Iterative adaption of the bidimensional wall of the French T2 wind tunnel around a C5 axisymmetrical model: Infinite variation of the Mach number at zero incidence and a test at increased incidence

The top and bottom two-dimensional walls of the T2 wind tunnel are adapted through an iterative process. The adaptation calculation takes into account the flow three-dimensionally. This method makes it possible to start with any shape of walls. The tests were performed with a C5 axisymmetric model at ambient temperature. Comparisons are made with the results of a true three-dimensional adaptation

Divergent evolution of the activity and regulation of the glutamate decarboxylase systems in Listeria monocytogenes EGD-e and 10403S : roles in virulence and acid tolerance

The glutamate decarboxylase (GAD) system has been shown to be important for the survival of Listeria monocytogenes in low pH environments. The bacterium can use this faculty to maintain pH homeostasis under acidic conditions. The accepted model for the GAD system proposes that the antiport of glutamate into the bacterial cell in exchange for γ-aminobutyric acid (GABA) is coupled to an intracellular decarboxylation reaction of glutamate into GABA that consumes protons and therefore facilitates pH homeostasis. Most strains of L. monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a glutamate decarboxylase dedicated to the intracellular GAD system (GADi), which produces GABA from cytoplasmic glutamate in the absence of antiport activity. We also compare the functionality of the GAD system between two commonly studied reference strains, EGD-e and 10403S with differences in terms of acid resistance. Through functional genomics we show that EGD-e is unable to export GABA and relies exclusively in the GADi system, which is driven primarily by GadD3 in this strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular and extracellular GAD system (GADi/GADe). Through experiments with a murinised variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant role in the overall virulence of this strain. Double mutants lacking either gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were significantly affected in their ability to cause infection following oral inoculation. Since EGDm exploits GADi but not GADe the results indicate that the GADi system makes a contribution to virulence within the mouse. Furthermore, we also provide evidence that there might be a separate line of evolution in the GAD system between two commonly used reference strains

Sleeping with the Enemy: How Intracellular Pathogens Cope with a Macrophage Lifestyle

Sleeping with the Enemy: How Intracellular Pathogens Cope with a Macrophage Lifestyl

Short-term consumption of a high-fat diet increases host susceptibility to Listeria monocytogenes infection

peer-reviewedBackground A westernized diet comprising a high caloric intake from animal fats is known to influence the development of pathological inflammatory conditions. However, there has been relatively little focus upon the implications of such diets for the progression of infectious disease. Here, we investigated the influence of a high-fat (HF) diet upon parameters that influence Listeria monocytogenes infection in mice. Results We determined that short-term administration of a HF diet increases the number of goblet cells, a known binding site for the pathogen, in the gut and also induces profound changes to the microbiota and promotes a pro-inflammatory gene expression profile in the host. Host physiological changes were concordant with significantly increased susceptibility to oral L. monocytogenes infection in mice fed a HF diet relative to low fat (LF)- or chow-fed animals. Prior to Listeria infection, short-term consumption of HF diet elevated levels of Firmicutes including Coprococcus, Butyricicoccus, Turicibacter and Clostridium XIVa species. During active infection with L. monocytogenes, microbiota changes were further exaggerated but host inflammatory responses were significantly downregulated relative to Listeria-infected LF- or chow-fed groups, suggestive of a profound tempering of the host response influenced by infection in the context of a HF diet. The effects of diet were seen beyond the gut, as a HF diet also increased the sensitivity of mice to systemic infection and altered gene expression profiles in the liver. Conclusions We adopted a systems approach to identify the effects of HF diet upon L. monocytogenes infection through analysis of host responses and microbiota changes (both pre- and post-infection). Overall, the results indicate that short-term consumption of a westernized diet has the capacity to significantly alter host susceptibility to L. monocytogenes infection concomitant with changes to the host physiological landscape. The findings suggest that diet should be a consideration when developing models that reflect human infectious disease.This research was funded by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement No. 641984, through funding of the List_MAPS consortium. We also acknowledge funding and support from Science Foundation Ireland (SFI) in the form of a center grant (APC Microbiome Ireland grant SFI/12/RC/2273)

The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases

MicroRNAs (miRNAs) are small, non-coding, RNA molecules that regulate gene expression. They have a long evolutionary history and are found in plants, viruses, and animals. Although initially discovered in 1993 in Caenorhabditis elegans, they were not appreciated as widespread and abundant gene regulators until the early 2000s. Studies in the last decade have found that miRNAs confer phenotypic robustness in the face of environmental perturbation, may serve as diagnostic and prognostic indicators of disease, underlie the pathobiology of a wide array of complex disorders, and represent compelling therapeutic targets. Pre-clinical studies in animal models have demonstrated that pharmacologic manipulation of miRNAs, mostly in the liver, can modulate metabolic phenotypes and even reverse the course of insulin resistance and diabetes. There is cautious optimism in the field about miRNA-based therapies for diabetes, several of which are already in various stages of clinical trials. This review will highlight both the promise and the most pressing challenges of therapeutic miRNA silencing in diabetes and related conditions

Group B Streptococcus GAPDH Is Released upon Cell Lysis, Associates with Bacterial Surface, and Induces Apoptosis in Murine Macrophages

Glyceraldehyde 3-phosphate dehydrogenases (GAPDH) are cytoplasmic glycolytic enzymes that, despite lacking identifiable secretion signals, have been detected at the surface of several prokaryotic and eukaryotic organisms where they exhibit non-glycolytic functions including adhesion to host components. Group B Streptococcus (GBS) is a human commensal bacterium that has the capacity to cause life-threatening meningitis and septicemia in newborns. Electron microscopy and fluorescence-activated cell sorter (FACS) analysis demonstrated the surface localization of GAPDH in GBS. By addressing the question of GAPDH export to the cell surface of GBS strain NEM316 and isogenic mutant derivatives of our collection, we found that impaired GAPDH presence in the surface and supernatant of GBS was associated with a lower level of bacterial lysis. We also found that following GBS lysis, GAPDH can associate to the surface of many living bacteria. Finally, we provide evidence for a novel function of the secreted GAPDH as an inducer of apoptosis of murine macrophages

Tracking a killer shrimp: Dikerogammarus villosus invasion dynamics across Europe

Aim: Invasive alien species are a growing problem worldwide due to their ecological, economic and human health impacts. The “killer shrimp” Dikerogammarus villosus is a notorious invasive alien amphipod from the Ponto-Caspian region that has invaded many fresh and brackish waters across Europe. Understandings of large-scale population dynamics of highly impactful invaders such as D. villosus are lacking, inhibiting predictions of impact and efficient timing of management strategies. Hence, our aim was to assess trends and dynamics of D. villosus as well as its impacts in freshwater rivers and streams. Location: Europe. Methods: We analysed 96 European time series between 1994 and 2019 and identified trends in the relative abundance (i.e. dominance %) of D. villosus in invaded time series, as well as a set of site-specific characteristics to identify drivers and determinants of population changes and invasion dynamics using meta-regression modelling. We also looked at the spread over space and time to estimate the invasion speed (km/year) of D. villosus in Europe. We investigated the impact of D. villosus abundance on recipient community metrics (i.e. abundance, taxa richness, temporal turnover, Shannon diversity and Pielou evenness) using generalized linear models. Results: Population trends varied across the time series. Nevertheless, community dominance of D. villosus increased over time across all time series. The frequency of occurrences (used as a proxy for invader spread) was well described by a Pareto distribution, whereby we estimated a lag phase (i.e. the time between introduction and spatial expansion) of approximately 28 years, followed by a gradual increase before new occurrences declined rapidly in the long term. D. villosus population change was associated with decreased taxa richness, community turnover and Shannon diversity. Main Conclusion: Our results show that D. villosus is well-established in European waters and its abundance significantly alters ecological communities. However, the multidecadal lag phase prior to observed spatial expansion suggests that initial introductions by D. villosus are cryptic, thus signalling the need for more effective early detection methods

The role of organisms in hyporheic processes : gaps in current knowledge, needs for future research and applications

Fifty years after the hyporheic zone was first defined (Orghidan, 1959), there are still gaps in the knowledge regarding the role of biodiversity in hyporheic processes. First, some methodological questions remained unanswered regarding the interactions between biodiversity and physical processes, both for the study of habitat characteristics and interactions at different scales. Furthermore, many questions remain to be addressed to help inform our understanding of invertebrate community dynamics, especially regarding the trophic niches of organisms, the functional groups present within sediment, and their temporal changes. Understanding microbial community dynamics would require investigations about their relationship with the physical characteristics of the sediment, their diversity, their relationship with metabolic pathways, their inter- actions with invertebrates, and their response to environmental stress. Another fundamental research question is that of the importance of the hyporheic zone in the global metabolism of the river, which must be explored in relation to organic matter recycling, the effects of disturbances, and the degradation of contaminants. Finally, the application of this knowledge requires the development of methods for the estimation of hydro- logical exchanges, especially for the management of sediment clogging, the optimization of self-purification, and the integration of climate change in environmental policies. The development of descriptors of hyporheic zone health and of new metrology is also crucial to include specific targets in water policies for the long-term management of the system and a clear evaluation of restoration strategies

In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis

The faunal Ponto-Caspianization of central and western European waterways

As alien invasive species are a key driver of biodiversity loss, understanding patterns of rapidly changing global species compositions depends upon knowledge of invasive species population dynamics and trends at large scales. Within this context, the Ponto-Caspian region is among the most notable donor regions for aquatic invasive species in Europe. Using macroinvertebrate time series collected over 52 years (1968–2020) at 265 sites across 11 central and western European countries, we examined the occurrences, invasion rates, and abundances of freshwater Ponto-Caspian fauna. We examined whether: (i) successive Ponto-Caspian invasions follow a consistent pattern of composition pioneered by the same species, and (ii) Ponto-Caspian invasion accelerates subsequent invasion rates. In our dataset, Ponto-Caspian macroinvertebrates increased from two species in 1972 to 29 species in 2012. This trend was parallelled by a non-significant increasing trend in the abundances of Ponto-Caspian taxa. Trends in Ponto-Caspian invader richness increased significantly over time. We found a relatively uniform distribution of Ponto-Caspian macroinvertebrates across Europe without any relation to the distance to their native region. The Ponto-Caspian species that arrived first were often bivalves (46.5% of cases), particularly Dreissena polymorpha, followed secondarily by amphipods (83.8%; primarily Chelicorophium curvispinum and Dikerogammarus villosus). The time between consecutive invasions decreased significantly at our coarse regional scale, suggesting that previous alien establishments may facilitate invasions of subsequent taxa. Should alien species continue to translocate from the Ponto-Caspian region, our results suggest a high potential for their future invasion success highly connected central and western European waters. However, each species’ population may decline after an initial 'boom' phase or after the arrival of new invasive species, resulting in different alien species dominating over time