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Profilaggrin belongs to the S100 fused-type protein family expressed in keratinocytes and is important for skin barrier integrity. Its N-terminus contains an S100 ("A") domain and a unique "B" domain with a nuclear localization sequence.
To determine whether profilaggrin B domain cooperates with the S100 domain to bind macromolecules. To characterize the biochemical and structural properties of the profilaggrin N-terminal "AB" domain and compare it to other S100 fused-type proteins.
We used biochemical (protease protection, light scattering, fluorescence spectroscopy, pull-down assays) and computational techniques (sequence analysis, molecular modeling with crystallographic structures) to examine human profilaggrin and S100 fused-type proteins.
Comparing profilaggrin S100 crystal structure with models of the other S100 fused-type proteins demonstrated each has a unique chemical composition of solvent accessible surface around the hydrophobic binding pocket. S100 fused-type proteins exhibit higher pocket hydrophobicity than soluble S100 proteins. The inter-EF-hand linker in S100 fused-type proteins contains conserved hydrophobic residues involved in binding substrates. Profilaggrin B domain cooperates with the S100 domain to bind annexin II and keratin intermediate filaments in a calcium-dependent manner using exposed cationic surface. Using molecular modeling we demonstrate profilaggrin B domain likely interacts with annexin II domains I and II. Steric clash analysis shows annexin II N-terminal peptide is favored to bind profilaggrin among S100 fused-type proteins.
The N-terminal S100 and B domains of profilaggrin cooperate to bind substrate molecules in granular layer keratinocytes to provide epidermal barrier functions.
The N-terminal S100 and B domains of profilaggrin cooperate to bind substrate molecules in granular layer keratinocytes to provide epidermal barrier functions.It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks and ribbons in mammalian cells. This ensures proper functioning of the Golgi apparatus in protein trafficking and processing. More recently, GRASP proteins have drawn extensive attention from researchers due to their diverse and essential roles in and out of the Golgi in different organisms. In this review, we summarize their established roles in Golgi structure formation and function under physiological conditions. We then highlight the emerging and divergent roles for individual GRASP proteins, focusing on GRASP65 in cell migration and apoptosis and GRASP55 in unconventional protein secretion and autophagy under stress or pathological conditions.
This is a basic science research.
Isolating excursion of the flexor digitorum profundus (FDP) in zones I and II is common practice in the current management after flexor tendon repair. During this procedure, the proximal interphalangeal joint is sometimes fully extended with unmeasured external forces at the middle phalanx when the distal interphalangeal joint is actively flexed.
The purpose of the study was to investigate the incremental effect of external force with palmar blocking versus lateral blocking and increased angles of flexion on internal tendon forces at the repair site for a safer application of force by the treating therapist.
Eight human cadaveric fingers were studied. To simulate palmar or lateral finger blocking, a compression force of blocking was applied from 5N (510 grams) to 25N (2,550 grams) on the skin surface of the palmar or the lateral aspect of each of these middle phalanges in 5N increments. iMDK The tensile load on the FDP tendon during distal interphalangeal joint flexion from 0° to 60° was measured in 10° increments.
During palmar blocking, the tensile load was significantly increased with increases in palmar blocking force. However, no significant increase in the tensile load on the FDP tendon was observed at any lateral blocking.
Lateral blocking exercise can be performed with less tensile force on the FDP tendon when performing blocking exercise after flexor tendon injury repair.
This study supports the concept that lateral blocking with incremental joint angles allows a safer application of force for the healing tendon.
This study supports the concept that lateral blocking with incremental joint angles allows a safer application of force for the healing tendon.
Due to the complex shape of the carpometacarpal (CMC) joint, a fixed joint collapse deformity of the thumb CMC (CMC1) and metacarpophalangeal (MCP1) joint can present in advanced stages of CMC1 osteoarthritis (OA), resulting in adduction of the first metacarpal (MC1) and hyperextension of the MCP1.
To determine whether joint collapse deformity is associated with worse pain and/or functional impairment.
Cross-sectional.
This study used the baseline data from 140 patients enrolled in a longitudinal study of treatment for CMC1 OA. (efficacy of combined conservative therapies on clinical outcomes in patients with CMC1 OA). Joint collapse was determined at baseline using a pinch gauge. Pain was assessed on a visual analog scale (0-100) and function was assessed using the Functional Index for Hand Osteoarthritis questionnaire (0-30). Pain and function and the presence of joint collapse were entered in a univariate logistic regression. The final adjusted model for pain and joint collapse included age and sex. The final adjusted model for function and joint collapse included Kellgren Lawrence grade and grip strength.
About 20% of participants demonstrated joint collapse on the tip-pinch test. The presence of joint collapse was associated with increased pain in the unadjusted [P=.047, OR=2.45, 95% CI (1.01, 5.910)] and adjusted model [P=.049, OR=2.45, 95% CI (1.00, 5.98)].
CMC1 patients with joint collapse reported increased pain compared with those without joint collapse. Future studies should determine the relationship between thumb hypermobility and joint collapse and how to manage these conditions effectively.
CMC1 patients with joint collapse reported increased pain compared with those without joint collapse. Future studies should determine the relationship between thumb hypermobility and joint collapse and how to manage these conditions effectively.
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