Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting the ecological footprint of selection

The structure of communities is influenced by many ecological and evolutionary processes, but the way this manifests in classic biodiversity patterns often remains unclear. Here, we aim to distinguish the ecological footprint of selection – through competition or environmental filtering – from that of neutral processes that are invariant to species identity. We build on existing Massive Eco-evolutionary Synthesis Simulations (MESS), which uses information from three biodiversity axes – species abundances, genetic diversity, and trait variation – to distinguish between mechanistic processes. In order to correctly detect and characterise competition, we add a new and more realistic form of competition that explicitly compares the traits of each pair of individuals. Our results are qualitatively different to those of previous work in which competition is based on the distance of each individual’s trait to the community mean. We find that our new form of competition is easier to identify in empirical data compared to the alternatives. This is especially true when trait data are available and used in the inference procedure. Our findings hint that signatures in empirical data previously attributed to neutrality may in fact be the result of pairwise-acting selective forces. We conclude that gathering more different types of data, together with more advanced mechanistic models and inference as done here, could be the key to unravelling the mechanisms of community assembly.
Epigenetic inheritance is gated by naïve pluripotency and Dppa2

Environmental factors can trigger cellular responses that propagate across mitosis or even generations. Perturbations to the epigenome could underpin such acquired changes, however, the extent and contexts in which modified chromatin states confer heritable memory in mammals is unclear. Here we exploit a modular epigenetic editing strategy to establish de novo heterochromatin domains (epialleles) at endogenous loci and track their inheritance in a developmental model. We find that naïve pluripotent phases systematically erase ectopic domains of heterochromatin via active mechanisms, which acts as an intergenerational safeguard against transmission of epialleles. Upon lineage specification however, acquired chromatin states can be probabilistically inherited under selectively favourable conditions, including propagation of p53 silencing through in vivo development. Using genome-wide CRISPR screening, we identify the mechanisms that block heritable silencing memory in pluripotent cells, and demonstrate removal of Dppa2 unlocks the potential for epigenetic inheritance uncoupled from DNA sequence. Our study outlines a mechanistic basis for how epigenetic inheritance is restricted in mammals, and reveals genomic- and developmental-contexts in which heritable memory is feasible.
Rapid analysis of strigolactone receptor activity in a Nicotiana benthamiana dwarf14 mutant

DWARF14 (D14) is an ɑ/β-hydrolase and receptor for the plant hormone strigolactone (SL) in angiosperms. Upon SL perception, D14 works with MORE AXILLARY GROWTH2 (MAX2) to trigger polyubiquitination and degradation of DWARF53(D53)-type proteins in the SUPPRESSOR OF MAX2 1-LIKE (SMXL) family. We used CRISPR-Cas9 to generate knockout alleles of the two homoeologous D14 genes in the Nicotiana benthamiana genome. The Nbd14a,b double mutant had several phenotypes that are consistent with the loss of SL perception in other plants, including increased axillary bud outgrowth, reduced height, shortened petioles, and smaller leaves. A ratiometric fluorescent reporter system was used to monitor degradation of SMXL7 from Arabidopsis thaliana (AtSMXL7) after transient expression in N. benthamiana and treatment with the strigolactone analog GR24. AtSMXL7 was degraded after treatment with GR245DS, which has the stereochemical configuration of SLs, as well as its enantiomer GR24ent-5DS . In Nbd14a,b leaves, AtSMXL7 abundance was unaffected by GR24. Transient coexpression of AtD14 with the AtSMXL7 reporter in Nbd14a,b restored the degradation response to GR24, but required an active catalytic triad. With this platform, we evaluated the ability of several AtD14 mutants that had not been characterized in plants to target AtSMXL7 for degradation.
A Non-redundant Role for T cell-derived IL-22 in Antibacterial Defense of Colonic Crypts

IL-22 is a key cytokine in immune defense against pathogens at barrier sites. In response to enteric attaching and effacing bacteria, IL-22 produced by type 3 innate lymphoid cells (ILC3s) is thought to be important early for induction of antimicrobial peptides (AMPs) that protect intestinal epithelial cells (IECs) in advance of T cell-derived IL-22 that arises later. Yet, the basis for a requirement for both innate and adaptive IL-22–producing immune cells in protecting the intestinal mucosa is unknown. Here, using novel mice that both report IL-22 expression and can be targeted for its lineage-specific deletion, we show that mice with deficiency of IL-22 targeted to innate immune cells, including ILC3s, have impaired STAT3 activation of surface colonic IECs colonized by bacteria early in infection. In contrast, mice with IL-22 deficiency limited to T cells have complete loss of STAT3 activation in IECs lining colonic crypts and fail to protect the crypts from bacterial invasion late despite ongoing production of IL-22 from ILC3s. T cell-derived IL-22 is required for upregulation of many host-protective genes by crypt IECs, including those encoding AMPs, neutrophil-recruiting chemokines, and mucins and mucin-related molecules, while also restricting pro-inflammatory genes downstream of IFNγ and TNF signals. Thus, T cell-derived IL-22 is indispensable for antibacterial defense and damage control of intestinal crypts.
Adult Male Rats Show Resilience to Adolescent Bisphenol A Effects on Hormonal and Behavioral Responses While Co-Exposure With Hop Extracts Supports Synergistic Actions

The adolescence period, marked by sexual and brain maturation, has shown sensitivity to various environmental disruptors. Exposure to the xenoestrogen bisphenol A (BPA) is known to alter physiological and behavioral responses although its role at this critical period remains largely unknown. Recent research further suggests biochemical and genomic effects of BPA to be mitigated by various natural compounds, while effects on behavior have not been examined. This study aimed to characterize (1) the effects of dietary BPA during adolescence on endogenous corticosterone (CORT) secretion, emotional behavior, and testosterone (T) in adulthood, and (2) the impact of combined exposure to BPA with hop extracts (Hop), a phytoestrogen with anxiolytic properties. To do so, four groups of male Wistar rats [postnatal day (PND) 28] were administered corn oil (control), BPA (40 mg/kg), hops (40 mg/kg), or BPA-hops by oral gavage for 21 days (PND 28–48). Blood droplets collected on PND 28, 48, and 71 served to measure CORT and T changes. As adults, rats were tested in the elevated plus maze (EPM), the social interaction test, and the forced swim test. Our findings demonstrated elevated anxiety and a trend toward depressive-like behaviors in BPA- compared to hops-exposed rats. However, BPA intake had no impact on basal CORT levels, or adulthood T secretion and sociability. Of note, BPA's anxiogenic effect manifested through decreased EPM open arm entries was abolished by hops co-supplementation. Together, our observations suggest the adolescence period to be less sensitive to deleterious effects of BPA than what has been reported upon gestational and perinatal exposure.
Dynamics of an SIR-Based COVID-19 Model With Linear Incidence Rate, Nonlinear Removal Rate, and Public Awareness

The paper studies the dynamics of the classical susceptible-infectious-removed (SIR) model when applied to the transmission of COVID-19 disease. The model includes the classical linear incidence rate but considers a nonlinear removal rate that depends on the hospital-bed population ratio. The model also includes the effects of media on public awareness. We prove that when the basic reproduction number is less than unity the model can exhibit a number of nonlinear phenomena including saddle-node, backward, and Hopf bifurcations. The model is fitted to COVID-19 data pertinent to Saudi Arabia. Numerical simulations are provided to supplement the theoretical analysis and delineate the effects of hospital-bed population ratio and public awareness on the control of the disease.
Monocyte-Derived Macrophages Contribute to Chitinase Dysregulation in Amyotrophic Lateral Sclerosis: A Pilot Study

Neuroinflammation significantly contributes to Amyotrophic Lateral Sclerosis (ALS) pathology. In lieu of this, reports of elevated chitinase levels in ALS are interesting, as they are established surrogate markers of a chronic inflammatory response. While post-mortem studies have indicated glial expression, the cellular sources for these moieties remain to be fully understood. Therefore, the objective of this pilot study was to examine whether the peripheral immune system also contributes to chitinase dysregulation in ALS. The temporal expression of CHIT1, CHI3L1, and CHI3L2 in non-polarized monocyte-derived macrophages (MoMas) from ALS patients and healthy controls (HCs) was examined. We demonstrate that while CHIT1 and CHI3L1 display similar temporal expression dynamics in both groups, profound between-group differences were noted for these targets at later time-points i.e., when cells were fully differentiated. CHIT1 and CHI3L1 expression were significantly higher in MoMas from ALS patients at both the transcriptomic and protein level, with CHI3L1 levels also being influenced by age. Conversely, CHI3L2 expression was not influenced by disease state, culture duration, or age. Here, we demonstrate for the first time, that in ALS, circulating immune cells have an intrinsically augmented potential for chitinase production that may propagate chronic neuroinflammation, and how the ageing immune system itself contributes to neurodegeneration.
Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen

The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn’t (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone.
Multicohort Analysis Identifies Monocyte Gene Signatures to Accurately Monitor Subset-Specific Changes in Human Diseases

Monocytes are crucial regulators of inflammation, and are characterized by three distinct subsets in humans, of which classical and non-classical are the most abundant. Different subsets carry out different functions and have been previously associated with multiple inflammatory conditions. Dissecting the contribution of different monocyte subsets to disease is currently limited by samples and cohorts, often resulting in underpowered studies and poor reproducibility. Publicly available transcriptome profiles provide an alternative source of data characterized by high statistical power and real-world heterogeneity. However, most transcriptome datasets profile bulk blood or tissue samples, requiring the use of in silico approaches to quantify changes in cell levels. Here, we integrated 853 publicly available microarray expression profiles of sorted human monocyte subsets from 45 independent studies to identify robust and parsimonious gene expression signatures, consisting of 10 genes specific to each subset. These signatures maintain their accuracy regardless of disease state in an independent cohort profiled by RNA-sequencing and are specific to their respective subset when compared to other immune cells from both myeloid and lymphoid lineages profiled across 6160 transcriptome profiles. Consequently, we show that these signatures can be used to quantify changes in monocyte subsets levels in expression profiles from patients in clinical trials. Finally, we show that proteins encoded by our signature genes can be used in cytometry-based assays to specifically sort monocyte subsets. Our results demonstrate the robustness, versatility, and utility of our computational approach and provide a framework for the discovery of new cellular markers.
Splitting the Difference: Heterogeneous Soil Moisture Availability Affects Aboveground and Belowground Reserve and Mass Allocation in Trembling Aspen

When exploring the impact of resource availability on perennial plants, artificial treatments often apply conditions homogeneously across space and time, even though this rarely reflects conditions in natural systems. To investigate the effects of spatially heterogeneous soil moisture on morphological and physiological responses, trembling aspen (Populus tremuloides) saplings were used in a split-pot experiment. Following the division of the root systems, saplings were established for a full year and then subjected to either heterogeneous (portion of the root system exposed to non-lethal drought) or homogeneous (whole root system exposed to non-lethal drought or well-watered) treatments. Above- and belowground growth and non-structural carbohydrate (NSC) reserves (soluble sugars and starch) were measured to determine how allocation of reserves and mass between and within organs changed in response to variation in soil moisture availability. In contrast to saplings in the homogeneous drought treatment, which experienced reduced shoot growth, leaf abscission and fine root loss, saplings exposed to the heterogeneous conditions maintained similar aboveground growth and increased root system allocation compared to well-watered saplings. Interestingly under heterogeneous soil moisture conditions, the portion of the root system that was resource limited had no root dieback and increased carbon reserve concentrations, while the portion of the root system that was not resource limited added new roots (30% increase). Overall, saplings subjected to the heterogeneous soil moisture regime over-compensated belowground, both in mass and NSC reserves. These results indicate that the differential allocation of mass or reserves between above- and belowground organs, but also within the root system can occur. While the mechanisms and processes involved in these patterns are not clear, these responses could be interpreted as adaptations and acclimations to preserve the integrity of the entire sapling and suggests that different portions of plant organs might respond autonomously to local conditions. This study provides further appreciation of the complexity of the mechanisms by which plants manage heterogeneous conditions and offers evidence that spatial and temporal variability of resource availability, particularly belowground, needs to be accounted for when extrapolating and modeling stress responses at larger temporal and spatial scales.
Metabolomics Reveals Differences in Aqueous Humor Composition in Patients With and Without Pseudoexfoliation Syndrome

Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60–70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (−31%, VIP = 2.38) and homo-arginine (−19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (−29%, VIP = 1.24) and decatrienoylcarnitine (−46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (−33%, VIP = 2.11) and hydroxyanthranilic acid (−33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (−29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.
Understanding and Managing Harmful Algal Bloom Risks in a Changing Climate: Lessons From the European CoCliME Project

This paper discusses the conceptual and methodological challenges to co-developing high-quality and transferable knowledge to understand and manage harmful algal bloom (HAB) risks as part of adaptation to changing aquatic ecosystems in Europe. Global HAB-climate change research efforts to date have focused on enhancing the credibility of scientific knowledge by conducting basic scientific research aimed at understanding the physical and biogeochemical drivers and mechanisms shaping HAB dynamics in order to predict their occurrence and prevent their societal and ecological impacts. However, the rapid and interconnected changes occurring in marine ecosystems worldwide necessitate a simultaneous shift toward enhancing the salience, legitimacy, usefulness, and usability of this knowledge for decision-making. To address this need, we present and discuss empirical findings from the marine-focused CoCliME project, which set out to co-develop user-oriented climate services to support HAB risk mitigation and adaptation in European coastal regions. We present lessons learned in relation to four areas of project implementation, across five regional cases, that emerged as essential for enhancing the quality of knowledge for managing HAB-climate risks: (1) Engaging stakeholders to understand their knowledge, experiences, interests and concerns; (2) Co-developing a shared terminology and framing of the “HAB-related problems”; (3) Advancing scientific understanding of drivers and interactions shaping HAB-climate risks and; (4) Co-producing prototype services that integrate social and HAB-climate data and knowledge to support decision-making. We find that efforts to reduce scientific knowledge gaps and uncertainties about HAB-climate linkages (efforts to enhance credibility), while important, risk overlooking key aspects of knowledge co-production and application that are necessary to render this knowledge more salient, legitimate, useful, and usable. Understanding the multi-risk decision-making context within which societal stakeholders appraise HAB and climate change risks and approaching knowledge co-production as a learning process, are vital lessons learned in this respect. Drawing on project learning, we highlight key priorities for enhancing the societal relevance and impact of HABs-climate research during the UN Decade of Ocean Science for Sustainable Development.
Medicinal Plant Leaf Extract From Sage and Lemon Verbena Promotes Intestinal Immunity and Barrier Function in Gilthead Seabream (Sparus aurata)

The inclusion of a medicinal plant leaf extract (MPLE) from sage (Salvia officinalis) and lemon verbena (Lippia citriodora), rich in verbascoside and triterpenic compounds like ursolic acid, was evaluated in gilthead seabream (Sparus aurata) fed a low fishmeal-based diet (48% crude protein, 17% crude fat, 21.7 MJ kg-1, 7% fishmeal, 15% fish oil) for 92 days. In particular, the study focused on the effect of these phytogenic compounds on the gut condition by analyzing the transcriptomic profiling (microarray analysis) and histological structure of the intestinal mucosa, as well as the histochemical properties of mucins stored in goblet cells. A total number of 506 differentially expressed genes (285 up- and 221 down-regulated) were found when comparing the transcriptomic profiling of the intestine from fish fed the control and MPLE diets. The gut transcripteractome revealed an expression profile that favored biological mechanisms associated to the 1) immune system, particularly involving T cell activation and differentiation, 2) gut integrity (i.e., adherens and tight junctions) and cellular proliferation, and 3) cellular proteolytic pathways. The histological analysis showed that the MPLE dietary supplementation promoted an increase in the number of intestinal goblet cells and modified the composition of mucins’ glycoproteins stored in goblet cells, with an increase in the staining intensity of neutral mucins, as well as in mucins rich in carboxylated and weakly sulfated glycoconjugates, particularly those rich in sialic acid residues. The integration of transcriptomic and histological results showed that the evaluated MPLE from sage and lemon verbena is responsible for the maintenance of intestinal health, supporting gut homeostasis and increasing the integrity of the intestinal epithelium, which suggests that this phytogenic may be considered as a promising sustainable functional additive for aquafeeds.