Biology subjects

Lopes, F.

Publications and source records attributed to Lopes, F..

17 recordsLinked to original sources

bioRxiv2026

Metabolic reorganization shapes the dynamics of a water kefir microbial community

Microbial fermentations emerge from the collective activity of interacting species whose relative abundances, metabolic functions, and environmental constraints continuously change over time. Water kefir provides a tractable model to investigate how multispecies communities coordinate their metabolic activities during fermentation. Here, we combined time-resolved community profiling, physicochemical measurements, metabolite quantification, and controlled co-culture assays to characterize the dynamics of a water kefir consortium comprising 19 detected microbial species. Our results reveal that water kefir fermentation is not adequately described as a simple succession of independently acting microbial groups. Instead, the community undergoes a reproducible reorganization of its collective metabolism around 20 h of fermentation. This transition marks a shift from an early regime characterized by the accumulation of soluble sugars and ethanol to a later regime dominated by enhanced sugar consumption and lactate production. Controlled interaction assays further showed that bacterial partners can alter carbon-use behaviour in Saccharomyces cerevisiae, highlighting the capacity of interspecies interactions to reshape metabolic phenotypes within the consortium. Together, these results support an ecological view of water kefir fermentation in which community-wide metabolic reorganization emerges from the interplay between microbial interactions, resource availability, and environmental change.

microbiology↗

bioRxiv2026

Phylogenomics resolves a 200-year-old puzzle: a revised tribal classification of Afro-Eurasian dung beetles (Coleoptera: Scarabaeinae)

BackgroundThe tribal classification of scarab dung beetles (Coleoptera: Scarabaeinae) is currently largely incomplete due to the lack of robust phylogenetic evidence supporting the assignment of many Afro-Eurasian and American genera to tribes. MethodsWe used ultraconserved elements (UCEs) to infer phylogenetic relationships across most Afro-Eurasian dung beetle lineages, including 25 of the 27 extant genera currently incertae sedis. ResultsWe recovered full support for the monophyly of previously recognised tribes and for several phylogenetically and morphologically clearly delimited new tribal-level clades, allowing us to propose a complete tribal classification for all Afro-Eurasian dung beetle genera. Thirteen new tribes are described and diagnosed: Aphengoecini trib. nov., Bohepilissini trib. nov., Catharsiini trib. nov., Chalconotini trib. nov., Circelliini trib. nov., Dwesasilvasedini trib. nov., Haroldiini trib. nov., Heliocoprini trib. nov., Janssensantini trib. nov., Macroderini trib. nov., Nesovinsoniini trib. nov., Pycnopanelini trib. nov. and Tanzanolini trib. nov. The tribe Coprini sensu novo is redefined as comprising three subtribes: Coprina, Onychothecina subtrib. nov. and Pedariina subtrib. nov. The tribe Odontolomini is downranked to a subtribe of Endroedyolini sensu novo, becoming Endroedyolini Odontolomina stat. nov. The tribe Onthophagini sensu novo is redefined and divided into three subtribes: Helictopleurina stat. nov., Oniticellina stat. nov. and Onthophagina; the remaining former subtribes of Oniticellini (Attavicinina, Drepanocerina and Liatongina) are synonymised with Oniticellina; the subtribe Alloscelina of Onthophagini is synonymised with Onthophagina (syn. nov.). The tribe Panelini stat. rev. and sensu novo, comprising the single genus Panelus, is revalidated and redefined. Updated morphological diagnoses of Elassocanthonini, Gymnopleurini, Onitini and Scarabaeini are provided. The genus Phaedotrogus is synonymised with Haroldius (Haroldiini) (syn. nov.). An identification key to all Afro-Eurasian dung beetle tribes is provided. DiscussionOur results establish a robust phylogenetic framework and revised tribal classification for Afro-Eurasian Scarabaeinae dung beetles, providing a foundation for future taxonomic, comparative and macroevolutionary research.

zoology↗

bioRxiv2026

The role and origins of human attitudes in Human-Wildlife Conflict responses: Insights from Spectacled Bears (Tremarctos ornatus) and other wild carnivores in Southern Ecuador

BackgroundHuman-wildlife conflict, which motivates retaliatory killings, is a major driver of species decline globally. Addressing an open question in human-wildlife conflict, we test whether evolutionary-rooted human attitudes, independent of economic losses, better predict retaliatory responses. MethodsWe examined human attitudes toward spectacled bears (Tremarctos ornatus) and other wild carnivores in a wildlife conflict-zone in southern Ecuador by conducting interviews in rural communities. We measured both established variables - such as education levels, age, and gender - and novel psychometric variables to identify predictors of human-wildlife conflict responses. ResultsPerceptions of animals emerged as the strongest predictor of conflict responses. Communities exhibiting high levels of vengefulness, particularly within an animal-directed Culture of Honor, where individuals, especially men, are expected to respond strongly or violently to perceived threats, were more likely to support lethal interventions. Conversely, individuals with strong environmental education backgrounds demonstrated more positive perceptions of wildlife, highlighting educations potential role in conflict mitigation. ConclusionEvolutionary-derived attitudes, rather than economic factors, primarily drive human responses to wildlife conflict. Effective strategies to reduce violence against wildlife should incorporate human perceptions and culturally rooted values to address the underlying social and psychological drivers of conflict.

ecology↗

bioRxiv2026

How farming practices and livestock management affect Human-Wildlife Conflict intensity in Southern Ecuador: The case of the Spectacled Bear (Tremarctos ornatus) and feral dogs

BackgroundHuman-Wildlife Conflict is emerging as one of the most critical conservation and socio-economic challenges in the Ecuadorian Andes, where both rural livelihoods and native fauna are under increasing pressure. Small-scale livestock producers in the region depend almost entirely on a limited number of cattle, meaning that the loss of even a single animal can lead to severe economic hardship. In response, antagonistic actions against wildlife are frequent, further threatening vulnerable species. At the same time, the recent proliferation of feral dogs adds a new dimension to conflict, posing risks to both livestock and native fauna. Despite the growing severity of this conflict, little is known of its drivers, spatial patterns, and socio-ecological consequences. This study seeks to fill that gap by generating insights to inform targeted conservation strategies for community-based mitigation of conflict with spectacled bears and feral dogs. MethodsTo assess the drivers and dynamics of HWC in southern Ecuador, we conducted structured interviews with livestock owners, quantifying the frequency and intensity of conflicts across multiple species and evaluating whether farm composition and management practices predict conflict patterns. ResultsOur results reveal that large carnivores cause significantly higher economic losses than smaller predators; furthermore, feral dogs have emerged as the primary source of financial damage over the past five years. Farms with a greater proportion of forest edge were associated with a higher probability of severe conflict, particularly with large carnivores. ConclusionsThese findings underscore the urgent need for proactive strategies to promote coexistence. Identifying predictive variables of conflict risk is crucial for vulnerability assessments and the design of effective mitigation policies. Controlling feral dog populations is likely to be a critical step in safeguarding both rural human livelihoods and native biodiversity in the Andean landscape.

ecology↗

bioRxiv2026

Twenty-five years of monitoring reveals that uninterrupted rodent control is the fundamental driver of breeding success in the Galapagos Petrel Pterodroma phaeopygia

The long-standing misconception that the Galapagos petrel (Pterodroma phaeopygia) and the Hawaiian petrel (Pterodroma sandwichensis) were conspecific masked the severe vulnerability of the Galapagos population. By the time its distinct status was recognized, the Galapagos petrel was already in marked decline, primarily due to invasive predators. Consequently, sustained rodent control programs have been implemented on Santa Cruz Island. An unintentional one-year failure in rodent control provided a rare quasi-experimental opportunity to quantify the demographic consequences of the invasive black rat predator. During this year, hatching success declined by [~]35% and breeding success by [~]40% relative to long-term means (66% and 62%, respectively), representing a substantial reproductive collapse. Fledging success exhibited a comparatively modest decline (from a long-term mean of 94% to 86% in 2017), suggesting stage-specific vulnerability. These results support the hypothesis that invasive black rats primarily affect early reproductive stages through egg predation and predation on small chicks, while older chicks surpass a critical size threshold that reduces susceptibility. Across the remaining managed years, reproductive metrics exhibited great stability, demonstrating the petrels resilience against other environmental or climatic stressors. Our findings provide robust empirical evidence that invasive rodent control is the dominant driver of reproductive success in this endangered seabird. The quasi-experimental failure underscored both the effectiveness and the necessity of continuous predator management, highlighting the severe and immediate consequences of even short-term lapses.

ecology↗

bioRxiv2026

Competition and niche partitioning of floral resources between two native stingless bees (Melipona mimetica and Scaptotrigona sp., Apidae: Meliponini) in a seasonally dry tropical forest of Ecuador

Stingless bees are key pollinators in tropical ecosystems, yet their ecological dynamics remain poorly understood in highly seasonal environments such as the seasonally dry tropical forests of Ecuador. These ecosystems experience pronounced climatic seasonality, with sharp transitions between dry and wet periods that strongly affect floral resource availability. Understanding interspecific competition and niche partitioning in such systems is critical, particularly given the global decline of pollinators. We investigated resource use and niche dynamics in two native stingless bees, Melipona mimetica and Scaptotrigona sp., by quantifying pollen, nectar, and resin collection across seasons. Log-linear models were used to test the effects of species, season, and their interaction on resource use, while non-metric multidimensional scaling (NMDS) assessed niche overlap. Contrary to the expectation that niche overlap increases under resource scarcity, we found greater overlap during the wet season, when resources are more abundant. This suggests that both species converge on high-quality floral resources during peak availability, reflecting an adaptive response to strong environmental seasonality. Pollen use remained stable across seasons, consistent with generalist foraging behavior. In contrast, nectar collection increased significantly during the wet season, while resin exhibited a shared seasonal peak, likely associated with synchronized nest construction or maintenance. These findings reveal context-dependent competition dynamics and highlight the role of environmental seasonality in shaping pollinator interactions. Our study provides new insights into the ecology of threatened stingless bees and contributes to their conservation in tropical dry forest ecosystems.

ecology↗

bioRxiv2026

Modulation of the RNAse P/MRP complex and mitochondrial ribosome enhances cytosolic ribosome coordination and sustains longevity

Aging is accompanied by a progressive decline in protein synthesis and ribosome abundance, yet paradoxically, genetic or pharmacological attenuation of translation extends lifespan across species. Whether the age-associated decline in translation is adaptive or reflects a pathological failure of ribosome homeostasis remains unclear. Here, we show that shortened lifespan is driven by dysregulated ribosome biogenesis (RiBi) and impaired ribosome assembly. Using Caenorhabditis elegans ncl-1 loss-of-function mutants as a model of accelerated aging, we find that nucleolar enlargement coincides with decoupling of precursor and mature rRNA, ribosomal protein (RP) transcripts, and protein abundance, loss of RP stoichiometry, defective ribosomal subunit joining, and compromised proteostasis. Strikingly, lifespan can be restored downstream of the nucleolus by targeting either the RNAse P/MRP complex or the mitochondrial ribosome. These interventions rebalance mature rRNA and RP abundance, improve ribosomal assembly, and reduce protein aggregation despite persistent nucleolar enlargement and elevated pre-rRNA levels. Our findings identify accelerated age-associated ribosome dysfunction as a qualitative failure of ribosomal biogenesis, and demonstrate that restoring ribosomal homeostasis is sufficient to improve proteostasis and extend lifespan.

cell biology↗

bioRxiv2025

Paternal over- and under-nutrition program fetal and placental development in a sex-specific manner in mice

The association between sub-optimal paternal diet and offspring well-being is becoming established. However, the underlying mechanisms are yet to be fully defined. The aim of this study was to establish the impact of over- and under-nutrition, with or without macronutrient supplementation, on male reproductive fitness and post-fertilisation development. Male C57/BL6J mice were fed either control diet (CD), isocaloric low protein diet (LPD), high fat/sugar Western diet (WD) or LPD or WD supplemented with methyl-donors and carriers (MD-LPD or MD-WD respectively) for 8 weeks before mating with virgin C57/BL6J females. Placental tissue was collected at embryonic day (E)8.5, to assess early placental (ectoplacental cone) morphology and metabolism and E17.5 for sex-specific transcriptomic profiling. Post-mating, stud male tissues were harvested for assessment of testicular morphology and gene expression, gut microbiota composition and metabolic status. WD and MD-WD males displayed increased adiposity, hepatic cholesterol and free fatty acids and gut microbiota dysbiosis when compared to CD fed males. In the testes, WD and MD-WD perturbed the expression of genes associated with metabolism and transcription regulation. Additionally, we observed differential expression of multiple genes within the Wnt signalling pathway, central in the regulation of cellular proliferation, migration, survival, and cell fate determination during development. Despite no impact on fundamental male fertility, significant changes in ectoplacental cone metabolism, fetal growth, and placental gene expression were observed in response to specific dietary regimens. Interestingly, while CD male and female placentas displayed 301 genome-wide, sexually-dimorphic genes, LPD, MD-LPD, WD and MD-WD male and female placentas possessed only 13, 0, 14 and 15 sexually-dimorphic genes respectively. Our data show that while sub-optimal paternal diet has minimal impact on male fertility, fetal and placental development are perturbed in a sex-specific manner.

developmental biology↗

bioRxiv2025

A review of Sisyphini Dung Beetles (Coleoptera: Scarabaeinae) endemic to Mauritius: insights from subfossil evidence and phylogenetic analysis

Five indigenous species of Scarabaeinae are known from Mauritius island, classified into two genera: the monotypic Nesovinsonia Martinez & Pereira, 1958 and Nesosisyphus Vinson, 1946. This study conducts a taxonomic review of the latter genus Nesosisyphus, and evaluates its recent extinction using historical and new occurrence records, subfossils, and niche modeling. We provide the first molecular phylogeny and evaluate the evolutionary relationships of Nesosisyphus by comparing two different phylogenetic trees: the first, based on a Ultraconserved Elements (UCEs hereafter) dataset, and the second one, on three loci (28S, 16S, COI). We identify five Mauritian Nesosisyphus species, including a new extinct one, Nesosisyphus draco sp. n., from a 4,000 yr old subfossil. We diagnose, illustrate, and provide an updated key to all the sisyphine species from Mauritius, as well as the occurrence map. Our niche modeling analysis reveals a broader past distribution range for Mauritian sisyphines, now confined to small, disjunct forest patches due to extensive forest contraction and local extinctions.

evolutionary biology↗

bioRxiv2023

From museum drawer to tree: historical DNA phylogenomics clarifies the systematics of rare dung beetles (Coleoptera: Scarabaeinae) from museum collections

Although several methods exist for extracting and sequencing historical DNA originating from drypreserved insect specimens deposited in natural history museums, no consensus exists as to what is the optimal approach. We demonstrate that a customized, low-cost archival DNA extraction protocol ([~] {euro}10 per sample), in combination with Ultraconserved Elements (UCEs), is an effective tool for insect phylogenomic studies. We successfully tested our approach by sequencing DNA from scarab dung beetles preserved in both wet and dry collections, including unique primary type and rare historical specimens from internationally important natural history museums in London, Paris and Helsinki. The focal specimens comprise enigmatic dung beetle genera (Nesosisyphus, Onychotechus and Helictopleurus) that varied in age and preservation. The oldest specimen, the holotype of the now possibly extinct Mauritian endemic Nesosisyphus rotundatus, was collected in 1944. We obtained high-quality DNA from all studied specimens to enable the generation of a UCE-based dataset that revealed an insightful and well-supported phylogenetic tree of dung beetles. The resulting phylogeny suggested the reclassification of Onychotechus (previously incertae sedis) within the tribe Coprini. Our approach demonstrates the feasibility and effectiveness of combining DNA data from historic and recent museum specimens to provide novel insights. The proposed archival DNA protocol is available at DOI 10.17504/protocols.io.81wgbybqyvpk/v1 HighlightsO_LIWe combined custom low-cost archival DNA extractions and Ultraconserved Element phylogenomics C_LIO_LIDNA from rare museum specimens of enigmatic dung beetles revealed their phylogenetic connections C_LIO_LIGenomic data was obtained from the holotype of a potentially extinct monoinsular endemic species C_LIO_LIGenomic data allowed a rare and enigmatic species of previously unknown affinity to be classified C_LIO_LIThe morphology of museum specimens remained intact following non-destructive DNA extraction C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/564347v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@34aad0org.highwire.dtl.DTLVardef@1ba597dorg.highwire.dtl.DTLVardef@1493c2dorg.highwire.dtl.DTLVardef@10dd2eb_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2023

Helminth-derived metabolites induce tolerogenic functional, metabolic, and transcriptional signatures in dendritic cells that attenuate experimental colitis

Helminth infections can restore immune tolerance and suppress intestinal inflammation, yet the molecular mediators underlying these effects are poorly defined. Here, we show that nonpolar metabolites derived from the helminth Heligmosomoides polygyrus bakeri (HnpM) program dendritic cells (DCs) toward a tolerogenic DC (tolDC) phenotype. Adoptive transfer of HnpM-treated DCs significantly ameliorated DSS-induced intestinal inflammation in mice. Transcriptomic and metabolomic profiling revealed that HnpM induces early metabolic reprogramming followed by gene expression signatures characteristic of tolerogenic DCs that are shared by established tolDC-inducing agents. Together, these findings identify that helminth-derived metabolites are a novel source of small molecule therapeutics to restore immune tolerance in immune-mediated disorders. Summary SentenceMetabolites produced by Heligmosomoides polygyrus induce metabolic and transcriptional changes in DCs consistent with tolDCs, and adoptive transfer of these DCs attenuate DSS-induced intestinal inflammation.

immunology↗

bioRxiv2022

Metagenomics reveals that Dung Beetles (Coleoptera: Scarabaeinae) broadly feed on Reptile dung and could feed on that of Dinosaurs

According to traditional views, the evolution of dung beetles (Coleoptera: Scarabaeinae) and their feeding habits are largely attributed to mammal dung. In this paper, we challenge this view and provide evidence that many dung beetle communities are actually associated with the dung of reptiles and birds (= Sauropsida). In turn, this indicates that sauropsid dung may have played a crucial evolutionary role that was previously underestimated. We argue that it is physiologically realistic to consider that coprophagy in dung beetles could have evolved during the Cretaceous in response to the massive amount of dung produced by dinosaurs. Furthermore, we demonstrate that sauropsid dung may be one of the major factors driving the emergence of insular dung beetle communities across the globe. We support our findings with amplicon-metagenomic analyses, trapping experiments, and meta-analysis of the published literature.

evolutionary biology↗

bioRxiv2022

Modeling foot-and-mouth disease dissemination in Brazil and evaluating the effectiveness of control measures

Foot-and-mouth disease (FMD) is known to infect multiple food-animal species and to spread among ungulate populations. We introduce a multiscale compartmental stochastic model that incorporates population dynamics, births, deaths, and species-specific transmission dynamics. The model integrates disease dynamics at both the between-farm and the within-farm levels. We developed four scenarios to evaluate the effectiveness of countermeasures, including movement standstill, vaccination, and depopulation. The base scenario involved vaccinating the animals on 20 farms and depopulating four infected farms. The three alternative control scenarios included increasing vaccination and depopulation capacities and no vaccination. Our findings indicate that bovines were the most frequently infected species, followed by swine and small ruminants. After ten days of initial spread, the number of infected farms ranged from 1 to 123, with most simulations (90.12%) predicting fewer than 50 infected farms. Most of the secondary spread occurred within a range of 25 km. Early response to initiating the control action reduces the number of days spent working on control actions while intensifying daily depopulation and vaccination capacity; this may be worth considering in decision-making processes for future control of FMD. Emergency vaccination proved to be efficient in reducing the magnitude and duration of outbreaks, whereas increasing depopulation without the use of vaccination also proved to be effective in eliminating the outbreaks.

ecology↗

bioRxiv2020

Effects of rumen-protected methionine supplementation on the performance of high production dairy cows in the tropics

Increasing methionine availability in dairy cow diets during the first third of lactation may enhance their performance and health. The aim of this study was to determine the effect of supplementing rumen-protected methionine (RPMet) in a lactation diet containing adequate protein and energy levels. Seventy-six multiparous Holstein cows (39.1 {+/-} 6.8 kg of milk/d and 65 {+/-} 28 DIM) were assigned to 1 of 2 dietary treatments (38/treatment) according to a randomized complete block design with a 2-wk (covariate) and 10-wk experimental period. Treatments were a basal diet (CON; 3.77 Lys:1Met); and CON + 14 g RPMet (2.97 Lys:1 Met). Individual milk samples were taken every 2 weeks to determine milk composition. Blood was collected from 24 cows on d+30 d to measure plasma AA levels. Body weight and body condition score (BCS) were measured at the beginning and the end of the experiment. The SM diet promoted higher milk yield (41.7 vs. 40.1 kg/d; P = 0.026), energy-corrected milk yield (41.0 vs. 38.0 kg/d; P [≤] 0.01), milk protein yield (1.30 vs. 1.18 kg/d; P [≤] 0.01), and milk fat yield (1.42 vs. 1.29 kg/d; P = 0.02). Higher milk protein (3.14% vs. 2.97%; P [≤] 0.01) and casein (2.39% vs. 2.28%; P[≤] 0.01) and a trend (P = 0.06) for higher milk fat % (3.41% vs. 3.21%) were also observed. Both diets resulted in similar body weight, but CON-fed cows tended (P = 0.08) to have higher BCS. Higher plasma methionine levels were determined with SM compared with CON (29.6 vs. 18.4 M; P < 0.01), but lysine and histidine were not different. Dietary supplementation of RPM improved productive performance by increasing milk yield and milk components yields, suggesting better dietary AA utilization when Met levels are adjusted in Lys-adequate lactation diets.

physiology↗

bioRxiv2020

Gene-tree Species-tree Discordance in the Eared Seals is best explained by Incomplete Lineage Sorting following Explosive Radiation in the Southern Hemisphere

AO_SCPLOWBSTRACTC_SCPLOWThe phylogeny and systematics of fur seals and sea lions (Otariidae) have long been studied with diverse data types, including an increasing amount of molecular data. However, only a few phylogenetic relationships have reached acceptance because of strong gene-tree species tree discordance. Divergence times estimates in the group also vary largely between studies. These uncertainties impeded the understanding of the biogeographical history of the group, such as when and how trans-equatorial dispersal and subsequent speciation events occurred. Here we used high-coverage genome-wide sequencing for 14 of the 15 species of Otariidae to elucidate the phylogeny of the family and its bearing on the taxonomy and biogeographical history. Despite extreme topological discordance among gene trees, we found a fully supported species tree that agrees with the few well-accepted relationships and establishes monophyly of the genus Arctocephalus. Our data support a relatively recent trans-hemispheric dispersal at the base of a southern clade, which rapidly diversified into six major lineages between 3 to 2.5 Ma. Otaria diverged first, followed by Phocarctos and then four major lineages within Arctocephalus. However, we found Zalophus to be non-monophyletic, with California (Z. californianus) and Steller sea lions (Eumetopias jubatus) grouping closer than the Galapagos sea lion (Z. wollebaeki) with evidence for introgression between the two genera. Overall, the high degree of genealogical discordance was best explained by incomplete lineage sorting resulting from quasi-simultaneous speciation within the southern clade with introgresssion playing a subordinate role in explaining the incongruence among and within prior phylogenetic studies of the family.

evolutionary biology↗

bioRxiv2018

Cathelicidin senses enteric pathogen Salmonella typhimurium/LPS for colonic chemokine generation: a new innate immune role for a host defense peptide

The mechanisms by which epithelia identify and respond to pathogens are manifold, nuanced and complex. Here, using human-colon derived HT29 epithelial cells, mouse and human primary colonoids, and cathelicidin null (Cramp) mice, we report a novel immunoregulatory role for the antimicrobial peptide, cathelicidin, that was found to recognize and synergise with Salmonella typhimurium or its derived virulence factor lipopolysaccharide (LPS) to promote epithelial synthesis of the chemokine IL-8/KC for neutrophil recruitment/activation during infectious colitis. Mechanistically, cathelicidin facilitated the internalization of LPS via GM1 lipid rafts and subsequent TLR4 activation to promote IL-8 production. Furthermore, IL-8 output required the integrated activity of two signal transduction pathways: NF-{kappa}B and MEK 1/2 kinase signaling was required for IL-8 mRNA synthesis, while Src-EGFR-p38MAPK (NF-{kappa}B independent) activity underlay IL-8 mRNA stabilization. This immunomodulatory function of cathelicidin was key in colon defense, since Cramp-/- mice infected with a natural murine Gram negative intestinal pathogen, Citrobacter rodentium, displayed diminished KC secretion, impaired mobilization and reduced clearance of the bacteria. Occurring at concentrations lower than those necessary for anti-microbial activity, cathelicidins capacity to sense pathogens/LPS and enhance neutrophil recruitment reveals a novel function for this peptide in directing innate immunity which may be of pivotal importance in the control of infections colitis.\n\nAuthor summaryThe gut lining has a well regulated immune system that tolerates resident bacteria and does not respond to them. However, when pathogenic bacteria enter, there needs to be a protective response. How the gut lining switches from passive to protective is of interest. In our study, we determined host defense cathelicidin peptide (either naturally occurring or administered) \"instructs\" the colon lining to produce a compound (IL-8) that attracts white blood cells in response to a pathogen (Salmonella typhimurium) or lipopolysaccharide, a component of this pathogens cell wall. We discovered a novel mechanism by which cathelicidin facilitates uptake of lipopolysaccharide by the lining of the colon and how it activates receptors to increase synthesis and release of IL-8. In addition, we also detected a synergistic action between cathelicidin and intestinal pathogens in laboratory cultures of colon tissues from mice and humans, as well as in a mouse model of colitis with another pathogenic bacterium. Cathelicidin induced production of IL-8 which attracted and stimulated more white blood cells. Therefore, in addition to potential direct actions to supress harmful bacteria, cathelicidin also acts as a biological sensor in the gut lining, recognizing pathogens or factors they produce and increasing white cell responses.

immunology↗

bioRxiv2018

Identification of rare de novo epigenetic variations in congenital disorders

Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. With recent dramatic advances in genomic technologies, genome-wide surveys of cohorts of patients with ND/CAs for point mutations and structural variations have greatly advanced our understanding of their genetic etiologies1,2. However, even after whole genome sequencing (WGS), a substantial fraction of such disorders remain unexplained3. In contrast, the possibility that constitutive epigenetic variations (epivariations) might underlie such traits has not been well explored. We hypothesized that some cases of ND/CA are caused by aberrations of DNA methylation that lead to a dysregulation of normal genome function. By comparing DNA methylation profiles from 489 individuals with ND/CAs against 1,534 population controls, we identified epivariations as a frequent occurrence in the human genome. De novo epivariations were significantly enriched in cases when compared to controls. RNAseq data from population studies showed that epivariations often have an impact on gene expression comparable to loss-of-function mutations. Additionally, we detected and replicated an enrichment of rare sequence mutations overlapping CTCF binding sites close to epivariations. Thus, some epivariations occur secondary to cis-linked mutations in regulatory regions, providing a rationale for interpreting non-coding genetic variation. We propose that epivariations likely represent the causative genomic defect in 5-10% of patients with unexplained ND/CAs. This constitutes a yield comparable to CNV microarrays, and as such has significant diagnostic relevance.

genomics↗