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This study addresses the urgent need to enhance food security in Algeria, exacerbated by nearby economic and geopolitical instabilities. It investigates six critical challenges, beginning with an overview of agricultural settings in Algeria. First, it questions the prioritization of strategic sectors, compelling a thorough reevaluation. Second, it highlights ongoing rural development issues, emphasizing insufficient investments in infrastructure. Third, it addresses price stability management by reconsidering the efficacy of different storage mechanisms. Fourth, the study examines agrarian structures, advocating for a meticulous evaluation to optimize land market efficiency. Fifth, it explores irrigation water management, questioning concerns of abundance and scarcity. Lastly, it confronts climate change challenges, emphasizing the need for more resilient agricultural practices. By analyzing these fundamental aspects, this study aspires to offer insights that can inform strategic policies and public interventions, ultimately contributing to the enhancement of Algerian food security in light of current and future challenges.

Abstract Phthalates constitute a family of anthropogenic chemicals developed to be used in the manufacture of plastics, solvents, and personal care products. Their dispersion and accumulation in many environments can occur at all stages of their use (from synthesis to recycling). However, many phthalates together with other accumulated engineered chemicals have been shown to interfere with hormone activities. These compounds are also in close contact with microorganisms that are free-living, in biofilms or in microbiota, within multicellular organisms. Herein, the activity of several phthalates and their substitutes were investigated on the opportunistic pathogen Legionella pneumophila, an aquatic microbe that can infect humans. Beside showing the toxicity of some phthalates, data suggested that Acetyl tributyl citrate (ATBC) and DBP (Di-n-butyl phthalate) at environmental doses (i.e. 10–6 M and 10–8 M) can modulate Legionella behavior in terms of motility, biofilm formation and response to antibiotics. A dose of 10–6 M mostly induced adverse effects for the bacteria, in contrast to a dose of 10–8 M. No perturbation of virulence towards Acanthamoeba castellanii was recorded. These behavioral alterations suggest that L. pneumophila is able to sense ATBC and DBP, in a cross-talk that either mimics the response to a native ligand, or dysregulates its physiology.

Fairness and ethical values in agro-food chain lay at the center of the current debate on agro-food chain sustainability. The food labels may contain elements focused on agro-food chain management fairness practices. The objective of the present study is to explore what types of fairness agro-food companies value in the food products they commercialize, and if the characteristics of agro-food companies have a relationship with the type of fairness valued. The research study collected 226 commercialized food products containing information on the agro-food chain fairness practices companies adopted to produce the food products. Data elaboration included a cluster analysis to identify groups of fair products, and a multinomial logistic regression to explore the relationship between the identified clusters and fairness types, organic, nutritional and functional claims, and price. Results support that fairness-oriented products provide information on different types of fairness that is distributive, procedural, and interactional. Some products provide economic information on the distribution of price between upstream and downstream actors. Other products focus on procedural and interactional fairness practices, such as dignity, respect and transparent relationship in agro-food chain; technologies used in the production and distribution of the product; and ethical certifications that companies hold. Fairness-oriented information differ depending both on the type of chain actor commercializing the product, and on the type of brand, that is whether commercial brand or private label. The main conclusion is that companies convey fairness-related information to consumers differently according to company’s role in the agro-food chain. Yet, there is need to exploit further the potential role of fairness practices in defining effective business strategies to contribute to higher equity and sustainability in the agro-food system.

The general consensus is that dense cities are more sustainable. However, high urban density or compact urban form may affect the health of city dwellers, more particularly when compactness is not associated with the provision of mass transit systems. This paper analyses the correlation between urban density indicators and air pollution in Oran (Algeria), a city that suffers a lack of public transport. It assesses the density of green space needed to reduce airborne pollutants in cities. The paper also examines the impacts of exposure to air pollution on respiratory mortality using a quantitative health impact assessment methodology. Findings show that population density and building density strongly correlates with air pollution, due to motorized transport and other human activities (e.g. industries, residential heating or lacking green space). Results indicate that for population density greater than 12100 inhabitants/ha with associated values exceeding 100 for building density and green space density, air pollution levels become higher than 40µg/m3 , exceeding the recommended limit at international level by WHO. In addition, 588 annual premature deaths (95% CI: 529-643), i.e. 0,2% of the total population of the eighteen districts and 3,7% of the total number of deaths, were directly or indirectly related to NOx concentration. This paper concludes that despite the conventional wisdom that more dense cities are more sustainable and healthier, higher density urban areas tend to be associated with poor air quality when there are no mass transit systems.

The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A–exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring’s metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.

Abstract We previously showed that the physiological concentration of 17β-estradiol in the vaginal environment is sufficient to affect the membrane dynamics and adhesion phenotype of the Lactobacillus crispatus strain CIP104459. However, L. crispatus is a heterogeneous species. Here, we investigated the effect of 17β-estradiol on the recently isolated L. crispatus vaginal strain V4, related to a cluster distant from CIP104459 and at the limit of being a different subspecies. Grown in the same medium, the two strains expressed a highly similar pool of proteins. However, in contrast to CIP104459, L. crispatus V4 showed high aggregation potential and 17β-estradiol promoted this phenotype. This effect was associated with large changes in cell-surface polarity and Lewis acid/base properties. In addition, we observed no effect on the membrane dynamics, contrary to CIP104459. These results can be explained by differences in the properties and organization of the S layer between the two strains. However, as for CIP104459, 17β-estradiol increased biosurfactant production of L. crispatus V4 and their adhesion to vaginal cells. This suggests that 17β-estradiol agonists would be valuable tools to favor a stable re-implantation of L. crispatus in the vaginal mucosa.

Abstract Background Malaria vector control has been implemented chiefly through indoor interventions targeting primary vectors resulting in population declines—pointing to a possible greater proportional contribution to transmission by secondary malaria vectors with their predominant exophagic and exophilic traits. With a historical focus on primary vectors, there is paucity of data on secondary malaria vectors in many countries in Africa. This study sought to determine the species compositions and bionomic traits, including proportions infected with Plasmodium falciparum and phenotypic insecticide resistance, of secondary vectors in three sites with high malaria transmission in Kisumu County, western Kenya. Methods Cross-sectional sampling of adult Anopheles was conducted using indoor and outdoor CDC light traps (CDC-LT) and animal-baited traps (ABTs) in Kakola-Ombaka and Kisian, while larvae were sampled in Ahero. Secondary vectors captured were exposed to permethrin using WHO bioassays and then analyzed by ELISA to test for proportions infected with P. falciparum sporozoites. All Anopheles were identified to species using morphological keys with a subset being molecularly identified using ITS2 and CO1 sequencing for species identification. Results Two morphologically identified secondary vectors captured—An. coustani and An. pharoensis—were determined to consist of four species molecularly. These included An. christyi, An. sp. 15 BSL-2014, an unidentified member of the An. coustani complex (An. cf. coustani) and a species similar to that of An. pharoensis and An. squamosus (An. cf. pharoensis). Standardized (Anopheles per trap per night) capture rates demonstrate higher proportions of secondary vectors across most trapping methods—with overall indoor and outdoor CDC-LTs and ABT captures composed of 52.2% (n = 93), 78.9% (n = 221) and 58.1% (n = 573) secondary vectors respectively. Secondary vectors were primarily caught outdoors. The overall proportion of secondary vectors with P. falciparum sporozoite was 0.63% (n = 5), with the unidentified species An. cf. pharoensis, determined to carry Plasmodium. Overall secondary vectors were susceptible to permethrin with a > 99% mortality rate. Conclusions Given their high densities, endophily equivalent to primary vectors, higher exophily and Plasmodium-positive proportions, secondary vectors may contribute substantially to malaria transmission. Unidentified species demonstrate the need for further morphological and molecular identification studies towards further characterization. Continued monitoring is essential for understanding their temporal contributions to transmission, the possible elevation of some to primary vectors and the development of insecticide resistance. Graphic Abstract

The aim of this study is to evaluate the performance of water-saving technologies (WST) through an investigation of its effect at the farm level. Indeed, the study attempts to estimate the economic value of WST use in Algerian farming, through the comparison of some farm performance indicators between WST adopters, drip irrigation system as a WST, and farmers practicing gravity irrigation as a traditional system. A cross-section data from a survey is conducted in an irrigated perimeter situated in the north-eastern Algeria (Jijel region) encompassing 106 small horticultural farms (including 60 pepper producers and 46 tomato producers). First, the study compares some performance indicators between the two groups of farms. Second, a stochastic production frontier model is used to estimate the productivity gain generated by the WST adoption. Main results show that water consumption, gross margin, and water productivity are statistically significant between the two groups of farms. The average water productivity differential between WST users and non-users is 29% and 25% for tomato and pepper, respectively. The regression model has shown that increasing the WST use by 1% help to increase water productivity of the region by 0.20% for pepper production and 0.11% for tomato production. The findings of this study confirm the hypothesis that WST economize on water quantity, positively affects crop yield and can enhance water productivity.

Fecal pollution in coastal areas is of a high concern since it affects bathing and shellfish harvesting activities. Wild waterbirds are non-negligible in the overall signal of the detectable pollution. Yet, studies on wild waterbirds’ gut microbiota focus on migratory trajectories and feeding impact on their shape, rare studies address their comparison to other sources and develop quantitative PCR (qPCR)-based Microbial Source Tracking (MST) markers to detect such pollution. Thus, by using 16S rRNA amplicon high-throughput sequencing, the aims of this study were (i) to explore and compare fecal bacterial communities from wild waterbirds (i.e., six families and 15 species, n = 275 samples) to that of poultry, cattle, pigs, and influent/effluent of wastewater treatment plants (n = 150 samples) and (ii) to develop new MST markers for waterbirds. Significant differences were observed between wild waterbirds and the four other groups. We identified 7,349 Amplicon Sequence Variants (ASVs) from the hypervariable V3–V4 region. Firmicutes and Proteobacteria and, in a lesser extent, Actinobacteria and Bacteroidetes were ubiquitous while Fusobacteria and Epsilonbacteraeota were mainly present in wild waterbirds. The clustering of samples in non-metric multidimensional scaling (NMDS) ordination indicated a by-group clustering shape, with a high diversity within wild waterbirds. In addition, the structure of the bacterial communities was distinct according to bird and/or animal species and families (Adonis R2 = 0.13, p = 10–4, Adonis R2 = 0.11, p = 10–4, respectively). The Analysis of Composition of Microbiomes (ANCOM) showed that the wild waterbird group differed from the others by the significant presence of sequences from Fusobacteriaceae (W = 566) and Enterococcaceae (W = 565) families, corresponding to the Cetobacterium (W = 1427) and Catellicoccus (W = 1427) genera, respectively. Altogether, our results suggest that some waterbird members present distinct fecal microbiomes allowing the design of qPCR MST markers. For instance, a swan- and an oystercatcher-associated markers (named Swan_2 and Oyscab, respectively) have been developed. Moreover, bacterial genera harboring potential human pathogens associated to bird droppings were detected in our dataset, including enteric pathogens, i.e., Arcobacter, Clostridium, Helicobacter, and Campylobacter, and environmental pathogens, i.e., Burkholderia and Pseudomonas. Future studies involving other wildlife hosts may improve gut microbiome studies and MST marker development, helping mitigation of yet unknown fecal pollution sources.

This paper examines aggregate supply response of 19 selected crops in Algerian agriculture during the 1966-2018 period by employing cointegration analysis and error correction model (ECM). It tests whether there has been a long-run equilibrium relationship between agricultural outputs and prices, besides a confirmation about the responsiveness of agricultural supply to economic incentives (prices). Findings indicate that the long-run elasticities of all selected crops with respect to prices are statistically significant and mostly low, whereas short-run elasticities are lower, which appeals to the adequacy of adjustment to economic incentives. Furthermore, the results of the ECM confirmed the positive responsiveness to prices with differential rates of adjustment for selected crops, ruling out the applicability of a presumed perverse supply response in Algerian agriculture.

The skin constitutes with its microbiota the first line of body defense against exogenous stress including air pollution. Especially in urban or sub-urban areas, it is continuously exposed to many environmental pollutants including gaseous nitrogen dioxide (gNO2). Nowadays, it is well established that air pollution has major effects on the human skin, inducing various diseases often associated with microbial dysbiosis. However, very few is known about the impact of pollutants on skin microbiota. In this study, a new approach was adopted, by considering the alteration of the cutaneous microbiota by air pollutants as an indirect action of the harmful molecules on the skin. The effects of gNO2 on this bacterial skin microbiota was investigated using a device developed to mimic the real-life contact of the gNO2 with bacteria on the surface of the skin. Five strains of human skin commensal bacteria were considered, namely Staphylococcus aureus MFP03, Staphylococcus epidermidis MFP04, Staphylococcus capitis MFP08, Pseudomonas fluorescens MFP05, and Corynebacterium tuberculostearicum CIP102622. Bacteria were exposed to high concentration of gNO2 (10 or 80 ppm) over a short period of 2 h inside the gas exposure device. The physiological, morphological, and molecular responses of the bacteria after the gas exposure were assessed and compared between the different strains and the two gNO2 concentrations. A highly significant deleterious effect of gNO2 was highlighted, particularly for S. capitis MFP08 and C. tuberculostearicum CIP102622, while S. aureus MFP03 seems to be the less sensitive strain. It appeared that the impact of this nitrosative stress differs according to the bacterial species and the gNO2 concentration. Thus the exposition to gNO2 as an air pollutant could contribute to dysbiosis, which would affect skin homeostasis. The response of the microbiota to the nitrosative stress could be involved in some pathologies such as atopic dermatitis.

The human gut microbiota has co-evolved with humans by exchanging bidirectional signals. This study aims at deepening the knowledge of this crucial relationship by analyzing phenotypic and interactive responses of the probiotic Enterococcus faecium NCIMB10415 (E. faecium SF68) to the top-down signals norepinephrine (NE) and serotonin (5HT), two neuroactive molecules abundant in the gut. We treated E. faecium NCIMB10415 with 100 µM NE and 50 µM 5HT and tested its ability to form static biofilm (Confocal Laser Scanning Microscopy), adhere to the Caco-2/TC7 monolayer, affect the epithelial barrier function (Transepithelial Electrical Resistance) and human dendritic cells (DC) maturation, differentiation, and cytokines production. Finally, we evaluated the presence of a putative hormone sensor through in silico (whole genome sequence and protein modelling) and in vitro (Micro-Scale Thermophoresis) analyses. The hormone treatments increase biofilm formation and adhesion on Caco-2/TC7, as well as the epithelial barrier function. No differences concerning DC differentiation and maturation between stimulated and control bacteria were detected, while an enhanced TNF-α production was observed in NE-treated bacteria. Investigations on the sensor support the hypothesis that a two-component system on the bacterial surface can sense 5HT and NE. Overall, the data demonstrate that E. faecium NCIMB10415 can sense both NE and 5HT and respond accordingly.

Biofilms are complex structures formed by a community of microbes adhering to a surface and/or to each other through the secretion of an adhesive and protective matrix. The establishment of these structures requires a coordination of action between microorganisms through powerful communication systems such as quorum-sensing. Therefore, auxiliary bacteria capable of interfering with these means of communication could be used to prevent biofilm formation and development. The phytopathogen Rhizobium rhizogenes, which causes hairy root disease and forms large biofilms in hydroponic crops, and the biocontrol agent Rhodococcus erythropolis R138 were used for this study. Changes in biofilm biovolume and structure, as well as interactions between rhizobia and rhodococci, were monitored by confocal laser scanning microscopy with appropriate fluorescent biosensors. We obtained direct visual evidence of an exchange of signals between rhizobia and the jamming of this communication by Rhodococcus within the biofilm. Signaling molecules were characterized as long chain (C14) N-acyl-homoserine lactones. The role of the Qsd quorum-quenching pathway in biofilm alteration was confirmed with an R. erythropolis mutant unable to produce the QsdA lactonase, and by expression of the qsdA gene in a heterologous host, Escherichia coli. Finally, Rhizobium biofilm formation was similarly inhibited by a purified extract of QsdA enzyme.

Bacterial burn is one of the major diseases affecting pear trees worldwide, with serious impacts on producers and economy. In Morocco, several pear trees (Pyrus communis) have shown leaf burns since 2015. To characterize the causal agent of this disease, we isolated fourteen bacterial strains from different parts of symptomatic pear trees (leaves, shoots, fruits and flowers) that were tested in planta for their pathogenicity on Louise bonne and Williams cultivars. The results showed necrotic lesions with a significant severity range from 47.63 to 57.77% on leaves of the Louise bonne cultivar inoculated with isolate B10, while the other bacterial isolates did not induce any disease symptom. 16S rRNA gene sequencing did not allow robust taxonomic discrimination of the incriminated isolate. Thus, we conducted whole-genome sequencing (WGS) and phylogenetic analyzes based on gyrA, gyrB and cdaA gene sequences, indicating that this isolate belongs to the Bacillus altitudinis species. This taxonomic classification was further confirmed by the Average Nucleotide Identity (ANI) and the in silico DNA-DNA hybridization (isDDH) analyzes compared to sixty-five Bacillus spp. type strains. The genome was mined for genes encoding carbohydrate-active enzymes (CAZymes) known to play a role in the vegetal tissue degradation. 177 candidates with functions that may support the in planta phytopathogenicity results were identified. To the best of our knowledge, this is the first data reporting B. altitudinis as agent of leaf burn in P. communis in Morocco. Our dataset will improve our knowledge on spread and pathogenicity of B. altitudinis genotypes that appears as emergent phytopathogenic agent, unveiling virulence factors and their genomic location (i.e., within genomic islands or the accessory genome) to induce trees disease.

This study aims to analyze the determinants of vertical integration (ownership and contract-ing) among peasant farmers in Northern Algeria. The choice of asset control is between ownership and a simple contracting. Thus, the integration of vertical stages of agricultural produc-tion leads to higher gross margins, influencesthe choice of marketing and supply channels, and improves market participation of farmers. Three different regression models were used to determine the likelihood of a peasant household to integrate vertically (and horizontally) in its enterprise. Data were collected from 635 smallholder farmers in Northern Algeria. Farm structure, farm size, farmers' age, farmers’ level of education, seasonality, and geographical location were assumed to be the key factors in accounting for a household’s likelihood to ver-tically integrate in its farming enterprise. These key factors affect the household’s likelihood of horizontal integration. The study, then, carries the implication that policy-makers should develop increased awareness of farm structure, its scale, seasonal and spatial nature of agricultural production, as well as of some farmers’social characteristics in order to be able to improve the agricultural productivity.

This study aims to investigate the effect of main socioeconomic factors of technology adoption, with special reference to the role of assets specificity in farm management. The contribution of this study is largely empirical by testing some hypotheses in Algerian context. We investigate the determinants of technology asset control choices in the agricultural production in order to conclude on the constraints of farm extent and its implications for farm management and economic efficiency. Our main results assert that the technology asset control choice is determined by the farm size, organizational form, human capital, social status, and geographical location. These findings corroborate the existing theories and generate some empirical implications, leading to propose some directions for future research.

On the question of the archetypal model of the Islamic city, several oriental researchers and orientalists tried to give some answers, each considering on his part on a specific aspect to the originality of these cities. Some even expressed great skepticism toward the concept of “Islamic city” as an urban ideal of the Muslim world. The purpose of this study is to confront various visions having a theoretical interest on this issue in order to trace the characteristics of the case study. As such, the medina of Tlemcen, capital of central Maghreb for nearly three centuries, is a privileged analysis field to study the type organization of Arab-Muslim cities. Thus, the hypothesis put forth is that this Medina had, in medieval and Ottoman period, a spatial configuration fully aligned with the model of “Islamic cities”; corroborating the idea of the existing common features shared by the historic cities of the Islamic world.

Background: Hypocalcemia is a well-recognized complication of thyroid surgery. The aim of this study was to determine the incidence of hypocalcemia after thyroid surgery and find out the risk factors involved regarding the patient’s age, gender, muscular build, clinical diagnosis, extent of surgery, ligation of the inferior thyroid artery, and pathology report. Patients and Methods: This case series study was carried out on 50 patients who have undergone thyroid surgery for various thyroid diseases at the surgical department of Al-Karama Teaching Hospital for the period between January 2016 and July 2017. Serial serum calcium measurements were recorded as well as details of the operation, patient’s age and gender, whether or not inferior thyroid artery was ligated, and the pathological report. Hypocalcemia was considered transient if it resolved within 6 months and permanent if it persisted after 6 months and the patient was maintained on supplementation therapy of calcium and vitamin D. Results: The study found that the incidence of post-thyroidectomy hypocalcemia was 30% and in the majority of the cases (24%) was transient, while it was permanent in only (6%) of the cases; and had occurred mainly after total thyroidectomy and in cases with ligation of the inferior thyroid artery. Conclusions: It was concluded that post thyroidectomy hypocalcemia is a relatively common complication but it is transient in the majority of the patients. Its incidence is related to the extent of the surgery and can be reduced by the good preparation of the patient preoperatively.

Background: Acute pancreatitis is an acute inflammatory condition. It's not an uncommon disease, in both the developed and developing countries, causes high morbidity and mortality, and inflicts a heavy economic burden. Severe acute pancreatitis is present in up to 25% of patients with acute pancreatitis, with considerable mortality. Changes in the management of acute pancreatitis in the last 2 decades contributed to reduce the mortality. Objective: was to review the diagnosis and management and outcomes of patients with acute pancreatitis of patients with acute pancreatitis in Al- Karama teaching hospital. Patients and Methods: This prospective study included 63 patients with acute pancreatitis in surgical and medical wards in Al- Karma teaching hospital from the 1st October 2014 to 30th September 2017. Results: 63 patients with acute pancreatitis were included 35 male and 28 female patients with upper abdominal pain in which the diagnosis was not confirmed by CT or serum amylase or by CRP are not included in this study. Age and gender had no significant relations to outcome. Medical therapy is the mainstay, with supportive therapy consisting of controlled volume resuscitation and enteral feeding. Minimally invasive drainage and debridement play a role in managing infective pancreatic necrosis but in general should not be used until at least 4weeks after the acute illness. Conclusions: Acute pancreatitis is a benign abdominal disorder in up to 85% of cases. In the remaining 10%-15% of cases the disorder is life threatening with management of the disorder requiring admission to an intensive care unit with cardiovascular, respiratory, and renal monitoring and support.

Pseudomonas aeruginosa PAO1 has an integrated Pf4 prophage in its genome, encoding a relatively well-characterized filamentous phage, which contributes to the bacterial biofilm organization and maturation. Pf4 variants are considered as superinfectives when they can re-infect and kill the prophage-carrying host. Herein, the response of P. aeruginosa H103 to Pf4 variant infection was investigated. This phage variant caused partial lysis of the bacterial population and modulated H103 physiology. We show by confocal laser scanning microscopy that a Pf4 variant-infection altered P. aeruginosa H103 biofilm architecture either in static or dynamic conditions. Interestingly, in the latter condition, numerous cells displayed a filamentous morphology, suggesting a link between this phenotype and flow-related forces. In addition, Pf4 variant-infection resulted in cell envelope stress response, mostly mediated by the AlgU and SigX extracytoplasmic function sigma factors (ECFσ). AlgU and SigX involvement may account, at least partly, for the enhanced expression level of genes involved in the biosynthesis pathways of two matrix exopolysaccharides (Pel and alginates) and bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) metabolism.

Background: Less-invasive percutaneous stimulation of the auricular branch of the vagus nerve (pVNS) gained importance as a possible nonpharmacological treatment for various diseases. The objective is to perform a sensitivity analysis of a realistic numerical model of pVNS and to investigate the effects of the model parameters on the excitation threshold for single and bundled axons. Methods: Sim4Life electrostatic solver and neural tissue models were combined for electromagnetic and neural simulation. The numerical model consisted of a high-resolution model of a human ear, blood vessels, nerves, and three needle electrodes. Investigated parameters include the axon diameter and number, model temperature, ear conductivity, and electrodes’ penetration depth and position. Results: The electric field distribution was evaluated. Model temperature and ear conductivity are the non-influential parameters. Axons fiber diameter and the electrodes’ penetration depth are the most influential parameters with a maximum threshold voltage sensitivity of 32 mV for each 1 μm change in the axon diameter and 38 mV for each 0.1 mm change in the electrodes’ penetration depth. Conclusions: The established sensitivity analysis allows the identification of the influential and the non-influential parameters with a sensitivity quantification. Results suggest that the electrodes’ penetration depth is the most influential parameter.

The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring's metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.

LecA and LecB tetrameric lectins take part in oligosaccharide-mediated adhesion-processes of Pseudomonas aeruginosa. Glycomimetics have been designed to block these interactions. The great versatility of P. aeruginosa suggests that the range of application of these glycomimetics could be restricted to genotypes with particular lectin types. The likelihood of having genomic and genetic changes impacting LecA and LecB interactions with glycomimetics such as galactosylated and fucosylated calix[4]arene was investigated over a collection of strains from the main clades of P. aeruginosa. Lectin types were defined, and their ligand specificities were inferred. These analyses showed a loss of lecA among the PA7 clade. Genomic changes impacting lec loci were thus assessed using strains of this clade, and by making comparisons with the PAO1 genome. The lecA regions were found challenged by phage attacks and PAGI-2 (genomic island) integrations. A prophage was linked to the loss of lecA. The lecB regions were found less impacted by such rearrangements but greater lecB than lecA genetic divergences were recorded. Sixteen combinations of LecA and LecB types were observed. Amino acid variations were mapped on PAO1 crystal structures. Most significant changes were observed on LecBPA7, and found close to the fucose binding site. Glycan array analyses were performed with purified LecBPA7. LecBPA7 was found less specific for fucosylated oligosaccharides than LecBPAO1, with a preference for H type 2 rather than type 1, and Lewisa rather than Lewisx. Comparison of the crystal structures of LecBPA7 and LecBPAO1 in complex with Lewisa showed these changes in specificity to have resulted from a modification of the water network between the lectin, galactose and GlcNAc residues. Incidence of these modifications on the interactions with calix[4]arene glycomimetics at the cell level was investigated. An aggregation test was used to establish the efficacy of these ligands. Great variations in the responses were observed. Glycomimetics directed against LecB yielded the highest numbers of aggregates for strains from all clades. The use of a PAO1lecB strain confirmed a role of LecB in this aggregation phenotype. Fucosylated calix[4]arene showed the greatest potential for a use in the prevention of P. aeruginosa infections.

The adverse effects observed in some cancer patients treated with erythropoiesis‐stimulating agents such as erythropoietin (EPO) might be due to the latter's well‐known immunosuppressive functions. Here, we used a mouse model of syngeneic triple‐negative breast cancer to explore EPO's immunomodulatory role in a tumour setting. Our results showed that EPO treatment promotes tumour growth, exacerbates the 'immune desert', and results in a 'cold tumour'. EPO treatment changed the immune cell distribution in peripheral blood, secondary lymphoid organs, and the tumour microenvironment (TME). Our in‐depth analysis showed that EPO mainly impacts CD4 T cells by accelerating their activation in the spleen and thus their subsequent exhaustion in the TME. This process is accompanied by a general elevation of CD39 expression by several immune cells (notably CD4 T cells in the tumour and spleen), which promotes an immunosuppressive TME. Lastly, we identified a highly immunosuppressive CD39+ regulatory T cell population (ICOS+, CTLA4+, Ki67+) as a potential biomarker of the risk of EPO‐induced tumour progression. EPO displays pleiotropic immunosuppressive functions and enhances mammary tumour progression in mice. [ABSTRACT FROM AUTHOR]

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