Creaky knees: Is there a reason for concern? A qualitative study of the perspectives of people with knee crepitus

Objective: Crepitus is a feature of osteoarthritis that may affect one's participation in exercise. An informed understanding is required of the perceptions that people have of their knee crepitus and how it affects their exercise behaviours. This study aims to investigate the role that crepitus may play in beliefs about exercise and knee health. Methods: Focus group and individual interviews were conducted online with participants who had knee crepitus. The transcripts were thematically analysed through an inductive approach. Results: Five main themes were identified from 24 participants: (1) individual variation of, (2) occurrence of, (3) meaning of knee crepitus, (4) attitudes and exercise behaviours regarding crepitus, and (5) knowledge deficits and needs concerning crepitus during exercise. The variety of crepitus sounds described occurred with a range of exercises or after inactivity. For those already with osteoarthritis or other symptoms, crepitus was of less concern than symptoms such as pain. Most participants had not ceased exercise but may have modified movement due to crepitus and associated symptoms; some had increased intentional strength training to try alleviating it. Participants agreed that more understanding about the processes causing crepitus and what exercise was safe for knee health would be beneficial. Conclusion: Crepitus does not appear to be a major cause of concern for people who experience it. However, it is a factor that influences exercise behaviours as is pain. If health professionals could guide people with concerns about their crepitus, they may be more confident in exercising to benefit their joint health

Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer

A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton microscopy to examine the fast Ca2+-induced transitions of acrylodan-labeled calmodulin. We find that the kinetic rates of the conformational changes in two homologous globular domains differ by more than an order of magnitude. The characteristic time constants are ≈490 μs for the transitions in the C-terminal domain and ≈20 ms for those in the N-terminal domain of the protein. We discuss possible mechanisms for the two distinct events and the biological role of the stable intermediate, half-saturated calmodulin

Comparative grading scales, statistical analyses, climber descriptors and ability grouping: International Rock Climbing Research Association position statement

The research base for rock climbing has expanded substantially in the past 3 decades as worldwide interest in the sport has grown. An important trigger for the increasing research attention has been the transition of the sport to a competitive as well as recreational activity and the potential inclusion of sport climbing in the Olympic schedule. The International Rock Climbing Research Association (IRCRA) was formed in 2011 to bring together climbers, coaches and researchers to share knowledge and promote collaboration. This position statement was developed during and after the 2nd IRCRA Congress which was held in Pontresina, in September 2014. The aim of the position statement is to bring greater uniformity to the descriptive and statistical methods used in reporting rock climbing research findings. To date there is a wide variation in the information provided by researchers regarding the climbers’ characteristics and also in the approaches employed to convert from climbing grading scales to a numeric scale suitable for statistical analysis. Our paper presents details of recommended standards of reporting that should be used for reporting climber characteristics and provides a universal scale for the conversion of climbing grades to a number system for statistical analysis

Classification of temporomandibular joint sounds based upon their reduced interference distribution

Temporomandibular joint (TMJ) sounds were recorded in 98 orthodontic retention patients, mean age 19 ± 8–6 (s.d.) years, by interview, auscultation and electronic recording. Sounds were found by auscultation in 41% and by interview in 32% of the subjects, more often in females than in males (P ≤ 0.05). A new method for time-frequency analysis, the reduced interference distribution (RID), was used to classify the electronic sound recordings into five subclasses, RID types 1–5, based upon location and number of their energy peaks. RID types 1–3 had a few energy peaks close in time. RID types 4–5, typical of subjects with crepitation, had multiple energy peaks occurring close in time for a period of 20–300 ms. RID type 1, found in 45% of the subjects, typical of patients with clicking, had its dominant energy peak located in a frequency range ≤600 Hz and was significantly more common in the female than in the male subjects (P≤ 0.01). RID type 2, found in 68% of the subjects, with the dominant peak in the range 600–1200 Hz, and RID type 3, found in 38% of the subjects, with the peak in the frequency range >1200 Hz, were found to have a similar gender distribution. RID type 4, found in 49% of the subjects, had the energy peaks distributed in the frequency range ≤600 Hz. RID type 5, found in 43% of the subjects, more often in females than in males (P≤ 0.05), had the peaks distributed over the whole frequency range from about 30 Hz up to about 3000 Hz. In conclusion, a more detailed classification could be made of the TMJ sounds by displaying the RIDs than by auscultation. This suggests that RID classification methods may provide a means for differentiating sounds indicating different types of pathology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74694/1/j.1365-2842.1996.tb00809.x.pd

Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

Cationic Amino Acids Specific Biomimetic Silicification in Ionic Liquid: A Quest to Understand the Formation of 3-D Structures in Diatoms

The intricate, hierarchical, highly reproducible, and exquisite biosilica structures formed by diatoms have generated great interest to understand biosilicification processes in nature. This curiosity is driven by the quest of researchers to understand nature's complexity, which might enable reproducing these elegant natural diatomaceous structures in our laboratories via biomimetics, which is currently beyond the capabilities of material scientists. To this end, significant understanding of the biomolecules involved in biosilicification has been gained, wherein cationic peptides and proteins are found to play a key role in the formation of these exquisite structures. Although biochemical factors responsible for silica formation in diatoms have been studied for decades, the challenge to mimic biosilica structures similar to those synthesized by diatoms in their natural habitats has not hitherto been successful. This has led to an increasingly interesting debate that physico-chemical environment surrounding diatoms might play an additional critical role towards the control of diatom morphologies. The current study demonstrates this proof of concept by using cationic amino acids as catalyst/template/scaffold towards attaining diatom-like silica morphologies under biomimetic conditions in ionic liquids

The Overlap of Small Molecule and Protein Binding Sites within Families of Protein Structures

Protein–protein interactions are challenging targets for modulation by small molecules. Here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. Specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. Of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250–1000 Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand and protein binding positions. These “bi-functional positions”, which bind both ligands and proteins, are particularly enriched in tyrosine and tryptophan residues, similar to “energetic hotspots” described previously, and are significantly less conserved than mono-functional and solvent exposed positions. Homology transfer identifies ligands whose binding sites overlap at least 20% of the protein interface for 35% of domain–domain and 45% of domain–peptide mediated interactions. The analysis recovered known small-molecule modulators of protein interactions as well as predicted new interaction targets based on the sequence similarity of ligand binding sites. We illustrate the predictive utility of the method by suggesting structural mechanisms for the effects of sanglifehrin A on HIV virion production, bepridil on the cellular entry of anthrax edema factor, and fusicoccin on vertebrate developmental pathways. The results, available at http://pibase.janelia.org, represent a comprehensive collection of structurally characterized modulators of protein interactions, and suggest that homologous structures are a useful resource for the rational design of interaction modulators