Classifying metal-binding sites with neural networks.

To advance our ability to predict impacts of the protein scaffold on catalysis, robust classification schemes to define features of proteins that will influence reactivity are needed. One of these features is a protein's metal-binding ability, as metals are critical to catalytic conversion by metalloenzymes. As a step toward realizing this goal, we used convolutional neural networks (CNNs) to enable the classification of a metal cofactor binding pocket within a protein scaffold. CNNs enable images to be classified based on multiple levels of detail in the image, from edges and corners to entire objects, and can provide rapid classification. First, six CNN models were fine-tuned to classify the 20 standard amino acids to choose a performant model for amino acid classification. This model was then trained in two parallel efforts: to classify a 2D image of the environment within a given radius of the central metal binding site, either an Fe ion or a [2Fe-2S] cofactor, with the metal visible (effort 1) or the metal hidden (effort 2). We further used two sub-classifications of the [2Fe-2S] cofactor: (1) a standard [2Fe-2S] cofactor and (2) a Rieske [2Fe-2S] cofactor. The accuracy for the model correctly identifying all three defined features was >95%, despite our perception of the increased challenge of the metalloenzyme identification. This demonstrates that machine learning methodology to classify and distinguish similar metal-binding sites, even in the absence of a visible cofactor, is indeed possible and offers an additional tool for metal-binding site identification in proteins.

Changes in the C-terminal, N-terminal, and histidine regions of amelogenin reveal the role of oligomer quaternary structure on adsorption and hydroxyapatite mineralization.

Adsorption interactions between amelogenin and calcium phosphate minerals are believed to be important to amelogenin's function in enamel formation, however, the role of specific amino acid residues and domains within the protein in controlling adsorption is not well known. We synthesized "mechanistic probes" by systematically removing charged regions of amelogenin in order to elucidate their roles. The probes included amelogenin without the charged residues in the N-terminus (SEKR), without two, three, or eight histidines (H) in the central protein region (H2, H3, H8), or without the C-terminal residues (Delta). In-situ atomic force microscopy (AFM) adsorption studies onto hydroxyapatite (HAP) single crystals confirmed that the C-terminus was the dominant domain in promoting adsorption. We propose that subtle changes in protein-protein interactions for proteins with histidines and N-terminal residues removed resulted in changes in the oligomer quaternary size and structure that also affected protein adsorption. HAP mineralization studies revealed that the oligomer-HAP binding energy and protein layer thickness were factors in controlling the amorphous calcium phosphate (ACP) to HAP induction time. Our studies with mechanistic probes reveal the importance of the oligomer quaternary structure in controlling amelogenin adsorption and HAP mineralization.

Reverse Shoulder Arthroplasty in Rheumatoid Arthritis: A Systematic Review.

BACKGROUND: Anatomical shoulder replacement for rheumatoid arthritis (RA) is complicated by a high incidence of rotator cuff tears and glenoid erosion. This can lead to poor function and early failure. Reverse shoulder arthroplasty (RSA) has gained popularity as an alternative. This systematic review attempts to further define the role of RSA in RA. METHODS: A systematic review identified seven studies reporting outcomes of RSA in RA patients. Studies were critically appraised, and data on outcomes, complications and technical considerations were extracted and analysed. RESULTS: One hundred and twenty one shoulders were included (mean follow up 46.9 months). Consistent improvements in the main outcome measures were noted between studies. Ninety five percent of patients described excellent to satisfactory outcomes. The minimum mean forward elevation reported in each study was 115 degrees. Symptomatic glenoid loosening (1.7%), deep infection (3.3%) and revision surgery (5%) rates were no higher than for a population of mixed aetiologies. DISCUSSION: Previous concerns regarding high pre- and peri-operative complication and revision rates in RA patients were not shown to be valid by the results of this review. Although associated cuff tears are common and glenoid bone loss can increase the technical complexity of surgery, RSA provides consistent and predictable improvements in key outcome measures and the revision and complication rates do not appear to be higher than reported in a large population of mixed aetiologies. CONCLUSION: The contemporary literature shows that RSA is a safe, effective and reliable treatment option in RA patients.

'Talking through what would happen with the emergency card worker made me plan and think about such things as where I store his medication. I felt I'd planned as much as possible after speaking with her. This gave me such peace of mind' Karen, a scheme user.

Who is a carer? A carer is someone who, in an unpaid capacity, provides care or support to another person. Many people do not class themselves as carers: they are mums and dads, husbands, wives, partners, brothers, sisters, friends and neighbours. Carers come from all walks of life, ages, ethnicities and backgrounds. Throughout our lives most of us will either be a carer or be cared for.