Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study.

Background & Aims: Teduglutide, a GLP-2-analog, has proven effective in two placebo-controlled studies in reducing parenteral support (PS) in patients with short bowel syndrome-associated intestinal failure (SBS-IF) after 24 weeks. The aim of this study was to describe in a real-life situation the effects of teduglutide treatment and their predictive factors.

Methods: We included 54 consecutive SBS-IF patients treated with teduglutide in France for at least 6 months from 10 expert centers.

Responses to climatic and pathogen threats differ in biodynamic and conventional vines.

Viticulture is of high socio-economic importance; however, its prevalent practices severely impact the environment and human health, and criticisms from society are raising. Vine managements systems are further challenged by climatic changes. Of the 8 million hectares grown worldwide, conventional and organic practices cover 90% and 9% of acreage, respectively.

Extracellular peptidase hunting for improvement of protein production in plant cells and roots.

Plant-based recombinant protein production systems have gained an extensive interest over the past few years, because of their reduced cost and relative safety. Although the first products are now reaching the market, progress are still needed to improve plant hosts and strategies for biopharming. Targeting recombinant proteins toward the extracellular space offers several advantages in terms of protein folding and purification, but degradation events are observed, due to endogenous peptidases.

Modeling strategies for pharmaceutical blend monitoring and end-point determination by near-infrared spectroscopy.

The implementation of a blend monitoring and control method based on a process analytical technology such as near infrared spectroscopy requires the selection and optimization of numerous criteria that will affect the monitoring outputs and expected blend end-point. Using a five component formulation, the present article contrasts the modeling strategies and end-point determination of a traditional quantitative method based on the prediction of the blend parameters employing partial least-squares regression with a qualitative strategy based on principal component analysis and Hotelling's T(2) and residual distance to the model, called Prototype. The possibility to monitor and control blend homogeneity with multivariate curve resolution was also assessed.

Modulation of the expression of ABC transporters in murine (J774) macrophages exposed to large concentrations of the fluoroquinolone antibiotic moxifloxacin.

Long-term exposure to pharmacological agents can select for cells that overexpress efflux transporters. We previously showed that mouse J774 macrophages cultivated for a prolonged period of time with toxic concentrations of the fluoroquinolone ciprofloxacin overexpress the efflux transporter Mrp4 and display a reduced accumulation of this antibiotic, but no change in the accumulation of moxifloxacin, a closely related molecule (Antimicrob. Agents Chemother.

ATP Binding Cassette transporters associated with chemoresistance: transcriptional profiling in extreme cohorts and their prognostic impact in a cohort of 281 acute myeloid leukemia patients.

Background: A major issue in the treatment of acute myeloid leukemia is resistance to chemotherapeutic drugs. An increasing number of ATP-Binding-Cassette transporters have been demonstrated to cause resistance to cancer drugs. The aim of this study was to highlight the putative role of other ATP-Binding-Cassette transporters in primary chemoresistant acute myeloid leukemia.

Sensor calibration models for a non-invasive blood glucose measurement sensor.

A calibration model was developed for a noninvasive blood glucose sensor, to determine how the blood glucose data measured by this sensor is related to blood glucose data measured with laboratory capillary finger sticks and to corrupting noise. The variability of calibration models for different patients was analyzed as well as the dynamics of the non-invasive blood glucose sensor according to reference blood glucose measurements and corrupting noise.

Endoscopic video manifolds.

Postprocedural analysis of gastrointestinal (GI) endoscopic videos is a difficult task because the videos often suffer from a large number of poor-quality frames due to the motion or out-of-focus blur, specular highlights and artefacts caused by turbid fluid inside the GI tract. Clinically, each frame of the video is examined individually by the endoscopic expert due to the lack of a suitable visualisation technique. In this work, we introduce a low dimensional representation of endoscopic videos based on a manifold learning approach.

New inhibitors of prion replication that target the amyloid precursor.

At present, there is no effective therapy for any of the neurodegenerative amyloidoses, despite renewed efforts to identify compounds active against the various implicated pathogenetic molecules. We have screened a library of 2960 natural and synthetic compounds in two cell lines chronically infected with mouse prions, and have identified eight new inhibitors of prion replication in vitro. They belong to two distinct chemical families that have not previously been recognised as effective in the field of transmissible spongiform encephalopathies: seven are 3-aminosteroids and one is a derivative of erythromycin A with an oxime functionality.

A new access to dihydrotropones through ring expansion of spirocyclohexadienones: synthesis and mechanism.

In this paper we report the rearrangement of spirocyclohexadienones into dihydrotropones in basic conditions as a new method for the preparation of seven-membered ring ketones, which are key building blocks for the synthesis of tropoloalkaloids. DFT calculations and deuterium labeling studies support the mechanism we propose for this rearrangement, involving the ring opening of a spirocyclopropane intermediate followed by successive base-catalyzed 1,3-hydrogen shifts. The X-ray structure of the resulting dihydrotropone shows near-perfect planarity and the conjugation gain is likely to be the driving force of the reaction.

A simple genetic algorithm for the optimization of multidomain protein homology models driven by NMR residual dipolar coupling and small angle X-ray scattering data.

Most proteins comprise several domains and/or participate in functional complexes. Owing to ongoing structural genomic projects, it is likely that it will soon be possible to predict, with reasonable accuracy, the conserved regions of most structural domains. Under these circumstances, it will be important to have methods, based on simple-to-acquire experimental data, that allow to build and refine structures of multi-domain proteins or of protein complexes from homology models of the individual domains/proteins.

Evidence for an association of high levels of endogenous Acetyl-Ser-Asp-Lys-Pro, a potent mediator of angiogenesis, with acute myeloid leukemia development.

Evidence from clinical and laboratory studies suggests that angiogenesis is important in the progression of solid tumours and hematologic malignancies. We have shown that the naturally occurring tetrapeptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a potent angiogenic factor normally present at nanomolar concentrations in the blood. A murine leukemia model was used to assess whether there was a correlation between levels of endogenous AcSDKP and the development of disease.

Indicators to assess temporal genetic diversity in the French Catalogue: no losses for maize and peas.

The aim of this study, led by the GEVES (Research and Control Group for Varieties and Seeds), was to suggest indicators to assess the diversity available to farmers since the French Official Catalogue for Plant Varieties and Species was initiated. The largest datasets of 1990 inbred maize lines and 578 pea lines from the last 50 years were analysed using morphological and enzymatic parameters. Lines were grouped into three to five periods.

Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site.

Human multidrug resistance protein 1 (MRP1) is a membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 contributes to chemotherapy failure by exporting a wide range of anti-cancer drugs when over expressed in the plasma membrane of cells. Here, we report the first high-resolution crystal structure of human MRP1-NBD1.

Operating characteristics of the Finapress system to predict elevated left ventricular filling pressure.

Background: Dyspnea is a common symptom and can be caused by many different conditions. The detection of congestive heart failure (CHF) is sometimes difficult.

Hypothesis: The pulse amplitude ratio (PAR) measured by the Finapress procedure during a Valsalva maneuver can detect elevated left ventricular end-diastolic pressure (LVEDP) accurately over a wide range of values.

[Cystic fibrosis: chemical drugs to cure genetic diseases].

Cystic Fibrosis is the most common lethal genetic disease among Caucasian population. Despite considerable efforts, no significant progress has been so far achieved by gene therapies approaches. On the basis of a surprising clinical observation, we have developed an approach using anti-cancer drugs promoting the over expression of ABC transporters closely related to the deficient protein CFTR, which seem able to share functions with it and to restore the missing function(s).

Attempts to characterize the NBD heterodimer of MRP1: transient complex formation involves Gly771 of the ABC signature sequence but does not enhance the intrinsic ATPase activity.

MRP1 (multidrug-resistance-associated protein 1; also known as ABCC1) is a member of the human ABC (ATP-binding cassette) transporter superfamily that confers cell resistance to chemotherapeutic agents. Considering the structural and functional similarities to the other ABC proteins, the interaction between its two NBDs (nucleotide-binding domains), NBD1 (N-terminal NBD) and NBD2 (C-terminal NBD), is proposed to be essential for the regulation of the ATP-binding/ATP-hydrolysis cycle of MRP1. We were interested in the ability of recombinant NBD1 and NBD2 to interact with each other and to influence ATPase activity.

Genetic diversity within Pisum sativum using protein- and PCR-based markers.

A collection of 148 Pisum accessions, mostly from Western Europe, and including both primitive germplasm and cultivated types, was structured using 121 protein- and PCR-based markers. This molecular marker-based classification allowed us to trace back major lineages of pea breeding in Western Europe over the last decades, and to follow the main breeding objectives: increase of seed weight, introduction of the afila foliage type and white flowers, and improvement of frost tolerance for winter-sown peas. The classification was largely consistent with the available pedigree data, and clearly resolved the different main varietal types according to their end-uses (fodder, food and feed peas) from exotic types and wild forms.

Characterization of Saccharomyces cerevisiae Ras1p and chimaeric constructs of Ras proteins reveals the hypervariable region and farnesylation as critical elements in the adenylyl cyclase signaling pathway.

Ras1p and Ras2p, from Saccharomyces cerevisiae, are GTP-binding proteins that are essential elements in the signaling cascade leading to the activation of adenylyl cyclase. To overcome proteolytic activities that have hampered biochemical studies of Ras1p so far, its gene was genetically modified after which full-length Ras1p could be obtained. The interaction of farnesylated and unprenylated Ras1p with guanine nucleotides, guanine nucleotide exchange factors, GTPase activating proteins, and adenylyl cyclase was compared to Ras2p and human Ha-Ras interactions.

Grass consensus STS markers: an efficient approach for detecting polymorphism in Lolium.

For ryegrass and many forage crops, characterization of varieties is often difficult for two reasons: few of discriminant morphological traits and a great within-varieties variation. Futhermore, few molecular markers are publicly accessible. In this paper we describe two approaches for the development of 42 sequence-tagged-site (STS) markers.

Biochemical characterization and NMR studies of the nucleotide-binding domain 1 of multidrug-resistance-associated protein 1: evidence for interaction between ATP and Trp653.

Multidrug-resistance-associated protein 1 (MRP1/ABCC1) is a human ATP-binding cassette transporter that confers cell resistance to antitumour drugs. Its NBDs (nucleotide-binding domains) bind/hydrolyse ATP, a key step in the activation of MRP1 function. To relate its intrinsic functional features to the mechanism of action of the full-size transporter, we expressed the N-terminal NBD1 domain (Asn(642) to Ser(871)) in Escherichia coli.

Homology modeling and calculation of the cobalt cluster charges of the Encephazlitozoon cuniculi methionine aminopeptidase, a potential target for drug design.

Fumagillin is a potent anti-angiogenic drug used in cancer treatments. It is also one of the few molecules active against the Enterocytozoon and Encephalitozoon parasites responsible for various clinical syndromes in HIV-infected or immunosuppressive treated patients. Its toxicity, however, makes desirable the design of more specific molecules.

New system for positive selection of recombinant plasmids and dual expression in yeast and bacteria based on the restriction ribonuclease RegB.

By coupling the toxic restriction endoribonuclease RegB, from the bacteriophage T4, to the prokaryotic T7 and the eukaryotic GAL1 promoters, we constructed a two-function plasmid called pTOXR-1. This plasmid is a zero-background cloning vector. It allows an efficient positive selection of recombinant plasmids without the need to completely digest, dephosphorylate, or purify the vector prior to the ligation step.

An insight into the role of human pancreatic lithostathine.

Human lithostathine was initially isolated from pancreatic stones in patients with alcoholic calcifying chronic pancreatitis. It is secreted into the pancreatic juice where it was believed to inhibit stone formation. The N-terminal undecapeptide was assumed to play an important role in the mechanism, by adsorption to the crystal surface.