About contamination by sterile females and residual male fertility on the effectiveness of the sterile insect technique. Impact on disease vector control and disease control.

The sterile insect technique (SIT) is a technique to control pests and vectors of diseases by releasing mainly sterile males. Several challenges need to be solved before large-scale field application in order to guarantee its success. In this paper we intend to focus on two important issues: residual fertility in released (sterile) males and contamination of each release by sterile females. Indeed, sterile males are never 100% sterile, that is there is always a small proportion, ɛ, of fertile males (sperm of) within the sterile males population. Among the sterile insects that are released, a certain proportion, ϵF, of them are sterile females due to imperfect mechanical sex-separation technique. This can be particularly problematic when arthropod viruses are circulating, because mosquito females, even sterile, are vectors of diseases. Various upper bound values are given in the entomological literature for ϵF and ɛ without clear explanations. In this work, we aim to show that these values are related to the biological parameters of the targeted vector, the sterile insects release rate, and the epidemiological parameters of a vector-borne disease, like Dengue. We extend results studied separately in Aronna and Dumont (2020), Dumont and Yatat-Djeumen (2022). To study the impact of both issues, we develop and study a SIT-entomological-epidemiological mathematical model, with application to Dengue. Qualitative analysis of the model is carried out to highlight threshold values that shape the overall dynamics of the system. We show that vector elimination is possible only when Nɛ<1, where N is the basic-offspring number related to the targeted wild population. To ensure the success of SIT control, we recommend that the issue of residual fertility be addressed as a priority and then that contamination by sterile females be minimized with each release.

Sterile insect technique with accidental releases of sterile females. Impact on mosquito-borne diseases control when viruses are circulating.

The sterile insect technique (SIT) is a technique to control some vectors of diseases by releasing sterile males. However, during these releases, sterilized females can be (accidentally) released and since only females are vectors of diseases, it is important to study their impact when arthropod viruses are circulating. To that aim, we develop and study an entomological-epidemiological model, considering either permanent or periodic releases. Qualitative analyses of the continuous and periodic models are conducted. We highlight a critical sterile males release rate, ΛMcrit, above which the control of wild population is always effective, using massive releases. Estimating the basic reproduction number of the epidemiological model, R02, we show that if it is above a certain threshold, R0,∗2, that depends on the basic offspring number, N, and the release rate of sterile females, the epidemiological risk can only be controlled using (very) massive releases. Otherwise, we can estimate the basic reproduction number of the SIT epidemiological model, R0,SIT2, that shapes the stability property of the (periodic) disease-free equilibrium. We show that it might be possible to take R0,SIT2 below 1 using non-massive, but large enough, releases. However, practically, it seems more efficient to consider massive releases, followed by small releases once the vector population is small enough. In addition to SIT, we also recommend mechanical control, i.e. the reduction of breeding sites, that greatly improves the efficacy of SIT, in terms of duration or size of the releases. Our results reveal that outside an epidemic period, the release of sterile females is not an issue, as long as the sterile males release rate is greater than ΛMcrit. Within an epidemic period, we show that sterile females releases do not really impact the SIT efficiency, as long as the release rate, ΛF, is lower than a critical value, ΛFcrit, that depends on the mosquito and epidemiological threshold parameters, N, and R02. To illustrate numerically our theoretical results, we consider Dengue parameters. We estimate all thresholds and also the effective reproduction number, Reff2, and highlight the importance of early permanent or periodic SIT control to prevent or mitigate the risk of a Dengue epidemic, with and without sterile females releases.

Antimicrobial susceptibility profiles of anaerobic bacteria, isolated from human clinical specimens, within different European and surrounding countries. A joint ESGAI study.

OBJECTIVES: Studies on the antimicrobial susceptibility profile of anaerobic bacteria are underrepresented in the literature. Within this study we aim to give an extensive overview of the differences in antimicrobial susceptibility profiles between different European and surrounding countries. METHODS: Minimal inhibitory concentration (MIC) data of different antibiotics were collected from 10 participating laboratories, representing an equal number of countries. All MIC's were determined using Etest, according to the protocol used by the participating laboratory. Anaerobic genera represented by at least 10 clinical isolates were included in the study. RESULTS: Each country tested different antibiotics, sometimes depending on the kind of infection and/or the anaerobic species isolated. All countries tested clindamycin and metronidazole. Resistance rates differed remarkably between the different countries. Especially in Kuwait, resistance was high for all tested antibiotics. Unexpected metronidazole resistance was observed for Finegoldia magna isolates, Peptoniphilus isolates and Eggerthella lenta isolates. CONCLUSIONS: Due to the extensive differences in antimicrobial susceptibility profile of anaerobic bacteria isolated within different countries, we strongly recommend to perform this kind of study on a regular basis.

FORTE - a multipurpose high-vacuum diffractometer for tender X-ray diffraction and spectroscopy at the SIRIUS beamline of Synchrotron SOLEIL.

A new high-vacuum multipurpose diffractometer (called FORTE from the French acronyms of the project) has recently been installed at the tender/hard X-ray SIRIUS beamline of Synchrotron SOLEIL, France. The geometry chosen allows one to work either in the classical Eulerian four-circle geometry for bulk X-ray diffraction (XRD) or in the z-axis geometry for surface XRD. The diffractometer nicely fits the characteristics of the SIRIUS beamline, optimized to work in the 1.1-4.5 keV range, and allows one to perform unprecedented diffraction anomalous fine structure (DAFS) experiments in the tender X-ray region, also around non-specular reflections, covering a large reciprocal-space volume. Installation of an X-ray fluorescence detector on a dedicated flange allows simultaneous DAFS and X-ray absorption (XAS) measurements. The access to the tender X-ray region paves the way to resonant investigations around the L-edges of second-row transition elements which are constituents of functional oxide materials. It also enables access to several edges of interest for semiconductors. Finally, the control architecture based on synchronized Delta Tau units opens up exciting perspectives for improvement of the mechanical sphere of confusion.

Investigation of pre-XDR Beijing Mycobacterium tuberculosis transmission to a healthcare worker in France, 2016.

A case of occupational contamination of a healthcare worker by a pre-extensively drug-resistant (pre-XDR) Beijing strain of Mycobacterium tuberculosis at the University Hospital of Montpellier, France is reported. The index case was identified using genetic fingerprinting of isolates. This report underscores the risk of healthcare-associated contamination by pre-XDR tuberculosis (TB) in low-incidence countries and the importance of molecular tools for TB care. It also calls for increased vigilance in the management of multi-drug-resistant/XDR TB patients.

An impulsive modelling framework of fire occurrence in a size-structured model of tree-grass interactions for savanna ecosystems.

Fires and mean annual rainfall are major factors that regulate woody and grassy biomasses in savanna ecosystems. Within the savanna biome, conditions of long-lasting coexistence of trees and grasses have been often studied using continuous-time modelling of tree-grass competition. In these studies, fire is a time-continuous forcing while the relationship between woody plant size and fire-sensitivity is not systematically considered. In this paper, we propose a new mathematical framework to model tree-grass interactions that takes into account both the impulsive nature of fire occurrence and size-dependent fire sensitivity (via two classes of woody plants). We carry out a qualitative analysis that highlights ecological thresholds and bifurcation parameters that shape the dynamics of the savanna-like systems within the main ecological zones. Through a qualitative analysis, we show that the impulsive modelling of fire occurrences leads to more diverse behaviors including cases of grassland, savanna and forest tristability and a more realistic array of solutions than the analogous time-continuous fire models. Numerical simulations are carried out with respect to the three main ecological contexts (moist, mesic, semi-arid) to illustrate the theoretical results and to support a discussion about the bifurcation parameters and the advantages of the model.

Human behaviors: A threat to mosquito control?

In this work, we consider a simple theoretical model that enables us to take into account private human decisions that may interfere with public mosquito control. The model reflects the trade-off between perceived costs and observed efficacy. Our theoretical results emphasize that households may reduce their protective behavior in response to mechanical elimination techniques piloted by a public agent, leading to an increase in the total number of mosquitoes in the surrounding environment and generating a barrier for vector-borne diseases control. Our study is sufficiently generic to be applied to different arboviral diseases. It also shows that vector-control models and strategies have to take into account individual behaviors.

Genome Sequences of Multiresistant Staphylococcus capitis Pulsotype NRCS-A and Methicillin-Susceptible S. capitis Pulsotype NRCS-C.

Here, we report the draft genome sequences of methicillin-susceptible Staphylococcus captis pulsotype NCRS-C (CR02 strain) and multiresistant Staphylococcus captis pulsotype NCRS-A (CR07 strain).

Direct evidence of Fe(2+)-Fe3+ charge ordering in the ferrimagnetic hematite-ilmenite Fe(1.35)Ti(0.65)O(3-δ) thin films.

In this Letter we highlight direct experimental evidence of Fe(2+)-Fe3+ charge ordering at room temperature in hematite-ilmenite Fe(1.35)Ti(0.65)O(3-δ) epitaxial thin films grown by pulsed laser deposition, using aberration-corrected scanning transmission electron microscopy coupled to high-resolution energy electron-loss spectroscopy. These advanced spectromicroscopy techniques demonstrate a strong modulation of the Fe2+ valence state along the c axis. Density functional theory calculations provide crucial information on the key role of oxygen vacancies in the observed charge distributions. Their presence at significant levels leads to the localization of extra electrons onto reduced Fe2+ sites, while Ti remains solely +4. The magnetic and transport properties of these films are reviewed in the light of the present results regarding their ferrimagnetic character correlated with the Fe2+ modulation and their semiconducting behavior interpreted by an Efros-Shklovskii variable-range hopping conduction regime via Fe2+ and Fe3+ centers. The experimental evidence of only one type of mixed valence state, i.e., Fe2+ and Fe3+, in the Fe(2-x)Ti(x)O(3-δ) system will thus help to interpret further the origin of its geomagnetic properties and to illuminate fundamental issues regarding its spintronic potential.

Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat.

Recent studies from our groups have shown that BIIE0246, a Y2 receptor antagonist, has antidepressant effect in olfactory bulbectomized (OBX) rat. However, its complex structure and high molecular weight limit its usefulness as an in vivo pharmacological tool. Alternatively, the novel and brain penetrant Y2 receptor antagonist, JNJ-31020028 is a useful tool to investigate the in vivo function of the Y2 receptor. In the present study, we evaluated the effect of chronic intracerebroventricular (icv) administration of JNJ-31020028 in a battery of behavioral tests in an animal model that mimics several deficits observed in the human depression, the OBX rat. Chronic administration of JNJ-31020028 induced a decrease in immobility time in the forced swim test in OBX while had no effect in control animals. Additionally, it decreased number of grooming events in OBX animals, but had no effects on some other behavioral deficits observed such as rearing and hyperlocomotion. Furthermore, JNJ-31020028 had no effect on behavior tests that are commonly used to evaluate anxiety, namely the social interaction test in both OBX and control animals. These data indicate that similar to BIIE0246, JNJ-31020028 also has antidepressant like effects in the OBX model.

Mathematical studies on the sterile insect technique for the Chikungunya disease and Aedes albopictus.

Chikungunya is an arthropod-borne disease caused by the Asian tiger mosquito, Aedes albopictus. It can be an important burden to public health and a great cause of morbidity and, sometimes, mortality. Understanding if and when disease control measures should be taken is key to curtail its spread. Dumont and Chiroleu (Math Biosc Eng 7(2):315-348, 2010) showed that the use of chemical control tools such as adulticide and larvicide, and mechanical control, which consists of reducing the breeding sites, would have been useful to control the explosive 2006 epidemic in Réunion Island. Despite this, chemical control tools cannot be of long-time use, because they can induce mosquito resistance, and are detrimental to the biodiversity. It is therefore necessary to develop and test new control tools that are more sustainable, with the same efficacy (if possible). Mathematical models of sterile insect technique (SIT) to prevent, reduce, eliminate or stop an epidemic of Chikungunya are formulated and analysed. In particular, we propose a new model that considers pulsed periodic releases, which leads to a hybrid dynamical system. This pulsed SIT model is coupled with the human population at different epidemiological states in order to assess its efficacy. Numerical simulations for the pulsed SIT, using an appropriate numerical scheme are provided. Analytical and numerical results indicate that pulsed SIT with small and frequent releases can be an alternative to chemical control tools, but only if it is used or applied early after the beginning of the epidemic or as a preventive tool.

On nonstandard finite difference schemes in biosciences.

We design, analyze and implement nonstandard finite difference (NSFD) schemes for some differential models in biosciences. The NSFD schemes are reliable in three directions. They are topologically dynamically consistent for onedimensional models. They can replicate the global asymptotic stability of the disease-free equilibrium of the MSEIR model in epidemiology whenever the basic reproduction number is less than 1. They preserve the positivity and boundedness property of solutions of advection-reaction and reaction-diffusion equations.

On a temporal model for the Chikungunya disease: modeling, theory and numerics.

Reunion Island faced two episodes of Chikungunya, a vector-borne disease, in 2005 and in 2006. The latter was of unprecedented magnitude: one third of the population was infected. Until the severe episode of 2006, our knowledge of Chikungunya was very limited. The principal aim of our study is to propose a model, including human and mosquito compartments, that is associated to the time course of the first epidemic of Chikungunya. By computing the basic reproduction number R(0), we show there exists a disease-free equilibrium that is locally asymptotically stable if the basic reproduction number is less than 1. Moreover, we give a necessary condition for global asymptotic stability of the disease-free equilibrium. Then, we propose a numerical scheme that is qualitatively stable and present several simulations as well as numerical estimates of the basic reproduction number for some cities of Reunion Island. For the episode of 2005, R(0) was less than one, which partly explains why no outbreak appeared. Using recent entomological results, we investigate links between the episode of 2005 and the outbreak of 2006. Finally, our work shows that R(0) varied from place to place on the island, indicating that quick and focused interventions, like the destruction of breeding sites, may be effective for controlling the disease.

Neuropeptide y: role in emotion and alcohol dependence.

Neuropeptide Y (NPY) is considered to be an important neuromodulator in the regulation of emotional behavior. For example, NPY is consistently involved in anxiety-related behaviors and there is increasing support for a role of this peptide in mood disorders such as depression. Furthermore, recent evidence suggests that NPY has a significant role in the neurobiological response to alcohol, including alcohol consumption, dependence, and withdrawal. In addition, NPY is beginning to emerge as an important modulator in the etiology of alcoholism that is independent from the addictive and reinforcing properties of the traditional system commonly associated with dopamine and instead, is strongly associated with innate emotionality. The recent developments elucidating the role of NPY in emotion and alcohol dependence are reviewed and the potential of the NPY system as a novel therapeutic strategy in the treatment of anxiety, depression and alcohol-related disorders is examined.

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia.

Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 muCi of iodinated LPS ((125)I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). (125)I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-alpha, IL-1beta and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1beta was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.

Blood pressure-independent effect of angiotensin AT1 receptor blockade on renal endothelin-1 production in hypertensive uremic rats.

OBJECTIVE: We recently reported that treatment of uremic rats with reduced renal mass with the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist losartan reduces endothelin-1 (ET-1) levels in blood vessels and in glomeruli. Although this suggests an important role for Ang II in the modulation of ET-1 production, the concomitant decrease in blood pressure may also be involved. The present study was designed to investigate whether the modulation of ET-1 production in uremic rats is related to tissue-specific effects of AT1 receptor blockade or to the antihypertensive effect of losartan. DESIGN: One week after renal mass reduction, uremic rats were treated with the conventional triple therapy (TRx) [reserpine (5 mg/l), hydralazine (80 mg/l) and hydrochlorothiazide (25 mg/l)] or losartan (20 mg/kg per day) for 6 weeks. Immunoreactive-ET-1 (ir-ET-1) levels in plasma and urine, as well as in vascular and renal tissues were measured by a specific radioimmunoassay after sample extraction and purification. RESULTS: Before treatment, systolic blood pressure was significantly higher in uremic animals compared to sham-operated controls (165+/-4 versus 123+/-2 mmHg, respectively; P < 0.01). Treatment with the TRx or with losartan normalized systolic blood pressure in uremic rats, whereas it was further increased in untreated uremic animals. At week 6, serum creatinine, proteinuria and urinary ET-1 and transforming growth factor-beta1 (TGF-beta1) excretion, as well as vascular and glomerular ET-1 content were increased in uremic rats compared to the controls (P < 0.01). Treatment of uremic rats with the TRx or with losartan reduced ET-1 content in the thoracic aorta and the mesenteric arterial bed (P < 0.01). However, losartan, but not the TRx, significantly attenuated the rise of serum creatinine, proteinuria and urinary ET-1 and TGF-beta1 excretion, as well as ET-1 content in glomeruli of uremic rats. Compared with the controls, renal preproET-1 mRNA expression was also significantly higher in uremic rats. Treatment of uremic rats with losartan prevented renal preproET-1 mRNA overexpression, indicating that changes in glomerular ET-1 content and urinary ET-1 excretion were related to modulation of renal ET-1 production. CONCLUSIONS: These findings indicate that the effect of losartan on ET-1 production in peripheral blood vessels may be mediated, in part, by the reduction of blood pressure. In contrast, the reduction of renal ET-1 production is mediated by tissue-specific effects of AT1 receptor blockade, and may contribute to the renal protective effects of losartan.

Autoradiographic distribution of adrenomedullin receptors in the rat brain.

The autoradiographic distribution of putative brain adrenomedullin receptors was investigated using [125I]human adrenomedullin(13-52) as a new radioligand. Specific [125I]human adrenomedullin(13-52) binding sites were very discretely distributed in the rat brain with enrichment seen in the choroid plexus and linings of the third, fourth and lateral ventricles, basolateral amygdaloid nuclei, neural lobe of the pituitary gland, the trigeminal nerves and in the granular cell layer of the cerebellum. To our knowledge, this is the first report on the discrete localization of adrenomedullin receptors in the mammalian brain.

Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226.

Neuropeptide FF (NPFF) is a part of a neurotransmitter system acting as a modulator of endogenous opioid functions. At this time, no non-peptide or peptide NPFF-antagonists have been discovered. Here, we demonstrate that Neuropeptide Y (NPY) ligands, in fact possess significant ability to interact with the human NPFF(2) receptors. NPY Y(1) antagonist BIBP3226 and mixed Y(1) antagonist/Y(4) agonist GR231118 are able to displace with low affinity, 50 -- 100 nM, the specific binding on NPFF receptors expressed in CHO cells as well as in rat dorsal spinal cord, an affinity however superior to those determined against Y(2), Y(4) or Y(5) receptors. Furthermore, BIBP3226 which is unable to inhibit the forskolin-stimulated cyclic AMP production mediated by NPFF(2) receptors, antagonizes the effect of NPFF, revealing the first antagonist of NPFF receptors. These properties of NPY ligands on Neuropeptide FF receptors must be considered when evaluating pharmacological activities of these drugs.

Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats.

BACKGROUND: We documented recently that increased endothelin-1 (ET-1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET-1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure. We investigated whether supplementation with L-arginine, the natural precursor of NO, improves NO synthesis in uraemic rats with reduced renal mass and modulates vascular and renal ET-1 production as well as blood pressure and renal failure progression. METHODS: One week after surgical renal mass reduction, the uraemic and sham-operated animals received either no treatment or 0.1% L-arginine in drinking water for 5 weeks. In another series of experiments, uraemic rats received 1% L-arginine for 5 weeks. Immunoreactive-ET-1 (ir-ET-1) levels in plasma, urine, and vascular and renal tissue preparations was measured by radioimmunoassay after sample extraction and purification. RESULTS: Before treatment, systolic blood pressure was significantly elevated in uraemic animals compared to sham-operated controls (156+/-7 vs 111+/-3 mmHg, respectively; P<0.01). Thereafter, systolic blood pressure increased further in uraemic-untreated rats (systolic blood pressure at week 5; 199+/-9 mmHg, P<0.01), whereas it remained similar in uraemic rats supplemented with 0.1% L-arginine (171+/-9 mmHg, NS). At the end of the study, serum creatinine and urea, proteinuria and ir-ET-1 excretion were significantly augmented, while creatinine clearance was reduced in uraemic animals compared to the controls. Ir-ET-1 level was also increased in glomeruli as well as in thoracic aorta, mesenteric arterial bed, and pre-glomerular arteries, and was associated with vascular hypertrophy as assessed by tissue weight. In contrast, ir-ET-1 level was diminished in the renal papilla of uraemic rats. Treatment with 0.1% L-arginine significantly reduced proteinuria and urinary ir-ET-1 excretion (P<0.05) as well as ir-ET-1 level in glomeruli (P<0.01) and in thoracic aorta (P<0.05). These changes were associated with increased plasma NO metabolites NO2/NO3 levels in L-arginine-treated animals (P<0.01) and reduced aortic hypertrophy (P<0.05). In contrast, supplementation with 1% L-arginine had no effect on systolic blood pressure in uraemic rats, but exacerbated proteinuria and urinary ir-ET-1 excretion and increased serum urea (P<0.05) were observed. CONCLUSIONS: These results indicate that improvement of NO release with a low dose but not with a high dose of L-arginine significantly attenuates the development of hypertension and the progression of renal insufficiency in rats with reduced renal mass. These protective effects may be mediated in part by the reduction of vascular and renal ET-1 production.

The molecular pharmacology of CGRP and related peptide receptor subtypes.

Calcitonin gene-related peptides (alpha and beta isoforms), better known as CGRPalpha and CGRPbeta, were isolated twenty years ago. In fact, these were the first peptides to be characterized using a molecular cloning strategy, which is not the traditional approach of biochemical extraction and purification. Paradoxically, progress in the characterization of CGRP receptor subtypes has been extremely slow as a result of difficulties in their cloning and the lack of selective receptor subtype agonists and antagonists. However, exciting progress has been made overthe pasttwo years and is briefly reviewed here.