Mitochondrial homeostasis is essential for providing cellular energy, particularly in resource‐demanding neurons, defects in which cause neurodegeneration, but the function of interferons (IFNs) in ...regulating neuronal mitochondrial homeostasis is unknown. We found that neuronal IFN‐β is indispensable for mitochondrial homeostasis and metabolism, sustaining ATP levels and preventing excessive ROS by controlling mitochondrial fission. IFN‐β induces events that are required for mitochondrial fission, phosphorylating STAT5 and upregulating PGAM5, which phosphorylates serine 622 of Drp1. IFN‐β signaling then recruits Drp1 to mitochondria, oligomerizes it, and engages INF2 to stabilize mitochondria–endoplasmic reticulum (ER) platforms. This process tethers damaged mitochondria to the ER to separate them via fission. Lack of neuronal IFN‐β in the Ifnb–/– model of Parkinson disease (PD) disrupts STAT5‐PGAM5‐Drp1 signaling, impairing fission and causing large multibranched, damaged mitochondria with insufficient ATP production and excessive oxidative stress to accumulate. In other PD models, IFN‐β rescues dopaminergic neuronal cell death and pathology, associated with preserved mitochondrial homeostasis. Thus, IFN‐β activates mitochondrial fission in neurons through the pSTAT5/PGAM5/S622Drp1 pathway to stabilize mitochondria/ER platforms, constituting an essential neuroprotective mechanism.
SYNOPSIS
How brain neurons cope with their high energy demands during periods of increased activity remains poorly understood. This genetic study reveals a role for IFN‐β in the control of nerve cell mitochondrial dynamics, ensuring fission and protecting against mitochondrial dysfunction and neurodegeneration in vivo.
Deficiency of neuronal Ifnb impairs mitochondrial fission, disrupting ATP production and oxidative stress response.
IFN‐β induces STAT5‐dependent expression of PGAM5 phosphatase, that is required for S622 phosphorylation of the mitochondrial regulator Drp1.
IFN‐β rescues mitochondrial defects and neuronal survival in Parkinson disease mouse models.
Mitochondrial dynamics and energy supply of brain neurons are controlled by IFN‐β in vivo.
The gut microbiota structure reflects both a host phylogenetic history and a signature of adaptation to the host ecological, mainly trophic niches. African cichlid fishes, with their array of closely ...related species that underwent a rapid dietary niche radiation, offer a particularly interesting system to explore the relative contribution of these two factors in nature. Here we surveyed the host intra- and interspecific natural variation of the gut microbiota of five cichlid species from the monophyletic tribe Perissodini of lake Tanganyika, whose members transitioned from being zooplanktivorous to feeding primarily on fish scales. The outgroup riverine species Astatotilapia burtoni, largely omnivorous, was also included in the study. Fusobacteria, Firmicutes and Proteobacteria represented the dominant components in the gut microbiota of all 30 specimens analysed according to two distinct 16S rRNA markers. All members of the Perissodini tribe showed a homogenous pattern of microbial alpha and beta diversities, with no significant qualitative differences, despite changes in diet. The recent diet shift between zooplantkon- and scale-eaters simply reflects on a significant enrichment of Clostridium taxa in scale-eaters where they might be involved in the scale metabolism. Comparison with the omnivorous species A. burtoni suggests that, with increased host phylogenetic distance and/or increasing herbivory, the gut microbiota begins differentiating also at qualitative level. The cichlids show presence of a large conserved core of taxa and a small set of core OTUs (average 13-15%), remarkably stable also in captivity, and putatively favoured by both restricted microbial transmission among related hosts (putatively enhanced by mouthbrooding behavior) and common host constraints. This study sets the basis for a future large-scale investigation of the gut microbiota of cichlids and its adaptation in the process of the host adaptive radiation.
Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies.
This prospective, interventional, multicenter clinical ...trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy.
Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio OR, 3.44 95% confidence interval {CI}, 1.30-9.08) and prophylaxis (33.3% vs 4.1%; OR, 11.75 95% CI, 2.31-59.71) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 95% CI, 7.89-237.96).
Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation.
NCT02550639.
Dispersal and recruitment are fundamental processes for population recovery following disturbances in sessile species. While both processes are well understood for many terrestrial species, they ...still remain poorly resolved for some macroalgal species. Here we experimentally investigated the effective dispersal and recruit survival of a mesophotic Mediterranean fucoid, Cystoseira zosteroides. In three isolated populations, four sets of settlement collectors were placed at increasing distances (from 0 to 10 m) and different orientations (North, South, East and West). We observed that effective dispersal was restricted to populations' vicinity, with an average of 6.43 m and not further than 13.33 m, following a Weibull distribution. During their first year of life, survival was up to 50%, but it was lower underneath the adult canopy, suggesting a negative density-dependence. To put our results in a broader context we compared the effective dispersal of other fucoid and kelp species reported in the literature, which confirmed the low dispersal ability of brown algae, in particular for fucoids, with an effective dispersal of few meters. Given the importance of recruitment for the persistence and recovery of populations after disturbances, these results underline the vulnerability of C. zosteroides and other fucoid species to escalating threats.
Compositional variation of the gut microbiota across host allopatric populations can reflect both adaptation and stochasticity since the time of separation. Major factors shaping this variation ...include the host phylogeographic and demographic history, the microbiota inheritance, environmental inputs and dispersal of bacteria. Here we explored the impact of these factors in driving gut community diversity in seven allopatric populations of the omnivorous lizard Podarcis lilfordi from the Menorcan coastal islets, all descending from an ancestral mainland population. Using 16S rRNA Illumina sequencing, we showed that 'islet' and 'age' (time since islet separation from mainland) were the only significant variables in microbial community clustering, suggesting a partial islet-restricted diversification following these lizards phylogeography. Despite a significant variation, islets/populations were characterized by a remarkably low bacterial uniqueness (2.4% of total OTUs) and a minor differential enrichment of taxa, indicating a negligible impact of local inputs and important host common constraints. Overall, the extant pattern of similarity/dissimilarity among islets is compatible with partial retention of the ancestral mainland microbial pool, with differences among islets potentially explained by a differential loss of bacteria following population fragmentation and bottlenecks (i.e. ecological drift). While more quantitative data are needed to validate this hypothesis, this study unveils the importance of considering both neutral and niche-driven processes in driving contemporary patterns of gut metacommunity diversity.
Cichlid fishes, with their repeated colonization of lakes and subsequent radiations at different scales of phylogenetic and ecological diversification, offer an excellent model system to understand ...the factors shaping the host-gut microbiota association in nature. Here, we characterized the gut microbiota of the
species complex from Central America (known as the Midas cichlid complex), encompassing 158 wild specimens (13 species) collected from seven Nicaraguan lakes, and combined these data with previously published data from two African lakes (spanning 29 species). Our aim was to comprehensively explore trends in microbiota variation and persistence along the large spatial and temporal scales of cichlid diversification (from the oldest radiation in L. Tanganyika, 9-12 My old, to young ones in Nicaraguan crater lakes, <0.5 My old), in allopatry and sympatry (within and across lakes), and across the range of dietary niches (from highly specialized to generalist feeders). Despite their extraordinary diversity, cichlids shared a remarkably conserved microbial taxonomic profile, which argues for a primary role of the host genetics in the assembly and maintenance of these microbial communities. Within this partly constrained microbiota profile, geographic isolation (continent and lake) represented the first level of discrimination. For the Midas cichlid, a partial congruency was found between host microbiota and genetic distances, suggesting that microbial communities have partly diversified along their cichlid phylogeographic history of crater lake colonization. In sympatry (within lakes), the young and poorly ecologically diversified cichlid assemblages of Central American lakes display largely unresolved gut microbiotas (in terms of both alpha and beta diversities), whereas the phylogenetically and ecologically diverse species found in African lakes showed greater microbial interspecific diversity. This pattern largely points to the level of habitat segregation, trophic niche overlap, and reproductive barriers as major modulators of the gut microbiota connectivity among sympatric species.
The extent to which deterministic rather than stochastic processes guide gut bacteria co-existence and ultimately their assembling into a community remains largely unknown. Co-occurrence networks of ...bacterial associations offer a powerful approach to begin exploring gut microbial community structure, maintenance and dynamics, beyond compositional aspects alone. Here we used an iconic model system, the cichlid fishes, with their multiple lake assemblages and extraordinary ecological diversity, to investigate a) patterns of microbial associations that were robust to major phylogeographical variables, and b) changes in microbial network structure along dietary shifts. We tackled these objectives using the large gut microbiota sequencing dataset available (nine lakes from Africa and America), building geographical and diet-specific networks and performing comparative network analyses.
Major findings indicated that lake and continental microbial networks were highly resembling in global topology and node taxonomic composition, despite the heterogeneity of the samples. A small fraction of the observed co-occurrences among operational taxonomic units (OTUs) was conserved across all lake assemblages. These were all positive associations and involved OTUs within the genera Cetobacterium and Turicibacter and several OTUs belonging to the families of Peptostreptococcaceae and Clostridiaceae (order Clostridiales). Mapping of diet contribution on the African Lake Tanganyika network (therefore excluding the geographic variable) revealed a clear community change from carnivores (C) to omnivores (O) to herbivores (H). Node abundances and effect size for pairwise comparisons between diets supported a strong contrasting pattern between C and H. Moreover, diet-associated nodes in H formed complex modules of positive interactions among taxonomically diverse bacteria (mostly Verrucomicrobia and Proteobacteria).
Conservation of microbial network topologies and specific bacterial associations across distinct lake assemblages point to a major host-associated effect and potential deterministic processes shaping the cichlid gut microbiota. While the origin and biological relevance of these common associations remain unclear, their persistence suggests an important functional role in the cichlid gut. Among the very diverse cichlids of L. Tanganyika, diet nonetheless represents a major driver of microbial community changes. By intersecting results from predictive network inferences and experimental trials, future studies will be directed to explore the strength of these associations, predict the outcome of community alterations driven by diet and ultimately help understanding the role of gut microbiota in cichlid trophic diversification.
1. Despite being among the most important habitat-forming organisms in temperate seas almost nothing is known about the demography of many algal species. This limits our ability to understand the ...effects of global and local stressors and to predict future trends under ongoing environmental change, which in turn hinders conservation actions. 2. Cystoseira species develop important forest-like assemblages along the sublittoral zone in the Mediterranean Sea. In this study we investigated the natural population dynamics and resilience patterns of a deep-water brown and canopy-forming macroalga, Cystoseira zosteroides. We used density-dependent and stochastic matrix models to estimate its basic life-history and compare it with other relevant habitat-forming marine (brown algae) and terrestrial (plants) species. We also evaluated the consequences of increasing the disturbances caused by storms and the impact of lost fishing gear, and their interaction, on C. zosteroides population dynamics. 3. The population dynamics of C. zosteroides showed similar patterns to terrestrial long-lived species such as shrubs and trees, with high survival due to their investment in structural biomass. Our data and models suggest that this species is able to buffer mortality pulses by increasing the number of recruits (and probably recruit survival) due to the new space liberated and, therefore, lower intraspecific competition. Nevertheless, when storm disturbances were more frequent than once every 50 years, their populations collapsed, and this effect worsened when several stressors acted simultaneously. 4. Our results improve our understanding about the demography of algal forests, and highlight the fact that increases in local and global stressors may erode the resilience of macroalgae, resulting in a loss of structural complexity in the benthic communities of temperate seas. 5. Synthesis. Our findings reveal that deep-water C. zosteroides forests display slow population dynamics, similar to terrestrial perennials and trees. The increase in disturbance frequencies due to global and local stressors and their interaction will cause the decline of underwater macroalgal forests and may induce profound changes in their population and community dynamics.
Species distribution models (SDMs) have been used to predict potential distributions of habitats and to model the effects of environmental changes. Despite their usefulness, currently there is no ...standardized sampling strategy that provides suitable and sufficiently representative predictive models for littoral marine benthic habitats. Here we aim to establish the best performing and most cost-effective sample design to predict the distribution of littoral habitats in unexplored areas. We also study how environmental variability, sample size, and habitat prevalence may influence the accuracy and performance of spatial predictions. For first time, a large database of littoral habitats (16,098 points over 562,895 km of coastline) is used to build up, evaluate, and validate logistic predictive models according to a variety of sampling strategies. A regularly interspaced strategy with a sample of 20% of the coastline provided the best compromise between usefulness (in terms of sampling cost and effort) and accuracy. However, model performance was strongly depen upon habitat characteristics. The proposed sampling strategy may help to predict the presence or absence of target species or habitats thus improving extensive cartographies, detect high biodiversity areas, and, lastly, develop (the best) environmental management plans, especially in littoral environments.
Ecoevolutionary dynamics of the gut microbiota at the macroscale level, that is, in across-species comparisons, are largely driven by ecological variables and host genotype. The repeated explosive ...radiations of African cichlid fishes in distinct lakes, following a dietary diversification in a context of reduced genetic diversity, provide a natural setup to explore convergence, divergence and repeatability in patterns of microbiota dynamics as a function of the host diet, phylogeny and environment. Here we characterized by 16S rRNA amplicon sequencing the gut microbiota of 29 cichlid species from two distinct lakes/radiations (Tanganyika and Barombi Mbo) and across a broad dietary and phylogenetic range. Within each lake, a significant deviation between a carnivorous and herbivorous lifestyle was found. Herbivore species were characterized by an increased bacterial taxonomic and functional diversity and converged in key compositional and functional community aspects. Despite a significant lake effect on the microbiota structure, this process has occurred with remarkable parallels in the two lakes. A metabolic signature most likely explains this trend, as indicated by a significant enrichment in herbivores/omnivores of bacterial taxa and functions associated with fiber degradation and detoxification of plant chemical compounds. Overall, compositional and functional aspects of the gut microbiota individually and altogether validate and predict main cichlid dietary habits, suggesting a fundamental role of gut bacteria in cichlid niche expansion and adaptation.
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