rubber dams are presented.

Troponin Structural Dynamics in the Native Cardiac Thin Filament Revealed by Cryo Electron Microscopy

Cardiac muscle contraction occurs due to repetitive interactions between myosin thick and actin thin filaments (TF) regulated by Ca2+ levels, active cross-bridges, and cardiac myosin-binding protein C (cMyBP-C). The cardiac TF (cTF) has two nonequivalent strands, each comprised of actin, tropomyosin (Tm), and troponin (Tn). Tn shifts Tm away from myosin-binding sites on actin at elevated Ca2+ levels to allow formation of force-producing actomyosin cross-bridges. The Tn complex is comprised of three distinct polypeptides – Ca2+-binding TnC, inhibitory TnI, and Tm-binding TnT. The molecular mechanism of their collective action is unresolved due to lack of comprehensive structural information on Tn region of cTF. C1 domain of cMyBP-C activates cTF in the absence of Ca2+ to the same extent as rigor myosin. Here we used cryo-EM of native cTFs to show that cTF Tn core adopts multiple structural conformations at high and low Ca2+ levels and that the two strands are structurally distinct. At high Ca2+ levels, cTF is not entirely activated by Ca2+ but exists in either partially or fully activated state. Complete dissociation of TnI C-terminus is required for full activation. In presence of cMyBP-C C1 domain, Tn core adopts a fully activated conformation, even in absence of Ca2+. Our data provide a structural description for the requirement of myosin to fully activate cTFs and explain increased affinity of TnC to Ca2+ in presence of active cross-bridges. We suggest that allosteric coupling between Tn subunits and Tm is required to control actomyosin interactions.

Dissecting the Interaction Fingerprints and Binding Affinity of BYL719 Analogs Targeting PI3Kα.

Phosphatidylinositol-3-kinase Alpha (PI3Kα) is a lipid kinase which regulates signaling pathways involved in cell proliferation. Dysregulation of these pathways promotes several human cancers, pushing for the development of anticancer drugs to target PI3Kα. One such medicinal chemistry campaign at Novartis led to the discovery of BYL719 (Piqray, Alpelicib), a PI3Kα inhibitor approved by the FDA in 2019 for treatment of HR+/HER2-advanced breast cancer with a PIK3CA mutation. Structure-based drug design played a key role in compound design and optimization throughout the discovery process. However, further characterization of potency drivers via structural dynamics and energetic analyses can be advantageous for ensuing PI3Kα programs. Here, our goal is to employ various in-silico techniques, including molecular simulations and machine learning, to characterize 14 ligands from the BYL719 analogs and predict their binding affinities. The structural insights from molecular simulations suggest that although the ligand-hinge interaction is the primary driver of ligand stability at the pocket, the R group positioning at C2 or C6 of pyridine/pyrimidine also plays a major role. Binding affinities predicted via thermodynamic integration (TI) are in good agreement with previously reported IC50s. Yet, computationally demanding techniques such as TI might not always be the most efficient approach for affinity prediction, as in our case study, fast high-throughput techniques were capable of classifying compounds as active or inactive, and one docking approach showed accuracy comparable to TI.

Moment-dependent rupture properties of deep-focus earthquakes in the Izu-Bonin subduction zone

SUMMARY The physical mechanisms controlling deep-focus earthquakes, or those observed at depths greater than 300 km, remain enigmatic. The leading processes by which deep-focus earthquakes are thought to occur include transformational faulting, thermal runaway and dehydration embrittlement, but distinguishing observations in support of one or more prevailing mechanisms are needed. In this study, we use a modified back-projection method, data recorded by the Hi-net array in Japan and a 3-D velocity model to produce source images of 19 deep-focus earthquakes within the Izu-Bonin subduction zone. We find that the rupture properties and fault plane orientations of imaged events separate according to reported moment magnitude, indicating the distinct operation of two moment-dependent causal mechanisms of deep-focus earthquakes in this region. We discuss these results in the context of previous observational, laboratory and numerical studies and emphasize the importance of continued research to validate the dual-mechanism hypothesis both in and outside Izu-Bonin. Such work may not only improve our understanding of the nucleation and propagation of deep-focus earthquakes, but also help clarify slab structure and subduction zone dynamics.

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications.

Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy-driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha-helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics-Poisson Boltzmann surface area calculations also indicated that non-polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans.

Assessing Drivers of Sustained Engagement in Collaborative Governance Arrangements

Abstract The formal engagement of diverse stakeholder groups in policy design and implementation has become a mainstay governance strategy. While much has been learned about collaborative governance arrangements in terms of their structure, processes, and participant dynamics, one particularly salient dynamic has been relatively underexplored: the factors contributing to sustained participation in collaborative venues. Public administration and policy have developed a variety of conceptual theories which draw attention to interpersonal interactions and the ability of stakeholders to garner political wins as important contributing factors to sustained participation. In this paper, we test four theoretically rooted hypotheses to investigate stakeholder attendance in the collaborative governance case of an environmental justice council. We analyze council meeting minute data using computational text analysis tools and a Stochastic Actor-Oriented Model to assess: (i) conflict and concord, measured in terms of repeated (dis)agreement with others; and (ii) interest advancement, or the extent to which a stakeholder makes positive, neutral, and negative comments towards topics which become the council’s annual objectives in relation to an individual’s attendance. Our interpersonal interaction results show increased positive relationships are associated with increased attendance, and increased negative relationships are associated with decreased attendance, but, for both cases, only when interactions are repeated and not one-off. Our interest advancement results show: (1) an increase in supported annual objectives is associated with decreases in attendance for an individual stakeholder, but (2) increased oppositional and neutral annual topics are associated with a greater likelihood of attendance. This paper contributes to existing scholarship on collaborative governance by offering additional insights into individual factors associated with sustained engagement in the collaborative venue. Furthermore, the paper offers a generalizable methodological approach for analyzing these dynamics drawing on computational text analysis of meeting minute data.

The effects of biological crowders on fibrillization, structure, diffusion, and conformational dynamics of α-synuclein.

α-synuclein is an intrinsically disordered protein (IDP) whose aggregation in presynaptic neuronal cells is a pathological hallmark of Lewy body formation and Parkinson's disease. This aggregation process is likely affected by the crowded macromolecular cellular environment. In this study, α-synuclein was studied in the presence of both a synthetic crowder, Ficoll70, and a biological crowder composed of lysed cells that better mimics the biocomplexity of the cellular environment. 15 N-1 H HSQC NMR results show similar α-synuclein chemical shifts in non-crowded and all crowded conditions implying that it remains similarly unstructured in all conditions. Nevertheless, both HSQC NMR and fluorescence measurements indicate that, only in the cell lysate, α-synuclein forms aggregates over a timescale of 48 h. 15 N-edited diffusion measurements indicate that all crowders slow down the α-synuclein's diffusivity. Interestingly, at high concentrations, α-synuclein diffuses faster in cell lysate than in Ficoll70, possibly due to additional soft (e.g., electrostatic or hydrophobic) interactions. 15 N-edited relaxation measurements show that some residues are more mobile in cell lysate than in Ficoll70; the rates that are most different are predominantly in hydrophobic residues. We thus examined cell lysates with reduced hydrophobicity and found slower dynamics (higher relaxation rates) in several α-synuclein residues. Taken together, these experiments suggest that while cell lysate does not substantially affect α-synuclein structure (HSQC spectra), it does affect chain dynamics and translational diffusion, and strongly affects aggregation over a timescale of days, in a manner that is different from either no crowder or an artificial crowder: soft hydrophobic interactions are implicated.

Structural dynamics and anti-biofilm screening of novel imidazole derivative to explore their anti-biofilm inhibition mechanism against Pseudomonas Aeruginosa

The biofilm formation is still prevalent mechanism of developing the drug resistance in the Pseudomonas aeruginosa, gram-negative bacteria, known for its major role in nosocomial, ventilator-associated pneumonia (VAP), lung infections and catheter-associated urinary tract infections. As best of our knowledge, current study first time reports the most potent inhibitors of LasR, a transcriptional activator of biofilm and virulence regulating genes in, Pseudomonas aeruginosa LasR, utilizing newly functionalized imidazoles (5a-d), synthesized via 1,3-dipolar cycloaddition using click approach. The synthesized ligands were characterized through Mass Spectrometry and 1H NMR. The binding potency and mode of biding of ligands. Quantum Mechanical(QM) methods were utilized to investigate the electronic basis, HOMO/LUMO and dipole moment of the geometry of the ligands for their binding potency. Dynamics cross correlation matrix (DCCMs) and protein surface analysis were further utilized to explore the structural dynamics of the protein. Free energy of binding of ligands and protein were further estimated using Molecular Mechanical Energies with the Poisson–Boltzmann surface area (MMPBSA) method. Molecular Docking studies revealed significant negative binding energies (5a − 10.33, 5b −10.09, 5c − 10.11, and 5d −8.33 KJ/mol). HOMO/LUMO and potential energy surface map estimation showed the ligands(5a) with lower energy gaps and larger dipole moments had relatively larger binding potency. The significant change in the structural dynamics of LasR protein due to complex formation with newlyfunctionalized imidazoles ligands. Hydrogen bond surface analysis followed by MMPBSA calculations of free energy of binding further complemented the Molecular docking revelations showing the specifically ligand (5a) having the relatively higher energy of binding(-65.22kj/mol). Communicated by Ramaswamy H. Sarma

β-Variational autoencoders and transformers for reduced-order modelling of fluid flows

Variational autoencoder architectures have the potential to develop reduced-order models for chaotic fluid flows. We propose a method for learning compact and near-orthogonal reduced-order models using a combination of a β-variational autoencoder and a transformer, tested on numerical data from a two-dimensional viscous flow in both periodic and chaotic regimes. The β-variational autoencoder is trained to learn a compact latent representation of the flow velocity, and the transformer is trained to predict the temporal dynamics in latent-space. Using the β-variational autoencoder to learn disentangled representations in latent-space, we obtain a more interpretable flow model with features that resemble those observed in the proper orthogonal decomposition, but with a more efficient representation. Using Poincaré maps, the results show that our method can capture the underlying dynamics of the flow outperforming other prediction models. The proposed method has potential applications in other fields such as weather forecasting, structural dynamics or biomedical engineering.

Influence of pump laser fluence on ultrafast myoglobin structural dynamics.

High-intensity femtosecond pulses from an X-ray free-electron laser enable pump-probe experiments for the investigation of electronic and nuclear changes during light-induced reactions. On timescales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer1,2. However, all ultrafast TR-SFX studies to date have employed such high pump laser energies that nominally several photons were absorbed per chromophore3-17. As multiphoton absorption may force the protein response into non-physiological pathways, it is of great concern18,19 whether this experimental approach20 allows valid conclusions to be drawn vis-à-vis biologically relevant single-photon-induced reactions18,19. Here we describe ultrafast pump-probe SFX experiments on the photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe-CO bond distance (predicted by recent quantum wavepacket dynamics21) are seen to depend strongly on pump laser energy, in line with quantum chemical analysis. Our results confirm both the feasibility and necessity of performing ultrafast TR-SFX pump-probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing both the design and theinterpretation of ultrafast TR-SFX pump-probe experiments20 such that mechanistically relevant insight emerges.

Structural dynamics of influenza A (H1N1) hemagglutinin protein: a comparative study of Indian (2018) isolate with its evolutionary neighbor, Californian (2009) strain

This work highlights the structure and dynamics of two trimeric HA proteins of the H1N1 virus from different origins, the pandemic Californian (HACal) and its closest Indian neighbor (HAInd), reported in 2009 and 2018, respectively. Because of mutation, HAInd acquires new N-glycosylation and epitope binding sites along with mutations at RBD, which might trigger an altered viral-host interaction mechanism. Molecular dynamics simulations performed on HA trimers for a period of 250 ns reveal the highly dynamic nature of HACal trimers inherited by the flexibility of HA monomers. In the trimer, the dynamics of one monomer are more pronounced compared to others, and the enhanced dynamics of RBD especially gain attention as they plays a key role during fusion. Conversely, the mutant HAInd trimer effectively establishes more H-bond interactions, and accordingly, the trimer undergoes more stabilized dynamics with a relatively lower amplitude of RBD dynamics, as endorsed by the reduced RMSD, Rg, and SASA variations. The cooperative and anti-cooperative motions dissected for the subdomains of both strains also reveal a prominent anticorrelative motion of RBD against other subdomains. In agreement, the free energy landscape of stable HAInd is also characterized by a single lowest wide energy basin instead of the two minimum energy basins of the HACal trimer. In essence, the mutant HAInd acquires a highly stable conformation with novel functional features, which calls for (i) further investigation on the emerging mutation-mediated variation in viral-host binding mechanism and (ii) the need for further design of site-specific potential inhibitors to face future challenges. Communicated by Ramaswamy H. Sarma

Accelerating structural dynamics simulations with localised phenomena through matrix compression and projection‐based model order reduction

AbstractIn this work, a novel approach is introduced for accelerating the solution of structural dynamics problems in the presence of localised phenomena, such as cracks. For this category of problems, conventional projection‐based Model Order Reduction (MOR) methods are either limited with respect to the range of system configurations that can be represented or require frequent solutions of the Full Order Model (FOM) to update the low‐dimensional spaces, in which solutions are represented. In the proposed approach, low‐dimensional spaces, constructed for the healthy structure, are enriched with appropriately selected columns of the flexibility matrix of the system. It can be shown that these spaces contain the solution to the original problem for the static case, while their dimension is much smaller. In order to allow their online construction for arbitrary localised features, the full flexibility matrix of the system should be available. To this end, a hierarchical representation is used for the matrices involved, allowing to compute the flexibility matrix efficiently and with reduced memory requirements. The resulting method offers significant speedups, without sacrificing the flexibility and accuracy of the full order model. The performance and limitations of the approach are studied through a series of examples in structural dynamics.

T-cell virtuosity in ''knowing thyself".

Major Histocompatibility Complex (MHC) I and II and the αβ T-cell antigen receptor (TCRαβ) govern fundamental traits of adaptive immunity. They form a membrane-borne ligand-receptor system weighing host proteome integrity to detect contamination by nonself proteins. MHC-I and -II exhibit the "MHC-fold", which is able to bind a large assortment of short peptides as proxies for self and nonself proteins. The ensuing varying surfaces are mandatory ligands for Ig-like TCRαβ highly mutable binding sites. Conserved molecular signatures guide TCRαβ ligand binding sites to focus on the MHC-fold (MHC-restriction) while leaving many opportunities for its most hypervariable determinants to contact the peptide. This riveting molecular strategy affords many options for binding energy compatible with specific recognition and signalling aimed to eradicated microbial pathogens and cancer cells. While the molecular foundations of αβ T-cell adaptive immunity are largely understood, uncertainty persists on how peptide-MHC binding induces the TCRαβ signals that instruct cell-fate decisions. Solving this mystery is another milestone for understanding αβ T-cells' self/nonself discrimination. Recent developments revealing the innermost links between TCRαβ structural dynamics and signalling modality should help dissipate this long-sought-after enigma.

Unlocking therapeutic potential: computational insights into TREM2 protein targeting with FDA-approved drugs for neurodegeneration

Neurodegenerative diseases such as Alzheimer’s disease (AD) pose a significant global health challenge that requires the exploration of innovative therapeutic strategies. Triggering receptor expressed on myeloid cells-2 (TREM2) is one of the critical proteins involved in immune regulation and neuroinflammation. It has emerged as a promising therapeutic target to develop treatments for neurodegenerative disorders like AD. Here, we employed a comprehensive virtual screening approach to identify potential small molecule inhibitors among FDA-approved drugs for TREM2. The docking study reveals significant binding affinity, ranging from −7.8 kcal/mol to −8.5 kcal/mol, for the elucidated hits against TREM2, accompanied by several crucial interactions. Among the repurposed drugs identified in the initial screening, Carpipramine, Clocapramine, and Pimozide stood out due to their notable binding potential and favorable drug profiling. Further, we conducted molecular dynamics (MD) simulations on the selected molecules that probed their structural dynamics and stability within the TREM2 binding pocket. The structural parameters and hydrogen bond dynamics remained remarkably stable throughout the simulated trajectories. Furthermore, we performed principal component analysis (PCA) and constructed free energy landscapes (FELs) to gain deeper insights into ligand binding and conformational flexibility of TREM2. The findings revealed that the elucidated molecules, Carpipramine, Clocapramine, and Pimozide, exhibited an exceptional fit within the binding pocket of TREM2 with remarkable stability and interaction patterns throughout the 500 ns simulation window. Interestingly, these molecules possessed a spectrum of anti-neurodegenerative properties and favorable drug profiles, which suggest their potential as promising drug candidates for repurposing in the treatment of AD. Communicated by Ramaswamy H. Sarma

The Dynamics of Stand Structure Development and Natural Regeneration of Common Beech (Fagus sylvatica L.) in Plitvice Lakes National Park

The authors investigate the structural characteristics, regeneration processes, growth, development, and survival of a young generation of common beech (Fagus sylvatica L.) based on three periodic measurements (1998, 2009, and 2018). The studied forest community (Lamio orvale-Fagetum sylvaticae (Ht. 1938) Bohridi 1963) is situated within a forest reserve in Plitvice Lakes National Park, Croatia. Monitoring was carried out according to UN/ECE (2000) for systematic and repeated research. The basic structural indicators, structural canopy elements, and appearance of the young generation were measured as the basic conditions of natural restoration in repeated phytocenological surveys (1980, 1988, 2004). The distribution of the number of trees of the first two measurements (1998–2009) indicates a distribution with pronounced right asymmetry. The structural dynamics observed during the surveys and alongside vegetation surveys indicate the dynamics of the growth and development of beech. The results show that the main drivers of development dynamics in protected forest ecosystems are structural breaks (gaps) that occur in stands due to the action of abiotic and biotic factors. The passive management model in effect in the national park should be replaced with a more active approach to facilitate natural processes with the aim of preserving and renewing the forest ecosystem.

Analytical Sensitivity Analysis of Dynamic Problems with Direct Differentiation of Generalized-α Time Integration

In this paper, the direct differentiation of generalized-α time integration is derived, equations are introduced and results are shown. Although generalized-α time integration has found usage, the derivation and the resulting equations for the analytical sensitivity analysis via direct differentiation are missing. Thus, here, the sensitivity equations of generalized-α time integration via direct differentiation are provided. Results with generalized-α are compared with Newmark-β time integration and their sensitivities with numerical sensitivities via forward finite differencing in terms of accuracy and performance. An example is shown for each linear structural dynamics and flexible multibody dynamics.

Nutrient structure dynamics and microbial communities at the water-sediment interface in an extremely acidic lake in northern Patagonia.

Lake Caviahue (37° 50 'S and 71° 06' W; Patagonia, Argentina) is an extreme case of a glacial, naturally acidic, aquatic environment (pH ~ 3). Knowledge of the bacterial communities in the water column of this lake, is incipient, with a basal quantification of the bacterioplankton abundance distribution in the North and South Basins of Lake Caviahue, and the described the presence of sulfur and iron oxidizing bacteria in the lake sediments. The role that bacterioplankton plays in nutrient utilization and recycling in this environment, especially in the phosphorus cycle, has not been studied. In this work, we explore this aspect in further depth by assessing the diversity of pelagic, littoral and sediment bacteria, using state of the art molecular methods and identifying the differences and commonalties in the composition of the cognate communities. Also, we investigate the interactions between the sediments of Lake Caviahue and the microbial communities present in both sediments, pore water and the water column, to comprehend the ecological relationships driving nutrient structure and fluxes, with a special focus on carbon, nitrogen, and phosphorus. Two major environmental patterns were observed: (a) one distinguishing the surface water samples due to temperature, Fe2+, and electrical conductivity, and (b) another distinguishing winter and summer samples due to the high pH and increasing concentrations of N-NH4+, DOC and SO42-, from autumn and spring samples with high soluble reactive phosphorus (SRP) and iron concentrations. The largest bacterial abundance was found in autumn, alongside higher levels of dissolved phosphorus, iron forms, and increased conductivity. The highest values of bacterial biomass were found in the bottom strata of the lake, which is also where the greatest diversity in microbial communities was found. The experiments using continuous flow column microcosms showed that microbial growth over time, in both the test and control columns, was accompanied by a decrease in the concentration of dissolved nutrients (SRP and N-NH4+), providing proof that sediment microorganisms are active and contribute significantly to nutrient utilization/mobilization.