Recognition surfaces of MHC class I

Summary: Recent crystallographic results have provided dose to atomic resolution views of the recognition events mediated by MHC class I molecules. The specificity-conferring interaction of MHC class I/peptide with a T-cell antigen receptor (TCR) appears dependent on certain key interactions with the MHC scaffold. These interactions, in particular those of the TCR Va domain, define a standard orientation for TCR binding. Previous studies on biologically significant variations in the TCR recognition surface presented by a series of MHC/variant peptide complexes can be reassessed in the light of this TCR-building mode. The interaction of CDS with MHC class I resembles that between antibody and antigen in the use of loops from the CD8 structure. The interaction is of very low affinity and buries equivalent surface area to that between the TCR and MHC class I but while the TCR/MHC interface shows poor surface shape complementarity the match in the conservative interaction between MHC and CDS is precise.     

Morphological and functional characteristics of myocytes isolated from human left ventricular aneurysms

Isolated single myocytes were prepared from myocardium of developing ventricular aneurysms and from myocardium within the scar of chronic ventricular aneurysms. The morphology and function of the individual cells were compared. The cells from developing aneurysms were rod-shaped, with a distinct sarcomeric structure, but did not contract even in the presence of high calcium concentrations. The sarcomere length was significantly higher than that of cells from chronic aneurysms and approached the theoretical point at which no contraction can occur. Cells from chronic aneurysms were either rod-shaped and contractile, or rounded due to hypercontracture of the myofilaments. Electron microscopy of cells from developing aneurysms confirmed the presence of elongated sarcomeres, a loss of the actin-myosin interdigitation, and damage to the contractile proteins which was particularly evident in the thin filaments. Cells with similar characteristics have also been isolated from a ruptured, ischaemic papillary muscle. These changes, which are due either to ischaemia or to overstretching of cells, may account for the weakness of the wall of developing aneurysms and be a cause of rupture or enlargement.     

Regeneration following tibial nerve crush in the rabbit: the effect of proximal constriction.

In order to test the regenerative capacity of atrophic axons, a constricting ligature was placed around the proximal tibial nerve of the rabbit, and the nerve crushed at the ankle one week later. Axonal atrophy with altered g ratios was subsequently confirmed in fibres distal to the site of ligature and proximal to the site of crush. In nerves with tight proximal ligatures the reinnervation of plantar muscles and the subsequent recovery of distal motor latency were delayed, indicating impaired regeneration. This result may be relevant to the "double-crush" theory of nerve damage.     

Crohn's disease with pelvic abscess appearing as lumbar disc herniation

Crohn's disease (regional enteritis) is a chronic inflammatory disease of the bowel with well-documented clinical manifestations and complications. This report of a 35-year-old woman with Crohn's disease outlines the clinical presentation and studies illustrating "quiescent" regional enteritis. The patient was treated for one of the complications of this disease entity. She was referred to the orthopedic clinic with symptoms of lumbar disc syndrome, as well as a painful hip. Crohn's disease was diagnosed and assumed to be well controlled. Physical examination revealed a subgluteal abscess, ostensibly caused by Crohn's disease. The abscess fistulized through the greater sciatic notch. The capricious nature of this disease entity is self-evident.     

Agonist-mediated conformational changes of β-adrenoceptors could occur independent of functional coupling to Ns

Summary Agonist and antagonist binding characteristics of -adrenoceptors in turkey erythrocyte ghosts were determined at different temperatures ranging between 7°C and 42°C. [³H]-DHA saturation binding experiments revealed that the antagonist-receptor interaction is entropy-driven with a small enthalpic contribution. Isoproterenol/[³H]-DHA competition binding followed the law of mass action at all the investigated temperatures. The agonist-receptor interaction is enthalpy driven with a small unfavorable decrease in entropy. This is consistent with the agonist's ability to favor an endoenergetic transconformation of the receptors.Only part of the agonist-bound receptors can undergo functional coupling to the stimulatory component of the adenylate cyclase system (Ns). This coupling process is associated with locking-in of the agonist and becomes persistent in the presence of the alkylating reagent N-ethylmaleimide. The number of agonist/N-ethylmaleimide-sensitive sites (i.e. coupling-prone receptors) increases with the temperature until it reaches a plateau value of 50% between 27–32°C. Qualitatively similar data were obtained for rat lung and turkey erythrocyte membranes. These observations suggest that the whole receptor population can undergo agonist-mediated conformational changes but that only part of them can couple to Ns.     

Remodeling of the ICF: A commentary

Since its publication in 2001 the International Classification of Functioning, Disability and Health (ICF) has attracted debate about the content and the model presented. After almost 20 years use, regular updating since 2008 and with the prospect of a new edition in 2020 there is increasing interest in the ICF as a tool to meet contemporary information requirements. Information on functioning is important across not only health systems, but all areas where change in functioning is important: education, employment, and social welfare for example. This commentary responds to the issues raised in a commentary by Mitra & Shakespeare in 2019 and supports review of the ICF in the current context by informing users and providers of data on human functioning how they might engage in the maintenance, updating, and modernisation of the ICF.     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

“Putting Meat on the Bones”: Understanding the Implementation of a Community-Based Early Intervention and Prevention Programme—Contextual,Person, and Programme Influences

Prevention Science - The adoption and effective delivery of evidence-based interventions within “real-world” community-based, primary health care service settings are of crucial...     

Deciphering the molecular effects of non-ablative Er:YAG laser treatment in an in vitro model of the non-keratinized mucous membrane

Lasers in Medical Science -