Coupled Analysis of In Vitro and Histology Tissue Samples to Quantify Structure-Function Relationship

The structure/function relationship is fundamental to our understanding of biological systems at all levels, and drives most, if not all, techniques for detecting, diagnosing, and treating disease. However, at the tissue level of biological complexity we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological tissues at the cellular and subcellular level, we cannot assemble it in a way that explains the correspondingly complex biological functions these structures perform. To help close this information gap we define here several quantitative temperospatial features that link tissue structure to its corresponding biological function. Both histological images of human tissue samples and fluorescence images of three-dimensional cultures of human cells are used to compare the accuracy of in vitro culture models with their corresponding human tissues. To the best of our knowledge, there is no prior work on a quantitative comparison of histology and in vitro samples. Features are calculated from graph theoretical representations of tissue structures and the data are analyzed in the form of matrices and higher-order tensors using matrix and tensor factorization methods, with a goal of differentiating between cancerous and healthy states of brain, breast, and bone tissues. We also show that our techniques can differentiate between the structural organization of native tissues and their corresponding in vitro engineered cell culture models

Subcutaneous fat patterning in athletes: selection of appropriate sites and standardisation of a novel ultrasound measurement technique: ad hoc working group on body composition, health and performance, under the auspices of the IOC Medical Commission.

Background: Precise and accurate field methods for body composition analyses in athletes are needed urgently. Aim: Standardisation of a novel ultrasound (US) technique for accurate and reliable measurement of subcutaneous adipose tissue (SAT). Methods: Three observers captured US images of uncompressed SAT in 12 athletes and applied a semiautomatic evaluation algorithm for multiple SAT measurements. Results: Eight new sites are recommended: upper abdomen, lower abdomen, erector spinae, distal triceps, brachioradialis, lateral thigh, front thigh, medial calf. Obtainable accuracy was 0.2 mm (18 MHz probe; speed of sound: 1450 m/s). Reliability of SAT thickness sums (N=36): R2=0.998, SEE=0.55 mm, ICC (95% CI) 0.998 (0.994 to 0.999); observer differences from their mean: 95% of the SAT thickness sums were within ±1 mm (sums of SAT thicknesses ranged from 10 to 50 mm). Embedded fibrous tissues were also measured. Conclusions: A minimum of eight sites is suggested to accommodate inter-individual differences in SAT patterning. All sites overlie muscle with a clearly visible fascia, which eases the acquisition of clear images and the marking of these sites takes only a few minutes. This US method reaches the fundamental accuracy and precision limits for SAT measurements given by tissue plasticity and furrowed borders, provided the measurers are trained appropriately

Relative body weight and standardised brightness-mode ultrasound measurement of subcutaneous fat in athletes: an international multicentre reliability study, under the auspices of the IOC Medical Commission.

Introduction: Fat is a metabolic fuel, but excess body fat is ballast mass and therefore many elite athletes reduce body fat to dangerously low levels. Uncompressed subcutaneous adipose tissue (SAT) thickness measured by brightness-mode ultrasound (US) provides an estimate of body fat content. Methods: The accuracy for determining tissue borders is about 0.1-0.2 mm and reliability (experienced measurers) was within ±1.4 mm (95% limit of agreement, LOA). We present here inter- and intra-measurer scores of three experienced US measurers from each of the centres C1 and C2, and of three novice measurers from each of the centres C3-C5. Each of the five centres measured 16 competitive adult athletes of national or international level, except for one centre where the number was 12. The following sports were included: artistic gymnastics, judo, pentathlon, power lifting, rowing, kayak, soccer, tennis, rugby, basketball, field hockey, water polo, volleyball, American football, triathlon, swimming, cycling, long distance running, mid distance running, hurdles, cross country skiing, snowboarding, and ice hockey. SAT-contour was detected semi-automatically: typically, 100 thicknesses of SAT at a given site (i.e. in a given image), with and without fibrous structures, were measured. Results: At SAT thickness sums DI (of eight standardised sites) between 6.0 and 70.0 mm, the LOA of experienced measurers was 1.2 mm, and the intra-class correlation coefficient ICC was 0.998; novice measurers: 3.1 mm and 0.988. Intra-measurer differences were similar. The median DI-value of all 39 female participants was 51 mm (11% fibrous structures) compared to 17 mm (18%) in the 37 male participants. Discussion: DI measurement accuracy and precision enables detection of fat mass changes of approximately 0.2 kg. Such reliability has not been reached with any other method. Although females' median body mass index and mass index were lower than those of males, females' median DI was three-times higher, and their percentage of fibrous structures was lower. The standardised US method provides a highly accurate and reliable tool for measuring SAT and thus changes in body fat, but training of measurers is important

NMR resonance assignments of the EVH1 domain of neurofibromins recruitment factor Spred1

Neurofibromin and Sprouty-related EVH1 domain-containing protein 1 (Spred1) both act as negative regulators of the mitogen-activated protein kinase pathway and are associated with the rare diseases Neurofibromatosis type 1 and Legius syndrome, respectively. Spred1 recruits the major GTPase activating protein (GAP) neurofibromin from the cytosol to the membrane in order to inactivate the small G protein Ras. These functions are dependent on the N-terminal EVH1 domain and the C-terminal Sprouty domain of Spred1 whereas the former specifically recognizes the GAP related domain of neurofibromin and the latter is responsible for membrane targeting. Within the GAP domain, Spred1 binding depends on the GAPex portion which is dispensable for Ras inactivation. In a first step towards the characterization of the Neurofibromin Spred1 interface in solution we assigned backbone and side chain 1H, 13C, and 15N chemical shifts of the Spred1 derived EVH1 domain. Our chemical shift data analysis indicate seven consecutive beta-strands followed by a C-terminal alpha-helix which is in agreement with the previously reported crystal structure of Spred1(EVH1). Our data provide a framework for further analysis of the function of patient-derived mutations associated with rare diseases.(VLID)460430

Reducing Injury Risk in Youth Sport

Professor Mark De Ste Croix's Inaugural Lecture, 12 February 2014. Mark De Ste Croix has worked in the area of paediatric sport and exercise physiology for over 17 years with a specific focus on enhancing our understanding of growth and maturation related changes in muscle strength. Mark studied for his PhD and held a post-doctoral research fellowship post at the world renowned Children’s Health and Exercise Research Centre at the University of Exeter. His early work significantly enhanced our understanding of the age and sex related changes in strength during childhood. Using isokinetic dynamometry and magnetic resonance imaging Mark’s work contributed to a greater understanding of the mechanisms associated with the age related development of muscle strength during childhood. His specific expertise in using isokinetic dynamometry with paediatric populations has contributed towards a national expert statement on assessment and interpretation using Isokinetic dynamometry. Since joining the University of Gloucestershire in 2003 Mark has employed his expertise in paediatric neuromuscular development to explore injury risk in youth sport. This has included securing competitive research grants from both FIFA and UEFA to explore the effects of football match play on injury risk in female youth footballers. Mark has also been commissioned by the English FA to conduct research into injury risk and injury incidence in female youth footballers. Mark also works closely with a number of football clubs around the world including Barcelona, Athletic Club Bilbao, and more locally with Bristol City and Bristol Ladies Academy. Mark has published over 60 articles on the topic in academic peer reviewed journals, co-edited 1 book, written 25 book chapters, presented at over 70 International Conferences and presented keynote lectures at 15 International conferences. Mark is currently the deputy-convener of the British Association of Sport and Exercise Science special interest group on paediatric sport and exercise, and co-director of the Exercise and Sport Research Centre at the University of Gloucestershire. In this lecture Mark will highlight the importance of understanding growth and maturation related changes in strength; explore the mechanisms associated with injury risk for youth sport; and propose appropriate pre-habilitation programmes for reducing injury risk