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ABSTRACTShigella spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates’ protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon Shigella oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (Shigella sonnei, Shigella flexneri 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased Shigella penetration into the colon epithelium layer in a Gulo−/− mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both Shigella infection strategies and immune responses to Shigella infection.

Populists are often anti-elitist and advocate for popular will over expertise. We show that these two populist characteristics are responses to mainstream parties leaving behind the majority of voters, the common people. Our model highlights two forces behind electoral success: numbers, which favor the common people, and knowledge, which favors the elite. Electoral competition may lead parties to cater to the elite. We identify conditions under which an elite bias encourages entry with an anti-elite platform. Finally, we identify conditions under which parties follow the common people's opinion when that group would benefit from parties relying on experts. [ABSTRACT FROM AUTHOR]

Abstract Background Several studies have reported the strong resistance of Anopheles gambiae s.l. complex species to pyrethroids. The voltage-dependent sodium channel (Vgsc) gene is the main target of pyrethroids and DDT. In Benin, the frequency of the resistant allele (L1014F) of this gene varies along the north-south transect. Monitoring the evolution of resistance is necessary to better appreciate the genetic structure of vector populations in localities subject to the intensive use of chemicals associated with other control initiatives. The purpose of this study was to map the distribution of pyrethroid insecticide resistance alleles of the Kdr gene in malaria vectors in different regions and ecological facies in order to identify the evolutionary forces that might be the basis of anopheline population dynamics. Methods The characterization of Anopheles gambiae s.l. populations and resistance mechanisms were performed using adult mosquitoes obtained from larvae collected in the four agroecological zones in southern Benin. Genomic DNA extraction was performed on whole mosquitoes. The extracted genomic DNA from them were used for the molecular identification of species in Anopheles gambiae s.l. complex and the identification of genotypes related to pyrethroid resistance as the Kdr gene amino acid position 1014 in sodium channel. Molecular speciation and genotyping of Kdr resistant alleles (1014) were done using PCR. Genepop software version 4.2 was used to calculate allelic and genotypic frequencies in each agroecological zone. The p value of the allelic frequency was determined using the binomial test function in R version 3.3.3. The Hardy-Weinberg equilibrium was checked for each population with Genetics software version 1.3.8.1. The observed heterozygosity and the expected heterozygosity as well as the fixation index and genetic differentiation index within and between populations were calculated using Genepop software version 4.2. Results During the study period, Anopheles coluzzii was the major species in all agroecological zones while Anopheles gambiae was scarcely represented. Regardless of the species, resistant homozygote individuals (L1014F/L1014F) were dominant in all agroecological zones, showing a strong selection of the resistant allele (L1014F). All populations showed a deficit of heterozygosity. No genetic differentiation was observed between the different populations of the two species. For Anopheles coluzzii, there was a small differentiation among the populations of the central cotton and bar-lands zones. The genetic differentiation was modest among the population of the fisheries zone (Fst = 0.1295). The genetic differentiation was very high in the population of Anopheles gambiae of the bar-lands zone (Fst = 0.2408). Conclusion This study revealed that the use of insecticides in Benin for years has altered the genetic structure of Anopheles gambiae s.s. populations in all agroecological zones of southern Benin. It would be desirable to orientate vector control efforts towards the use of insecticides other than pyrethroids and DDT or combinations of insecticides with different modes of action.

We present a database of observational constraints on past Antarctic Ice Sheet changes during the last glacial cycle intended to consolidate the observations that represent our understanding of past Antarctic changes and for state-space estimation and paleo-model calibrations. The database is a major expansion of the initial work of Briggs and Tarasov (2013). It includes new data types and multi-tier data quality assessment. The updated constraint database, AntICE2 (https://theghub.org/resources/4884 , Lecavalier et al., 2022), consists of observations of past grounded- and floating-ice-sheet extent, past ice thickness, past relative sea level, borehole temperature profiles, and present-day bedrock displacement rates. In addition to paleo-observations, the present-day ice sheet geometry and surface ice velocities are incorporated to constrain the present-day ice sheet configuration. The method by which the data are curated using explicitly defined criteria is detailed. Moreover, the observational uncertainties are specified. The methodology by which the constraint database can be applied to evaluate a given ice sheet reconstruction is discussed. The implementation of the AntICE2 database for Antarctic Ice Sheet model calibrations will improve Antarctic Ice Sheet predictions during past warm and cold periods and yield more robust paleo-model spin ups for forecasting future ice sheet changes. [ABSTRACT FROM AUTHOR]

Shigella is a pathovar of Escherichia coli comprising 4 groups, Shigella flexneri, Shigella sonnei, Shigella dysenteriae, and Shigella boydii, each of them, with the exception of S. sonnei, comprising several serotypes. Shigella accounts for the majority of dysentery causing infections occurring world-wide each year. Recent advancements in the Shigella field have led to a better understanding of the molecular mechanisms underlying host epithelial cell invasion and immune cell function manipulation, mainly using S. flexneri as a model. Host-cell invasion is the final step of the infection process, as Shigella virulence strategy relies also on its ability to survive hostile conditions during its journey through the gastro-intestinal tract, to compete with the host microbiota and to cross the intestinal mucus layer. Hence, the diversity of the virulence strategies among the different Shigella species has not yet been deeply investigated, which might be an important step to understand the epidemiological spreading of Shigella species worldwide and a key aspect for the validation of novel vaccine candidates. The recent development of high Throughput screening and sequencing methods will facilitate these complex comparison studies.In this review we discuss several of the major avenues that the Shigella research field has taken over the past few years and hopefully gain some insights into the questions that remain surrounding this important human pathogen.

ABSTRACT Bacterial cell division requires the formation of a mature divisome complex positioned at the midcell. The localization of the divisome complex is determined by the correct positioning, assembly, and constriction of the FtsZ ring (Z-ring). Z-ring constriction control remains poorly understood and (to some extent) controversial, probably due to the fact that this phenomenon is transient and controlled by numerous factors. Here, we characterize ZapE, a novel ATPase found in Gram-negative bacteria, which is required for growth under conditions of low oxygen, while loss of zapE results in temperature-dependent elongation of cell shape. We found that ZapE is recruited to the Z-ring during late stages of the cell division process and correlates with constriction of the Z-ring. Overexpression or inactivation of zapE leads to elongation of Escherichia coli and affects the dynamics of the Z-ring during division. In vitro, ZapE destabilizes FtsZ polymers in an ATP-dependent manner. IMPORTANCE Bacterial cell division has mainly been characterized in vitro. In this report, we could identify ZapE as a novel cell division protein which is not essential in vitro but is required during an infectious process. The bacterial cell division process relies on the assembly, positioning, and constriction of FtsZ ring (the so-called Z-ring). Among nonessential cell division proteins recently identified, ZapE is the first in which detection at the Z-ring correlates with its constriction. We demonstrate that ZapE abundance has to be tightly regulated to allow cell division to occur; absence or overexpression of ZapE leads to bacterial filamentation. As zapE is not essential, we speculate that additional Z-ring destabilizing proteins transiently recruited during late cell division process might be identified in the future.

We present a database of observational constraints on past Antarctic ice sheet changes during the last glacial cycle intended to consolidate the observations that represent our understanding of past Antarctic changes, for state-space estimation, and paleo-model calibrations. The database is a major expansion of the initial work of Briggs and Tarasov (2013). It includes new data types and multi-tier data quality assessment. The updated constraint database "AntICE2" consists of observations of past grounded and floating ice sheet extent, past ice thickness, past relative sea level, borehole temperature profiles, and present-day bedrock displacement rates. In addition to paleo-observations, the present-day ice sheet geometry and surface ice velocities are incorporated to constrain the present-day ice sheet configuration. The method by which the data is curated using explicitly defined criteria is detailed. Moreover, the observational uncertainties are specified. The methodology by which the constraint database can be applied to evaluate a given ice sheet reconstruction is discussed. The implementation of the "AntICE2" database for Antarctic ice sheet model calibrations will improve Antarctic ice sheet predictions during past warm and cold periods and yield more robust paleo model spin ups for forecasting future ice sheet changes. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease‐inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. Objective: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. Methods: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti‐BP180 NC16A and anti‐BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. Results: An association between higher serum anti‐BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase‐4 (DPP4) inhibitors, inhibitors of platelet aggregation and L‐thyroxine. The use of DPP4 inhibitors was associated with less anti‐BP180 and anti‐BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti‐BP180 and anti‐BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L‐thyroxine. Conclusion: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD. [ABSTRACT FROM AUTHOR]

The evolution of ants (Hymenoptera: Formicidae) is increasingly well-understood due to recent phylogenetic analyses, along with estimates of divergence times and diversification rates. Yet, leading hypotheses regarding the ancestral habitat of ants conflict with new findings that early ant lineages are cryptic and subterranean. Where the ants evolved, in respect to habitat, and how habitat shifts took place over time have not been formally tested. Here, we reconstruct the habitat transitions of crown-group ants through time, focusing on where they nest and forage (in the canopy, litter, or soil). Based on ancestral character reconstructions, we show that in contrast to the current consensus based on verbal arguments that ants evolved in tropical leaf litter, the soil is supported as the ancestral stratum of all ants. We also find subsequent movements up into the litter and, in some cases, into the canopy. Given the global importance of ants, because of their diversity, ecological influence and status as the most successful eusocial lineage on Earth, understanding the early evolution of this lineage provides insight into the factors that made this group so successful today.