Transient postnatal over nutrition induces long-term alterations in cardiac NLRP3-inflammasome pathway.

BACKGROUND AND AIMS: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice. METHODS AND RESULTS: Based on a model of mice exposed to PNOF through litter size reduction, we observed increased cardiac protein expression levels of NLRP3 and ETS-1 associated with alterations in insulin signaling. Additionally, miR-193b levels were down-regulated in the adult hearts of overfed animals. In a cardiomyocyte cell line, transfection with miR-193b induced down-regulation of ETS-1 and NLRP3 and improved insulin signaling. CONCLUSIONS: These findings suggest that the miR-193b could be involved in cardiac phenotypic changes observed in adulthood induced by PNOF likely through the regulation of ETS-1 and NLRP3 expression, and through this of insulin signaling.

The Brucella suis IbpA heat-shock chaperone is not required for virulence or for expression of the VirB type IV secretion system VirB8 protein.

UNLABELLED: Brucella suis, facultative intracellular bacterial pathogen of mammals, and Agrobacterium tumefaciens, a plant pathogen, both use a VirB type IV secretion system (T4SS) to translocate effector molecules into host cells. HspL, an α-crystalline-type small heat-shock protein, acts as a chaperone for the Agrobacterium VirB8 protein, an essential component of the VirB system. An Agrobacterium mutant lacking hspL is attenuated due to a misfunctional T4SS. We have investigated whether IbpA (BRA0051), the Brucella HspL homologue, plays a similar role. Unlike HspL, IbpA does not interact with VirB8, and an IbpA mutant shows full virulence and no defect in VirB expression. These data show that the Brucella α-crystalline-type small heat-shock protein IbpA is not required for Brucella virulence. SIGNIFICANCE AND IMPACT OF STUDY: Many bacteria use type IV secretion systems (T4SS), multi-protein machines, to translocate DNA and protein substrates across their envelope. Understanding how T4SS function is important as they play major roles in the spread of plasmids carrying antibiotic resistance and in pathogenicity. In the plant pathogen Agrobacterium tumefaciens, HspL, an α-crystalline-type small heat-shock protein, acts as a chaperone for the essential type IV secretion system component VirB8. Here, we show that this is not the case for all T4SS; in the zoonotic pathogen Brucella suis, IbpA, the protein most related to HspL, does not play this role.

Draft genome sequence of Citreicella aestuarii strain 357, a member of the Roseobacter clade isolated without xenobiotic pressure from a petroleum-polluted beach.

Citreicella aestuarii 357 is a member of the Roseobacter clade that was isolated without xenobiotic pressure from an oil-polluted sand sample from the Galician coast (Spain). Its genome sequence suggests an organoheterotrophic metabolism, including a wide catabolic potential for aromatic hydrocarbons.

Intrauterine growth restriction: Clinical consequences on health and disease at adulthood.

Intrauterine growth restriction (IUGR) affects 10-15% of all pregnancies worldwide. IUGR may result from maternal, placental or fetal origin. Maternal malnutrition before and during pregnancy represents the most prevalent non-genetic or placental cause. IUGR reflects an abnormal adaptive fetal growth in a deleterious environment. Individuals born after IUGR are more susceptible to develop diseases related to subsequent stressors through a lifetime. Animal models help to decipher the underlying causes of dysregulated pathways and molecular modifications conditioning health and disease in adult offspring born after IUGR. The aim of this review is to summarize current knowledge on long term consequences of IUGR, integrating animal models and human studies for a better care of IUGR-born individuals in a life course perspective.

Delineation of cellular stages and identification of key proteins for reduction and biotransformation of Se(IV) by Stenotrophomonas bentonitica BII-R7.

The widespread use of selenium (Se) in technological applications (e.g., solar cells and electronic devices) has led to an accumulation of this metalloid in the environment to toxic levels. The newly described bacterial strain Stenotrophomonas bentonitica BII-R7 has been demonstrated to reduce mobile Se(IV) to Se(0)-nanoparticles (Se(0)NPs) and volatile species. Amorphous Se-nanospheres are reported to aggregate to form crystalline nanostructures and trigonal selenium. We investigated the molecular mechanisms underlying the biotransformation of Se(IV) to less toxic forms using differential shotgun proteomics analysis of S. bentonitica BII-R7 grown with or without sodium selenite for three different time-points. Results showed an increase in the abundance of several proteins involved in Se(IV) reduction and stabilization of Se(0)NPs, such as glutathione reductase, in bacteria grown with Se(IV), in addition to many proteins with transport functions, including RND (resistance-nodulation-division) systems, possibly facilitating Se uptake. Notably proteins involved in oxidative stress defense (e.g., catalase/peroxidase HPI) were also induced by Se exposure. Electron microscopy analyses confirmed the biotransformation of amorphous nanospheres to trigonal Se. Overall, our results highlight the potential of S. bentonitica in reducing the bioavailability of Se, which provides a basis both for the development of bioremediation strategies and the eco-friendly synthesis of biotechnological nanomaterials.

[Systematic family screening in case of infant pertussis]. / Dépistage familial systématique dans la coqueluche du nourrisson.

The origin of contamination in pertussis of young infants is generally the close relatives. From 2000 to 2004, only serology and culture were available in our hospital. The families of 16 young infants (age below one year) hospitalized for pertussis were screened using serological tests: 21/48 contacts were positive. After 2004, PCR was available for exploration of index cases and families: 35/85 contacts were positive. Of the mothers tested 23/46 were positive compared to 14/41 fathers. Only one parent presented with a typical paroxystic pertussis cough, 60% presented with a nonparoxystic cough having lasted for more than five days and 40% of positive adults did not present with cough. Despite official recommendations, none of these young parents had received an antipertussis booster vaccination. This study shows the high frequency of atypical or nonsymptomatic pertussis in adults in the close family of infected young infants. These adults contribute to spreading the disease.

Identification, expression, and endocrine-disruption of three ecdysone-responsive genes in the sentinel species Gammarus fossarum.

Taking advantage of a large transcriptomic dataset recently obtained in the sentinel crustacean amphipod Gammarus fossarum, we developed an approach based on sequence similarity and phylogenetic reconstruction to identify key players involved in the endocrine regulation of G. fossarum. Our work identified three genes of interest: the nuclear receptors RXR and E75, and the regulator broad-complex (BR). Their involvement in the regulation of molting and reproduction, along with their sensitivity to chemical contamination were experimentally assessed by studying gene expression during the female reproductive cycle, and after laboratory exposure to model endocrine disrupting compounds (EDCs): pyriproxyfen, tebufenozide and piperonyl butoxide. RXR expression suggested a role of this gene in ecdysis and post-molting processes. E75 presented two expression peaks that suggested a role in vitellogenesis, and molting. BR expression showed no variation during molting/reproductive cycle. After exposure to the three EDCs, a strong inhibition of the inter-molt E75 peak was observed with tebufenozide, and an induction of RXR after exposure to pyriproxyfen and piperonyl butoxide. These results confirm the implication of RXR and E75 in hormonal regulation of female reproductive cycles in G. fossarum and their sensitivity towards EDCs opens the possibility of using them as specific endocrine disruption biomarkers.

Effect of early postnatal nutrition on chronic kidney disease and arterial hypertension in adulthood: a narrative review.

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin-angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Pertussis in young infants: apnoea and intra-familial infection.

This study investigated 41 infants, aged <4 months, who were hospitalised with symptoms compatible with pertussis. Of these, 16 had Bordetella pertussis infection confirmed by real-time PCR. For four of these 16 patients, the initial sample was PCR-negative, but samples collected 5-7 days after the onset of infection were PCR-positive. PCR was also positive with samples from 15/16 families and 20/41 household contacts. Nine of the 20 positive household contacts were asymptomatic. Among the 16 infants with proven pertussis, apnoea was more frequent than in a control group for whom PCR was negative with both children and household contacts (69% vs. 28%). It was concluded that real-time PCR performed with samples from household contacts facilitates the diagnosis of infants suspected clinically of having pertussis, thereby enabling earlier treatment.

[Simultaneous outbreaks of rotavirus and respiratory syncytial virus in Paris: a 12-year survey]. / Coïncidence des épidémies de rotavirus et de virus respiratoire syncytial à Paris: 12 ans de surveillance.

OBJECTIVE: The authors had for aim to study the coincidence of RSV and rotavirus epidemic peaks in pediatric patients hospitalized in the Paris area. METHODOLOGY: A retrospective hospital-based monocentric cohort study was made over a 12-year period (1993-2004). Clinical and laboratory findings were prospectively collected on admission. RESULTS: Three thousand and four hundred ninety-six stool samples were positive for rotavirus; 3,507 nasopharyngeal aspirates were positive for RSV. The coincidence of epidemic peaks for both viruses in November, December, and January was observed during the 12 years of the study. CONCLUSION: The exact coincidence of winter outbreaks of RSV and rotavirus is a characteristic of the Paris area. It contributes to increase overcrowding in pediatric units and nosocomial infections.

Reannotation of Genomes by Means of Proteomics Data.

Omics approaches have become popular in biology as powerful discovery tools, and currently gain in interest for diagnostic applications. Establishing the accurate genome sequence of any organism is easy, but the outcome of its annotation by means of automatic pipelines remains imprecise. Some protein-encoding genes may be missed as soon as they are specific and poorly conserved in a given taxon, while important to explain the specific traits of the organism. Translational starts are also poorly predicted in a relatively important number of cases, thus impacting the protein sequence database used in proteomics, comparative genomics, and systems biology. The use of high-throughput proteomics data to improve genome annotation is an attractive option to obtain a more comprehensive molecular picture of a given organism. Here, protocols for reannotating prokaryote genomes are described based on shotgun proteomics and derivatization of protein N-termini with a positively charged reagent coupled to high-resolution tandem mass spectrometry.

Exoproteomics of Pathogens: Analysis of Toxins and Other Virulence Factors by Proteomics.

Pathogens are known to release in their environment a large range of toxins and other virulence factors. Their pathogenicity relies on this arsenal of exoproteins and their orchestrated release upon changing environmental conditions. Exoproteomics aims at describing and quantifying the proteins found outside of the cells, thus takes advantage of the most recent methodologies of next-generation proteomics. This approach has been applied with great success to a variety of pathogens increasing the fundamental knowledge on pathogenicity. In this chapter, we describe how the exoproteome should be prepared and handled for high-throughput identification of exoproteins and their quantitation by label-free shotgun proteomics. We also mentioned some bioinformatics tools for extracting information such as toxin similarity search.

Assessing the relevance of a multiplexed methodology for proteomic biomarker measurement in the invertebrate species Gammarus fossarum: A physiological and ecotoxicological study.

Recently, a protein sequence database was built specifically for the sentinel non-model species Gammarus fossarum using a proteogenomics approach. A quantitative multiplexed targeted proteomics assay (using Selected Reaction Monitoring mass spectrometry) was then developed for a fast and simultaneous quantification of dozens of biomarker peptides specific of this freshwater sentinel crustacean species. In order to assess the relevance of this breakthrough methodology in ecotoxicology, the response patterns of a panel of 26 peptides reporting for 20 proteins from the Gammarus fossarum proteome with putative key functional roles (homeostasis, osmoregulation, nutrition, reproduction, molting,…) were recorded through male and female reproductive cycles and after exposure to environmental concentrations of cadmium and lead in laboratory-controlled conditions. Based on these results, we validated the implication of annotated vtg-like peptides in the oogenesis process, and the implication of Na+/K+ ATPase proteins in the molt cycle of organisms. Upon metal (cadmium and lead) contamination, peptides belonging to proteins annotated as involved in antioxidant and detoxification functions, immunity and molting were significantly down-regulated. Overall, this multiplex assay allowed gaining relevant insights upon disruption of different main functions in the sentinel species Gammarus fossarum. This breakthrough methodology in ecotoxicology offers a valid and high throughput alternative to currently used protocols, paving the way for future practical applications of proteogenomics-derived protein biomarkers in chemical risk assessment and environmental monitoring.

Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches.

Individuals born after intrauterine growth restriction (IUGR) have an increased risk of perinatal morbidity/mortality, and those who survive face long-term consequences such as cardiovascular-related diseases, including systemic hypertension, atherosclerosis, coronary heart disease and chronic kidney disease. In addition to the demonstrated long-term effects of decreased nephron endowment and hyperactivity of the hypothalamic-pituitary-adrenal axis, individuals born after IUGR also exhibit early alterations in vascular structure and function, which have been identified as key factors of the development of cardiovascular-related diseases. The endothelium plays a major role in maintaining vascular function and homeostasis. Therefore, it is not surprising that impaired endothelial function can lead to the long-term development of vascular-related diseases. Endothelial dysfunction, particularly impaired endothelium-dependent vasodilation and vascular remodeling, involves decreased nitric oxide (NO) bioavailability, impaired endothelial NO synthase functionality, increased oxidative stress, endothelial progenitor cells dysfunction and accelerated vascular senescence. Preventive approaches such as breastfeeding, supplementation with folate, vitamins, antioxidants, L-citrulline, L-arginine and treatment with NO modulators represent promising strategies for improving endothelial function, mitigating long-term outcomes and possibly preventing IUGR of vascular origin. Moreover, the identification of early biomarkers of endothelial dysfunction, especially epigenetic biomarkers, could allow early screening and follow-up of individuals at risk of developing cardiovascular and renal diseases, thus contributing to the development of preventive and therapeutic strategies to avert the long-term effects of endothelial dysfunction in infants born after IUGR.

Experimental separation steps influence the protein content of corona around mesoporous silica nanoparticles.

In order to direct nanocarriers to their targets efficiently, we have to understand the interactions occurring at the nano-bio interface between nanocarriers and human proteins, which forms the layer called the corona. However, experiments aiming to identify and quantify the proteins in the corona, especially critical steps in the separation of nanoparticles from biological media may affect the corona composition. Here, we used nano-LC MS/MS to compare the protein corona contents obtained after using two different separation methods. We showed that applying centrifugation versus magnetization to isolate nanoparticles surrounded by a corona resulted in protein loss and a reshuffling of their respective abundances.

[Medication errors in pediatric inpatients: a multicentric prospective study]. / Erreurs de prescription médicamenteuse en pédiatrie hospitalière: enquête prospective multicentrique. Implications pour la prévention.

OBJECTIVE: To improve the knowledge of medication errors in paediatrics: rate of occurrence, error characteristics, risk factors. PATIENTS AND METHODS: Our prospective study included nine uninformed teaching paediatric wards (general paediatrics, emergency departments, intensive care units) using a describing questionnaire built from medical reports analysis (event description, medical issues, contributing personal and structural factors) during a two-months period. RESULTS: Seventy-five questionnaires were collected and analysed. Medical errors reported concerned prescription: 21 cases and administration: 45 cases. Ten errors led to adverse effects. An attributable factor was noted in 39 cases. Concerning prescription errors, no respect to protocol: 11 cases, lack of knowledge: 3 cases, personal communication failure: 3 cases were noted. Concerning administration errors, human mistakes (lack of experience, miscommunication, calculation error): 8 cases, unclear prescription: 6 cases and system flaws: 6 cases were noted. Several attribuable causes were reported in 8 cases. CONCLUSIONS: Medication errors in paediatrics inpatients are common and contributing factors intricated. Paediatricians should help hospitals develop effective programs for safety providing medications, reporting medication errors, errors analysis strategy and creating a safe environment of medication for all hospitalised paediatric patients.

Production of a full length Tat protein in E. coli and its purification.

A full length tat gene was constructed by a combination of polymerase chain reaction (PCR) for the first exon and chemical synthesis for the second exon. This gene was expressed in E. coli under the control of the strongly regulated araB promoter, either directly or fused to a secretion signal encoding sequence. We then defined a rapid, three-step procedure for the purification of the Tat protein.

[Sudden death and chronic cardiac insufficiency]. / Mort subite et insuffisance cardiaque chronique.

Sudden death accounts for about 35% of the mortality of cardiac failure and its incidence does not decrease with the use of angiotensin converting enzyme inhibitors. Non-sustained ventricular tachycardia on Holter monitoring, late ventricular potentials and tachycardia induced by programmed ventricular stimulation have no formal predictive value of sudden death, underlining the varied character of the mechanisms underlying sudden death during cardiac failure. Sustained ventricular tachycardia degenerating to ventricular fibrillation is only one of the rhythmic factors implicated together with inaugural ventricular fibrillation, bradyarrhythmias and electromechanical dissociation. The underlying cardiac disease plays a role in the initiation of the fatal arrhythmia. In coronary artery disease, recurrent acute ischaemia is the principal trigger factor in patients who often have triple vessel disease. This explains the fact that classic markers of arrhythmia in the post-infarction period, which are only the reflection of the arrhythmogenic substrate of ventricular tachycardia, usually due to reentry around the fibrous scar of the infarct, are not valid in patients with progressive ischaemic cardiomyopathy. The most effective antiarrhythmic treatment in this type of patient is the prevention of ischaemia, when possible. In primary dilated cardiomyopathy, the mechanism underlying sudden death could be different at each stage. In NYHA Stages I and II, ventricular tachyarrhythmias could play a major part in unexpected sudden death in patients whose stable haemodynamic status suggested a more prolonged survival. The value of an implantable defibrillator would seem to be proved in this group of patients, at least in secondary prevention. In Stages III and IV, ventricular arrhythmias only indicate the degree of ventricular dysfunction and sudden death may follow bradyarrhythmias and electromechanical dissociation due to the precarious haemodynamic status.

[Enterocolitis as a complication of late-diagnosed Hirschsprung disease]. / Entérocolite compliquant une maladie de Hirschsprung diagnostiquée tardivement.

Enterocolitis is the most serious complication of Hirschsprung disease. Early management of these patients can decrease the severity of this complication. Hirschsprung disease is more common in patients with trisomy 21 than in the general population. Furthermore, the risk of developing enterocolitis is higher in this population. We report on an infant with trisomy 21 who developed enterocolitis as a complication of Hirschsprung disease that was diagnosed late when the infant presented with septic shock leading to death of the patient.