Biology subjects

Barbier, M.

Publications and source records attributed to Barbier, M..

At least 19 recordsLinked to original sources

bioRxiv2025

Defining the role of Pseudomonas aeruginosa PilY1 in signaling and virulence

Pseudomonas aeruginosa (Pa) is an important opportunistic pathogen that has many virulence factors expressed in a coordinated manner to cause infection. External appendages, such as the type IV pili (T4P), can be used for signal transduction changing gene expression using a mechanism termed mechanosensing. An important role for the minor pilin, PilY1, is to signal that the bacterium has attached to a surface such as a host cell. This mechanosensing is important for triggering changes in bacterial gene expression allowing colonization of host tissues. In this study, we identify new PilY1-controlled genes and demonstrate the importance of PilY1 in controlling second messengers, including cAMP. Genetic analysis showed that PilY1 is important in controlling cAMP levels by regulating the expression of the main adenylate cyclase, cyaB. PilY1 also controls the expression of PA4781 a putative cyclic di-GMP phosphodiesterase. PilY1 also controls the expression of the algZ/R operon by preventing autoregulation of this system. Furthermore, the minor pilin PilY1 functions in different P. aeruginosa strains, including mucoid strains, demonstrating conservation of function. Surprisingly, bacterial survival in the lung, liver, and blood did not require PilY1. Overall, these findings suggest that PilY1 is critical for regulating second messengers by preventing the AlgZ/R system from functioning. Our work provides insight into the mechanisms that P. aeruginosa uses to modulate second messengers which are important in biofilm formation and virulence. Importance. PilY1, a component of type IV pili, is important for signaling environmental cues into the bacterial cell. However, the signaling pathway PilY1 controls is poorly understood. We determined that PilY1 is involved in the regulation of cAMP. Transcriptomic analysis identified new PilY1-controlled genes. We also demonstrate the functionality of PilY1 in other strains, including mucoid strains commonly found in chronic infections. We elucidate the importance of PilY1 controlling cAMP by repressing the AlgZ/R system and preventing cyaB expression. Our data help to explain how regulatory systems interact in P. aeruginosa providing insight that may be useful for therapeutic development.

microbiology↗

bioRxiv2024

Interplay of structured and random interactions in many-species ecological dynamics

Minimal models for complex ecosystems often assume random interactions, whose statistics suffice to predict dynamical and macroecological patterns. However, ecological networks commonly possess a variety of properties, such as hierarchies or functional groups, that structure species interactions. Here, we ask how conclusions from random interaction models are altered by the presence of such community-level network structures. We consider a Lotka-Volterra model where pairwise species interactions combine structure and randomness, and study macroscopic community-level observables, abundance distributions and dynamical regimes. Randomness and structure combine in a surprisingly yet deceptively straightforward way: contributions from each component to community patterns are largely independent. Yet, their interplay has non-trivial consequences, notably out of equilibrium. We conclude that whether interaction structure matters depends on the pattern: when breaking species equivalence, static patterns of species presence and abundance predicted from random interaction models are less robust than the qualitative nature of dynamical regimes. Author summaryEcological communities with many species are a challenge for theoretical ecology, since they harbour many and very diverse interactions. A common approach is to focus on aggregated quantities, such as the abundance of broad taxonomic or functional groups, thus neglecting all the diversity at finer scales. We develop a theoretical framework that combines both ecological structure and fine-grained heterogeneity, which we represent with randomness. We find that structure and randomness contribute to ecosystem properties with effects that can be largely disentangled, allowing a continuous transition between two simple effective descriptions of the community dynamics. Still, they interact in unexpected ways. For instance, we show that species heterogeneity can simplify the dynamics of functional groups, countering the idea that complexity should always destabilize large ecosystems. Data availability statement: The source code used to produce the results and analyses presented in this manuscript is freely available at the GitHub repository: https://github.com/juanelogiral/interplay-structure-randomness.git

ecology↗

bioRxiv2024

Top-down origins of the predator-prey power law?

The ratio of predator-to-prey biomass density is not constant along ecological gradients: denser ecosystems tend to have fewer predators per prey, following a scaling relation known as the "predator-prey power law". The origin of this surprisingly general pattern, particularly its connection with environmental factors and predator-prey dynamics, is unknown. Here, we explore some ways that a sublinear predator-prey scaling could emerge from density-dependent interactions among predators and between predators and prey (which we call a top-down origin), rather than among prey (bottom-up origin) as proposed in Hatton et al. (2015). We combine two complementary theoretical approaches. First, we use phenomenological differential equations to explore the role of environmental parameters and dynamical properties in controlling the predator-prey ratio. Second, we simulate an agent-based model with tunable predator self-regulation to investigate the emergence of predator-prey scaling from plausible microscopic rules. While we cannot rule out alternative explanations, our results show that density-dependent mechanisms relative to predation and intraspecific predator interactions, including prey saturation, predator interference, and predator self-regulation, offer potential explanations for the predator-prey power law.

ecology↗

bioRxiv2024

Collective dynamical regimes predict invasion success and impacts in microbial communities

Invasions of microbial communities by species such as pathogens can have significant impacts on ecosystem services and human health1-9. Predicting the outcomes of these invasions, however, remains a challenge. Various theories propose that these outcomes depend on either characteristics of the invading species10-12 or attributes of the resident community13-16, including its composition and biodiversity3,17-19. Here we used a combination of experiments and theory to show that the interplay between dynamics, interaction strength, and diversity determine the invasion outcome in microbial communities. We found that the communities with fluctuations in species abundance are both more invasible and more diverse than stable communities, leading to a positive diversity-invasibility relationship among communities assembled in the same environment. As predicted by theory, increasing interspecies interaction strength and species pool size leads to a decrease of invasion probability in our experiment. Although diversity-invasibility relationships are qualitatively different depending upon how the diversity is changed, we provide a unified perspective on the diversity-invasibility debate by showing a universal positive correspondence between invasibility and survival fraction of resident species across all conditions. Communities composed of strongly interacting species can exhibit an emergent priority effect in which invader species are less likely to colonize than species in the original pool. However, in this regime of strong interspecies interactions, if an invasion is successful, it causes larger ecological effects on the resident community than when interactions are weak. Our results demonstrate that the invasibility and invasion effect are emergent properties of interacting species, which can be predicted by simple community-level features.

ecology↗

bioRxiv2023

Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing in Shank3-deficient rats

Social behaviors are crucial for human connection and belonging, often impacted in conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (VTA and NAc) plays a pivotal role in social behavior and is implicated in ASD. However, the impact of ASD-related mutations on social reward processing remains insufficiently explored. This study focuses on the Shank3 mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using the Shank3-deficient rat model. Our findings indicate that Shank3-deficient rats exhibit atypical social interactions and have difficulty adjusting behavior based on reward values, associated with modified neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, we demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects of Shank3 mutations on social reward and behavior, and identify a potential neural pathway for intervention.

neuroscience↗

bioRxiv2023

Loss of ninein interferes with osteoclast formation and causes premature ossification

Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human ninein gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.

developmental biology↗

bioRxiv2023

A taxonomy of multiple stable states in complex ecological communities

Many natural and man-made systems, from financial markets to ecosystems or the human brain, are built from multiple interconnected units. This complex high-dimensionality hinders our capacity to understand and predict the dynamics, functioning and fragility of these systems. One fragility scenario, particularly relevant to ecological communities of interacting species, concerns so-called regime shifts: abrupt and unexpected transitions from healthy, species-rich communities towards states of degraded ecosystem function and services. The accepted explanation for these shifts is that they arise as abrupt transitions between alternative stable states: multiple stable configurations of a system under the same internal and external conditions. These alternative states are well-understood in low-dimensional systems, but how they upscale with system complexity remains a debated question. In the present work we investigate the emergence of multiple stable states in a number of complex system models. We find that high-dimensional models with random interactions can unfold at least four different regimes of multistability, each emerging under a specific interaction scheme. More importantly, each multistability regime leaves a distinct and quantifiable fingerprint, providing a framework to analyze experimental evidence of abrupt shifts. By bridging previous results and studying multistability regimes, their fingerprints and their correlation with empirical evidence in ecology, our study helps define a common ground to understand and classify multiple stable states in complex systems.

ecology↗

bioRxiv2023

Getting More by Asking for Less: Linking Species Interactions to Species Co-Distributions in Metacommunities

One of the more difficult challenges in community ecology is inferring species interactions on the basis of patterns in the spatial distribution of organisms. At its core, the problem is that distributional patterns reflect the realized niche, the net result of a complex interplay of processes involving dispersal, environmental, and interaction effects. Disentangling these effects can be difficult on at least two distinct levels. From a statistical point of view, splitting a populations variation into contributions from its interaction partners, abiotic environment and spatial proximity requires natural experiments where all three factors somehow vary independently from each other. On a more conceptual level, it is not even clear how to meaningfully separate these processes: for instance, species interactions could depend on the state of the abiotic and biotic environment, and these two processes may combine in highly non-additive ways. Here we show that the latter issue arises almost inescapably, even in a simple theoretical setting designed to minimize it. Using a model of competitive metacommunity dynamics where direct species interactions are assumed to be context-independent, we show that inferring these interactions accurately from cross-species correlations is a major challenge under all but the most restrictive assumptions. However, we also find that it is possible to estimate the statistical moments (mean value and variance) of the species interactions distribution much more robustly, even if the precise values cannot be inferred. Consequently, we argue that study of multi-species spatial patterns can still be informative for theoretical approaches that build on statistical distributions of species parameters to predict macroscopic outcomes of community assembly.

ecology↗

bioRxiv2023

Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice

As the COVID-19 pandemic transitions to endemic, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen- based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD- specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS- CoV-2.

immunology↗

bioRxiv2023

Social Interaction Elicits Activity in Glutamatergic Neurons in the Posterior Intralaminar Complex of the Thalamus

BackgroundThe posterior intralaminar (PIL) complex of the thalamus is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social behaviors in male and female rodents. Glutamatergic neurons are a major component of the PIL; however, their specific activity and role during social interactions has not yet been assessed. MethodsWe used immunohistochemistry for the immediate early gene c-fos as a proxy for neuronal activity in the PIL of mice exposed to a novel social stimulus, a novel object stimulus, or no stimulus. We then used fiber photometry to record neural activity of glutamatergic neurons in the PIL in real-time during social and non-social interactions. Finally, we used inhibitory DREADDs in glutamatergic PIL neurons and tested social preference and social habituation-dishabituation. ResultsWe observed significantly more c-fos-positive cells in the PIL of mice exposed to social versus object or no stimuli. Neural activity of PIL glutamatergic neurons was increased when male and female mice were engaged in social interaction with a same-sex juvenile or opposite-sex adult, but not a toy mouse. Neural activity positively correlated with social investigation bout length and negatively correlated with chronological order of bouts. Social preference was unaffected by inhibition; however, inhibiting activity of glutamatergic neurons in the PIL delayed the time it took female mice to form social habituation. ConclusionsTogether these findings suggest that glutamatergic PIL neurons respond to social stimuli in both male and female mice and may regulate perceptual encoding of social information to facilitate recognition of social stimuli.

neuroscience↗

bioRxiv2023

Addition of adjuvant to DTaP modulates vaccine-induced immunological responses but is insufficient to improve protection in CD-1 mice

3.1Pertussis is a vaccine-preventable respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. While vaccination rates remain high in developed countries, incidence of pertussis has increased following the transition from wP vaccines to aP vaccines. The reemergence of pertussis is attributed, in part, to waning immunity induced by aP vaccination. Therefore, the objective of this work was to determine if addition of adjuvant to DTaP can modulate the immune response and improve protection compared to DTaP alone. In this study we immunized outbred, female CD-1 mice with 1/320th the human dose of vehicle control, DTaP, and DTaP supplemented with adjuvant. Markers of early vaccine-induced memory were measured using a chemokine assay or by flow cytometry. Protection was assessed by measuring serological responses and quantifying bacterial burden in the respiratory tract at day 3 post-challenge. From this work we identified a partially protective aP vaccine dose to use for vaccination and challenge studies. We observed that MPLA and SWE promote robust anti-B. pertussis antibody responses and stimulate significant increases in early markers of vaccine-induced memory such as CXCL13, FDCs, and TFH cells. Quil-A induced Th1 responses compared to DTaP alone, but none of the adjuvants improved protection against challenge with B. pertussis. Overall, the data suggests that addition of adjuvant modulates the protective immune responses induced by aPs. Further studies are needed to evaluate the B cell compartment and longevity of protection.

immunology↗

bioRxiv2023

The heme-responsive PrrH sRNA regulates Pseudomonas aeruginosa pyochelin gene expression

Pseudomonas aeruginosa is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, P. aeruginosa expresses the PrrF1 and PrrF2 small regulatory RNAs (sRNAs), which post-transcriptionally repress expression of non-essential iron-containing proteins thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH. While the functions of PrrF1 and PrrF2 have been studied extensively, the role of PrrH in P. aeruginosa physiology and virulence is not well understood. In this study, we performed transcriptomic and proteomic studies to identify the PrrH regulon. In shaking cultures, the pyochelin synthesis proteins were increased in two distinct prrH mutants compared to wild type, while the mRNAs for these proteins were not affected by prrH mutation. We identified complementarity between the PrrH sRNA and sequence upstream of the pchE mRNA, suggesting potential for PrrH to directly regulate expression of genes for pyochelin synthesis. We further showed that pchE mRNA levels were increased in the prrH mutants when grown in static but not shaking conditions. Moreover, we discovered controlling for the presence of light was critical for examining the impact of PrrH on pchE expression. As such, our study reports on the first likely target of the PrrH sRNA and highlights key environmental variables that will allow for future characterization of PrrH function. ImportanceIn the human host, iron is predominantly in the form of heme, which Pseudomonas aeruginosa can acquire as an iron source during infection. We previously showed that the iron-responsive PrrF sRNAs are critical for mediating iron homeostasis during P. aeruginosa infection; however the function of the heme-responsive PrrH sRNA remains unclear. In this study, we identified genes for pyochelin siderophore biosynthesis, which mediate uptake of inorganic iron, as a novel target of PrrH regulation. This study therefore highlights a novel relationship between heme availability and siderophore biosynthesis in P. aeruginosa.

microbiology↗

bioRxiv2022

How collectively integrated are ecological communities?

Beyond abiotic conditions, do population dynamics mostly depend on the species direct predators, preys and conspecifics? Or can indirect feedbacks that ripple across the whole community be equally important? Here we show that the spectral radius of a communitys interaction matrix controls the length of indirect interaction pathways that actually contribute to community-level dynamical patterns, such as the depth of a perturbations reach, or the contribution of biotic processes to realized species niches. The spectral radius is a measure of collectivity that integrates existing approaches to complexity, interaction structure and indirect interactions, while also being accessible from imperfect knowledge of biotic interactions. Our work provides an original perspective on the question of to what degree communities are more than loose collections of species or simple interaction motifs; and explains when reductionist approaches focusing on particular species and small interaction motifs, ought to suffice or fail when applied to ecological communities.

ecology↗

bioRxiv2022

Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants

There is a continued need for sarbecovirus vaccines that can be manufactured and distributed in low- and middle-income countries (LMICs). Subunit protein vaccines are manufactured at large scales at low costs, have less stringent temperature requirements for distribution in LMICs, and several candidates have shown protection against SARS-CoV-2. We previously reported an engineered variant of the SARS-CoV-2 Spike protein receptor binding domain antigen (RBD-L452K-F490W; RBD-J) with enhanced manufacturability and immunogenicity compared to the ancestral RBD. Here, we report a second-generation engineered RBD antigen (RBD-J6) with two additional mutations to a hydrophobic cryptic epitope in the RBD core, S383D and L518D, that further improved expression titers and biophysical stability. RBD-J6 retained binding affinity to human convalescent sera and to all tested neutralizing antibodies except antibodies that target the class IV epitope on the RBD core. K18-hACE2 transgenic mice immunized with three doses of a Beta variant of RBD-J6 displayed on a virus-like particle (VLP) generated neutralizing antibodies (nAb) to nine SARS-CoV-2 variants of concern at similar levels as two doses of Comirnaty. The vaccinated mice were also protected from challenge with Alpha or Beta SARS-CoV-2. This engineered antigen could be useful for modular RBD-based subunit vaccines to enhance manufacturability and global access, or for further development of variant-specific or broadly acting booster vaccines.

bioengineering↗

bioRxiv2022

Oxytocin activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in-situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.

neuroscience↗

bioRxiv2022

Diet induced obesity and type 2 diabetes drives exacerbated sex-associated disease profiles in K18-hACE2-mice challenged with SARS-CoV-2

SARS-CoV-2 infection results in wide-ranging disease manifestation from asymptomatic to potentially lethal. Infection poses an increased threat of severity to at-risk populations including those with hypertension, diabetes, and obesity. Type 2 Diabetes (T2DM), is characterized, in part, by insulin insensitivity and impaired glucose regulation. T2DM patients have increased disease severity and poorer outcomes with COVID-19. We utilized the diet-induced obesity (DIO) model of Type 2 Diabetes in SARS-CoV-2-susceptible K18-hACE2 transgenic mice to better understand the obesity co-morbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to normal diet mice. Increase in susceptibility to SARS-CoV2 in female DIO was associated with increased total viral RNA burden compared to male mice. RNAseq analysis was performed on the lungs of non-challenged, challenged, females, males, of either normal diet or DIO cohorts to determine the disease specific transcriptional profiles. DIO female mice had more total activated genes than normal diet mice after challenge; however, male mice experienced a decrease. GO term analysis revealed the DIO condition increased interferon response signatures and interferon gamma production following challenge. Male challenged mice had robust expression of antibody-related genes suggesting antibody producing cell localization in the lung. DIO reduced antibody gene expression in challenged males. Collectively this study establishes a preclinical T2DM/obesity co-morbidity model of COVID-19 in mice where we observed sex and diet specific responses that begin to explain the effects of obesity and diabetes on COVID-19 disease.

immunology↗

bioRxiv2022

SARS-CoV-2 Delta variant induces enhanced pathology and inflammatory responses in K18-hACE2 mice

The COVID-19 pandemic has been fueled by novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal dose of Delta was higher than Alpha or Beta strains. To characterize the differences in the Delta strains pathogenesis, a time-course experiment was performed to evaluate the overall host response to Alpha or Delta variant challenge. qRT-PCR analysis of Alpha- or Delta- challenged mice revealed no significant difference between viral RNA burden in the lung, nasal wash or brain. However, histopathological analysis revealed high lung tissue inflammation and cell infiltration following Delta- but not Alpha-challenge at day 6. Additionally, pro-inflammatory cytokines were highest at day 6 in Delta-challenged mice suggesting enhanced pneumonia. Total RNA-sequencing analysis of lungs comparing infected to uninfected mice revealed that Alpha-challenged mice have more total genes differentially activated, conversely, Delta-challenged mice have a higher magnitude of differential gene expression. Delta-challenged mice have increased interferon-dependent gene expression and IFN-{gamma} production compared to Alpha. Analysis of TCR clonotypes suggested that Delta challenged mice have increased T-cell infiltration compared to Alpha challenged. Our data suggest that Delta has evolved to engage interferon responses in a manner that may enhance pathogenesis. The in vivo and in silico observations of this study underscore the need to conduct experiments with VOC strains to best model COVID-19 when evaluating therapeutics and vaccines. ImportanceThe Delta variant of SARS-CoV-2 is known to be more transmissible and cause severe disease in human hosts due to mutations in its genome that are divergent from previous variants of concern (VOC). Our study evaluates the pathogenesis of Delta in the K18-hACE2 mouse model compared to the Alpha VOC. We observed that relative to Alpha, Delta challenge results in enhanced inflammation and tissue damage with stronger antiviral responses. These observations provide insight into Deltas unique pathogenesis.

immunology↗

bioRxiv2021

Emergent phases of ecological diversity and dynamics mapped in microcosms

Natural ecological communities display striking features, such as high biodiversity and a wide range of dynamics, that have been difficult to explain in a unified framework. Using experimental bacterial microcosms, we perform the first direct test of recent complex systems theory predicting that simple aggregate parameters dictate emergent behaviors of the community. As either the number of species or the strength of species interactions is increased, we show that microbial ecosystems transition between distinct qualitative dynamical phases in the predicted order, from a stable equilibrium where all species coexist, to partial coexistence, to emergence of persistent fluctuations in species abundance. Under the same conditions, high biodiversity and fluctuations allow and require each other. Our results demonstrate predictable emergent diversity and dynamics in ecological communities. One-Sentence SummaryA phase diagram of ecological dynamics and diversity as a function of coarse-grained features of species interaction network.

biophysics↗