Analysis of uncertainty of neural fingerprint-based models.

Machine learning has gained popularity for predicting molecular properties based on molecular structure. This study explores the uncertainty estimates of neural fingerprint-based models by comparing pure graph neural networks (GNN) to classical machine learning algorithms combined with neural fingerprints. We investigate the advantage of extracting the neural fingerprint from the GNN and integrating it into a method known for producing better-calibrated probability estimates.

MolPipeline: A Python Package for Processing Molecules with RDKit in Scikit-learn.

The open-source package scikit-learn provides various machine learning algorithms and data processing tools, including the Pipeline class, which allows users to prepend custom data transformation steps to the machine learning model. We introduce the MolPipeline package, which extends this concept to cheminformatics by wrapping standard RDKit functionality, such as reading and writing SMILES strings or calculating molecular descriptors from a molecule object. We aimed to build an easy-to-use Python package to create completely automated end-to-end pipelines that scale to large data sets.

Transformers for Molecular Property Prediction: Lessons Learned from the Past Five Years.

Molecular Property Prediction (MPP) is vital for drug discovery, crop protection, and environmental science. Over the last decades, diverse computational techniques have been developed, from using simple physical and chemical properties and molecular fingerprints in statistical models and classical machine learning to advanced deep learning approaches. In this review, we aim to distill insights from current research on employing transformer models for MPP.

A Divalent Metal Cation-Metabolite Interaction Model Reveals Cation Buffering and Speciation.

I present the perspective that the divalent metalome and the metabolome can be modeled as a network of chelating interactions instead of separate entities. I review progress in understanding the complex cellular environment, in particular recent contributions to modeling metabolite-Mg interactions. I then demonstrate a simple extension of these strategies based approximately on intracellular concentrations.

Towards an informed research agenda for the field of personality disorders by experts with lived and living experience and researchers.

Background: We describe a collection of themes for a research agenda for personality disorders that was originally formulated for the ESSPD Borderline Congress in 2022.

Methods: Experts with lived and living experience (EE), researchers and clinicians met virtually, exchanged ideas and discussed research topics for the field of personality disorders. The experts - patients, relatives, significant others - named the topics they thought most relevant for further research in the field.

In vivo-like nearest neighbor parameters improve prediction of fractional RNA base-pairing in cells.

We conducted a thermodynamic analysis of RNA stability in Eco80 artificial cytoplasm, which mimics in vivo conditions, and compared it to transcriptome-wide probing of mRNA. Eco80 contains 80% of Escherichia coli metabolites, with biological concentrations of metal ions, including 2 mM free Mg2+ and 29 mM metabolite-chelated Mg2+. Fluorescence-detected binding isotherms (FDBI) were used to conduct a thermodynamic analysis of 24 RNA helices and found that these helices, which have an average stability of -12.

Searching similar local 3D micro-environments in protein structure databases with MicroMiner.

The available protein structure data are rapidly increasing. Within these structures, numerous local structural sites depict the details characterizing structure and function. However, searching and analyzing these sites extensively and at scale poses a challenge.

Modeling with Alternate Locations in X-ray Protein Structures.

In many molecular modeling applications, the standard procedure is still to handle proteins as single, rigid structures. While the importance of conformational flexibility is widely known, handling it remains challenging. Even the crystal structure of a protein usually contains variability exemplified in alternate side chain orientations or backbone segments.

MeltR software provides facile determination of nucleic acid thermodynamics.

Thermodenaturation (melting) curves of macromolecules are used to determine folding thermodynamic parameters. Notably, this insight into RNA and DNA stability underlies nearest neighbor theory and diverse structure prediction tools. Analysis of UV-detected absorbance melting curves is complex and multivariate, requiring many data preprocessing, regression, and error analysis steps.

Co-curricular Immersion as a Public-Private Capacity Building Activity.

The COVID-19 pandemic exacerbated the already increasing challenge of establishing immersive, co-curricular activities for engineering students, particularly for biomedical-related activities. In the current work, we outline a strategy for co-curricular learning that leverages a private-public partnership in which methods for capacity-building have enabled mutually beneficial outcomes for both organizations. A contemporary issue for many non-profits is identifying effective ways to build capacity for consistent service delivery while at the same time embracing the volunteer activities of students; a challenge is that the lifecycle of a university student is often not aligned (much shorter) with the needs of the non-profit.

The Metabolome Weakens RNA Thermodynamic Stability and Strengthens RNA Chemical Stability.

We examined the complex network of interactions among RNA, the metabolome, and divalent Mg under conditions that mimic the cytoplasm. We determined Mg binding constants for the top 15 metabolites, comprising 80% of the metabolome by concentration at physiological pH and monovalent ion concentrations. These data were used to inform the development of an artificial cytoplasm that mimics conditions, which we term "Eco80".

Genome-wide analysis of the tRNA structurome reveals RNA structural and modification dynamics under heat stress.

RNA structure plays roles in myriad cellular events including transcription, translation, and RNA processing. Genome-wide analyses of RNA secondary structure in vivo by chemical probing have revealed critical structural features of mRNAs and long ncRNAs. Here, we examine the in vivo secondary structure of a small RNA class, tRNAs.

ProteinsPlus: a comprehensive collection of web-based molecular modeling tools.

Upon the ever-increasing number of publicly available experimentally determined and predicted protein and nucleic acid structures, the demand for easy-to-use tools to investigate these structural models is higher than ever before. The ProteinsPlus web server (https://proteins.plus) comprises a growing collection of molecular modeling tools focusing on protein-ligand interactions.

Analyzing structural features of proteins from deep-sea organisms.

Protein adaptations to extreme environmental conditions are drivers in biotechnological process optimization and essential to unravel the molecular limits of life. Most proteins with such desirable adaptations are found in extremophilic organisms inhabiting extreme environments. The deep sea is such an environment and a promising resource that poses multiple extremes on its inhabitants.

Differential methamphetamine-induced behavioral effects in male and female mice lacking regulator of G Protein signaling 4.

Methamphetamine-induced behavioral effects are mediated by several neurotransmitters that act via the G-protein coupled receptors (GPCRs). The functioning of GPCRs are negatively regulated by regulators of G-protein signaling (RGS) proteins. The goal of this study was to assess the role of two specific RGS proteins namely the RGS2 and the RGS4 proteins in methamphetamine-induced behaviors.

RNA sequence and structure control assembly and function of RNA condensates.

Intracellular condensates formed through liquid-liquid phase separation (LLPS) primarily contain proteins and RNA. Recent evidence points to major contributions of RNA self-assembly in the formation of intracellular condensates. As the majority of previous studies on LLPS have focused on protein biochemistry, effects of biological RNAs on LLPS remain largely unexplored.

Functional Roles of Chelated Magnesium Ions in RNA Folding and Function.

RNA regulates myriad cellular events such as transcription, translation, and splicing. To perform these essential functions, RNA often folds into complex tertiary structures in which its negatively charged ribose-phosphate backbone interacts with metal ions. Magnesium, the most abundant divalent metal ion in cells, neutralizes the backbone, thereby playing essential roles in RNA folding and function.

Regulation of OmpA Translation and Shigella dysenteriae Virulence by an RNA Thermometer.

RNA thermometers are -acting riboregulators that mediate the posttranscriptional regulation of gene expression in response to environmental temperature. Such regulation is conferred by temperature-responsive structural changes within the RNA thermometer that directly result in differential ribosomal binding to the regulated transcript. The significance of RNA thermometers in controlling bacterial physiology and pathogenesis is becoming increasingly clear.

Design, Implementation, and Evaluation of a Head and Neck MRI RF Array Integrated with a 511 keV Transmission Source for Attenuation Correction in PET/MR.

The goal of this work is to further improve positron emission tomography (PET) attenuation correction and magnetic resonance (MR) sensitivity for head and neck applications of PET/MR. A dedicated 24-channel receive-only array, fully-integrated with a hydraulic system to move a transmission source helically around the patient and radiofrequency (RF) coil array, is designed, implemented, and evaluated. The device enables the calculation of attenuation coefficients from PET measurements at 511 keV including the RF coil and the particular patient.

In Need of Bias Control: Evaluating Chemical Data for Machine Learning in Structure-Based Virtual Screening.

Reports of successful applications of machine learning (ML) methods in structure-based virtual screening (SBVS) are increasing. ML methods such as convolutional neural networks show promising results and often outperform traditional methods such as empirical scoring functions in retrospective validation. However, trained ML models are often treated as black boxes and are not straightforwardly interpretable.

Extrinsic wheat fibre consumption enhances faecal bulk and stool frequency; a randomized controlled trial.

The beneficial effect of wheat fibres on faecal bulk and stool pattern has mainly been observed with intact wheat fibres. This study investigates the effect of extrinsic wheat fibre (VITACEL® wheat fibre), which can be easily incorporated in many food products, on faecal bulk, stool pattern, gastrointestinal complaints, satiety and food liking. In a double-blind randomized crossover trial, healthy male volunteers received meal boxes for 10 days, containing various food products enriched with extrinsic wheat fibre (∼20 grams of additional fibre per day) or control food products containing conventional levels of fibre with similar taste, appearance and caloric values.

A head coil system with an integrated orbiting transmission point source mechanism for attenuation correction in PET/MRI.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) provides a benefit for diagnostic imaging. Still, attenuation correction (AC) is a challenge in PET/MRI compared to stand-alone PET and PET-computed tomography (PET/CT). In the absence of photonic transmission sources, AC in PET/MRI is usually based on retrospective segmentation of MR images or complex additional MR-sequences.

Flexible 23-channel coil array for high-resolution magnetic resonance imaging at 3 Tesla.

Purpose: The purpose of this work is the design, implementation and evaluation of a mechanically flexible receive-only coil array for magnetic resonance imaging (MRI) at 3 T that can be applied to various target organs and provides high parallel imaging performance.

Methods: A 23-channel array was designed based on a rigid-flex printed circuit board (PCB). The flexible multi-layer part contains the copper traces forming the coil elements.

A flexible 12-channel transceiver array of transmission line resonators for 7 T MRI.

A flexible transceiver array based on transmission line resonators (TLRs) combining the advantages of coil arrays with the possibility of form-fitting targeting cardiac MRI at 7 T is presented. The design contains 12 elements which are fabricated on a flexible substrate with rigid PCBs attached on the center of each element to place the interface components, i.e.

StructureProfiler: an all-in-one tool for 3D protein structure profiling.

Motivation: Three-dimensional protein structures are important starting points for elucidating protein function and applications like drug design. Computational methods in this area rely on high quality validation datasets which are usually manually assembled. Due to the increase in published structures as well as the increasing demand for specially tailored validation datasets, automatic procedures should be adopted.