Alternative States Research Articles

Alternative State Licensure and Board Certification Pathways for International Medical Graduates.

Alternative State Licensure and Board Certification Pathways for International Medical Graduates.

Evidence for state shift and generation of fire feedback loops in mesic forest driven by extreme fire severity and high fire frequency

Abstract The extent of severe fires is projected to increase with climate change. Furthermore, changes to the fire regime, including the frequency, severity or seasonality of fire, can reduce resilience and promote persistent changes in ecosystem state. Wet sclerophyll forests are found in potentially dynamic mosaics of rainforest and dry sclerophyll forests and contain species from both these contrasting community types. As such, they create an opportunity to study alternative state theory in which states are mediated by fire regimes. To assess the resilience of wet sclerophyll forests to extreme fire events we specifically asked; do mortality rates and recruitment after fire differ between sclerophyllous and non-sclerophyllous components of wet sclerophyll forests, how do these impacts differ along gradients of fire severity and frequency, and is there evidence of positive fire feedback loops, and if so what levels of fire severity and frequency thresholds influence state shifts towards dry sclerophyll forest? We surveyed all canopy (upper and mid canopy) and grass species, to represent three key plant groups; Eucalyptus trees, non-sclerophyllous trees and grasses. We found strong evidence that fire frequency and severity determined the initial trajectory of wet sclerophyll forest recovery. Key findings showed that extreme fire severity can have significant impacts on non-sclerophyllous tree mortality, with an average of 72% of trees killed, much greater than in Eucalyptus species (mean mortality = 9%). However, our findings also highlighted the importance of analysing past fire regime variables, with sites experiencing 4-5 fires in 60 years also experiencing mortality rates of above 75% for non-sclerophyllous trees. Our results support the conclusion that a long multi-decadal fire-free interval is essential for these recovering wet sclerophyll forests, both to rebuild the resilience of their non-sclerophyllous biota and to reduce the risk of recurrent high severity fires in future.

AFsample2 predicts multiple conformations and ensembles with AlphaFold2

Understanding protein dynamics and conformational states is crucial for insights into biological processes and disease mechanisms, which can aid drug development. Recently, several methods have been devised to broaden the conformational predictions made by AlphaFold2 (AF2). We introduce AFsample2, a method using random MSA column masking to reduce co-evolutionary signals, enhancing structural diversity in AF2-generated models. AFsample2 effectively predicts alternative states for various proteins, producing high-quality end states and diverse conformational ensembles. In the OC23 dataset, alternate state models improved (ΔTM>0.05) in 9 out of 23 cases without affecting preferred state generation. Similar results were seen in 16 membrane protein transporters, with 11 out of 16 targets showing improvement. TM-score improvements to experimental end states were substantial, sometimes exceeding 50%, improving from 0.58 to 0.98. Additionally, AFsample2 increased the diversity of intermediate conformations by 70% compared to standard AF2, producing highly confident models potentially representing intermediate states. For four targets, predicted intermediate states were structurally similar to known structural homologs in the PDB, suggesting that they are true intermediate states. These findings indicate that AFsample2 can used to provide structural insights into proteins with multiple states, as well as potential paths between the states.

Leveraging Sequence Purification for Accurate Prediction of Multiple Conformational States with AlphaFold2.

AlphaFold2 (AF2) has transformed protein structure prediction by harnessing co-evolutionary constraints embedded in multiple sequence alignments (MSAs). MSAs not only encode static structural information, but also hold critical details about protein dynamics, which underpin biological functions. However, these subtle co-evolutionary signatures, which dictate conformational state preferences, are often obscured by noise within MSA data and thus remain challenging to decipher. Here, we introduce AF-ClaSeq, a systematic framework that isolates these co-evolutionary signals through sequence purification and iterative enrichment. By extracting sequence subsets that preferentially encode distinct structural states, AF-ClaSeq enables high-confidence predictions of alternative conformations. Our findings reveal that the successful sampling of alternative states depends not on MSA depth but on sequence purity. Intriguingly, purified sequences encoding specific structural states are distributed across phylogenetic clades and superfamilies, rather than confined to specific lineages. Expanding upon AF2's transformative capabilities, AF-ClaSeq provides a powerful approach for uncovering hidden structural plasticity, advancing allosteric protein and drug design, and facilitating dynamics-based protein function annotation.

Emergence of alternative stable states in microbial communities undergoing horizontal gene transfer

Microbial communities living in the same environment often display alternative stable states, each characterized by a unique composition of species. Understanding the origin and determinants of microbiome multistability has broad implications in environments, human health, and microbiome engineering. However, despite its conceptual importance, how multistability emerges in complex communities remains largely unknown. Here, we focused on the role of horizontal gene transfer (HGT), one important aspect mostly overlooked in previous studies, on the stability landscape of microbial populations. Combining mathematical modeling and numerical simulations, we demonstrate that, when mobile genetic elements (MGEs) only affect bacterial growth rates, increasing HGT rate in general promotes multistability of complex microbiota. We further extend our analysis to scenarios where HGT changes interspecies interactions, microbial communities are subjected to strong environmental selections and microbes live in metacommunities consisting of multiple local habitats. We also discuss the role of different mechanisms, including interspecies interaction strength, the growth rate effects of MGEs, MGE epistasis and microbial death rates in shaping the multistability of microbial communities undergoing HGT. These results reveal how different dynamic processes collectively shape community multistability and diversity. Our results provide key insights for the predictive control and engineering of complex microbiota.

Emergence of alternative stable states in microbial communities undergoing horizontal gene transfer.

Microbial communities living in the same environment often display alternative stable states, each characterized by a unique composition of species. Understanding the origin and determinants of microbiome multistability has broad implications in environments, human health, and microbiome engineering. However, despite its conceptual importance, how multistability emerges in complex communities remains largely unknown. Here, we focused on the role of horizontal gene transfer (HGT), one important aspect mostly overlooked in previous studies, on the stability landscape of microbial populations. Combining mathematical modeling and numerical simulations, we demonstrate that, when mobile genetic elements (MGEs) only affect bacterial growth rates, increasing HGT rate in general promotes multistability of complex microbiota. We further extend our analysis to scenarios where HGT changes interspecies interactions, microbial communities are subjected to strong environmental selections and microbes live in metacommunities consisting of multiple local habitats. We also discuss the role of different mechanisms, including interspecies interaction strength, the growth rate effects of MGEs, MGE epistasis and microbial death rates in shaping the multistability of microbial communities undergoing HGT. These results reveal how different dynamic processes collectively shape community multistability and diversity. Our results provide key insights for the predictive control and engineering of complex microbiota.

How hydrodynamic conditions drive the regime shift towards a bacterial state with lower carbon emissions in river bends.

How hydrodynamic conditions drive the regime shift towards a bacterial state with lower carbon emissions in river bends.

Magnitude Shifts in Aeolian Sediment Transport Associated With Degradation and Restoration Thresholds in Drylands

AbstractVegetation change in drylands can influence wind erosion and sand and dust storms (SDS) with far‐reaching consequences for Earth systems and society. Although vegetation is recognized as an important control on wind erosion and SDS, the interactions are not well described at the landscape level or in the context of dryland ecosystem change. The transition of sites from one ecological state to another (e.g., grassland to shrubland) is typically associated with changes in the composition, cover, and structure of vegetation, which influence drag partitioning and wind shear velocities that drive aeolian sediment transport. Here, we quantify the magnitude and direction of aeolian sediment transport responses to ecological state change in the northern Chihuahuan Desert and identify thresholds associated with state transitions. Our results show aeolian sediment mass flux (Q) increased from ∼1 to 10 g m−1 d−1 in historical grassland with scattered shrubs to ∼10–100 g m−1 d−1 following shrub invasion and decline in perennial grass cover to ∼100–10,000 g m−1 d−1 in shrubland following complete grass loss. The magnitude shifts were associated with critical perennial grass cover thresholds governing nonlinear increases in Q across ecological state transitions. Grass recovery in shrubland reduced Q to rates similar to those in historical grasslands—a multiple order of magnitude reduction. Our results show that crossing degradation and restoration thresholds between alternative ecological states can have a profound effect on the magnitude and spatiotemporal variability of aeolian sediment transport and primacy in determining patterns of wind erosion and dust emissions in vegetated drylands.

The Role of Phenotypic Plasticity and Within-Environment Trait Variability in the Assembly of the Nectar Microbiome and Plant-Microbe-Animal Interactions.

The study of the rules that govern the relationship between phenotypic plasticity, genetic structure, and ecological success has traditionally focused on animals, plants, and a few model microbial species, whereas non-model microorganisms have received much less attention in this regard. The floral nectar of angiosperms is an ephemeral, island-like habitat for different highly adapted yeasts and bacteria. The growth of microorganisms in floral nectar depends on their ability to efficiently use the available nutrients and tolerate challenging physicochemical conditions, including high osmotic pressures, unbalanced carbon-to-nitrogen ratios, and the presence of diverse defensive compounds of plant origin. The production of alternative phenotypic states in response to environmental cues (i.e., phenotypic plasticity) or independently from these (within-environment trait variability) might be particularly relevant in floral nectar, in which rapid growth is needed for population persistence and to improve the chance of animal-mediated dispersal. In this article, we use the nectar microbiome as an example to encourage further research on the causes and ecological consequences of phenotypic plasticity and within-environment trait variability of microbes. We review previous work on the mechanisms and potential ecological significance of the phenotypic plasticity and within-environment trait variability displayed by nectar yeasts and bacteria. Additionally, we provide an overview of some topics that require further attention, including potential trade-offs between different traits that are relevant for adaptation to dynamic nectar environments and the direct and indirect effects of phenotypic variability on the fitness of plants, flower-visiting animals, and other nectar microbes. We conclude that further research on the causes and ecological consequences of phenotypic plasticity and within-environment trait variability of microbes is essential to get a better understanding of community assembly and the establishment of ecological interactions in floral nectar and other similar highly dynamic and strongly selective microbial habitats.

Equilibrium analysis of discrete stochastic population models with gamma distribution.

Equilibrium analysis of discrete stochastic population models with gamma distribution.

The Late-Quaternary Extinctions Gave Rise to Functionally Novel Herbivore Assemblages.

Various authors have suggested that extinctions and extirpations of large mammalian herbivores during the last ca. 50,000 years have altered ecological processes. Yet, the degree to which herbivore extinctions have influenced ecosystems has been difficult to assess because past changes in herbivore impact are difficult to measure directly. Here, we indirectly estimated changes in (theorised) herbivore impact by comparing the functional composition of current large (≥ 10 kg) mammalian herbivore assemblages to those of a no-extinction scenario. As an assemblage's functional composition determines how it interacts with its environment, changes in functional compositions should correspond to changes in ecological impacts. We quantified functional composition using the body mass, diet and life habit of all wild herbivorous mammal species (n = 502) present during the last 130,000 years. Next, we assessed whether these changes in functional composition were large enough that the resulting assemblages could be considered functionally novel. Finally, we assessed where novel herbivore assemblages would most likely lead to changes in biome state. We found that 47% of assemblages are functionally novel, indicating fundamental changes in herbivore impacts occurred across much of the planet. On 20% of land, functionally novel herbivore assemblages have arisen in areas where alternative biome states are possible depending on the disturbance regime. Thus, in many regions, the late-Quaternary extinctions and extirpations altered herbivore assemblages so profoundly that there were likely major consequences for ecosystem functioning.

Use of the Alternative Stable States Concept in Tropical Terrestrial Ecosystem Research—A Systematic Literature Review

Use of the Alternative Stable States Concept in Tropical Terrestrial Ecosystem Research—A Systematic Literature Review

A Busse Balloon in the Lagoon: Herbivore Behaviour Generates Spatial Patterns in Coral Reef Ecosystems.

Spatial processes, particularly scale-dependent feedbacks, may play important and underappreciated roles in the dynamics of bistable ecosystems. For example, self-organised spatial patterns can allow for stable coexistence of alternative states outside regions of bistability, a phenomenon known as a Busse balloon. We used partial differential equations to explore the potential for such dynamics in coral reefs, focusing on how herbivore behaviour and mobility affect the stability of coral- and macroalgal-dominated states. Herbivore attraction to coral resulted in a Busse balloon that enhanced macroalgal resilience, with patterns persisting in regions of parameter space where nonspatial models predict uniform coral dominance. Thus, our work suggests herbivore association with coral (e.g., for shelter) can prevent reefs from reaching a fully coral-dominated state. More broadly, this study illustrates how consumer space use can prevent ecosystems from undergoing wholesale state transitions, highlighting the importance of explicitly accounting for space when studying bistable systems.

Stimuli-Responsive Multifunctional Iridium(III) Complex Exhibiting Thermo-, Vapochromism, and Double Catalytic Activity.

Multifunctional compounds with properties that may be triggered by different external stimuli are highly desirable yet challenging in their design and synthesis. Herein, we report a cyclometalated iridium(III) complex based on bulky 1,2-diphenylphenanthroimidazole (C^N) that can easily change its molecular geometry from trigonal-bipyramidal to octahedral or from a monomeric to dimeric state in response to external stimuli (temperature and solvent variations). The extensive characterization including variable-temperature 1H NMR, single-crystal and powder X-ray diffraction corroborated by density functional theory calculations strongly indicates that the thermochromic behavior of the complex is attributed to the dimer-monomer transformations both in solution and in the solid state. The five-coordinated monomer instantaneously reacts with coordinating solvents (L = CH3CN, CH3OH, pyridine) affording octahedral complexes [Ir(C^N)2(L)Cl]. Binding constants for the formation of the complexes with acetonitrile and methanol were estimated by UV-vis titration. Enabled by the ability to switch between the alternative structural states depending on the medium, the monomer exhibits an unprecedented combination of properties, including a reversible vapochromic behavior and switchable catalytic activity. As illustrative examples, transfer hydrogenation and photoinduced reductive debromination were successfully performed by using the monomer as a catalyst.

Dynamics of Alternative States and Basin Transition of a Plant-Volatile-Induced Tritrophic System

Plants transmit messages through chemical blends, namely Volatile Organic Compounds (VOCs), regarding the news of herbivory to the neighboring plants and natural carnivorous enemies of herbivores. Qualitatively and quantitatively, the blends of Herbivore-induced Plant Volatile (HIPV) help to improve plant growth by recruiting natural enemies of herbivores. We present HIPV-mediated model-based analysis of plant–herbivore–carnivorous natural enemy interaction and explore the complex dynamical behavior. We emphasize the interplay between system parameters, mainly the predation rate and HIPV-induced recruitment rate of natural enemies of herbivores, and emergent dynamical states. The proposed system experiences various changes like oscillatory state to steady-state through Hopf-bifurcation, alternative steady states, and collision of two coexistence equilibria through saddle-node bifurcation. We simultaneously explore the characteristics of basin of attraction, basin transition, and its correlation with system parameters. We thoroughly explain the importance of alternative steady states on plant fitness and the existence of all populations. Based on the high-dimensional Bendixson criterion, we show the global stability of the coexistence equilibrium point. Moreover, we perform numerical simulation to support all possible analytical outcomes and discuss some concluding remarks on the positive impact of HIPV in enhancing plant growth after herbivory damage by signaling natural enemies of herbivores as a reinforcement.

Hidden Structural States of Proteins Revealed by Conformer Selection with AlphaFold-NMR.

We introduce AlphaFold-NMR, a novel approach to NMR structure determination that reveals previously undetected protein conformational states. Unlike conventional NMR methods that rely on NOE-derived spatial restraints, AlphaFold-NMR combines AI-driven conformational sampling with Bayesian scoring of realistic protein models against NOESY and chemical shift data. This method uncovers alternative conformational states of the enzyme Gaussia luciferase, involving large-scale changes in the lid, binding pockets, and other surface cavities. It also identifies similar yet distinct conformational states of the human tumor suppressor Cyclin-Dependent Kinase 2-Associated Protein 1. These studies demonstrate the potential of AI-based modeling with enhanced sampling to generate diverse structural models followed by conformer selection and validation with experimental data as an alternative to traditional restraint-satisfaction protocols for protein NMR structure determination. The AlphaFold-NMR framework enables discovery of conformational heterogeneity and cryptic pockets that conventional NMR analysis methods do not distinguish, providing new insights into protein structure-function relationships.

Norwegian lemmings, Lemmus lemmus: a case for a strong herbivore–plant interaction

In his classical contributions, Olavi Kalela proposed that, due to the low primary productivity of the tundra, Norwegian lemmings are locked in a strong interaction with their winter forage plants. Proposedly, Norwegian lemmings respond to the threat of critical resource depletion by conducting long‐range migrations at their population peaks. A tacit premise of this conjecture is that predation pressure on the Fennoscandian tundra is too weak to prevent runaway increases of lemming populations, creating violent boom–crash dynamics. Our results on the dynamics of Norwegian lemmings on the Finnmarksvidda tundra during 1977–2017 are in line with the predictions of Kalela's hypothesis. In contrast to the Siberian and North American tundra, densities of avian predators in our study area have been low even during lemming years, and efficient ones have been lacking from lemming habitats. Lemmings have thus increased unhinged in peak summers and crashed to densities below the trappability threshold during post‐peak winters. Each lemming crash has been accompanied by massive habitat destruction. Indications of predator activity have been concentrated to productive shrublands, where lemmings have never reached high densities. Young lemmings have responded to high densities by becoming extremely mobile: they have been trapped in large numbers on islands, including a small island in the middle of Iešjávri, a 10 × 8 km tundra lake. Many lemmings have been seen swimming across the lake, and many drowned lemmings have been observed. The dynamics and behavior of Norwegian lemmings recorded by us differ radically from those of other Lemmus spp., indicating that cycles generated by lemming–vegetation interactions have two alternative states – one with and the other without intense summer predation. We propose that the cycles of Norwegian lemmings shifted to the latter state during their unique evolutionary history, when they survived the Last Glacial Maximum in a tiny refugium archipelago.

Temporary dietary fiber depletion prompts rapid and lasting gut microbiota restructuring in mice.

In this article, the authors explore the impact of a diet with reduced fiber content on the gut microbiota-host symbiosis in a mouse model. More importantly, they examine the resilience of the intestinal symbiosis after the return to a standard (chow) diet. Some of the measured parameters (intestinal barrier impairment and bacterial glycan-degrading enzymatic activities) returned to control values. However, this was not the case for bacterial richness-the number of different bacteria observed-which remained durably reduced. Among related bacteria, some groups receded and remained undetected until 6 weeks after the return to the chow diet while others saw their abundance increase in replacement. The authors find that a temporary fiber deprivation lasting as little as 3 weeks can cause a transition to an alternative stable microbiota state, i.e., a lasting change in intestinal microbiota composition.

Historical reindeer corrals in northern boreal forests reveal divergent post‐disturbance reorganization by forest type

AbstractCurrent theoretical frameworks on alternative ecosystem states in boreal forests do not contain a clear prediction on how the sensitivity for state transitions depends on site productivity, which forms a major gap in understanding how disturbances impact these ecosystems. Here, we compared 26 historical reindeer (Rangifer tarandus L.) corrals used in animal husbandry between the late 1800s and early 1960s with reference forests in the northern boreal forest zone in Finland. We found that mesic forests experienced strong forest reorganization that involved shifts in both tree species composition and density. Sub‐xeric forests were most commonly on a trajectory toward the pre‐disturbance state due to strong self‐thinning. No state transitions in understory vegetation occurred. There was little difference in understory vegetation recovery between mesic and sub‐xeric forests; however, disturbance increased spatial heterogeneity in understory vegetation. These findings from historical sites support a high resilience of northern boreal forests to disturbances. They also indicate that disturbances may more likely induce reorganization in more productive mesic sites. Although stronger environmental constraints in less productive sub‐xeric sites may slow down recovery, they also direct post‐disturbance trajectories toward the pre‐disturbance state.

Multiomics Analyses Demonstrate the Attenuation of Metabolic Cardiac Disorders Associated With Type2 Diabetes by Stachydrine in Relation With the Transition of Gastrointestinal Microbiota.

Stachydrine (STA) has therapeutic effects on heart disorders. The current study assessed its effects on Type 2 diabetes (T2D) induced cardiac disorders by focusing on the heart-gut axis. Mice were subjected to high-fat diet (HFD) and streptozocin (STZ) to induce cardiac disorders such as inflammation and structural deteriorations, which were handled with STA. Changes regarding the composition and metabolism of gastrointestinal (GI) microbiota were then determined using a multiomics strategy, including amplicon sequencing and metabolomics. The data showed that STA improved heart function, reduced intestinal permeability, and suppressed inflammation in mice in a dose-dependent manner. However, the compound had little influence on the overall alpha diversity of gut microbiota, while it did influence the beta diversity. The analyses based on the multiomics strategy demonstrated that certain GI microbial groups, including Paramuribaculum, Allobaculum, Bifidobacterium, and Adlercreutzia, responded to the STA administration, which contributed to the alternatives of metabolites in the gut. Correlation analyses showed that Duncaniella and Ruminococcus negatively impacted health, while Muribaculum, Paramuribaculum, and Prevotella positively influenced intestinal permeability and heart health. Collectively, STA attenuated T2D-induced cardiac disorders by improving heart structure and function and suppressing inflammation, during which the GI homeostasis of the T2D mice changed to an alternative state that was different from that of healthy mice.