Histology and ultrastructure of a tissue-engineered collagen meniscus before and after implantation

The collagen meniscus implant (CMI) is a tissue-engineering technique designed to stimulate regeneration of meniscus-like tissue in cases of irreparable tears or previous meniscectomy. CMI morphology was investigated before and after implantation by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). In a case series biopsy specimens were harvested from four patients who underwent a second arthroscopic look 6 months after placement of the CMI. CMI sections appeared composed of parallel connective laminae of 10-30 mu m, connected by smaller bundles (5-10 mu m). This connective network formed lacunae with diameters between 40 and 60 mu m. At greater magnification, the walls of the lacunae demonstrated tightly packed and randomly distributed collagen fibrils, with diameters ranging from 73 to 439 nm. In the biopsy specimens, the lacunae were filled with connective tissue that contained newly formed vessels and fibroblast-like cells, presenting an abundant rough endoplasmic reticulum and several mitochondria. In the extracellular matrix, the collagen fibrils showed uniform diameters (126 nm +/- 32 nm). The original structure of CMI was still recognizable, and no inflammatory cells were detected within the implant. The morphological findings of this case series demonstrate that CMI provides a three-dimensional scaffold suitable for colonization by precursor cells and vessels and leading to the formation of a fully functional tissue

BANKING REFORM BY STATUTE

The lamentable failure of our banking system to function satisfactorily in the performance of its duties to the public raises at the outset two kinds of questions. Is there something fundamentally unsound about the structure of our banking machinery or does the trouble reside merely in a lack of understanding on the part of bankers of the proper management of the detailed activities in which banks necessarily engage? Or may the unsatisfactory result be ascribed to a combination of these two alternatives? The position taken in this paper is that the structure of our banking system is inherently unsound and that far too large a proportion of bankers have no conception of the fundamental principles of sound banking. When we turn our attention to possible remedies for these defects we are at once confronted not only with the problem of what changes might be efficacious, but also with the question as to the power of the federal government to prescribe by statute the necessary alterations for other than national banks

Wage Against the Machine: How Women Took on Workplace Inequality

This paper focuses on the life and work of Esther Peterson, a key figure in the fight for workplace equality, particularly for women. It explores her significant contributions to labor legislation, including the Equal Pay Act of 1963, and her efforts to empower women in the workforce. The research traces Peterson’s career path through the historical context of women\u27s labor participation from the 1940s through the 1960s, highlighting her impact on creating policies aimed at gender equality in the workplace and her lasting influence on generations of women striving for economic justice

Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by Munc18c <i>In Vitro</i>

Background: Translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the plasma membrane is responsible for the increased rate of glucose transport into fat and muscle cells in response to insulin. This represents a specialised form of regulated membrane trafficking. Intracellular membrane traffic is subject to multiple levels of regulation by conserved families of proteins in all eukaryotic cells. Notably, all intracellular fusion events require SNARE proteins and Sec1p/Munc18 family members. Fusion of GLUT4-containing vesicles with the plasma membrane of insulin-sensitive cells involves the SM protein Munc18c, and is regulated by the formation of syntaxin 4/SNAP23/VAMP2 SNARE complexes. Methodology/Principal Findings Here we have used biochemical approaches to characterise the interaction(s) of Munc18c with its cognate SNARE proteins and to examine the role of Munc18c in regulating liposome fusion catalysed by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. We demonstrate that Munc18c makes contacts with both t- and v-SNARE proteins of this complex, and directly inhibits bilayer fusion mediated by the syntaxin 4/SNAP23/VAMP2 SNARE complex. Conclusion/Significance Our reductionist approach has enabled us to ascertain a direct inhibitory role for Munc18c in regulating membrane fusion mediated by syntaxin 4/SNAP23/VAMP2 SNARE complex formation. It is important to note that two different SM proteins have recently been shown to stimulate liposome fusion mediated by their cognate SNARE complexes. Given the structural similarities between SM proteins, it seems unlikely that different members of this family perform opposing regulatory functions. Hence, our findings indicate that Munc18c requires a further level of regulation in order to stimulate SNARE-mediated membrane fusion

Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters

Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters however has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions indicating that Ras proteins engage in isoform-selective lipid sorting, and accounting for different signal outputs from each Ras isoform. Phosphatidylserine is a common constituent of all Ras nanoclusters but is only an obligate structural component of K-Ras nanoclusters. Segregation of K-Ras and H-Ras into spatially and compositionally distinct lipid assemblies is exquisitely sensitive to plasma membrane phosphatidylserine levels. Phosphatidylserine spatial organization is also modified by Ras nanocluster formation. In consequence Ras nanoclusters engage in remote lipid-mediated communication, whereby activated H-Ras disrupts the assembly and operation of spatially segregated K-Ras nanoclusters. Computational modeling and experiment reveal that complex effects of caveolin and cortical actin on Ras nanoclustering are similarly mediated through regulation of phosphatidylserine spatiotemporal dynamics. We conclude that phosphatidylserine maintains the lateral segregation of diverse lipid-based assemblies on the plasma membrane and that lateral connectivity between spatially remote lipid assemblies offers important, previously unexplored opportunities for signal integration and signal processing