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Competing Interests: Funding Support and Author Disclosures Dr Mangner has received personal fees from Edwards Lifesciences, Medtronic, Novartis, Sanofi Genzyme, AstraZeneca, Pfizer, Bayer, Abbott, Abiomed, B. Braun, and Boston Scientific outside the submitted work. Dr Fassl has received speaker fees from CSL Behring and Edwards Lifesciences outside the submitted work. Dr Haussig has received speaker honoraria and consulting fees from Edwards Lifesciences, Abbott, and Boston Scientific outside the submitted work. Dr Linke has received grants from Novartis; personal fees from Medtronic, Abbott, Edwards Lifesciences, Boston Scientific, AstraZeneca, Novartis, Pfizer, Abiomed, Bayer, and Boehringer; and personal fees from Picardia, Transverse Medical, and Claret Medical outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The immunoglobulin fold (Ig fold) domain is a super-secondary structural motif consisting of a sandwich with two layers of β-sheets that is present in many proteins with very diverse biological functions covering a wide range of physiological processes. This domain presents a modular architecture built with β strands connected by variable length loops that has a highly conserved structural core of four β-strands and quite variable β-sheet extensions in the two sandwich layers that enable both divergent and convergent evolutionary mechanisms in the known Ig fold proteome. The central role of this Ig fold's structural plasticity in the evolutionary success of antibodies in our immune system is well established. Nature has also utilized this Ig fold in all domains of life in many different physiological contexts that go way beyond the immune system. Here we will present a structural and functional overview of the utilization of the Ig fold in different biological processes and in different cellular contexts to highlight some of the innumerable ways that this structural motif can interact in multidomain proteins to enable their diversity of functions. This includes shareable specific protein structure visualizations behind those functions that serve as starting points for further explorations of the biomolecular interactions spanning the Ig fold proteome. This overview also highlights how this Ig fold is being utilized through natural adaptation, engineering, and even building from scratch for a range of biotechnological applications., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: The aim of the study was quantitative and qualitative assessments of scrotal abnormalities diagnosed in boys 8 to 36 months old during ultrasound screening and estimation if these abnormalities influence testes volume., Materials and Methods: High frequency scrotal ultrasound was performed in 1448 patients aged 8-36 months as additional exam during screening ultrasound program for children including cervical and abdominal ultrasound. The mean age of examined boys was 17 months. For further analysis the children were divided in 5 age groups., Results: The abnormalities in scrotal ultrasound were found in 20.1% of boys. Undescended, cryptorchid testes were found in 4.8% of patients, mobile testicle in 7.6% and hydrocele in 2.8%. The volume of undescended testes was statistically lower than volume of the descended testes in 3 youngest groups of boys (p=0.003-0.011). The volume of mobile testicles did not increase with age, while in patients with hydrocele the testicular volume decreased with age., Conclusion: Scrotal screening ultrasound performed in boys up to 3 years old may deliver information about the number and type of existing pathologies as well as their influence on the testicular volume. The volume of the pathological testes was lower than the volume of the normal ones. Improper growth of testes may potentially have important clinical implication for the function of testes in the future., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The modulation of protein-protein interactions (PPIs) by small drug-like molecules is a relatively new area of research and has opened up new opportunities in drug discovery. However, the progress made in this area is limited to a handful of known cases of small molecules that target specific diseases. With the increasing availability of protein structure complexes, it is highly important to devise strategies exploiting homologous structure space on a large scale for discovering putative PPIs that could be attractive drug targets. Here, we propose a scheme that allows performing large-scale screening of all protein complexes and finding putative small-molecule and/or peptide binding sites overlapping with protein-protein binding sites (so-called "multibinding sites"). We find more than 600 nonredundant proteins from 60 protein families with multibinding sites. Moreover, we show that the multibinding sites are mostly observed in transient complexes, largely overlap with the binding hotspots and are more evolutionarily conserved than other interface sites. We investigate possible mechanisms of how small molecules may modulate protein-protein binding and discuss examples of new candidates for drug design., (Published by Elsevier Ltd.)

Glycosylation is an important aspect of epigenetic regulation. Glycosyltransferase is a key enzyme in the biosynthesis of glycans, which glycosylates more than half of all proteins in eukaryotes and is involved in a wide range of biological processes. It has been suggested previously that homooligomerization in glycosyltransferases and other proteins might be crucial for their function. In this study, we explore functional homooligomeric states of glycosyltransferases in various organisms, trace their evolution, and perform comparative analyses to find structural features that can mediate or disrupt the formation of different homooligomers. First, we make a structure-based classification of the diverse superfamily of glycosyltransferases and confirm that the majority of the structures are indeed clustered into the GT-A or GT-B folds. We find that homooligomeric glycosyltransferases appear to be as ancient as monomeric glycosyltransferases and go back in evolution to the last universal common ancestor (LUCA). Moreover, we show that interface residues have significant bias to be gapped out or unaligned in the monomers, implying that they might represent features crucial for oligomer formation. Structural analysis of these features reveals that the majority of them represent loops, terminal regions, and helices, indicating that these secondary-structure elements mediate the formation of glycosyltransferases' homooligomers and directly contribute to the specific binding. We also observe relatively short protein regions that disrupt the homodimer interactions, although such cases are rare. These results suggest that relatively small structural changes in the nonconserved regions may contribute to the formation of different functional oligomeric states and might be important in regulation of enzyme activity through homooligomerization., (Published by Elsevier Ltd.)

An audit cycle has been completed looking at the availability of information about different types of anaesthesia in labour, their usage and the degree of maternal satisfaction. The initial audit 7 years ago led to the production of an information leaflet on pain relief in labour. The current audit (1996) demonstrated that the majority of patients receive the leaflet and find the information useful. The leaflet may have helped improve satisfaction and selection of analgesia in primigravide. However, the leaflet needs updating to include some information on caesarean section now that this has become such a common form of delivery.

We describe a computational approach to protein tertiary structure prediction that combines ideas from the three-dimensional (3D) profile method of Bowie, Lüthy and Eisenberg and the associative memory Hamiltonians of Friedrichs and Wolynes. The ultimate goal of our work is to extend and generalize the capabilities of these heuristics so as to be able to predict novel structures that might be found in nature or designed proteins. In our approach we approximate the interactions between residues through a pseudo-potential function similar to an associative memory Hamiltonian. This function is constructed based on 3D environment principles. Favorable inter-residue contacts for each residue in a target protein are inferred by using 3D environment propensities of the residues and a collection of 3D environment templates derived from a dataset of protein crystal structures. A Hamiltonian encoding this information is used to guide an optimization phase via molecular dynamics with annealing, which then leads to the folded structure. With our algorithm we can recover the structure of dataset proteins and have also succeeded in constructing the fold for a protein with little sequence similarity to any dataset protein.