ing patients at increased risk of relapse.The genome packaging motor of tailed bacteriophages and herpesviruses is a powerful nanomachine built by several copies of a large (TerL) and a small (TerS) terminase subunit. The motor assembles transiently at the portal vertex of an empty precursor capsid (or procapsid) to power genome encapsidation. Terminase subunits have been studied in-depth, especially in classical bacteriophages that infect Escherichia coli or Salmonella, yet, less is known about the packaging motor of Pseudomonas-phages that have increasing biomedical relevance. Here, we investigated the small terminase subunit from three Podoviridae phages that infect Pseudomonas aeruginosa. We found TerS is polymorphic in solution but assembles into a nonamer in its high-affinity heparin-binding conformation. The atomic structure of Pseudomonas phage PaP3 TerS, the first complete structure for a TerS from a cos phage, reveals nine helix-turn-helix (HTH) motifs asymmetrically arranged around a β-stranded channel, too narrow to accommodate DNA. PaP3 TerS binds DNA in a sequence-specific manner in vitro. X-ray scattering and molecular modeling suggest TerS adopts an open conformation in solution, characterized by dynamic HTHs that move around an oligomerization core, generating discrete binding crevices for DNA. We propose a model for sequence-specific recognition of packaging initiation sites by lateral interdigitation of DNA.

Nontraditional combination of existing therapies is often the only option to avoid surgery in refractory inflammatory bowel disease (IBD) patients. We aim to assess the efficacy and safety of concomitant use of 2 biologic therapies or combination of biologic and tofacitinib in a refractory pediatric IBD cohort.

As part of an ongoing single-center observational cohort study of therapeutic outcomes in pediatric IBD patients (younger than 18 years), data were collected for patients receiving dual therapy. Primary outcome was 6 months of steroid-free remission. Secondary outcomes included time to steroid-free remission, change in serum biomarkers (C-reactive protein and erythrocyte sedimentation rate) and albumin between baseline and 6 months, and adverse events.

Sixteen children (9 ulcerative colitis/IBD-unspecified, 7 Crohn’s disease), with a disease duration of 3 (2.1-5.0) years, initiated dual therapy at an age of 15.9 (13.5-16.8) years after failing ≥2 biologic therapies. Nine (56%) were treated with vy data observed.Peptide-drug conjugates are organic molecules composed of (i) a small drug molecule, (ii) a peptide and (iii) a linker. The drug molecule is mandatory for the biological action, however, its efficacy can be enhanced by targeted delivery, which often also reduces unwanted side effects. For site-specificity the peptide part is mainly responsible. The linker attaches chemically the drug to the peptide, but it could also be biodegradable which ensures controlled liberation of the small drug. Despite the importance of the field, there is no public comprehensive database on these species. Herein we describe ConjuPepBD, a freely available, fully annotated and manually curated database of peptide drug conjugates. ConjuPepDB contains basic information about the entries, e.g. CAS number. Furthermore, it also implies their biomedical application and the type of chemical conjugation employed. It covers more than 1600 conjugates from ∼230 publications. The web-interface is user-friendly, intuitive, and useable on several devices, e.g. phones, tablets, PCs. The webpage allows the user to search for content using numerous criteria, chemical structure and a help page is also provided. Besides giving quick insight for newcomers, ConjuPepDB is hoped to be also helpful for researchers from various related fields. The database is accessible at https//conjupepdb.ttk.hu/.

Cucumbers found in retail markets are often waxed to improve visual appeal and retard moisture loss. This waxing may affect bacterial survival, and the waxing process may facilitate cross-contamination between cucumbers. This study assessed the survival of Salmonella on waxed and unwaxed cucumbers and the potential for Salmonella cross-contamination during the waxing process. Fresh waxed or unwaxed cucumbers were spot inoculated with a cocktail of Salmonella enterica strains. Three different wax coatings (mineral oil, vegetable oil, or petroleum wax) were manually applied to unwaxed cucumbers using polyethylene brushes. Salmonella transfer from inoculated cucumbers to the brush or to uninoculated cucumbers was quantified. Higher Salmonella concentrations were observed on waxed cucumbers during the first 3 days of storage, but the final concentration on unwaxed cucumbers was higher than on waxed cucumbers at the end of storage, regardless of storage temperature. The wax formulation did affect the survival of Salmonella inoculated directly into waxes, with a significant decline in Salmonella populations observed in vegetable-based wax coating but with populations unchanged over 7 days at 7 or 21°C in mineral oil-based and petroleum-based waxes. Salmonella cells could transfer from inoculated unwaxed cucumbers to brushes used for waxing and then to uninoculated cucumbers during waxing. A significantly higher log percentage of transfer to brushes was observed when cucumbers were waxed with vegetable oil (0.71 log percent, P = 0.00441) than with mineral oil (0.06 log percent) or petroleum (0.05 log percent). Transfer to uninoculated cucumbers via brushes was also quantified (0.18 to 0.35 log percent transfer). GSK2578215A manufacturer Salmonella remaining on contaminated cucumbers after waxing could be detected for up to 7 days, and Salmonella survived better on cucumbers treated with a petroleum-based wax. These findings should be useful in managing the risk of Salmonella contamination in cucumbers during postharvest handling.

HbVar (http//globin.bx.psu.edu/hbvar) is a widely-used locus-specific database (LSDB) launched 20 years ago by a multi-center academic effort to provide timely information on the numerous genomic variants leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Here, we report several advances for the database. We made clinically relevant updates of HbVar, implemented as additional querying options in the HbVar query page, allowing the user to explore the clinical phenotype of compound heterozygous patients. We also made significant improvements to the HbVar front page, making comparative data querying, analysis and output more user-friendly. We continued to expand and enrich the regular data content, involving 1820 variants, 230 of which are new entries. We also increased the querying potential and expanded the usefulness of HbVar database in the clinical setting. These several additions, expansions and updates should improve the utility of HbVar both for the globin research community and in a clinical setting.