Cryo-EM structures of a LptDE transporter in complex with Pro-macrobodies offer insight into lipopolysaccharide translocation.

Lipopolysaccharides are major constituents of the extracellular leaflet in the bacterial outer membrane and form an effective physical barrier for environmental threats and for antibiotics in Gram-negative bacteria. The last step of LPS insertion via the Lpt pathway is mediated by the LptD/E protein complex. Detailed insights into the architecture of LptDE transporter complexes have been derived from X-ray crystallography.

Synthetic single domain antibodies for the conformational trapping of membrane proteins.

Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies.

[Imaging strategy for children after a first episode of pyelonephritis].

Pyelonephritis is a common bacterial disease in young children and is a serious infection because of its potential to produce renal scarring. One of the concerns of physicians is therefore the diagnosis of uropathy at risk for recurrence of pyelonephritis, especially high-grade reflux. There are no French recommendations on imaging evaluation after a first episode of pyelonephritis.

Real-time monitoring of binding events on a thermostabilized human A2A receptor embedded in a lipid bilayer by surface plasmon resonance.

Membrane proteins (MPs) are prevalent drug discovery targets involved in many cell processes. Despite their high potential as drug targets, the study of MPs has been hindered by limitations in expression, purification and stabilization in order to acquire thermodynamic and kinetic parameters of small molecules binding. These bottlenecks are grounded on the mandatory use of detergents to isolate and extract MPs from the cell plasma membrane and the coexistence of multiple conformations, which reflects biochemical versatility and intrinsic instability of MPs.

Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1.

Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase IIIα (TopIIIα) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIIIα influences it to behave as a hemicatenane dissolvase, rather than as an enzyme that relaxes DNA topology, is unknown.

Randomized trial of oral versus sequential IV/oral antibiotic for acute pyelonephritis in children.

Objective: To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions.

Methods: In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups.

Atomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues.

Pentameric ligand-gated ion channels (pLGICs) are widely expressed in the animal kingdom and are key players of neurotransmission by acetylcholine (ACh), gamma-amminobutyric acid (GABA), glycine and serotonin. It is now established that this family has a prokaryotic origin, since more than 20 homologues have been discovered in bacteria. In particular, the GLIC homologue displays a ligand-gated ion channel function and is activated by protons.

Crystal structure of the extracellular domain of a bacterial ligand-gated ion channel.

The crystal structure of the extracellular domain (ECD) of the pentameric ligand-gated ion-channel from Gloeobacter violaceus (GLIC) was solved at neutral pH at 2.3 A resolution in two crystal forms, showing a surprising hexameric quaternary structure with a 6-fold axis replacing the expected 5-fold axis. While each subunit retains the usual beta-sandwich immunoglobulin-like fold, small deviations from the whole GLIC structure indicate zones of differential flexibility.

Bleeding complications after ritual circumcision: about six children.

Circumcision is the most common surgical procedure in boys. Even if the procedure is frequent, circumcision can have tragic complications. We report the cases of six children, seen over 1 year at the emergency department for bleeding complication or mutilation after ritual home circumcision.

X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.

Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue (GLIC) at pH 4.

A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family.

Ligand-gated ion channels (LGICs) mediate excitatory and inhibitory transmission in the nervous system. Among them, the pentameric or 'Cys-loop' receptors (pLGICs) compose a family that until recently was found in only eukaryotes. Yet a recent genome search identified putative homologues of these proteins in several bacterial species.

[Metered-dose inhaler with spacer vs nebulization for severe and potentially severe acute asthma treatment in the pediatric emergency department].

Objective: To compare treatment with beta 2 agonist delivered either by a spacer device or a nebulizer in children with severe or potentially severe acute asthma.

Methods: In this randomized trial, children 4 to 15 years, cared for in the emergency department for severe or potentially severe acute asthma, received 6 times either nebulizations of salbutamol (0.15mg/kg) or puffs of a beta 2 agonist (salbutamol 50 microg/kg or terbutaline 125 microg/kg).

[Hematemesis in an 11-month-old child: an unusual symptom revealing a foreign body in the stomach].

Ingestion of foreign body has often no consequence. We report on a case in an 11-month-old girl who was referred for mild hematemesis and anorexia. Upper digestive tract endoscopy found a small metallic foreign body in the gastric antrum.

[Oral morphine administration for children's traumatic pain].

Objectives: To study the compliance of prescription, the efficacity and the adverse events of oral morphine used in the pediatric emergency department (ED) in traumatic pains.

Method: This prospective study was conducted in the ED from october 2002 to september 2003. Children aged six months to 16 years with a visual analogic scale (VAS) score higher than 70 or with a traumatic member deformation received oral morphine (0,5 mg/kg).

[Analgesia in the pediatric emergency department].

Pain concerns more than 50% of the children cared in the emergency unit. After evaluation, it has to be cured with drugs adapted to its level and its origin. Residual pain needs therapeutic adjustment.

Steroid-sensitive nephrotic syndrome: from childhood to adulthood.

Background: The clinical presentation, treatment, and outcome of steroid-sensitive nephrotic syndrome (SSNS) during childhood have been extensively studied. Conversely, few data regarding the outcome in adulthood of childhood SSNS have been published previously. We undertook to conduct a retrospective study of the outcome in adulthood of a large cohort of patients diagnosed with an SSNS during childhood.

[Effect of racecadotril in the management of acute diarrhea in infants and children].

Background: The treatment of diarrhoea relies on the maintenance or restoration of hydration with maintenance of an adequate nutritional intake. Racecadotril has been shown to reduce the stools output during acute diarrhoea. The present work was aimed at measuring the number of emergency department visits for acute diarrhoea either the children received racecadotril or not.

[Benefits of ipratropium bromide in the management of asthmatic crises in the emergency department].

Background: To determine if the addition of ipratropium bromide in the emergency department (ED) for the treatment of childhood asthma reduces rates of hospitalization and relapses for moderate and severe exacerbations.

Methods: Patients were given an oral corticosteroid treatment (2 mg/kg) and received every 20 minutes either three nebulizations with albuterol (0.15 mg/kg) and ipratropium bromide (250 micrograms) or six nebulizations with albuterol alone (control group).

[Drugs for pediatric emergencies].

Drugs for pediatric emergencies are useful for respiratory (croup, asthma), cardiologic (hypertensive crisis, acute congestive heart failure, arrhythmias, hypoxic spells), neurologic (seizures), metabolic (dehydration, hypoglycaemia), infectious (meningococcemia) or allergic (anaphylaxis) distresses. Pain management is always important whether to relieve or to prevent the discomfort which would happen during diagnosis or therapeutic procedures.

[Assessing the cost of the first episode of bronchiolitis].

Background: Each year, a quarter of the children younger than 24 months has respiratory syncytial virus bronchiolitis. The morbidity among high-risk infants and the possible association with the development of asthma lead to propose preventive measures whose cost-effectiveness relationship is unknown. The present work was aimed at measuring costs of a first attack of bronchiolitis.

WT1 splice-site mutations are rarely associated with primary steroid-resistant focal and segmental glomerulosclerosis.

Background: Donor splice-site de novo heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) have been reported in Frasier syndrome, which is defined by the association of focal and segmental glomerulosclerosis (FSGS), male pseudohermaphroditism, and gonadoblastoma. These splice-site mutations alter the WT1 alternative splicing leading to two WT1 isoforms, with (+) or without (-) three amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. The aim of this work was to investigate the possibility that some cases of primary steroid-resistant nephrotic syndrome associated with FSGS may be caused by WT1 splice-site mutations.

Mother-to-child transmitted WT1 splice-site mutation is responsible for distinct glomerular diseases.

Mutations in the Wilms' tumor suppressor gene (WT1) are linked with Denys-Drash syndrome (DDS), a rare childhood disease characterized by diffuse mesangial sclerosis and renal failure of early onset, XY pseudohermaphroditism, and high risk of Wilms' tumor. KTS (lysine-threonine-serine) splice site mutations in WT1 intron 9 have been described in patients with Frasier syndrome, another rare syndrome defined by focal and segmental glomerulosclerosis (FSGS), XY pseudohermaphroditism, and frequent occurrence of gonadoblastoma. Cases of Frasier syndrome raise the question whether splice site mutations may also be found in XX females with isolated FSGS.