Biology subjects

Martin, C.

Publications and source records attributed to Martin, C..

At least 91 records · Page 5Linked to original sources

bioRxiv2022

Activating words without language: Beta and theta oscillations reflect lexical access and control processes during verbal and non-verbal object recognition tasks

The intention to name an object modulates neural responses during object recognition tasks. However, the nature of this modulation is still unclear. We established whether a core operation in language, i.e., lexical access, can be observed even when the task does not require language (size-judgment task), and whether response selection in verbal versus non-verbal semantic tasks relies on similar neuronal processes. We measured and compared neuronal oscillatory activities and behavioural responses to the same set of pictures of meaningful objects, while the type of task participants had to perform (picture-naming versus size-judgment) and the type of stimuli to measure lexical access (cognate versus non-cognate) were manipulated. Despite activation of words was facilitated when the task required explicit word-retrieval (picture-naming task), lexical access occurred even without the intention to name the object (non-verbal size-judgment task). Activation of words and response selection were accompanied by beta (25-35 Hz) desynchronisation and theta (3-7 Hz) synchronisation, respectively. These effects were observed in both picture-naming and size-judgment tasks, suggesting that words became activated via similar mechanisms, irrespective of whether the task involves language explicitly. This finding has important implications to understand the link between core linguistic operations and performance in verbal and non-verbal semantic tasks.

neuroscience↗

bioRxiv2022

The addiction-susceptibility TaqIA/Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) controls reward and metabolism through dopamine receptor type 2 (DR2)-expressing neurons

Significant evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the Taq1A polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) near the dopamine D2 dopamine receptor (DR2) gene. Depending on race it affects 30 to 80% of the population and its homozygous expression of the A1 allele correlates with a 30 to 40% reduction of striatal DR2, a typical feature of addiction, over-eating and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior is unknown. Here we used transgenic and viral-mediated strategies to reveal the role of ANKK1 in the regulation of activity and functions of the striatum. We found that Ankk1 is preferentially enriched in striatal DR2 expressing neurons and that Ankk1 loss-of-function in dorsal and ventral striatum leads to alteration in learning, impulsive, and flexible behaviors resembling the endophenotypes described in A1 carriers. We also observed an unsuspected role of ANKK1 in striatal DR2-expressing neurons in the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with versus without the A1 allele. Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for ANKK1 in the regulation of body metabolism.

neuroscience↗

bioRxiv2022

An ERP investigation of accented isolated single word processing

Previous studies show that there are differences in native and non-native speech processing (Lev-Ari, 2018). However, less is known about the differences between processing native and dialectal accents. Is dialectal processing more similar to foreign or native speech? To address this, two theories have been proposed. The Perceptual Distance Hypothesis states that the mechanisms underlying dialectal accent processing are attenuated versions of those of foreign (Clarke & Garrett, 2004). Conversely, the Different Processes Hypothesis argues that the mechanisms of foreign and dialectal accent processing are qualitatively different (Floccia et al, 2009). The present study addresses these hypotheses. Electroencephalographic data was recorded from 25 participants who listened to 40 isolated words in different accents. Event-Related Potential mean amplitudes were extracted: P2 [150-250 ms], PMN [250-400 ms] and N400 [400-600 ms]. Support for the Different Processes Hypothesis was found in different time windows. Results show that early processing mechanisms distinguish only between native and non-native speech, with a reduced P2 amplitude for foreign accent processing, supporting the Different Processes Hypothesis. Furthermore, later processing mechanisms show a similar binary difference in the processing of the accents, with a larger PMN negativity elicited in the foreign accent than the others, further supporting the Different Processes Hypothesis. Results contribute to the understanding of single word processing, in which it is uniquely difficult to extract acoustic characteristics from foreign accent, and in which foreign accented speech is associated with the largest cost, as compared to native and dialectal speech, of phonological matching between representations and acoustic input. HighlightsO_LIAccent affects early speech processing mechanisms at the level of the isolated word C_LIO_LIAcoustic characteristic extraction is more difficult for foreign-accented speech C_LIO_LIPhonological normalization of foreign-accented speech is uniquely difficult C_LIO_LIAccent no longer affects later speech processing mechanisms at the isolated word C_LI

neuroscience↗

bioRxiv2022

GIP receptor reduces osteoclast activity and improves osteoblast survival by activating multiple signaling pathways

Bone is a dynamic tissue that is remodeled throughout life by bone resorbing osteoclasts and bone forming osteoblasts, to adapt to physiological or mechanical demands. These processes are impaired in osteoporosis, and understanding how bone remodeling is regulated could improve anti-osteoporotic treatments. Clinical investigations show that short-term treatment with glucose-dependent insulinotropic polypeptide (GIP) acutely decreases serum markers of bone resorption and may increase bone formation. However, evidence for direct effects of GIP intracellular signaling and functions in mature human osteoclasts and osteoblasts have not been investigated. We report that the GIP receptor (GIPR) is robustly expressed in mature human osteoclasts. Exposure of osteoclasts to GIP inhibits osteoclastogenesis, delays bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways (cAMP, Src, Akt, calcium, p38) to impair nuclear translocation of nuclear factor of activated T cells 1 (NFATc1) and nuclear factor-{kappa}B (NF{kappa}B). Human osteoblasts also express GIPR, and GIP improves osteoblast survival via cAMP and Akt-mediated pathways. GIP treatment of co-cultures of osteoclasts and osteoblasts also decreased bone resorption. Antagonizing GIPR with GIP(3-30)NH2 abolished the effects of GIP on osteoclasts and osteoblasts. This study demonstrates that GIP inhibits bone resorption and improves survival of human osteoblasts, which could increase bone mass and strength, supporting clinical investigations of the effect of GIP on bone. Moreover, this study demonstrates that GIPR agonism could be beneficial in the treatment of disorders of bone remodeling, such as osteoporosis. One-sentence SummaryGIP acts directly on bone cells to regulate bone remodeling

cell biology↗

bioRxiv2022

The metabolic influence of the core ciliate Entodinium caudatum within the rumen microbiome

Protozoa comprise a major fraction of the microbial biomass in the rumen microbiome, of which the entodiniomorphs (order: Entodiniomorphida) and holotrichs (order: Vestibuliferida) are consistently observed to be dominant across a diverse genetic and geographical range of ruminant hosts. Despite the apparent core role that protozoal species exert, their major biological and metabolic contributions to rumen function remain largely undescribed in vivo. Here, we have leveraged (meta)genome-centric metaproteomes from rumen fluid samples originating from both cattle and goats fed diets with varying inclusion levels of lipids and starch, to detail the specific metabolic niches that protozoa occupy in the context of their microbial co-habitants. Initial proteome estimations via total protein counts and label-free quantification highlight that entodiniomorph species Entodinium and Epidinium as well as the holotrichs Dasytricha and Isotricha comprise an extensive fraction of the total rumen metaproteome. Proteomic detection of protozoal metabolism such as hydrogenases (Dasytricha, Isotricha, Epidinium, Enoploplastron), carbohydrate-active enzymes (Epidinium, Diplodinium, Enoploplastron, Polyplastron), microbial predation (Entodinium) and volatile fatty acid production (Entodinium and Epidinium) was observed at increased levels in high methane-emitting animals. Despite certain protozoal species having well-established reputations for digesting starch, they were unexpectedly less detectable in low methane emitting-animals fed high starch diets, which were instead dominated by propionate/succinate-producing bacterial populations suspected of being resistant to predation irrespective of host. Finally, we reaffirmed our abovementioned observations in geographically independent datasets, thus illuminating the substantial metabolic influence that under-explored eukaryotic populations have in the rumen, with greater implications for both digestion and methane metabolism.

microbiology↗

bioRxiv2022

Butyrate differentiates permissiveness to Clostridioides difficile infection and influences growth of diverse C. difficile isolates

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome are short chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known decrease the fitness of C. difficile in vitro and that high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI relative to healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCEClostridioides difficile is a leading cause of infectious diarrhea in humans and it imposes a tremendous burden on the healthcare system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.

microbiology↗

bioRxiv2022

Hypothalamic astrocyte control systemic glucose metabolism and energy balance via regulation of extra-synaptic glutamate signaling

The hypothalamus is key in the control of energy balance. However, to this day strategies targeting hypothalamic neurons failed to provide viable option to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism and energy balance. Such process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals respectively worsen or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocyte in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.

physiology↗

bioRxiv2021

CaMK1D signaling in AgRP neurons promotes ghrelin-mediated food intake

Hypothalamic AgRP/NPY neurons are key players in the control of feeding behavior. Ghrelin, a major hormone released under fasting conditions, activates orexigenic AgRP/NPY neurons to stimulate food intake and adiposity. However, cell-autonomous ghrelin-dependent signaling mechanisms in AgRP/NPY neurons remain poorly defined. Here we demonstrate that calcium/calmodulin-dependent protein kinase ID (CaMK1D), a genetic hot spot in type 2 diabetes, is activated in hypothalamus upon ghrelin stimulation and acts in AgRP neurons to promote ghrelin-dependent food intake. Global CaMK1D knockout mice are resistant to the orexigenic action of ghrelin, gain less body weight and are protected against high-fat diet-induced obesity. Deletion of CaMK1D in AgRP but not in POMC neurons is sufficient to recapitulate above phenotypes. Lack of CaMK1D attenuates phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP/NPY as well as the amount of AgRP fiber projections to the Paraventricular nucleus (PVN), while electrical activity of AgRP neurons and 5 AMP-activated protein kinase (AMPK) signaling are unaffected. Hence, CaMK1D links ghrelin action to transcriptional control of orexigenic neuropeptide availability in AgRP neurons. HighlightsO_LIWhole-body deletion of CaMK1D in mice reduces food intake, ghrelin sensitivity and protects against obesity. C_LIO_LIAgRP/NPY neuron-specific deletion of CaMK1D reduces food intake, ghrelin sensitivity, energy expenditure and protects against obesity. C_LIO_LICaMK1D is dispensable for ghrelin-stimulated electrical activity of AgRP neurons and hypothalamic AMPK signaling. C_LIO_LICaMK1D controls phosphorylation of CREB and CREB-dependent expression of the orexigenic neuropeptides AgRP and NPY. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/471546v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@40d7d7org.highwire.dtl.DTLVardef@11a8c64org.highwire.dtl.DTLVardef@1f6fad3org.highwire.dtl.DTLVardef@1cd5581_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2021

Trophic specialization on unique resources in one of the most celebrated examples of sympatric speciation, Barombi Mbo crater lake cichlids

Divergent ecological selection often results in trophic niche partitioning and is one of the central processes underlying sympatric speciation. However, there are still few studies of niche partitioning in putative examples of sympatric speciation in the wild. Here we conducted the first quantitative study of dietary niche partitioning in one of the most celebrated examples of sympatric speciation, Barombi Mbo cichlids, using stomach contents and stable isotope analyses. We found little evidence for trophic niche partitioning among any Barombi Mbo cichlids, even among the nine species coexisting in sympatry in the littoral zone. Stable isotope analyses supported these conclusions of minimal dietary overlap. However, we did find extraordinary dietary specialization in some species, including spongivory and feeding on terrestrial ants, both unique feeding strategies among freshwater fishes. Stomach contents of the spongivore (Pungu maclareni) were 20% freshwater sponge, notable considering that only 0.04% of all fishes consume sponges. Overall, we conclude that while there is less trophic niche partitioning than expected among Barombi Mbo cichlids, there is evidence for dietary specialization on rare resources in support of Liems paradox.

evolutionary biology↗

bioRxiv2021

Femtosecond laser microdissection isolating regenerating C. elegans neurons for single cell RNA sequencing

Our understanding of nerve regeneration can be enhanced by delineating its underlying molecular activities at single neuron resolution in small model organisms such as Caenorhabditis elegans. Existing cell isolation techniques cannot isolate regenerating neurons from the nematode. We present femtosecond laser microdissection (fs-LM), a new single cell isolation method that dissects intact cells directly from living tissue by leveraging the micron-scale precision of fs-laser ablation. We show that fs-LM facilitated sensitive and specific gene expression profiling by single cell RNA-sequencing, while mitigating the stress related transcriptional artifacts induced by tissue dissociation. Single cell RNA-sequencing of fs-LM isolated regenerating C. elegans neurons revealed transcriptional program leading to successful regeneration in wild-type animals or regeneration failure in animals lacking DLK-1/p38 kinase. The ability of fs-LM to isolate specific neurons based on phenotype of interest allowed us to study the molecular basis of regeneration heterogeneity displayed by neurons of the same type. We identified gene modules whose expression patterns were correlated with axon regrowth rate at a single neuron level. Our results establish fs-LM as a highly specific single cell isolation method ideal for precision and phenotype-driven studies.

bioengineering↗

bioRxiv2021

Nonadaptive radiation of the gut microbiome in an adaptive radiation of Cyprinodon pupfishes with minor shifts for scale-eating

Adaptive radiations offer an excellent opportunity to understand the eco-evolutionary dynamics of gut microbiota and host niche specialization. In a laboratory common garden, we compared the gut microbiota of two novel trophic specialists, a scale-eater and a molluscivore, to a set of four outgroup generalist populations from which this adaptive radiation originated. We predicted an adaptive and highly divergent microbiome composition in the specialists matching their rapid rates of craniofacial diversification in the past 10 kya. We measured gut lengths and sequenced 16S rRNA amplicons of gut microbiomes from lab-reared fish fed the same high protein diet for one month. In contrast to our predictions, gut microbiota largely reflected 5 Mya phylogenetic divergence times among generalist populations in support of phylosymbiosis. However, we did find significant enrichment of Burkholderiaceae bacteria in both lab-reared scale-eater populations. These bacteria sometimes digest collagen, the major component of fish scales, supporting an adaptive shift. We also found some enrichment of Rhodobacteraceae and Planctomycetacia in lab-reared molluscivore populations, but these bacteria target cellulose. Minor shifts in gut microbiota appear adaptive for scale-eating in this radiation, whereas overall microbiome composition was phylogenetically conserved. This contrasts with predictions of adaptive radiation theory and observations of rapid diversification in all other trophic traits in these hosts, including craniofacial morphology, foraging behavior, aggression, and gene expression, suggesting that microbiome divergence proceeds as a nonadaptive radiation.

evolutionary biology↗

bioRxiv2020

Direct differentiation of Dental Pulp Pluripotent-like Stem Cells differentiation into Hepatocyte-like Cells

Liver diseases are a major cause of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSC) are a considerable promise in tissue engineering and regenerative medicine as a source of tissue-specific cells, therefore this study aims to demonstrate their ability to generate functional hepatocyte-like cells in vitro. Cells were differentiated on a collagen scaffolds in serum free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6, AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.

cell biology↗

bioRxiv2020

Hippocampal Egr1-dependent neuronal ensemblesnegatively regulate motor learning

Motor skills learning is classically associated with brain regions including cerebral and cerebellar cortices and basal ganglia. Less is known about the role of the hippocampus in the acquisition and storage of motor skills. Here we show that mice receiving a long-term training in the accelerating rotarod display marked transcriptional changes in the striatum and hippocampus when compared with short-term trained mice. We identify Egr1 as a modulator of gene expression in the hippocampus during motor learning. Using mice in which neural ensembles are permanently labeled in an Egr1 activity-dependent fashion we identify ensembles of Egr1-expressing pyramidal neurons in CA1 activated in short- and long-term trained mice in the rotarod task. When Egr1 is downregulated or these neuronal ensembles are depleted, motor learning is improved whereas their chemogenetic stimulation impairs motor learning performance. Thus, Egr1 organizes specific CA1 neuronal ensembles during the accelerating rotarod task that limit motor learning.

neuroscience↗

bioRxiv2020

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

The regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and counteract food-reward disorders.

neuroscience↗

bioRxiv2020

Rapid Evolution of Plastic-degrading Enzymes Prevalent in the Global Ocean

Estimates of marine plastic stocks, a major threat to marine life (1), are far lower than expected from exponentially-increasing litter inputs, suggesting important loss factors (2, 3). These may involve microbial degradation, as the plastic-degrading polyethylene terephthalate enzyme (PETase) has been reported in marine microbial communities (4). An assessment of 416 metagenomes of planktonic communities across the global ocean identifies 68 oceanic PETase variants (oPETase) that evolved from ancestral enzymes degrading polycyclic aromatic hydrocarbons. Twenty oPETases show predicted efficiencies comparable to those of laboratory-optimized PETases, suggesting strong selective pressures directing the evolution of these enzymes. We found oPETases in 90.1% of samples across all oceans and depths, particularly abundant at 1,000 m depth, with a strong dominance of Pseudomonadales containing putative highly-efficient oPETase variants in the dark ocean. Enzymatic degradation may be removing plastic from the marine environment while providing a carbon source for bathypelagic microbial communities.

evolutionary biology↗

bioRxiv2020

Translational profiling of mouse dopaminoceptive neurons reveals a role of PGE2 in dorsal striatum

Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinsons disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum.

neuroscience↗

bioRxiv2020

Diminutive, degraded but dissimilar: Wolbachia genomes from filarial nematodes do not conform to a single paradigm

Wolbachia are alpha-proteobacteria symbionts infecting a large range of arthropod species and two different families of nematodes. Interestingly, these endosymbionts are able to induce diverse phenotypes in their hosts: they are reproductive parasites within many arthropods, nutritional mutualists within some insects and obligate mutualists within their filarial nematode hosts. Defining Wolbachia "species" is controversial and so they are commonly classified into 16 different phylogenetic lineages, termed supergroups, named A to S. However, available genomic data remains limited and not representative of the full Wolbachia diversity; indeed, of the 24 complete genomes and 55 draft genomes of Wolbachia available to date, 84% belong to supergroups A and B, exclusively composed of Wolbachia from arthropods. For the current study, we took advantage of a recently developed DNA enrichment method to produce four complete genomes and two draft genomes of Wolbachia from filarial nematodes. Two complete genomes, wCtub and wDcau, are the smallest Wolbachia genomes sequenced to date (863,988bp and 863,427bp, respectively), as well as the first genomes representing supergroup J. These genomes confirm the validity of this supergroup, a controversial clade due to weaknesses of the multi-locus system typing (MLST) approach. We also produced the first draft Wolbachia genome from a supergroup F filarial nematode representative (wMhie), two genomes from supergroup D (wLsig and wLbra) and the complete genome of wDimm from supergroup C. Our new data confirm the paradigm of smaller Wolbachia genomes from filarial nematodes containing low levels of transposable elements and the absence of intact bacteriophage sequences, unlike many Wolbachia from arthropods, where both are more abundant. However, we observe differences among the Wolbachia genomes from filarial nematodes: no global co-evolutionary pattern, strong synteny between supergroup C and supergroup J Wolbachia, and more transposable elements observed in supergroup D Wolbachia compared to the other supergroups. Metabolic pathway analysis indicates several highly conserved pathways (haem and nucleotide biosynthesis for example) as opposed to more variable pathways, such as vitamin B biosynthesis, which might be specific to certain host-symbiont associations. Overall, there appears to be no single Wolbachia- filarial nematode pattern of co-evolution or symbiotic relationship. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY RepositoriesData generated are available in GenBank: BioProject PRJNA593581; BioSample SAMN13482485 for wLsig, Wolbachia endosymbiont of Litomosoides sigmodontis (genome: CP046577); Biosample SAMN15190311 for the nematode host Litomosoides sigmodontis (genome: JABVXW000000000); BioSample SAMN13482488 for wDimm, Wolbachia endosymbiont of Dirofilaria (D.) immitis (genome: CP046578); Biosample SAMN15190314 for the nematode host Dirofilaria (D.) immitis (genome: JABVXT000000000); BioSample SAMN13482046 for wCtub, Wolbachia endosymbiont of Cruorifilaria tuberocauda (genome: CP046579); Biosample SAMN15190313 for the nematode host Cruorifilaria tuberocauda (genome: JABVXU000000000); BioSample SAMN13482057 for wDcau, Wolbachia endosymbiont of Dipetalonema caudispina (genome: CP046580); Biosample SAMN15190312 for the nematode host Dipetalonema caudispina (genome: JABVXV000000000); BioSample SAMN13482459 for wLbra, Wolbachia endosymbiont of Litomosoides brasiliensis (genome: WQM000000000); Biosample SAMN15190311 for the nematode host Litomosoides brasiliensis (genome: JABVXW000000000); BioSample SAMN13482487 for wMhie, Wolbachia endosymbiont of Madathamugadia hiepei (genome: WQMP00000000); Biosample SAMN15190315 for the nematode host Madathamugadia hiepei (genome: JABVXS000000000). The raw data are available in GenBank as Sequence Read Archive (SRA): SRR10903008 to SRR10903010; SRR10902913 to SRR10902914; SRR10900508 to SRR10900511; SRR10898805 to SRR10898806. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Eleven Supplementary tables and two supplementary files are available with the online version of this article. Impact StatementWolbachia are endosymbiotic bacteria infecting a large range of arthropod species and two different families of nematodes, characterized by causing diverse phenotypes in their hosts, ranging from reproductive parasitism to mutualism. While available Wolbachia genomic data are increasing, they are not representative of the full Wolbachia diversity; indeed, 84% of Wolbachia genomes available on the NCBI database to date belong to the two main studied clades (supergroups A and B, exclusively composed of Wolbachia from arthropods). The present study presents the assembly and analysis of four complete genomes and two draft genomes of Wolbachia from filarial nematodes. Our genomics comparisons confirm the paradigm that smaller Wolbachia genomes from filarial nematodes contain low levels of transposable elements and the absence of intact bacteriophage sequences, unlike many Wolbachia from arthropods. However, data show disparities among the Wolbachia genomes from filarial nematodes: no single pattern of co-evolution, stronger synteny between some clades (supergroups C and supergroup J) and more transposable elements in another clade (supergroup D). Metabolic pathway analysis indicates both highly conserved and more variable pathways, such as vitamin B biosynthesis, which might be specific to certain host-symbiont associations. Overall, there appears to be no single Wolbachia-filarial nematode pattern of symbiotic relationship.

genomics↗

bioRxiv2020

Natural killer activation for bladder cancer elimination can be achieved in vitro by heat-killed BCG

Immunotherapy, via intravesical instillations of Bacillus Calmette-Guerin (BCG) is the therapy of choice for patients with high risk non-muscle invasive bladder cancer. The subsequent recruitment of lymphocytes and myeloid cells, as well as the release of cytokines and chemokines, induces a local immune response that contributes to eliminate these tumours. The history of BCG development resulted in a large number of genetically diverse BCG substrains which could stimulate the immune system in different ways. Here, while investigating the capacity of different BCG substrains to promote the activation of NK cells, we confirmed that all the evaluated substrains could activate a cytotoxic CD56bright NK cell population which efficiently degranulated against bladder cancer cells; Tice, Connaught and Moreau were the substrains having a stronger effect. Dead mycobacteria also stimulated PBMC cultures and we demonstrate that subcellular fractions of BCG-Tice could contribute to the induction of this NK cell response. Lipids from BCG-Tice, but not from Mycobacterium bovis, stimulated NK cell activation and degranulation, however the aqueous fraction of either bacteria did not activate lymphocytes. Delipidated BCG-Tice activated effector cells (CD3+CD56+ and NK). These data suggest that different immune subpopulations could be stimulated using different fractions of mycobacteria for cancer elimination.

immunology↗