Structure-function Specialisation of the Interfascicular Matrix in the Human Achilles Tendon

ABSTRACTObjectiveTendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency; these tendons are prone to debilitating injuries, the incidence of which increases with ageing. In equine tendons, energy storage is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the positional anterior tibialis and energy storing Achilles tendons, testing the hypothesis that the Achilles IFM has specialised composition and mechanical properties, which are lost with ageing.MethodsWe used a multidisciplinary combination of mechanical testing, immunolocalisation and proteomics to investigate structure-function specialisations in functionally distinct human tendons and how these are altered with ageing.ResultsThe IFM in the energy storing Achilles tendon is more elastic and fatigue resistant than the IFM in the positional anterior tibialis tendon, with a trend towards decreased fatigue resistance with age in the Achilles IFM. With ageing, alterations occur predominantly to the proteome of the Achilles IFM.ConclusionThe Achilles tendon IFM is specialised for energy storage, and changes to its proteome with ageing are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of key energy storing specialisations and their changes with ageing offers insight towards developing effective treatments for tendinopathy.Key messagesWhat is already known about this subject?Energy storing tendons in animals and humans are particularly prone to injury and the incidence increases with increasing age.Previous work in some animal models has shown that the specialisation of tendon properties for energy storage is achieved primarily through adaptation of the interfascicular matrix, with specialisation lost in ageing. However, the structural specialisations that provide the human Achilles tendon with its energy storing ability, and how these are affected by ageing, remain to be established.What does this study add?We demonstrate that the interfascicular matrix in the human Achilles tendon is specialised for energy storing, with increased elastic recoil and fatigue resistance, and that these specialisations are partially lost with ageing, likely due to alterations to the proteome of the interfascicular matrix.How might this impact on clinical practice or future developments?Short term, the specialist IFM mechanics we have demonstrated can be detected with new developments in ultrasound functional imaging, offering improved opportunities for contextual tendinopathy diagnostics. Personalised rehabilitation programmes can now be explored and designed specifically to target IFM mechanics.Longer term, the knowledge of key specialisations in injury prone energy storing tendons and how they are affected by ageing, offers crucial insight towards developing cell or tissue engineering treatments targeted at restoring tendon structure and function post-injury, specifically targeted at the IFM.

Download Full-text

Instrumental Assessment in Cleft Palate Care

Perspectives on Speech Science and Orofacial Disorders ◽

10.1044/ssod23.2.49 ◽

2013 ◽

Vol 23 (2) ◽

pp. 49-61 ◽

Cited By ~ 3

Author(s):

Jamie Perry ◽

Graham Schenck

Keyword(s):

Cleft Palate ◽

New Developments ◽

Perceptual Evaluation ◽

Advantages And Disadvantages ◽

Instrumental Assessment ◽

Speech Language Pathologist ◽

Hypernasal Speech ◽

Perceptual Assessment ◽

Velopharyngeal Function ◽

And Function

Despite advances in surgical management, it is estimated that 20–30% of children with repaired cleft palate will continue to have hypernasal speech and require a second surgery to create normal velopharyngeal function (Bricknell, McFadden, & Curran, 2002; Härtel, Karsten, & Gundlach, 1994; McWilliams, 1990). A qualitative perceptual assessment by a speech-language pathologist is considered the most important step of the evaluation for children with resonance disorders (Peterson-Falzone, Hardin-Jones, & Karnell, 2010). Direct and indirect instrumental analyses should be used to confirm or validate the perceptual evaluation of an experienced speech-language pathologist (Paal, Reulbach, Strobel-Schwarthoff, Nkenke, & Schuster, 2005). The purpose of this article is to provide an overview of current instrumental assessment methods used in cleft palate care. Both direct and indirect instrumental procedures will be reviewed with descriptions of the advantages and disadvantages of each. Lastly, new developments for evaluating velopharyngeal structures and function will be provided.

Download Full-text

Clues for Understanding the Structure and Function of a Prototypic Human Integrin: The Platelet Glycoprotein IIb/IIIa Complex

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648803 ◽

1994 ◽

Vol 72 (01) ◽

pp. 001-015 ◽

Cited By ~ 124

Author(s):

Juan J Calvete

Keyword(s):

Structure Function ◽

Thrombus Formation ◽

Platelet Glycoprotein ◽

Primary Role ◽

Clot Retraction ◽

Inhibitory Peptide ◽

Rgd Sequence ◽

Platelet Receptor ◽

Adhesive Proteins ◽

And Function

SummaryThe glycoprotein (GP) IIb/IIIa, a Ca2+-dependent heterodimer, is the major integrin on the platelet plasma membrane. On resting platelets GPIIb/IIIa is maintained in an inactive conformation and serves as a low affinity adhesion receptor for surface-coated fibrinogen, whereas upon platelet activation signals within the cytoplasma alter the receptor function of GPIIb/IIIa (inside-out signalling), which undergoes a measurable conformational change within its exoplasmic domains, and becomes a competent receptor for soluble fibrinogen and some other RGD sequence-containing plasma adhesive proteins. Upon ligand binding, further structural alterations trigger the association of receptor-occupied GPIIb/IIIa complexes with themselves within the plane of the membrane. The simultaneous binding of dimeric fibrinogen molecules to GPIIb/IIIa clusters on adjacent platelets leads to platelet aggregation, which promotes attachment of fibrinogen-GPIIb/IIIa clusters to the cytoskeleton (outside-in signalling). This, in turn, provides the necessary physical link for clot retraction to occur, and generates a cascade of intracellular biochemical reactions which result in the formation of a multiprotein signalling complex at the cytoplasmic domains of GPIIb/IIIa. Glycoprotein IMIIa, also called αIIbβ3 in the integrin nomenclature, plays thus a primary role in both platelet adhesion and thrombus formation at the site of vascular injury. In addition, the human glycoprotein Ilb/IIIa complex is the most thoroughly studied integrin receptor, its molecular biology and major features of its primary structure having been elucidated mainly during the last six years. Furthermore, localization of functionally relevant monoclonal antibody epitopes, determination of the cross-linking sites of inhibitory peptide ligands, proteolytic dissection of the isolated integrin, and analysis of natural and artificial GPIIb/IIIa mutants have recently provided a wealth of information regarding structure-function relationships of human GPIIb/IIIa. The aim of this review is to summarize these many structural and functional data in the perspective of an emerging model. Although most of the interpretations based on structural elements of this initial biochemical model require independent confirmation, they may help us to understand the structure-function relationship of this major platelet receptor, and of other members of the integrin superfamily, as well as to perform further investigations in order to test current hypotheses.

Download Full-text

Immediate weight bearing and function following surgery for neglected Achilles tendon ruptures

10.26226/morressier.570fc33ed462b8029237ef1f ◽

2016 ◽

Author(s):

ADRIANA AVILA

Keyword(s):

Achilles Tendon ◽

Weight Bearing ◽

Tendon Ruptures ◽

And Function

Download Full-text

Task shifting in the care for patients with hand osteoarthritis. Protocol for a randomized controlled non-inferiority trial

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04019-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ingvild Kjeken ◽

Kjetil Bergsmark ◽

Ida K. Haugen ◽

Toril Hennig ◽

Merete Hermann-Eriksen ◽

...

Keyword(s):

Health Care ◽

Disease Activity ◽

Primary Outcome ◽

Hand Osteoarthritis ◽

List Type ◽

Specialist Care ◽

Randomized Controlled ◽

Number Of Patients ◽

Specialist Health Care ◽

And Function

Abstract Background Current health policy states that patients with osteoarthritis (OA) should mainly be managed in primary health care. Still, research shows that patients with hand OA have poor access to recommended treatment in primary care, and in Norway, they are increasingly referred to rheumatologist consultations in specialist care. In this randomized controlled non-inferiority trial, we will test if a new model, where patients referred to consultation in specialist health care receive their first consultation by an occupational therapy (OT) specialist, is as safe and effective as the traditional model, where they receive their first consultation by a rheumatologist. More specifically, we will answer the following questions: What are the characteristics of patients with hand OA referred to specialist health care with regards to joint affection, disease activity, symptoms and function? Is OT-led hand OA care as effective and safe as rheumatologist-led care with respect to treatment response, disease activity, symptoms, function and patient satisfaction? Is OT-led hand OA care equal to, or more cost effective than rheumatologist-led care? Which factors, regardless of hand OA care, predict improvement 6 and 12 months after baseline? Methods Participants will be patients with hand OA diagnosed by a general practitioner and referred for consultation at one of two Norwegian departments of rheumatology. Those who agree will attend a clinical assessment and report their symptoms and function in validated outcome measures, before they are randomly selected to receive their first consultation by an OT specialist (n = 200) or by a rheumatologist (n = 200). OTs may refer patients to a rheumatologist consultation and vice versa. The primary outcome will be the number of patients classified as OMERACT/OARSI-responders after six months. Secondary outcomes are pain, function and satisfaction with care over the twelve-month trial period. The analysis of the primary outcome will be done by logistic regression. A two-sided 95% confidence interval for the difference in response probability will be formed, and non-inferiority of OT-led care will be claimed if the upper endpoint of this interval does not exceed 15%. Discussion The findings will improve access to evidence-based management of people with hand OA. Trial registration ClinicalTrials.gov, NCT03102788. Registered April 6th, 2017, https://clinicaltrials.gov/ct2/show/NCT03102788?term=Kjeken&draw=2&rank=1 Date and version identifier: December 17th, 2020. First version.

Download Full-text

Structure, Function, and Tort Law

Journal of Tort Law ◽

10.1515/jtl-2020-2001 ◽

2020 ◽

Vol 13 (1) ◽

pp. 31-79

Author(s):

Dan Priel

Keyword(s):

Structure Function ◽

Tort Law ◽

Structure And Function ◽

Vicarious Liability ◽

Causal Uncertainty ◽

Popular View ◽

And Function

AbstractA popular view among tort theorists is that an explanation of tort law must take account its “structure,” since this structure constitutes the law’s “self-understanding.” This view is used to both criticize competing functional accounts of tort law, especially economic ones, that are said to ignore tort law’s structure, and, more constructively, as a basis for explaining various tort doctrines. In this essay, I consider this argument closely and conclude that it is faulty. To be valid, one needs a non-question begging way of identifying the essence of tort law. I argue that law’s “self-understanding” can only make sense if it means the understanding of certain people. Examining those, I conclude that the claim of structuralists is false, for there are many people who take its function to be central. I then further show that if one wishes to understand the development of tort law’s doctrine one must take both structure and function into account. I demonstrate this claim by examining the development of the doctrine dealing with causal uncertainty and vicarious liability.

Download Full-text

Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽

10.1007/s10753-021-01507-x ◽

2021 ◽

Author(s):

Shangrila Parvin ◽

Clintoria R. Williams ◽

Simone A. Jarrett ◽

Sandra M. Garraway

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Inflammatory Cytokine ◽

Cardiovascular Health ◽

Mrna Levels ◽

Post Injury ◽

Cord Injury ◽

And Function ◽

The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

Download Full-text

2P034 High-speed AFM observation of structure and function of MukB(01B. Protein: Structure & Function,Poster,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Seibutsu Butsuri ◽

10.2142/biophys.54.s200_4 ◽

2014 ◽

Vol 54 (supplement1-2) ◽

pp. S200

Author(s):

Kenta Yagi ◽

Koichi Yano ◽

Noriyuki Kodera ◽

Hironori Niki ◽

Toshio Ando

Keyword(s):

Protein Structure ◽

Structure Function ◽

Annual Meeting ◽

High Speed ◽

Structure And Function ◽

Biophysical Society ◽

And Function ◽

Afm Observation

Download Full-text

Network-based approaches to quantify multicellular development

Journal of The Royal Society Interface ◽

10.1098/rsif.2017.0484 ◽

2017 ◽

Vol 14 (135) ◽

pp. 20170484 ◽

Cited By ~ 13

Author(s):

Matthew D. B. Jackson ◽

Salva Duran-Nebreda ◽

George W. Bassel

Keyword(s):

Structure Function ◽

Spatial Relations ◽

Higher Order ◽

Cellular Interaction ◽

Cellular Organization ◽

Multicellular Development ◽

Cell Organization ◽

Function Relationship ◽

And Function ◽

The Relationship

Multicellularity and cellular cooperation confer novel functions on organs following a structure–function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure–function relationships that can guide future organ design.

Download Full-text