Design of Highly Stabilized β-Hairpin Peptides through Cation−π Interactions of Lysine and N -Methyllysine with an Aromatic Pocket †

Two tryptophan residues were incorporated on one face of a β-hairpin peptide to form an aromatic pocket that interacts with a lysine or N-methylated lysine via cation-π interactions. The two tryptophan residues were found to pack against the lysine side chain forming an aromatic pocket similar to those observed in trimethylated lysine receptor proteins. Thermal analysis of methylated lysine variant hairpin peptides revealed an increase in thermal stability as the degree of methylation was increased resulting in the most thermally stable β-hairpin reported to date

Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

Acknowledgements We thank Dr. Andrea Augello and Dr. Donna MacCallum for advice and help with animal procedures, Susan Clark and Denise Tosh for general technical help and support, and the Arthritis and Regenerative Medicine Laboratory and Arthritis and Musculoskeletal Medicine Programme for general support and scientific discussions. We acknowledge the Iain Fraser Cytometry Centre, the animal facility staff and the Microscopy and Histology Facility, in particular Kevin Mackenzie, Gillian Milne and Lucy Wight for their support. This work was supported by Arthritis Research UK (grants 19271, 19429 and 20050). AHKR is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (grant WT 085664).Peer reviewedPublisher PD

Controlling Peptide Folding with Repulsive Interactions between Phosphorylated Amino Acids and Tryptophan

Phosphorylated amino acids were incorporated into a designed β-hairpin peptide to study the effect on β-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in same β-hairpin system. It was found that phosporylation destabilizes the hairpin structure by approximately 1.0 kcal/mol regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function

No Change in Executive Function or Stress Hormones Following a Bout of Moderate Treadmill Exercise in Preadolescent Children

International Journal of Exercise Science 13(5): 1650-1666, 2020. Several studies suggest that acute bouts of exercise improve executive function in preadolescent children. However, the mechanisms underlying these effects are not completely understood. Specifically, no studies have examined the relationship between the stress hormone response to exercise and improvements in executive function in preadolescent children. The purpose of this study was to examine the effects of a bout of moderate intensity exercise versus rest on working memory (List Sorting Working Memory Task) and selective inhibition/attention (Eriksen flanker task) in preadolescent children, as well as to investigate whether changes in stress hormones (salivary cortisol and alpha-amylase) could explain any differences in performance on these tasks. Twenty-four children completed both a 30-minute moderate intensity bout of treadmill walking and seated rest in a laboratory setting. Tests of executive function and salivary stress hormone analyses were completed before and after each condition. 2x2 Repeated Measures ANOVAs were used to test the effects of time, condition, and time*condition on all executive function and hormonal outcomes. Linear regression models were used to determine if changes in executive function measures were related to changes in stress hormones in the exercise condition. Likely due to methodological limitations, there were no effects of time, condition, nor an interactive effect on working memory, selective inhibition, salivary cortisol, or salivary alpha-amylase. However, there was a trend observed, where the magnitude of the increase in salivary alpha-amylase levels in the exercise condition marginally predicted the improvement in reaction time on the Eriksen flanker task. This suggests that exercise-induced changes in alpha-amylase may underlie improvements in executive function and highlights the need for additional research to more fully understand these relationships in preadolescent children

Joint morphogenetic cells in the adult mammalian synovium

The authors thank all members of the Arthritis & Regenerative Medicine Laboratory, particularly Dr Ana Sergijenko; Drs David Kingsley, Grigori Enikolopov, Fernando Camargo and Lora Heisler for sharing transgenic mice; Drs Henning Wackerhage, Neil Vargesson, Lynda Erskine, Chris Buckley, Francesco Dell’Accio and Frank Luyten for support and helpful discussions; Staff at the University of Aberdeen’s Animal Facility, Microscopy & Histology Facility and Iain Fraser Cytometry Centre for their support. C.D.B. is grateful to Dr Frank Luyten’s support for the experiment in Fig. 8, performed in his laboratory at KU Leuven, Belgium. We are grateful for the following funding: Arthritis Research UK (Grants No. 20050, 19429 and 20775), Medical Research Council (Grant No. MR/L020211/1) and Tenovus Scotland (Grant No. G13/14). A.H.K.R. is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant No. WT 085664).Peer reviewedPublisher PD

Carbohydrate−π Interactions: What Are They Worth?

Protein-carbohydrate interactions play an important role in many biologically important processes. The recognition is mediated by a number of noncovalent interactions including an interaction between the α-face of the carbohydrate and the aromatic side chain. To this end, this interaction has been studied in the context of a β-hairpin in aqueous solution, in which the interaction can be investigated in the absence of other cooperative noncovalent interactions. In this β-hairpin system both the aromatic side chain as well as the carbohydrate was varied in an effort to gain greater insight into the driving force and magnitude of the carbohydrate-π interaction. The magnitude of the interaction was found to vary from -0.5 to -0.8 kcal/mol, depending on the nature of the aromatic ring and the carbohydrate. Replacement of the aromatic ring with an aliphatic group resulted in a decrease in interaction energy to -0.1 kcal/mol, providing evidence for the contribution of CH-π interactions to the driving force. These findings demonstrate the significance of carbohydrate-π interactions within biological systems and also demonstrate its utility as a molecular recognition element in designed system

Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

Funding: This research was funded by Versus Arthritis, grant numbers 18480, 19429 and 21156, and the Medical Research Council, grant number MR/L010453/1. Acknowledgments: We thank Pat Evans and Martin Pritchard, Histopathology Dept, RJAH Orthopaedic Hospital, for guidance on histology; Meso Scale Diagnostics, LLC for advice and the loan of equipment for analyte analyses; all members of the Arthritis and Regenerative Medicine Laboratory at the University of Aberdeen, particularly Hui Wang, Sharon Ansboro and Ausra Lionikiene for their help with mouse surgeries and tissue collection, as well as staff at the University of Aberdeen’s animal facility and microscopy and hystology facility for their supportPeer reviewedPublisher PD

BMP signalling : A significant player and therapeutic target for osteoarthritis

Acknowledgements We are immensely grateful to Prof. YiPing Chen at Tulane University, USA, for the gift of mouse strains. We thank Prof. Frank Beier of Western University, Ontario, Canada for teaching APJ the method of ACL transection. We sincerely thank Shuchi Arora and Ankita Jena for their critical comments on the manuscript. We are highly grateful to Niveda Udaykumar and Saahiba Thaleshwari for their help in blind OARSI scoring. We thank Mr. Naresh Gupta for assistance with mouse experiments. Funding This work was supported by grants from the Department of Biotechnology, India (DBT) BT/PR17362/MED/30/1648/2017 and BT/IN/DENMARK/08/JD/2016 to A.B.; Versus Arthritis Grants 19667 and 21156 to CDB and AJR, Fellowships to APJ, BK, and SFI are supported by fellowships from the Ministry of Education, Govt. of India. Fellowship to AKS was supported by Science and Engineering Research Board, Govt. of India. APJ travelled to Western University Canada with Shastri Research Student Fellowship (SRSF, 2015-‘16). A.H.K.R. was supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant No. WT 085664).Peer reviewedPostprin

Targeting the IL-6-Yap-Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis

ACKNOWLEDGEMENTS The authors thank staff at the University of Aberdeen’s Animal Facility, Microscopy and Histology Facility, qPCR Facility, and the Iain Fraser Cytometry Centre for their expert support. The authors also thank the NHS Grampian Biorepository for facilitating the collection of human tissue samples. Additionally, thanks is given to Denis Evseenko for critical review of the manuscript. Funding This work was supported by funding from the Medical Research Council (grants MR/L020211/1, MR/L022893/1), Versus Arthritis (formerly Arthritis Research UK, grants 20775, 19429, 21156, 20050, 19667, 20865, 21800), Tenovus Scotland (grant G13/14), and European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska Curie (Grant 642414).Peer reviewedPublisher PD