HEIDI: an experiment-management platform enabling high-throughput fragment and compound screening.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.

Fast fragment and compound screening pipeline at the Swiss Light Source.

Crystallography-based fragment screening is a highly effective technique employed in structure-based drug discovery to expand the range of lead development opportunities. It allows screening and sorting of weakly binding, low molecular mass fragments, which can be developed into larger high-affinity lead compounds. Technical improvements at synchrotron beamlines, design of innovative libraries mapping chemical space efficiently, effective soaking methods and enhanced data analysis have enabled the implementation of high-throughput fragment screening pipelines at multiple synchrotron facilities.

Fast fragment- and compound-screening pipeline at the Swiss Light Source.

Over the last two decades, fragment-based drug discovery (FBDD) has emerged as an effective and efficient method to identify new chemical scaffolds for the development of lead compounds. X-ray crystallography can be used in FBDD as a tool to validate and develop fragments identified as binders by other methods. However, it is also often used with great success as a primary screening technique.

A Sodium-Translocating Module Linking Succinate Production to Formation of Membrane Potential in Prevotella bryantii.

Ruminants such as cattle and sheep depend on the breakdown of carbohydrates from plant-based feedstuff, which is accomplished by the microbial community in the rumen. Roughly 40% of the members of the rumen microbiota belong to the family , which ferments sugars to organic acids such as acetate, propionate, and succinate. These substrates are important nutrients for the ruminant.

Community pharmacist-administered seasonal influenza vaccination: a national customer survey.

Background: In Switzerland, the influenza vaccination is recommended for high-risk groups and people who have contact with high-risk groups. Since 2015, Swiss pharmacists are allowed to vaccinate healthy adults after acquiring a certificate of competence for vaccination and blood sampling techniques. We aimed to assess customers of the seasonal influenza vaccination in pharmacies in regard to their satisfaction, motivation, and reasons.

Concise Synthesis of 1,4-Benzoquinone-Based Natural Products as Mitochondrial Complex I Substrates and Substrate-Based Inhibitors.

A short, efficient one-step synthesis of 2-methyl-5-(3-methyl-2-butenyl)-1,4-benzoquinone, a natural product from Pyrola media is described. The synthesis is based on a direct late C-H functionalization of the quinone scaffold. The formation of the natural product was confirmed by means of 2D-NMR spectroscopy.

Full-Thickness Skin Grafts and Quilting Sutures for the Reconstruction of Internal Nasal Lining.

Restoration of the inner nasal lining is an essential factor in successful nasal reconstruction. Among various methods, free full-thickness skin grafting represents a readily available and feasible technique. A prerequisite for success is a secure and immobile fixation to the undersurface of the nourishing forehead flap.

Warhead biosynthesis and the origin of structural diversity in hydroxamate metalloproteinase inhibitors.

Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the chelation of metal ions in the catalytic center of target enzymes. Actinonin and matlystatins are  potent metalloproteinase inhibitors that comprise rare N-hydroxy-2-pentyl-succinamic acid warheads. Here we report the identification and characterization of their biosynthetic pathways.

[Histone deacetylase inhibitors: new synergistic third-line option in multiple myeloma].

Despite advances in drug therapy of the orphan disease multiple myeloma, patients relapse or become refractory to first-line therapy, and the disease remains incurable. Therefore, histone deacetylase inhibitors have emerged as a new class of anti-myeloma drugs, with synergistic results on progression free survival when given in combination to current first-line therapy. Histone deacetylase inhibitors influence gene expression of target genes.

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations.

Background: Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).

Aim: To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.

Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen.

The generation of effective immune responses by mucosal vaccination without the use of inflammatory adjuvants, that compromise the epithelial barrier and recruit new cellular targets, is a key goal of vaccines designed to protect against sexually acquired pathogens. In the present study we use a model HIV antigen (CN54gp140) conjugated to transferrin (Tf) and evaluate the ability of the natural transferrin receptor CD71 to modulate immunity. We show that the conjugated transferrin retained high affinity for its receptor and that the conjugate was specifically transported across an epithelial barrier, co-localizing with MHC Class II(+) cells in the sub-mucosal stroma.

Preanesthetic medication with rectal midazolam in children undergoing dental extractions.

Three different dosages (0.25, 0.35, and 0.

Paradoxical reactions to rectal midazolam as premedication in children.

Eighty healthy children, between the ages of 2 and 7 years, who were to undergo oral surgical procedures under general anaesthesia, were allocated randomly to 4 groups. Three groups received rectal midazolam, and the other group a placebo (saline) as premedication 30 min prior to induction of anaesthesia. Group A children received midazolam 0.