A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonyl) benzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m- sulfamoylbenzamide analogues

Molecular priming as an approach to induce tolerance against abiotic and oxidative stresses in crop plants

Abiotic stresses, including drought, salinity, extreme temperature, and pollutants, are the main cause of crop losses worldwide. Novel climate-adapted crops and stress tolerance-enhancing compounds are needed increasingly to counteract the negative effects of unfavorable stressful environments. A number of natural products and synthetic chemicals can protect model and crop plants against abiotic stresses through the ectopic induction of molecular and physiological defense mechanisms, a process known as molecular priming. In addition to their stress-protective effect, some of these compounds can also stimulate plant growth. Here, we provide an overview of the known physiological and molecular mechanisms behind the compounds that induce molecular priming, together with a survey of approaches to discover and functionally study new stress-alleviating chemicals

Petroselinic acid purification and its use for the fermentation of new sophorolipids

Petroselinic acid, a positional isomer of oleic acid, was isolated from the vegetable oil of Coriandrum sativum fruits. This uncommon fatty acid was subsequently used as substrate for sophorolipid fermentation with a Starmerella bombicola lactone esterase overexpression (oe sble) strain. A petroselinic acid based diacetylated sophorolipid lactone was obtained in high purity without incorporation of de novo synthesized fatty acids such as oleic acid. A total production of 40 g/L was obtained. The petroselinic acid based sophorolipid lactone was subsequently hydrolyzed towards the petroselinic acid based sophorolipid acid. For both compounds, their critical micelle concentration (CMC) and corresponding surface tension were compared to their oleic acid based counterparts. Both petroselinic acid based sophorolipids displayed a much lower CMC value than their oleic acid based counterparts, although their minimal surface tension was the same. Besides, the sophorolipid fermentation product was chemically modified towards a novel C12 sophorolipid aldehyde. This derivative constitutes an interesting building block for further modification towards new-to-nature sophorolipids with high potential for self-assembly applications

Chemical genetics approach identifies abnormal inflorescence meristem 1 as a putative target of a novel sulfonamide that protects catalase2-deficient Arabidopsis against photorespiratory stress

Alterations of hydrogen peroxide (H2O2) levels have a profound impact on numerous signaling cascades orchestrating plant growth, development, and stress signaling, including programmed cell death. To expand the repertoire of known molecular mechanisms implicated in H2O2 signaling, we performed a forward chemical screen to identify small molecules that could alleviate the photorespiratory-induced cell death phenotype of Arabidopsisthaliana mutants lacking H2O2-scavenging capacity by peroxisomal catalase2. Here, we report the characterization of pakerine, an m-sulfamoyl benzamide from the sulfonamide family. Pakerine alleviates the cell death phenotype of cat2 mutants exposed to photorespiration-promoting conditions and delays dark-induced senescence in wild-type Arabidopsis leaves. By using a combination of transcriptomics, metabolomics, and affinity purification, we identified abnormal inflorescence meristem 1 (AIM1) as a putative protein target of pakerine. AIM1 is a 3-hydroxyacyl-CoA dehydrogenase involved in fatty acid β-oxidation that contributes to jasmonic acid (JA) and salicylic acid (SA) biosynthesis. Whereas intact JA biosynthesis was not required for pakerine bioactivity, our results point toward a role for β-oxidation-dependent SA production in the execution of H2O2-mediated cell death

Loss-of-Function Variants in EFEMP1 Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations

Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in EFEMP1. Hence, we identified EFEMP1 as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT.</jats:p

Model-Based Design to Enhance Neotissue Formation in Additively Manufactured Calcium-Phosphate-Based Scaffolds

peer reviewedIn biomaterial-based bone tissue engineering, optimizing scaffold structure and composition remains an active field of research. Additive manufacturing has enabled the production of custom designs in a variety of materials. This study aims to improve the design of calcium-phosphatebased additively manufactured scaffolds, the material of choice in oral bone regeneration, by using a combination of in silico and in vitro tools. Computer models are increasingly used to assist in design optimization by providing a rational way of merging different requirements into a single design. The starting point for this study was an in-house developed in silico model describing the in vitro formation of neotissue, i.e., cells and the extracellular matrix they produced. The level set method was applied to simulate the interface between the neotissue and the void space inside the scaffold pores. In order to calibrate the model, a custom disk-shaped scaffold was produced with prismatic canals of different geometries (circle, hexagon, square, triangle) and inner diameters (0.5 mm, 0.7 mm, 1 mm, 2 mm). The disks were produced with three biomaterials (hydroxyapatite, tricalcium phosphate, and a blend of both). After seeding with skeletal progenitor cells and a cell culture for up to 21 days, the extent of neotissue growth in the disks’ canals was analyzed using fluorescence microscopy. The results clearly demonstrated that in the presence of calcium-phosphate-based materials, the curvature-based growth principle was maintained. Bayesian optimization was used to determine the model parameters for the different biomaterials used. Subsequently, the calibrated model was used to predict neotissue growth in a 3D gyroid structure. The predicted results were in line with the experimentally obtained ones, demonstrating the potential of the calibrated model to be used as a tool in the design and optimization of 3D-printed calcium-phosphate-based biomaterials for bone regeneration

NHG-guideline acute cough

Acute cough is one of the most common reasons for patients to visit a general practitioner. In this revised guideline acute cough is defined as cough lasting less than 3 weeks at presentation. The guideline covers the diagnosis, treatment, and education of patients with cough, pneumonia, bronchiolitis, croup, whooping cough, and Q-fever. It is important to distinguish an uncomplicated respiratory tract infection from a complicated respiratory tract infection that requires antibiotic treatment. In most cases, cough is caused by an uncomplicated respiratory tract infection (viral or bacterial) A patient with an uncomplicated respiratory tract infection has no risk factors for complications (age &gt; 3 months and &lt; 75 years, no relevant comorbidity), is not very ill, doesn't have signs of a complicated respiratory tract infection and has a fever &lt; 7 days. The symptoms (cough) can last up to 4 weeks. There is no effective therapy. There are two groups of patients with a complicated respiratory tract infection. 1 Patients with a pneumonia (severely ill [tachypnea, tachycardia, hypotension or confusion] OR moderately ill and one-sided auscultatory findings, CRP &gt; 100 mg/l [a CRP of 20-100 mg/l doesn't exclude a pneumonia, [management depends on presentation and risk-factors], infiltrate on chest X-ray or sick &gt; 7 days with fever and a cough). These patients are prescribed an antibiotic. 2 Patients with other risk factors for complications (age &lt; 3 months or &gt; 75 years and/or relevant comorbidity [in children cardial and pulmonary disease not being astma, in adults congestive heart failure, severe chronic obstructive pulmonary disease, diabetes mellitus, neurological disorders, severe renal failure, compromised immunity]). In these patients, the decision to prescribe antibiotics is based on the presentation, supported, if necessary, by measurement of CRP. Specific management recommendations are made for croup, bronchiolitis and whooping cough. In cases of moderate croup, a single dose of corticosteroid (e.g. dexamethasone, 0.15 mg/kg, oral or intramuscular, or 2 mg of nebulized budesonide) should be given. Mild croup is self-limiting; children with severe croup should be referred to a paediatrician. Children with bronchiolitis and dyspnoea should be monitored regularly during the first few days. Use of medication has not proven to be effective. In whooping cough antibiotics might be useful in preventing secondary cases only Additional investigations should be performed if there is suspicion of whooping cough in a patient from a family with unvaccinated or incomplete vaccinated children younger than 1 year or with a pregnant woman of more than 34 weeks gestation. Main changes to the previous issue of these guidelines: - The measurement of C-reactive protein can help differentiate between pneumonia and mild respiratory tract infection in moderately ill adults with general and/ or local symptoms. This recommendation does not apply to children. - The increasing resistance to doxycyclin and macrolide antibiotics makes amoxicillin (for 5 days) the drug of first choice for pneumonia, with doxycyclin as second choice. Doxycyclin remains the first-choice drug if there is an increased risk of pneumonia caused by Coxiella burnetii (Q-fever) or Legionella. - Because of lack of evidence on the effectiveness of noscapine and codeine and their known side effects these drugs are not recommended.</p

Thermoplastic cassava starch-chitosan bilayer films containing essential oils

[EN] Starch-chitosan bilayer films, containing or not essential oils in the casted chitosan layer were obtained by thermo-compression. Bilayer films exhibited a good interfacial adhesion and better mechanical resistance than starch monolayers, although they were less stretchable and less transparent. Starchchitosan films were effective at controlling the bacterial growth in pork meat, but the thermal treatment applied to obtain the bilayers reduced their antimicrobial properties as compared to chitosan monolayers. The addition of essential oils did not promote any antimicrobial action in chitosan mono and bilayer films applied to pork meat. The final amount of essential oils in the films was very limited probably due to the losses occurred during film processing method. Other strategies to incorporate the essential oils into chitosan-based films should be used to improve their final retention in the film matrix and their effective release into the coated food. (C) 2017 Elsevier Ltd. All rights reserved.The authors acknowledge the financial support provided by the Spanish Ministerio de Economia y Competividad (Projects AGL2013-42989-R and AGL2016-76699-R). Author Cristina Valencia-Sullca thanks the Peruvian Grant National Program (PRONABEC).Valencia-Sullca, CE.; Vargas, M.; Atarés Huerta, LM.; Chiralt, A. (2018). Thermoplastic cassava starch-chitosan bilayer films containing essential oils. Food Hydrocolloids. 75:107-115. https://doi.org/10.1016/j.foodhyd.2017.09.008S1071157