AMPing Up the Search: A Structural and Functional Repository of Antimicrobial Peptides for Biofilm Studies, and a Case Study of Its Application to Corynebacterium striatum, an Emerging Pathogen

Antimicrobial peptides (AMPs) have been recognized for their ability to target processes important for biofilm formation. Given the vast array of AMPs, identifying potential anti-biofilm candidates remains a significant challenge, and prompts the need for preliminary in silico investigations prior to extensive in vitro and in vivo studies. We have developed Biofilm-AMP (B-AMP), a curated 3D structural and functional repository of AMPs relevant to biofilm studies. In its current version, B-AMP contains predicted 3D structural models of 5544 AMPs (from the DRAMP database) developed using a suite of molecular modeling tools. The repository supports a user-friendly search, using source, name, DRAMP ID, and PepID (unique to B-AMP). Further, AMPs are annotated to existing biofilm literature, consisting of a vast library of over 10,000 articles, enhancing the functional capabilities of B-AMP. To provide an example of the usability of B-AMP, we use the sortase C biofilm target of the emerging pathogen Corynebacterium striatum as a case study. For this, 100 structural AMP models from B-AMP were subject to in silico protein-peptide molecular docking against the catalytic site residues of the C. striatum sortase C protein. Based on docking scores and interacting residues, we suggest a preference scale using which candidate AMPs could be taken up for further in silico, in vitro and in vivo testing. The 3D protein-peptide interaction models and preference scale are available in B-AMP. B-AMP is a comprehensive structural and functional repository of AMPs, and will serve as a starting point for future studies exploring AMPs for biofilm studies. B-AMP is freely available to the community at https://b-amp.karishmakaushiklab.com and will be regularly updated with AMP structures, interaction models with potential biofilm targets, and annotations to biofilm literature.

The PENELOPE Physics Models and Transport Mechanics. Implementation into Geant4

A translation of the penelope physics subroutines to C++, designed as an extension of the Geant4 toolkit, is presented. The Fortran code system penelope performs Monte Carlo simulation of coupled electron-photon transport in arbitrary materials for a wide energy range, nominally from 50 eV up to 1 GeV. Penelope implements the most reliable interaction models that are currently available, limited only by the required generality of the code. In addition, the transport of electrons and positrons is simulated by means of an elaborate class II scheme in which hard interactions (involving deflection angles or energy transfers larger than pre-defined cutoffs) are simulated from the associated restricted differential cross sections. After a brief description of the interaction models adopted for photons and electrons/positrons, we describe the details of the class-II algorithm used for tracking electrons and positrons. The C++ classes are adapted to the specific code structure of Geant4. They provide a complete description of the interactions and transport mechanics of electrons/positrons and photons in arbitrary materials, which can be activated from the G4ProcessManager to produce simulation results equivalent to those from the original penelope programs. The combined code, named PenG4, benefits from the multi-threading capabilities and advanced geometry and statistical tools of Geant4.

Recent highlights from GENIE v3

The release of GENIE v3.0.0 was a major milestone in the long history of the GENIE project, delivering several alternative comprehensive neutrino interaction models, improved charged-lepton scattering simulations, a range of beyond the Standard Model simulation capabilities, improved experimental interfaces, expanded core framework capabilities, and advanced new frameworks for the global analysis of neutrino scattering data and tuning of neutrino interaction models. Steady progress continued following the release of GENIE v3.0.0. New tools and a large number of new physics models, comprehensive model configurations, and tunes have been made publicly available and planned for release in v3.2.0. This article highlights some of the most recent technical and physics developments in the GENIE v3 series.

The geometry of Bayesian programming

We give two geometry of interaction models for a typed λ-calculus with recursion endowed with operators for sampling from a continuous uniform distribution and soft conditioning, namely a paradigmatic calculus for higher-order Bayesian programming. The models are based on the category of measurable spaces and partial measurable functions, and the category of measurable spaces and s-finite kernels, respectively. The former is proved adequate with respect to both a distribution-based and a sampling-based operational semantics, while the latter is proved adequate with respect to a sampling-based operational semantics.

Maternal Secondhand Smoke Exposure Enhances Macrosomia Risk Among Pregnant Women Exposed to PM2.5: A New Interaction of Two Air Pollutants in a Nationwide Cohort

Background: Fine particulate matter (PM2.5) is one of the most common outdoor air pollutants, and secondhand smoking (SHS) is an important source of inhalable indoor air pollution. Previous studies were controversial and inconsistent about PM2.5 and SHS air pollutants on neonatal birth weight outcomes, and no studies assessed the potential interactive effects between PM2.5 and SHS on birth weight outcomes.Purpose: To investigate the interaction between gestational PM2.5 and SHS air pollution exposure on the risk of macrosomia among pregnant women and examine the modifying effect of SHS exposure on the association of PM2.5 air pollution and birth weight outcomes during pregnancy.Methods: Research data were derived from the National Free Preconception Health Examination Project (NFPHEP), which lasted 3 years from January 1, 2010, to December 31, 2012. At least 240,000 Chinese women from 220 counties were enrolled in this project. PM2.5 exposure concentration was obtained using a hindcast model specific for historical PM2.5 estimation from satellite-retrieved aerosol optic depth. Different interaction models about air pollution exposure on birth weight outcomes were established, according to the adjustment of different confounding factors and different pregnancy stages. The establishment of interaction models was based on multivariable logistic regression, and the main confounding factors were maternal age at delivery and pre-pregnancy body mass index (BMI) of participants. SHS subgroups analysis was conducted to further confirm the results of interaction models.Results: In total, 197,877 participants were included in our study. In the full-adjusted interaction model, maternal exposure to PM2.5 was associated with an increased risk of macrosomia in whole, the first-, second-, and third trimesters of pregnancy (p < 0.001). The interactive effect was statistically significant between maternal exposure to PM2.5 and SHS on the risk of macrosomia in the whole (interaction p < 0.050) and the first-trimester pregnancy (interaction p < 0.050), not in the second (interaction p > 0.050) or third trimester (interaction p > 0.050) of pregnancy. The higher frequency of SHS exposure prompted the stronger interaction between the two air pollutants in the whole pregnancy and the first-trimester pregnancy.Conclusions: In the whole and first-trimester pregnancy, maternal exposure to SHS during pregnancy enhanced the risk of macrosomia among pregnant women exposed to PM2.5 air pollutants, and the interaction became stronger with the higher frequency of SHS exposure.