Engaging the public or asking your friends? Analysing science-related crowdfunding using behavioural and survey data.

Science-related crowdfunding enables public engagement with science. However, we know little about citizens engaging with science this way: Who are the people engaging with and donating to science through crowdfunding - and how do they decide how much to give? This study analyses behavioural and survey data from the Swiss crowdfunding platform ( = 576). Results illustrate that a small, non-representative segment of the public engages with science through crowdfunding.

Biocatalytic production of bicyclic β-lactams with three contiguous chiral centres using engineered crotonases.

There is a need to develop asymmetric routes to functionalised β-lactams, which remain the most important group of antibacterials. Here we describe biocatalytic and protein engineering studies concerning carbapenem biosynthesis enzymes, aiming to enable stereoselective production of functionalised carbapenams with three contiguous chiral centres. Structurally-guided substitutions of wildtype carboxymethylproline synthases enable tuning of their C-N and C-C bond forming capacity to produce 5-carboxymethylproline derivatives substituted at C-4 and C-6, from amino acid aldehyde and malonyl-CoA derivatives.

Colon capsule versus computed tomography colonography for colorectal cancer screening in patients with positive fecal occult blood test who refuse colonoscopy: a randomized trial.

Objective: Some patients (10 % - 32 %) with a positive guaiac fecal occult blood test (gFOBT) do not undergo the recommended colonoscopy. The aim of this study was to compare video capsule endoscopy (VCE) and computed tomography colonography (CTC) in terms of participation rate and detection outcomes when offered to patients with a positive gFOBT who did not undergo the recommended colonoscopy.

Methods: An invitation letter offering CTC or VCE was sent to selected patients after randomization.

BeerDeCoded: the open beer metagenome project.

Next generation sequencing has radically changed research in the life sciences, in both academic and corporate laboratories. The potential impact is tremendous, yet a majority of citizens have little or no understanding of the technological and ethical aspects of this widespread adoption. We designed BeerDeCoded as a pretext to discuss the societal issues related to genomic and metagenomic data with fellow citizens, while advancing scientific knowledge of the most popular beverage of all.

TIE-2-expressing monocytes are lymphangiogenic and associate specifically with lymphatics of human breast cancer.

In experimental mouse models of cancer, increasingly compelling evidence point toward a contribution of tumor associated macrophages (TAM) to tumor lymphangiogenesis. Corresponding experimental observations in human cancer remain scarce although lymphatic metastasis is widely recognized as a predominant route for tumor spread. We previously showed that, in malignant tumors of untreated breast cancer (BC) patients, TIE-2-expressing monocytes (TEM) are highly proangiogenic immunosuppressive cells and that TIE-2 and VEGFR signaling pathways drive TEM immunosuppressive function.

Homogeneous time-resolved G protein-coupled receptor-ligand binding assay based on fluorescence cross-correlation spectroscopy.

G protein-coupled receptors (GPCRs) mediate many important physiological functions and are considered as one of the most successful therapeutic target classes for a wide spectrum of diseases. Drug discovery projects generally benefit from a broad range of experimental approaches for screening compound libraries and for the characterization of binding modes of drug candidates. Owing to the difficulties in solubilizing and purifying GPCRs, assay formats have been so far mainly limited to cell-based functional assays and radioligand binding assays.

Studies on the Glutathione-Dependent Formaldehyde-Activating Enzyme from Paracoccus denitrificans.

Formaldehyde is a toxin and carcinogen that is both an environmental pollutant and an endogenous metabolite. Formaldehyde metabolism, which is probably essential for all aerobic cells, likely proceeds via multiple mechanisms, including via a glutathione-dependent pathway that is widely conserved in bacteria, plants and animals. However, it is unclear whether the first step in the glutathione-dependent pathway (i.

Bone marrow-derived cells are implicated as a source of lymphatic endothelial progenitors in human breast cancer.

Bone marrow-derived endothelial progenitor cells (EPCs) infiltrate into sites of neovascularization in adult tissues and mature into functional blood endothelial cells (BECs) during a process called vasculogenesis. Human marrow-derived EPCs have recently been reported to display a mixed myeloid and lymphatic endothelial cell (LEC) phenotype during inflammation-induced angiogenesis; however, their role in cancer remains poorly understood. We report the in vitro differentiation of human cord blood CD133CD34 progenitors into podoplanin cells expressing both myeloid markers (CD11b, CD14) and the canonical LEC markers vascular endothelium growth factor receptor 3 (VEGFR-3), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and prospero homeobox 1 (PROX-1).

Prognostic factors in patients with refractory ascites treated by transjugular intrahepatic porto-systemic shunt: From the liver to the kidney.

Background: The aim of this retrospective study was to evaluate the prognostic value of different scores (including Child-Pugh and Model for End Stage Liver Diseases) in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt for refractory ascites.

Methods: Overall, 111 patients with transjugular intrahepatic porto-systemic shunt insertion between January 1998 and July 2012 were included.

Results: Survival rates (without transplantation) were 82.

Comparison of the substrate selectivity and biochemical properties of human and bacterial γ-butyrobetaine hydroxylase.

2-Oxoglutarate and iron dependent oxygenases have potential for the stereoselective hydroxylation of amino acids and related compounds. The biochemical and kinetic properties of recombinant γ-butyrobetaine hydroxylase from human and Pseudomonas sp. AK1 were compared.

Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases.

Deacetoxycephalosporin C synthase (DAOCS) catalyzes the oxidative ring expansion of penicillin N (penN) to give deacetoxycephalosporin C (DAOC), which is the committed step in the biosynthesis of the clinically important cephalosporin antibiotics. DAOCS belongs to the family of non-heme iron(II) and 2-oxoglutarate (2OG) dependent oxygenases, which have substantially conserved active sites and are proposed to employ a consensus mechanism proceeding via formation of an enzyme·Fe(II)·2OG·substrate ternary complex. Previously reported kinetic and crystallographic studies led to the proposal of an unusual "ping-pong" mechanism for DAOCS, which was significantly different from other members of the 2OG oxygenase superfamily.

Stereoselective preparation of lipidated carboxymethyl-proline/pipecolic acid derivatives via coupling of engineered crotonases with an alkylmalonyl-CoA synthetase.

The trisubstituted enolate- and C-C bond-forming capacities of engineered carboxymethylproline synthases CMPSs are coupled with the malonyl-CoA synthetase MatB to enable stereoselective preparation of 5- and 6-membered N-heterocycles functionalised with alkyl-substituted carboxymethyl side chains, starting from achiral alkyl-substituted malonic acids and L-amino acid semialdehydes. The results illustrate the biocatalytic utility of crotonases in tandem enzyme-catalysed reactions for stereoselective synthesis.

TIE-2 and VEGFR kinase activities drive immunosuppressive function of TIE-2-expressing monocytes in human breast tumors.

Purpose: Tumor-associated TIE-2-expressing monocytes (TEM) are highly proangiogenic cells critical for tumor vascularization. We previously showed that, in human breast cancer, TIE-2 and VEGFR pathways control proangiogenic activity of TEMs. Here, we examine the contribution of these pathways to immunosuppressive activity of TEMs.

The enzymes of β-lactam biosynthesis.

The β-lactam antibiotics and related β-lactamase inhibitors are amongst the most important small molecules in clinical use. Most, but not all, β-lactams including penicillins, cephalosporins, and clavulanic acid are produced via fermentation or via modification of fermented intermediates, with important exceptions being the carbapenems and aztreonam. The desire for more efficient routes to existing antibiotics and for access to new and synthetically challenging ones stimulates continued interest in β-lactam biosynthesis.

γ-Butyrobetaine hydroxylase catalyses a Stevens type rearrangement.

γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II)-dependent oxygenase that catalyses the final step of L-carnitine biosynthesis in animals. BBOX catalyses the oxidation of 3-(2,2,2-trimethylhydrazinium)propionate (THP), a clinically used BBOX inhibitor, to form multiple products including 3-amino-4-(methyamino)butanoic acid (AMBA), which is proposed to be formed via a Stevens type rearrangement mechanism. We report the synthesis of AMBA and confirm that it is a product of the BBOX catalysed oxidation of THP.

Crotonase catalysis enables flexible production of functionalized prolines and carbapenams.

The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase.

Structural and mechanistic studies on γ-butyrobetaine hydroxylase.

The final step in carnitine biosynthesis is catalyzed by γ-butyrobetaine (γBB) hydroxylase (BBOX), an iron/2-oxoglutarate (2OG) dependent oxygenase. BBOX is inhibited by trimethylhydrazine-propionate (THP), a clinically used compound. We report structural and mechanistic studies on BBOX and its reaction with THP.

Right-sided posttraumatic diaphragmatic rupture and delayed hepatic hernia.

The early diagnosis of posttraumatic diaphragmatic lesions is often difficult which explains the 30 to 50% of non diagnosed cases. This is due to the lack of sensitivity and specificity of the radiographic exams. Missed diaphragmatic lesions results in herniation of abdominal contents into the chest and may be revealed many years from the time of the original trauma.

[Multiple gastro-intestinal stromal tumors (GIST) in a patient with type I neurofibromatosis revealed by chronic bleeding: pre-operative radiological diagnosis].

Recent studies have pointed out a high incidence of GIST, usually multiple and of small intestinal location, in patients with type I neurofibromatosis. We here report an additional case, revealed by chronic gastro-intestinal bleeding and diagnosed at pre-operative imaging studies. A 56-year-old patient, with known type I neurofibromatosis, was referred to our department for the exploration of chronic gastro-intestinal bleeding during anti-aggregant therapy.

Prevalence of anal incontinence in adults and impact on quality-of-life.

Objective: To investigate the prevalence of anal incontinence in the general population and in patients consulting gastroenterologist and gynecologist practices in the Rhône Alpes area.

Methods: For the first study a questionnaire was sent to a sample of 2800 people selected randomly from the electoral roll. Another study of patients selected randomly among patients attending gynecology and gastroenterology consultations was performed.