Creatine and guanidinoacetate reference values in a French population.

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range.

A new strategy for sequential assignment of intrinsically unstructured proteins based on 15N single isotope labelling.

We describe a new efficient strategy for the sequential assignment of amide resonances of a conventional (15)N-(1)H HSQC spectrum of intrinsically unfolded proteins, based on composite NOESY-TOCSY and TOCSY-NOESY mixing times. These composite mixing times lead to a Hα-proton mediated unidirectional transfer of amide to amide proton. We have implemented the composite mixing times in an HSQC-NOESY-HSQC manner to obtain directional connectivity between amides of neighbouring residues.

The identification of MAFB mutations in eight patients with multicentric carpo-tarsal osteolysis supports genetic homogeneity but clinical variability.

Multicentric carpo-tarsal osteolysis (MCTO) with or without nephropathy is a rare osteolysis disorder beginning in early childhood and involving mainly carpal and tarsal bones. Renal disease appears later in life in the majority of cases and evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance has been demonstrated, with a high frequency of sporadic cases.

Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management.

For septic patients, delaying the initiation of antimicrobial therapy or choosing an inappropriate antibiotic can considerably worsen their prognosis. This study evaluated the impact of rapid microbial identification (RMI) from positive blood cultures on the management of patients with suspected sepsis. During a 6-month period, RMI by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for all new episodes of bacteraemia.

Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B.

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures.

Interaction of transportin-SR2 with Ras-related nuclear protein (Ran) GTPase.

The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are capable of infecting non-dividing cells and, therefore, need to be imported into the nucleus before integration into the host cell chromatin. Transportin-SR2 (TRN-SR2, Transportin-3, TNPO3) is a cellular karyopherin implicated in nuclear import of HIV-1. A model in which TRN-SR2 imports the viral preintegration complex into the nucleus is supported by direct interaction between TRN-SR2 and HIV-1 integrase (IN).

An integrated diagnosis strategy for congenital myopathies.

Congenital myopathies are severe muscle disorders affecting adults as well as children in all populations. The diagnosis of congenital myopathies is constrained by strong clinical and genetic heterogeneity. Moreover, the majority of patients present with unspecific histological features, precluding purposive molecular diagnosis and demonstrating the need for an alternative and more efficient diagnostic approach.

Thermodynamics of HIV-1 reverse transcriptase in action elucidates the mechanism of action of non-nucleoside inhibitors.

HIV-1 reverse transcriptase (RT) is a heterodimeric enzyme that converts the genomic viral RNA into proviral DNA. Despite intensive biochemical and structural studies, direct thermodynamic data regarding RT interactions with its substrates are still lacking. Here we addressed the mechanism of action of RT and of non-nucleoside RT inhibitors (NNRTIs) by isothermal titration calorimetry (ITC).

The remarkable conformational plasticity of alpha-synuclein: blessing or curse?

The aggregation of the protein alpha-synuclein (α-SYN) is believed to be a critical event in Parkinson's disease (PD). α-SYN is characterized by a remarkable conformational plasticity, adopting different conformations depending on the environment. In vitro, α-SYN lacks a well-defined structure.

[Primary mucinous carcinoma of the eyelid. Case report].

Primary cutaneous mucinous carcinoma, a tumor of the sweat glands, is a rare tumor localized to the eyelid in 40% of cases. We report a case of a primary cutaneous mucinous carcinoma of the upper eyelid in a 53-year-old Caucasian male who appeared to have a chalazion. Histology showed rows and lobules of epithelial cells with discretely anisonucleotic nuclei and few mitotic figures scattered throughout the tumor cells, surrounded by a mucoid substance.

Variations in catheter-related bloodstream infections rates based on local practices.

Background: Catheter-related bloodstream infection (CRBSI) surveillance serves as a quality improvement measure that is often used to assess performance. We reviewed the total number of microbiological samples collected in three Belgian intensive care units (ICU) in 2009-2010, and we described variations in CRBSI rates based on two factors: microbiological documentation rate and CRBSI definition which includes clinical criterion for coagulase-negative Staphylococcus (CNS) episode.

Findings: CRBSI rates were 2.

Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran sulfate sodium-induced colon carcinogenesis.

Sulfiredoxin (Srx) is the enzyme that reduces the hyperoxidized inactive form of peroxiredoxins. To study the function of Srx in carcinogenesis in vivo, we tested whether loss of Srx protects mice from cancer development. Srx null mice were generated and colon carcinogenesis was induced by an azoxymethane (AOM) and dextran sulfate sodium (DSS) protocol.

[SOS children: from the beginning to this day S. Godinas et M. Gérard].

Child abuse is a major and critical public health concern. We aim to present the "Abused Children Intervention Program" of the National Office for Childcare, and to delineate the current situation, using our recent experience at the Saint-Pierre's Teaching Hospital in Brussels. The SOS Children teams focus on children protection while providing support for abusing parents.

Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms.

A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD). Urine guanidinoacetate (GAA) and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.

Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressors.

Objective: Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular binding partner of HIV-1 integrase and a crucial cofactor for HIV-1 replication. Here, we study two LEDGF/p75 exonic variants I436S and T473I, identified in HIV-1 long-term nonprogressors, together with Q472L.

Methods: In-vitro binding assays, cell culture complementation, and functional rescue.

P2-substituted N-acylprolylpyrrolidine inhibitors of prolyl oligopeptidase: biochemical evaluation, binding mode determination, and assessment in a cellular model of synucleinopathy.

We have investigated the effect of regiospecifically introducing substituents in the P2 part of the typical dipeptide derived basic structure of PREP inhibitors. This hitherto unexplored modification type can be used to improve target affinity, selectivity, and physicochemical parameters in drug discovery programs focusing on PREP inhibitors. Biochemical evaluation of the produced inhibitors identified several substituent types that significantly increase target affinity, thereby reducing the need for an electrophilic "warhead" functionality.

Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.

The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID).

Aberrantly inserted chordae tendineae without significant mitral regurgitation.

Aberrantly inserted chordae tendineae in the left atrial side are a rare find. We report here the case of a young patient with aberrantly inserted chordae tendineae not causing significant mitral regurgitation. Because the patient remained asymptomatic and the anomalous chord of the left atrium could be considered within normal human anatomic variation, the authors decided to only monitor the patient's condition for the time being.

Predictive value of thromboembolic risk scores before an atrial fibrillation ablation procedure.

Introduction: It is not clear whether transesophageal echocardiography (TEE) should be performed prior to a planned atrial fibrillation (AF) ablation in all patients.

Methods And Results: The objectives of this study were to determine in 681 consecutive patients: (i) the relationship between the CHADS2 and CHA2DS2-VASc scores, the presence of a thrombogenic milieu and left atrial (LA) volume; (ii) the need for TEE in patients with low and intermediate thromboembolic risk assessed; and (iii) the predictive accuracy of the these 2 scores for the presence of thrombi in the LA/LAA (LA appendage) before a planned AF ablation. The prevalence of thrombi was 1%.

Bromodomain-dependent stage-specific male genome programming by Brdt.

Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program.

Pre- and postnatal phenotype of 6p25 deletions involving the FOXC1 gene.

FOXC1 deletion, duplication, and mutations are associated with Axenfeld-Rieger anomaly, and Dandy-Walker malformation spectrum. We describe the clinical history, physical findings, and available brain imaging studies in three fetuses, two children, and one adult with 6p25 deletions encompassing FOXC1. Various combinations of ocular and cerebellar malformations were found.

Return to use and performance following exploratory celiotomy for colic in horses: 195 cases (2003-2010).

Reasons For Performing Study: There are few objective data on return to use and performance in horses following colic surgery.

Objective: To investigate return to functional use of horses following colic surgery and factors associated with a negative outcome.

Methods: The North Carolina State University Equine Colic Database was reviewed for horses that underwent exploratory celiotomy for colic (2003-2010).

Nail and phalangeal agenesis in a patient with 4pter and 9pter duplication.

We report on an 8-month-old girl with intra-uterine growth retardation, microcephaly, incomplete cleft lip, axial hypotonia, failure to thrive, and brachydactyly type B (phalangeal agenesis and absence of nails). She carried a supernumerary marker chromosome derived from chromosomes 4 and 9, leading to 4pter-q12 and 9pter-p21.2 duplication.

Design and performance of a combined secondary ion mass spectrometry-scanning probe microscopy instrument for high sensitivity and high-resolution elemental three-dimensional analysis.

State-of-the-art secondary ion mass spectrometry (SIMS) instruments allow producing 3D chemical mappings with excellent sensitivity and spatial resolution. Several important artifacts however arise from the fact that SIMS 3D mapping does not take into account the surface topography of the sample. In order to correct these artifacts, we have integrated a specially developed scanning probe microscopy (SPM) system into a commercial Cameca NanoSIMS 50 instrument.