Specific processing of tenascin-C by the metalloprotease meprinbeta neutralizes its inhibition of cell spreading

The metalloprotease meprin has been implicated in tissue remodelling due to its capability to degrade extracellular matrix components. Here, we investigated the susceptibility of tenascin-C to cleavage by meprinbeta and the functional properties of its proteolytic fragments. A set of monoclonal antibodies against chicken and human tenascin-C allowed the mapping of proteolytic fragments generated by meprinbeta. In chicken tenascin-C, meprinbeta processed all three major splicing variants by removal of 10kDa N-terminal and 38kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern was found for large human tenascin-C variant where two N-terminal peptides (10 or 15kDa) and two C-terminal fragments (40 and 55kDa) were removed from the intact subunit. N-terminal sequencing revealed the exact amino acid positions of cleavage sites. In both chicken and human tenascin-C N-terminal cleavages occurred just before and/or after the heptad repeats involved in subunit oligomerization. In the human protein, an additional cleavage site was identified in the alternative fibronectin type III repeat D. Whereas all these sites are known to be attacked by several other proteases, a unique cleavage by meprinbeta was located to the 7th constant fibronectin type III repeat in both chicken and human tenascin-C, thereby removing the C-terminal domain involved in its anti-adhesive activity. In cell adhesion assays meprinbeta-digested human tenascin-C was not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Whereas the expression of meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibited many meprinbeta-positive leukocytes in regions where tenascin-C was strongly induced. Our data indicate that, at least under pathological conditions, meprinbeta might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity.

Excitability properties of mouse motor axons in the mutant SOD1(G93A) model of amyotrophic lateral sclerosis

Non-invasive excitability studies of motor axons in patients with amyotrophic lateral sclerosis (ALS) have revealed a changing pattern of abnormal membrane properties with disease progression, but the heterogeneity of the changes has made it difficult to relate them to pathophysiology. The SOD1(G93A) mouse model of ALS displays more synchronous motoneuron pathology. Multiple excitability measures of caudal and sciatic nerves in mutant and wild-type mice were compared before onset of signs and during disease progression (4-19 weeks), and they were related to changes in muscle fiber histochemistry. Excitability differences indicated a modest membrane depolarization in SOD1(G93A) axons at about the time of symptom onset (8 weeks), possibly due to deficient energy supply. Previously described excitability changes in ALS patients, suggesting altered sodium and potassium conductances, were not seen in the mice. This suggests that those changes relate to features of the human disease that are not well represented in the animal model.

Lateral ridge augmentation using equine- and bovine-derived cancellous bone blocks: a feasibility study in dogs

OBJECTIVES: The aim of the present study was to histologically evaluate and compare a new prototype collagen type I/III-containing equine- (EB) and a bovine- (BB) derived cancellous bone block in a dog model. MATERIALS AND METHODS: Four standardized box-shaped defects were bilaterally created at the buccal aspect of the alveolar ridge in the lower jaws of five beagle dogs and randomly allocated to either EB or BB. Each experimental site was covered by a native (non-crosslinked) collagen membrane and left to heal in a submerged position for 12 weeks. Dissected blocks were processed for semi-/and quantitative analyses. RESULTS: Both groups had no adverse clinical or histopathological events (i.e. inflammatory/foreign body reactions). BB specimens revealed no signs of biodegradation and were commonly embedded in a fibrous connective tissue. New bone formation and bony graft integration were minimal. In contrast, EB specimens were characterized by a significantly increased cell (i.e. osteoclasts and multinucleated giant cells)-mediated degradation of the graft material (P<0.001). The amount and extent of bone ingrowth was consistently higher in all EB specimens, but failed to reach statistical significance in comparison with the BB group (P>0.05). CONCLUSIONS: It was concluded that the application of EB may not be associated with an improved bone formation than BB.

Radiation dose optimized lateral expansion of the field of view in synchrotron radiation X-ray tomographic microscopy

Volumetric data at micrometer level resolution can be acquired within a few minutes using synchrotron-radiation-based tomographic microscopy. The field of view along the rotation axis of the sample can easily be increased by stacking several tomograms, allowing the investigation of long and thin objects at high resolution. On the contrary, an extension of the field of view in the perpendicular direction is non-trivial. This paper presents an acquisition protocol which increases the field of view of the tomographic dataset perpendicular to its rotation axis. The acquisition protocol can be tuned as a function of the reconstruction quality and scanning time. Since the scanning time is proportional to the radiation dose imparted to the sample, this method can be used to increase the field of view of tomographic microscopy instruments while optimizing the radiation dose for radiation-sensitive samples and keeping the quality of the tomographic dataset on the required level. This approach, dubbed wide-field synchrotron radiation tomographic microscopy, can increase the lateral field of view up to five times. The method has been successfully applied for the three-dimensional imaging of entire rat lung acini with a diameter of 4.1 mm at a voxel size of 1.48 microm.

Differential activation of the lateral premotor cortex during action observation

Background Action observation leads to neural activation of the human premotor cortex. This study examined how the level of motor expertise (expert vs. novice) in ballroom dancing and the visual viewpoint (internal vs. external viewpoint) influence this activation within different parts of this area of the brain. Results Sixteen dance experts and 16 novices observed ballroom dance videos from internal or external viewpoints while lying in a functional magnetic resonance imaging scanner. A conjunction analysis of all observation conditions showed that action observation activated distinct networks of premotor, parietal, and cerebellar structures. Experts revealed increased activation in the ventral premotor cortex compared to novices. An internal viewpoint led to higher activation of the dorsal premotor cortex. Conclusions The present results suggest that the ventral and dorsal premotor cortex adopt differential roles during action observation depending on the level of motor expertise and the viewpoint.

Trigonal and peritrigonal lesions of the lateral ventricle-surgical considerations and outcome analysis of 20 patients

The aim of this study is to review the results and clinical outcome of patients with surgically treated lesions within the trigone of the lateral ventricle. This is a retrospective case series of 20 (eight male, 12 female) patients with lesions of the trigone of the lateral ventricle operated between 1998 and 2008. All lesions were removed via the transcortical temporal and transcortical parietal route. Surgical complications and outcome were assessed using the modified Rankin Scale (mRS). There were four children and 16 adults with a mean age of 42?±?22 years (min?=?1, max?=?74). Eight (40%) lesions grew within the trigone of the dominant hemisphere. In 17 cases, the lesion was purely intraventricular, and in three cases, a slight paraventricular extension was seen. The mean size was 4.5 cm of maximal diameter. Surgical removal was achieved via the transcortical parietal route in 13 cases (65%) and the transcortical temporal route in seven cases (35%). In all cases, complete resection was possible. According to the mRS, 13 patients improved, five remained the same, and two were lost to follow-up. One patient had an increased visual field deficit postoperatively and new hemiparesis and aphasia, but returned to the preoperative level within a few weeks. In one patient, an acute myocardial infarction occurred due to previous cardiac stent placement and in-stent stenosis. Even large trigonal lesions can be resected with low morbidity using a transcortical approach depending on the peritrigonal extension of the tumor.

Local pain and spreading hyperalgesia induced by intramuscular injection of nerve growth factor are not reduced by local anesthesia of the muscle

Injections with local anesthesia for therapeutic and diagnostic purposes are common clinical practice. This double-blind placebo controlled study explores the rational of local anesthetic blocks for the detection of muscle pain as the primary generator in spreading hyperalgesic conditions.

[Laparoscopic management of genital prolapse by lateral suspension using mesh: a series of 377 patients]

Genital prolapse is frequent and can be found in about 50% of parous women. Its etiology is complex and multifactorial. Predisposing factors include: genetics (connective tissue disorders, family history); general state (age, parity, weight, smoking, obstructive pulmonary disease); trauma (carrying heavy loads, intense physical exercise); or iatrogenic (post hysterectomy). Treatment can be conservative or surgical and depends mainly on the severity of symptoms. Developments in surgical techniques and synthetic material in the last 20 years enabled us to use minimally invasive procedures with improved post operative course and decreased recurrence rates.

Demonstration of epitope-spreading phenomena in bullous pemphigoid: results of a prospective multicenter study

Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period. Epitope-spreading (ES) events were detected in 17 of 35 BP patients (49%). They preferentially occurred in an early stage of the disease and were significantly related to disease severity at diagnosis. Moreover, in three patients, spreading of IgG reactivity to intracellular epitopes of BP180 and BP230 was preceded by recognition of the BP180 ectodomain. Finally, IgG reactivity with extracellular epitopes of BP180 and intracellular epitopes of BP230 correlated with the severity of BP in disease course. These findings support the idea that IgG recognition of the BP180 ectodomain is an early and crucial event in BP disease, followed by variable intra- and intermolecular ES events, which likely shape the individual course of BP.

Callosal connections of primary visual cortex predict the spatial spreading of binocular rivalry across the visual hemifields

In binocular rivalry, presentation of different images to the separate eyes leads to conscious perception alternating between the two possible interpretations every few seconds. During perceptual transitions, a stimulus emerging into dominance can spread in a wave-like manner across the visual field. These traveling waves of rivalry dominance have been successfully related to the cortical magnification properties and functional activity of early visual areas, including the primary visual cortex (V1). Curiously however, these traveling waves undergo a delay when passing from one hemifield to another. In the current study, we used diffusion tensor imaging (DTI) to investigate whether the strength of interhemispheric connections between the left and right visual cortex might be related to the delay of traveling waves across hemifields. We measured the delay in traveling wave times (ΔTWT) in 19 participants and repeated this test 6 weeks later to evaluate the reliability of our behavioral measures. We found large interindividual variability but also good test-retest reliability for individual measures of ΔTWT. Using DTI in connection with fiber tractography, we identified parts of the corpus callosum connecting functionally defined visual areas V1-V3. We found that individual differences in ΔTWT was reliably predicted by the diffusion properties of transcallosal fibers connecting left and right V1, but observed no such effect for neighboring transcallosal visual fibers connecting V2 and V3. Our results demonstrate that the anatomical characteristics of topographically specific transcallosal connections predict the individual delay of interhemispheric traveling waves, providing further evidence that V1 is an important site for neural processes underlying binocular rivalry.

Lateral ridge augmentation using a PCL-TCP scaffold in a clinically relevant but challenging micropig model

In implant dentistry, there is a need for synthetic bone substitute blocks to support ridge augmentation in situations where large bone volumes are missing. Polycaprolactone-based scaffolds demonstrated excellent results in bone tissue engineering applications. The use of customized polycaprolactone-tricalcium phosphate (PCL-TCP) displayed promising results from recent rat femur and rabbit calvaria studies. However, data from clinically representative models in larger animals do not exist.