Biology subjects

Hernandez, L.

Publications and source records attributed to Hernandez, L..

At least 19 recordsLinked to original sources

bioRxiv2026

The Salmonella effector SspH2 disrupts F-actin cytoskeletal organization to inhibit macrophage migration

The facultative intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) causes gastroenteritis in humans and persistent infections in animals, enabling widespread environmental reservoirs. Intracellular survival of S. Typhimurium depends on a suite of type III secretion system effectors encoded within Salmonella Pathogenicity Island 2 (SPI-2), many of which also impair host cell migration. Among these, SspH2 is a novel E3 ubiquitin ligase (NEL) effector, but how it inhibits host cell movement has remained unclear. By using a combination of time-lapse microscopy and wound-healing assays, we show that SspH2 is required for S. Typhimurium to fully suppress migration of macrophage-like RAW264.7 cells and that conditional expression of SspH2 alone is sufficient to restrict their movement. SspH2 expression led to a marked reduction in F-actin and fewer cells containing higher-order F-actin structures, indicating cytoskeletal remodeling. In contrast, the catalytically inactive mutant SspH2C580A had no effect, demonstrating that E3 ligase activity is essential for these phenotypes. Knockdown of the host cytoskeletal factor vinculin, a core component of podosomes and focal adhesions, mimicked SspH2's effect on cell migration. When vinculin expression was reduced, SspH2 did not further inhibit migration, suggesting that SspH2 requires vinculin-associated F-actin-rich structures to block cell migration. These findings reveal a new pathway by which S. Typhimurium limits host cell movement, potentially enhancing immune evasion and fitness within the host.

microbiology↗

bioRxiv2026

In vivo isogenic modelling unveils a TP53-mediated relapse phenotype in T-cell acute lymphoblastic leukemia

Many patients with T-cell acute lymphoblastic leukemia (T-ALL) relapse into a treatment-resistant disease. The mechanisms driving relapse remain largely elusive, in part due to the lack of faithful experimental models. Here, we leveraged patient-derived xenograft (PDX) pairs generated from diagnosis and relapse T-ALLs to functionally address the cellular mechanisms driving TP53-altered relapse. Beyond inter-T-ALL variability, comparative analyses revealed a unique, cell-intrinsic relapse phenotype that includes greater leukemia-initiating capacity and that can be conferred to diagnosis cells by TP53 silencing. Transcriptomic profiling linked the relapse phenotype to deregulated OXPHOS metabolism and MYC signaling. Integration of single-cell profilings uncovered TP53-wildtype cell populations at diagnosis expressing a relapse profile, possibly reflecting a pre-existing modulation of TP53 signaling. These cells sequentially evolved towards biallelic TP53 inactivation at relapse. Collectively, our findings support a model in which T-ALL relapses emerge from a selected pre-existing transcriptional state characterized by deregulated metabolism that favors subsequent TP53 inactivation.

cancer biology↗

bioRxiv2026

Ryanodine receptor 1 is dispensable for CD4+ T-cell differentiation and effector function in intestinal inflammation models

T-cell receptor signaling is necessary for the activation and differentiation of CD4 T cells. Calcium (Ca2+) signaling is essential for this process, and the complexity of Ca2+ channels presents a potential therapeutic target for modulating the strength of T-cell receptor signaling and further differentiation of CD4 T cells. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobilizing second messenger that triggers Ca2+ release through ryanodine receptor 1 (RYR1) in T cells. While the molecular and biophysical properties of NAADP-induced Ca2+ microdomains in T cells have been thoroughly investigated, and the function of the NAADP-HN1L/JPT2-RYR1 axis has been proven in T-cell activation and proliferation, its role in intestinal inflammation in vivo remains to be elucidated. In this study, we generated a conditional knockout mouse with Ryr1 deleted in {beta} T cells to investigate the functional relevance of RYR1 signaling in CD4 T cells. Ryr1 deletion in CD4+ T cells decreased TCR-induced Ca2+ microdomain formation, reduced peak Ca2+ amplitude and delayed initial velocity of global Ca2+ signaling in vitro. However, Ryr1 expression in CD4 T cells was dispensable for their pathogenicity in murine models of intestinal inflammation. Thus, Ryr1 expression in CD4+ T cells plays a redundant role in intestinal inflammation.

immunology↗

bioRxiv2025

BAP1 deletion in hepatocytes primes an inflammatory transcriptional response

BackgroundBRCA1-associated protein 1 (BAP1) is a deubiquitinase, frequently altered in cancers including hepatocellular carcinoma and cholangiocarcinoma. While Bap1 has been shown to play key roles in metabolism, maintenance of tissue homeostasis, and immune cell development, little is known about its normal functions in the liver in vivo. This study aims to identify Bap1 specific effects on the livers immune microenvironment and biological functions. MethodsUsing AAV8-mediated CRISPR/CAS9 genome editing we generated a mouse hepatocyte-specific model of Bap1 knockout to define the changes that occur in liver biology in an in vivo system and characterize how loss of Bap1 alters the livers response to injury. Single-cell resolution spatial transcriptomics were performed in conjunction with immunohistochemistry to analyze cell-type composition and immune cell recruitment changes. Bulk RNA-sequencing was performed for further assessment of the impact of Bap1 loss on transcription. ResultsHepatocyte-specific depletion of Bap1 induced transcriptional changes shared with acute injury. We observed a strong dysregulation of inflammatory pathways associated with BAP1 loss. Moreover, the transcriptional response of Bap1 depletion in hepatocytes to damage was markedly different than in control liver, with Bap1-deleted livers showing a decreased hepatocyte identity based on gene expression. Spatial transcriptomics and quantitative texture analysis of immunohistochemistry revealed an altered immune environment prior to damage and an impaired recruitment of immune cells in Bap1 depleted livers after damage. ConclusionsUsing a hepatocyte-specific Bap1 deletion we identified Bap1 as a critical modulator in the livers immune cell response. We show that Bap1 loss leads to an inflammatory environment prior to damage and disrupts the recruitment immune cells. Our quantitative spatial analysis highlights the power of such approaches to characterize the spatial distribution of different cell types in a tissue.

genetics↗

bioRxiv2025

Brain injury contributes to dopaminergic neurodegeneration, Lewy body pathology, and Parkinsonism preclinically with outcomes altered by T cell modulation

Traumatic brain injury (TBI) increases the risk of Parkinsons disease (PD) development later in life, but much remains unknown regarding the mechanisms driving this relationship. A single, mild brain injury triggers resident and peripheral neuroinflammatory pathways that are similarly activated in PD patients, which could possibly increase susceptibility to neurodegeneration. In this study, we used preclinical mouse models of mild TBI (mTBI) and PD to evaluate how injury-induced immune signaling may exacerbate PD-associated pathologies. Dopaminergic (DA) neurons showed upregulation of genes associated with neuroinflammation, adaptive immunity, and PD following mTBI. mTBI caused degeneration of DA neurons in the substantia nigra (SN) and increased the spread of Lewy body (LB) pathology to other brain regions, such as the ipsilateral cortex, in a preclinical model of PD. Reducing adaptive immune infiltration into the central nervous system (CNS) with a transgenic model lacking mature lymphocytes, or directly by in vivo depletion of T cells or B cells individually, improved neurodegenerative outcomes of DA neurons following brain injury. Our results indicate the possibility of a sustained, chronic peripheral immune cell infiltration which negatively affects both DA neurons and alpha synuclein (-syn) fibril propagation, providing insight on therapeutic windows to reduce DA neuron vulnerability.

neuroscience↗

bioRxiv2025

Teleost-specific ictacalcins exhibit similar structural organization, cation-dependent activation and transcriptional regulation as human S100 proteins

S100 proteins are highly versatile calcium-binding proteins from vertebrates. Following extracellular release, they become instrumental in immune and antimicrobial defenses, initiating the inflammatory response through receptor signaling and providing direct control of bacterial invaders via nutritional immunity. While mammalian S100s have been extensively studied, very little is known about the more recently discovered S100 proteins from teleost fish, including those with no strict orthologs in mammals. Comparable functioning between both clades would allow to expand their study into the highly popular zebrafish model, particularly suited for live imaging and mechanistic exploration of immune and inflammatory processes. To fill the gap of knowledge on teleost S100s, we here provide a detailed structural and biochemical characterization of S100i1 and S100i2 from Danio rerio, two teleost-specific S100s absent in mammals. We demonstrate that they nevertheless share conserved tertiary and quaternary organization with mammalian S100s. In addition, they exhibit comparable calcium binding properties and undergo a similar calcium-dependent activation mechanism. Furthermore, they display analogous expression pattern, being enriched in tissues highly exposed to the environment like gills and skin, the latter constituting an important reservoir of S100 proteins in mammals. Finally, our results show, for the very first time, that s100i2/i2 gene expression is differentially modulated in sterile disease conditions associated with sustained inflammation or high hypoxic state. Altogether, these findings underline the strong parallelism existing between mammalian and teleost-specific S100 proteins despite their divergent evolution, opening up new avenues to explore their biology in the zebrafish model.

immunology↗

bioRxiv2024

The Association Between Prevotella copri and Advanced Fibrosis in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), driven by obesity and metabolic syndrome, is increasingly prevalent and a significant contributor to liver fibrosis, cirrhosis, and liver-related mortality. Emerging research implicates the gut microbiome as a critical player in MASLD progression, yet specific microbial drivers remain poorly understood. Here, we explore the role of Prevotella copri (P. copri) in MASLD progression through both human patient cohorts and a mouse model of diet-induced obesity. Using 16S rRNA sequencing, we identified elevated P. copri abundance in MASLD patients with advanced fibrosis, linked with significant shifts in microbial diversity and bacterial network connectivity. To investigate causality, experimental colonization of P. copri in mice on a high-fat diet worsened MASLD progression, with P. copri-colonized mice showing significant increases in hepatic steatosis, liver triglyceride accumulation, and body weight, independent of caloric intake. At the molecular level, P. copri colonization downregulated key lipid metabolism genes, such as Carnitine Palmitoyltransferase 1, Diacylglycerol Acyltransferase, and Adipose Triglyceride Lipase, and impaired tight intestinal junction integrity through the downregulation of cluadins, occludin, and zonula occludens-1. Collectively, our findings position P. copri as a possible driver of MASLD progression by promoting hepatic steatosis through lipid and triglyceride accumulation and fibrosis through decreased tight junction integrity. These insights suggest a promising therapeutic avenue to target specific microbial signatures like P. copri to curb MASLD progression and mitigate the associated risk of advanced fibrosis.

microbiology↗

bioRxiv2024

Microbial Differences Accurately Identifies Global SERT KO Phenotype in Mice

Altered serotonin signaling is a well-established contributor to depression, with the serotonin transporter gene (SERT) playing a critical role in regulating serotonin reuptake. Mice lacking SERT (SERT -/-) serve as a robust model for depression, exhibiting significant depressive-like behaviors compared to littermate wild-type (SERT +/+) controls. In this study, we aimed to determine the relationship between gut microbiota composition and depressive behaviors in SERT -/- mice. Behavioral assays, including the Forced Swim Test (FST) and Tail Suspension Test (TST), confirmed that SERT -/- mice exhibited significantly increased immobility times compared to SERT +/+ mice (FST: p = 0.004; TST: p = 0.080), consistent with a depressive phenotype. Utilizing littermate controls, shotgun metagenomic sequencing of fecal samples revealed significant differences in alpha diversity between the two groups of mice, as measured by the Shannon entropy index (p = 0.05). Additionally, our bacterial co-occurrence network analysis uncovered distinct structural differences in microbial interactions between SERT -/- and SERT +/+ mice (p = 0.001), suggesting shifts in microbiome stability and functionality between the groups. We created a microbial depression score utilizing the top five bacteria taxa that were differentially abundant between SERT -/- and SERT +/+ mice: Clostridium sp. MD294, Acetatifactor MGBC165152, Desulfovibrio MGBC129232, Oscillibacter MGBC161747, and Schaedlerella MGBC000001. This microbial depression score correlated strongly with immobility times in the FST (r = 0.705, p < 0.0006) and TST (r = 0.401, p < 0.09). A random forest classifier based on these taxa accurately distinguished SERT -/- from SERT +/+ mice (accuracy = 0.82). These findings suggest that gut microbial species composition is highly associated with depressive-like behaviors in SERT -/- mice, likely via alterations in serotonin signaling pathways, and may offer potential targets for microbiome-based interventions in depression.

microbiology↗

bioRxiv2024

Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.

cancer biology↗

bioRxiv2022

A lipopolysaccharide-dependent phage infects a pseudomonad phytopathogen and can evolve to evade phage resistance

Bacterial pathogens are major causes of crop diseases, leading to significant production losses. For instance, kiwifruit canker, caused by the phytopathogen Pseudomonas syringae pv. actinidiae (Psa), has posed a global challenge to kiwifruit production. Treatment with copper and antibiotics, whilst initially effective, is leading to the rise of bacterial resistance, requiring new biocontrol approaches. Previously, we isolated a group of closely related Psa phages with biocontrol potential, which represent environmentally sustainable antimicrobials. However, their deployment as antimicrobials requires further insight into their properties and infection strategy. Here, we provide an in-depth examination of the genome of {Phi}Psa374-like phages and show that they use lipopolysaccharides (LPS) as their main receptor. Through proteomics and cryo-electron microscopy of {Phi}Psa374, we revealed the structural proteome and that this phage possess a T=9 capsid triangulation, unusual for myoviruses. Furthermore, we show that {Phi}Psa374 phage resistance arises in planta through mutations in a glycosyltransferase involved in LPS synthesis. Lastly, through in vitro evolution experiments we showed that phage-resistance is overcome by mutations in a tail fiber and structural protein of unknown function in {Phi}Psa374. This study provides new insight into the properties of {Phi}Psa374-like phages that informs their use as antimicrobials against Psa. Originality-Significance StatementThe rise of phytopathogen resistance to agrichemicals poses a significant threat to crop production, and requires urgent attention. The work presented here examines a phage genus, members of which utilize LPS as a receptor, and show potential as biocontrol agents of Psa. Studies in planta showed the development of Psa resistance to the phage, whilst maintaining bacterial virulence. This finding underscores the importance of examining phages in their ecological context for the informed design of phage cocktails that are effective in phytopathogen control.

microbiology↗

bioRxiv2022

Mitochondrial Matrix Protease ClpP Agonists inhibit Cancer Stem Cell Function in Breast Cancer Cells by Disrupting Mitochondrial Homeostasis

Mitochondria are multifaceted organelles which are important for bioenergetics, biosynthesis and signaling in metazoans. Mitochondrial functions are frequently altered in cancer to promote both the energy and the necessary metabolic intermediates for biosynthesis required for tumor growth. Cancer stem cells (CSCs) contribute to chemotherapy resistance, relapse, and metastasis. Recent studies have shown that while non-stem, bulk cancer cells utilize glycolysis, breast CSCs are more dependent on oxidative phosphorylation (OxPhos) and therefore targeting mitochondria may inhibit CSC function. We previously reported that small molecule ONC201, which is an agonist for the mitochondrial caseinolytic protease (ClpP), induces mitochondrial dysfunction in breast cancer cells. In this study, we report that ClpP agonists inhibit breast cancer CSC function in vitro and in vivo. Mechanistically, we found that OxPhos inhibition downregulates multiple pathways required for CSC function, such as the mevalonate pathway, YAP, Myc, and the HIF pathway. ClpP agonists showed significantly greater inhibitory effect on CSC functions compared with other mitochondria-targeting drugs. Further studies showed that ClpP agonists deplete NAD(P)+ and NAD(P)H and induce redox imbalance, and dysregulate one-carbon metabolism and proline biosynthesis. Downregulation of these pathways by ClpP agonists further contribute to the inhibition of CSC function. In conclusion, ClpP agonists inhibit breast CSC functions by disrupting mitochondrial homeostasis in breast cancer cells and inhibiting multiple pathways critical to CSC function.

cancer biology↗

bioRxiv2021

A cellular and molecular portrait of endometriosis subtypes

Endometriosis is a common, benign condition characterized by extensive heterogeneity in lesion appearance and patient symptoms. We profiled transcriptomes of 207,949 individual cells from endometriomata (n=7), extra-ovarian endometriosis (n=19), eutopic endometrium (n=4), unaffected ovary (n=1) and endometriosis-free peritoneum (n=4) to create a cellular atlas of endometrial-type epithelial cells, endometrial-type stromal cells and microenvironmental cell populations across tissue sites. Signatures of endometrial-type epithelium and stroma differed markedly across eutopic endometrium, endometrioma, superficial extra-ovarian disease and deep infiltrating endometriosis, suggesting that extensive transcriptional reprogramming is a core component of the disease process. Endometriomas were notable for the dysregulation of pro-inflammatory pathways and upregulation of complement proteins C3 and C7. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic factor SOX17 and remodeling of the endothelial cell compartment. Finally, signatures of endometriosis-associated endometrial-type epithelial clusters were enriched in ovarian cancers, reinforcing the epidemiologic associations between these two diseases.

genomics↗

bioRxiv2021

In-solution buffer-free digestion for the analysis of SARS-CoV-2 RBD proteins allows a full sequence coverage and detection of post-translational modifications in a single ESI-MS spectrum

Subunit vaccines based on the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, are among the most promising strategies to fight the COVID-19 pandemic. The detailed characterization of the protein primary structure by mass spectrometry (MS) is mandatory, as described in ICHQ6B guidelines. In this work, several recombinant RBD proteins produced in five expression systems were characterized using a non-conventional protocol known as in-solution buffer-free digestion (BFD). In a single ESI-MS spectrum, BFD allowed very high sequence coverage ([≥] 99 %) and the detection of highly hydrophilic regions, including very short and hydrophilic peptides (2-8 amino acids), the His6-tagged C-terminal peptide carrying several post-translational modifications at Cys538 such as cysteinylation, glutathionylation, cyanilation, among others. The analysis using the conventional digestion protocol allowed lower sequence coverage (80-90 %) and did not detect peptides carrying some of the above-mentioned post-translational modifications. The two C-terminal peptides of a dimer [RBD(319-541)-(His)6]2 linked by an intermolecular disulfide bond (Cys538-Cys538) with twelve histidine residues were only detected by BFD. This protocol allows the detection of the four disulfide bonds present in the native RBD and the low-abundance scrambling variants, free cysteine residues, O-glycoforms and incomplete processing of the N-terminal end, if present. Artifacts that might be generated by the in-solution BFD protocol were also characterized. BFD can be easily implemented and we foresee that it can be also helpful to the characterization of mutated RBD.

biochemistry↗

bioRxiv2020

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

Radial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted "intermediate" precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

developmental biology↗

bioRxiv2020

Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17

After optic nerve crush (ONC), the cell bodies and distal axons of most retinal ganglion cells (RGCs) degenerate. RGC somal and distal axon degeneration were previously thought to be controlled by two distinct pathways, involving activation of the kinase DLK and loss of the axon survival factor NMNAT2, respectively. However, we found that mutual palmitoylation by the palmitoyl acyltransferase ZDHHC17 couples the DLK and NMNAT2 signals, which together form a "trust, but verify system". In healthy optic nerves, ZDHHC17-dependent palmitoylation ensures NMNAT-dependent distal axon integrity, while following ONC, ZDHHC17-dependent palmitoylation is critical for DLK-dependent somal degeneration. We found that ZDHHC17 also controls survival-versus-degeneration decisions in sensory neurons and identified motifs in NMNAT2 and DLK that govern their ZDHHC17-dependent regulation. These findings suggest that the control of somal and distal axon integrity should be considered as a single, holistic process, involving two palmitoylation-dependent pathways acting in concert.

neuroscience↗

bioRxiv2020

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

The human fallopian tube harbors the cell-of-origin for the majority of high-grade serous ovarian cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We performed single-cell transcriptomic profiling in 12 primary fallopian specimens from 8 patients, analyzing around 53,000 individual cells to map the major immune, fibroblastic and epithelial cell types present in this organ. We identified 10 epithelial sub-populations, characterized by diverse transcriptional programs including SOX17 (enriched in secretory epithelial cells), TTF3 and RFX3 (enriched in ciliated cells) and NR2F2 (enriched in early, partially differentiated secretory cells). Based on transcriptional signatures, we reconstructed a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3high intermediate. Computational deconvolution of the cellular composition of advanced HGSCs based on epithelial subset signatures identified the early secretory population as a likely precursor state for the majority of HGSCs. The signature of this rare population of cells comprised both epithelial (EPCAM, KRT) and mesenchymal (THY1, ACTA2) features, and was enriched in mesenchymal-type HGSCs (P = 6.7 x 10-27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.

genomics↗

bioRxiv2020

Effectiveness of fusion peptide-based vaccine TT-P0 on the dynamics of salmon lice (Lepeophtheirus salmonis) infection in Atlantic salmon (Salmo salar L.)

Infection with parasitic copepod salmon louse Lepeophtheirus salmonis, represents one of the most important limitations to sustainable Atlantic salmon (Salmo salar L.) farming today in the North Atlantic region. The parasite exerts negative impact on health, growth and welfare of farmed fish as well as impact on wild salmonid populations. It is therefore central to ensure continuous low level of salmon lice with the least possible handling of the salmon and drug use. To address this, vaccination is a cost-effective and environmentally friendly control approach. In this study, efficacy of a vaccine candidate, containing a peptide derived from ribosomal protein P0, was validated post infestation with L. salmonis, at the lab-scale. The sampling results showed good potential of the vaccine candidate when administered intraperitoneally in the host, in reducing the ectoparasite load, through reduction of adult female lice counts and fecundity and with greater presumptive effect in F1 lice generation. The sampling results correlated well with the differential modulation of pro-inflammatory, Th1, Th2 and T regulatory mediators at the transcript level at different lice stages. Overall, the results supports the effectiveness of the vaccine candidate in controlling salmon lice infestation load. However, further validation is necessary under field conditions.

immunology↗

bioRxiv2020

Measuring Nestedness: A comparative study of the performance of different metrics

O_LINestedness is a property of interaction networks widely observed in natural mutualistic communities, like plant-pollinators or plant-seed dispersers, among other systems. A perfectly nested network is characterized by the peculiarity that the interactions of any node form a subset of the interactions of all nodes with higher degree. Despite a widespread interest on this pattern, no general consensus exists on how to measure it. Instead, several metrics aiming at quantifying nestedness, based on different but not necessarily independent properties of the networks, coexist in the literature blurring the comparison between ecosystems. C_LIO_LIIn this work we present a detailed critical study of the behavior of six popular nestedness metrics and the variants of two of them. In order to evaluate their performance, we compare the obtained values of the nestedness of a large set of real networks among them and against a maximum entropy and maximum likelihood null model. We also analyze the dependencies of each metrics on different network parameters as size, fill and eccentricity. C_LIO_LIOur results point out, first, that the metrics do not rank the degree of nestedness of networks universally. Furthermore, several metrics show significant undesired dependencies on the network properties considered. The study of these dependencies allows us to understand some of the systematic shifts between the real values of nestedness and the average over the null model. C_LIO_LIThis paper intends to provide readers with a critical guide on how to measure nestedness patterns, by explaining the functioning of six standard metrics and two of its variants, and then disclosing its qualities and flaws. By doing so, we also aim to extend the application of the recently proposed null models based on maximum entropy to the still largely unexplored area of ecological networks. C_LIO_LIFinally, to complement the guide, we provide a fully-documented repository named nullnest which gathers the codes to produce the null model and calculate the nestedness index -both the real value and the null expectation-using the studied metrics. The repository contains, moreover, the main results of the null model applied to a large dataset of more than 200 bipartite networks. C_LI

ecology↗