Key Matrix Research Articles

Structural and compositional diversity of fibrillin microfibrils in human tissues

Elastic fibers comprising fibrillin microfibrils and elastin are present in many tissues, including the skin, lungs, and arteries, where they confer elasticity and resilience. Although fibrillin microfibrils play distinct and tissue-specific functional roles, it is unclear whether their ultrastructure and composition differ between elastin-rich (skin) and elastin-poor (ciliary body and zonule) organs or after in vitro synthesis by cultured cells. Here, we used atomic force microscopy, which revealed that the bead morphology of fibrillin microfibrils isolated from the human eye differs from those isolated from the skin. Using newly developed pre-MS preparation methods and LC-MS/MS, we detected tissue-specific regions of the fibrillin-1 primary structure that were differentially susceptible to proteolytic extraction. Comparing tissue- and culture-derived microfibrils, we found that dermis- and dermal fibroblast–derived fibrillin microfibrils differ in both bead morphology and periodicity and also exhibit regional differences in fibrillin-1 proteolytic susceptibility. In contrast, collagen VI microfibrils from the same dermal or fibroblast samples were invariant in ultrastructure (periodicity) and protease susceptibility. Finally, we observed that skin- and eye-derived microfibril suspensions were enriched in elastic fiber– and basement membrane–associated proteins, respectively. LC-MS/MS also identified proteins (such as calreticulin and protein-disulfide isomerase) that are potentially fundamental to fibrillin microfibril biology, regardless of their tissue source. Fibrillin microfibrils synthesized in cell culture lacked some of these key proteins (MFAP2 and -4 and fibrillin-2). These results showcase the structural diversity of these key extracellular matrix assemblies, which may relate to their distinct roles in the tissues where they reside.

Bi‐directional Macrophage‐Fibroblast Crosstalk Directs Wound Resolution Factors

IntroductionDuring the wound repair process, fibroblasts secrete abundant extracellular matrix (ECM) proteins and participate in remodeling of the provisional ECM. Macrophages and other immune cells also play an important role in all stages of wound healing. Classically activated macrophages (CAMs/M1) contribute to inflammation early on, while alternatively activated macrophages (AAMs/M2) secrete ECM‐degrading enzymes including matrix metallopeptidases (MMPs) during the resolution phase. It is also understood that macrophages instruct fibroblast activities and that crosstalk is largely coordinated by secreted factors. However, the differential effect of CAMs and AAMs on fibroblasts remains elusive. CXCR3 is a chemokine receptor known to modulate both fibroblast and macrophage activity during wound healing and its activation acts as a critical stop signal to halt continuous ECM remodeling by fibroblasts. Yet, the importance of CXCR3 in macrophage‐fibroblast crosstalk during tissue repair remains explored. Therefore, the goal of this study was to investigate the interplay between macrophages and fibroblasts and elucidate the role of CXCR3 signaling in this interaction.MethodsWe differentiated naïve bone marrow‐derived macrophages (M0) into either CAMs/M1 using IFN‐gamma and LPS, or AAMs/M2 using IL‐4. To study the effects of secreted and cell‐contact dependent factors, we used both indirect and direct co‐culture systems. The role of CXCR3 in macrophages and fibroblasts was examined using cells from wild‐type (WT) and CXCR3−/− knockout mice.ResultsCytokine profiling revealed that fibroblasts treated with media conditioned (CM) by CAMs secreted higher levels of CXCR3 ligands CXCL10 and CXCL11 compared to untreated fibroblasts. Because both fibroblasts and macrophages express CXCR3, it was unclear which cell type might respond to these ligands. Investigation using qRT‐PCR, showed that treatment with WT CAM CM resulted in increased fibroblast expression of MMP8 and MMP9 compared to no treatment. Fibroblast induction of MMPs by WT CAM CM persisted when CXCR3−/− fibroblasts were treated with WT CAM CM, but was greatly diminished when fibroblasts were cultured with CXCR3−/− CAM CM, suggesting that this crosstalk requires CXCR3 expression on CAMs but not on fibroblasts. The influence of macrophage subtypes on MMP8, MMP9, and TGF‐β‐induced α‐SMA and ECM protein production was observed by IF staining.ConclusionsOur data indicate that CAMs induce fibroblast expression of CXCR3 ligands and key matrix degrading enzymes MMP8 and MMP9, with MMP expression requiring CXCR3 expression on CAMs. Thus, our study suggests for the first time that paracrine interaction between fibroblasts and macrophages dictate the effector functions of fibroblasts and the wound healing process.Support or Funding InformationSupported by grants from NIAMS and NIAD (AR68317 CCY and R56A1097679 NI), and support in kind from the Pittsburgh VA Medical Center (AW), the School of Nursing, and McGowan Institute of Regenerative Medicine (BNB, CCY).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Macroporous click-elastin-like hydrogels for tissue engineering applications

Elastin is a key extracellular matrix (ECM) protein that imparts functional elasticity to tissues and therefore an attractive candidate for bioengineering materials. Genetically engineered elastin-like recombinamers (ELRs) maintain inherent properties of the natural elastin (e.g. elastic behavior, bioactivity, low thrombogenicity, inverse temperature transition) while featuring precisely controlled composition, the possibility for biofunctionalization and non-animal origin. Recently the chemical modification of ELRs to enable their crosslinking via a catalyst-free click chemistry reaction, has further widened their applicability for tissue engineering. Despite these outstanding properties, the generation of macroporous click-ELR scaffolds with controlled, interconnected porosity has remained elusive so far. This significantly limits the potential of these materials as the porosity has a crucial role on cell infiltration, proliferation and ECM formation. In this study we propose a strategy to overcome this issue by adapting the salt leaching/gas foaming technique to click-ELRs. As result, macroporous hydrogels with tuned pore size and mechanical properties in the range of many native tissues were reproducibly obtained as demonstrated by rheological measurements and quantitative analysis of fluorescence, scanning electron and two-photon microscopy images. Additionally, the appropriate size and interconnectivity of the pores enabled smooth muscle cells to migrate into the click-ELR scaffolds and deposit extracellular matrix. The macroporous structure together with the elastic performance and bioactive character of ELRs, the specificity and non-toxic character of the catalyst-free click-chemistry reaction, make these scaffolds promising candidates for applications in tissue regeneration. This work expands the potential use of ELRs and click chemistry systems in general in different biomedical fields.

Interleukin 6 Plays a Role in the Migration of Magnetically Levitated Mesenchymal Stem Cells Spheroids

Mesenchymal stem cells (MSCs) reside quiescently within a specialised ‘niche’ environment in the bone marrow. However, following appropriate signalling cues, MSCs mobilise and migrate out from the niche, typically toward either sites of injury (a regenerative response) or toward primary tumours (an intrinsic homing response, which promotes MSCs as cellular vectors for therapeutic delivery). To date, very little is known about MSC mobilisation. By adopting a 3D MSC niche model, whereby MSC spheroids are cultured within a type I collagen gel, recent studies have highlighted interleukin-6 (IL-6) as a key cytokine involved in MSC migration. Herein, the ability of IL-6 to induce MSC migration was further investigated, and the key matrix metalloproteinases used to effect cell mobilisation were identified. Briefly, the impact of IL-6 on the MSC migration in a two-dimensional model systems was characterised—both visually using an Ibidi chemotaxis plate array (assessing for directional migration) and then via a standard 2D monolayer experiment, where cultured cells were challenged with IL-6 and extracted media tested using an Abcam Human MMP membrane antibody array. The 2D assay displayed a strong migratory response toward IL-6 and analysis of the membrane arrays data showed significant increases of several key MMPs. Both data sets indicated that IL-6 is important in MSC mobilisation and migration. We also investigated the impact of IL-6 induction on MSCs in 3D spheroid culture, serving as a simplistic model of the bone marrow niche, characterised by fluorescently tagged magnetic nanoparticles and identical membrane antibody arrays. An increase in MMP levels secreted by cells treated with 1 ng/mL IL-6 versus control conditions was noted in addition to migration of cells away from the central spheroid mass.

Cardiometabolic response of juvenile rainbow trout exposed to dietary selenomethionine

Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1–0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Previous studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can cause significant cardiotoxicity and alter aerobic metabolic capacity, energy homeostasis and swimming performance. The goal of this study aims to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular and metabolic implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in juvenile rainbow trout (Oncorhynchus mykiss). Juvenile rainbow trout were fed either control food (1.3 μg Se/g d.m.) or Se-Met spiked food (6.4, 15.8 or 47.8 μg Se/g d.m.) for 60 d at 3% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function in vivo. Chronic dietary exposure to Se-Met significantly increased stroke volume, cardiac output, and ejection fraction. Fish fed with Se-Met spiked food had elevated liver glycogen and triglyceride stores, suggesting impaired energy homeostasis. Exposure to Se-Met significantly decreased mRNA abundance of citrate synthase (CS) in liver and serpin peptidase inhibitor, clad H1 (SERPINH) in heart, and increased mRNA abundance of sarcoplasmic reticulum calcium ATPase (SERCA) and key cardiac remodelling enzyme matrix metalloproteinase 9 (MMP9) in heart. Taken together, these responses are consistent with a compensatory cardiac response to increased susceptibility to oxidative stress, namely a decrease in ventricular stiffness and improved cardiac function. These cardiac alterations in trout hearts were linked to metabolic disruption in other major metabolic tissues (liver and skeletal muscle), impaired glucose tolerance with increased levels of the toxic glucose metabolite, methylglyoxal, increased lipid peroxidation in skeletal muscle, development of cataracts and prolonged feeding behaviour, indicative of visual impairment. Therefore, although juvenile rainbow trout hearts were apparently able to functionally compensate for adverse metabolic and anti-oxidant changes after chronic dietary exposure Se-Met, complications associated with hyperglycemia in mammalian species were evident and would threaten survival of juvenile and adult fish.

Multiscale Co-Design Analysis of Energy, Latency, Area, and Accuracy of a ReRAM Analog Neural Training Accelerator

Neural networks are an increasingly attractive algorithm for natural language processing and pattern recognition. Deep networks with >50M parameters are made possible by modern GPU clusters operating at <50 pJ per op and more recently, production accelerators capable of <5pJ per operation at the board level. However, with the slowing of CMOS scaling, new paradigms will be required to achieve the next several orders of magnitude in performance per watt gains. Using an analog resistive memory (ReRAM) crossbar to perform key matrix operations in an accelerator is an attractive option. This work presents a detailed design using a state of the art 14/16 nm PDK for of an analog crossbar circuit block designed to process three key kernels required in training and inference of neural networks. A detailed circuit and device-level analysis of energy, latency, area, and accuracy are given and compared to relevant designs using standard digital ReRAM and SRAM operations. It is shown that the analog accelerator has a 270x energy and 540x latency advantage over a similar block utilizing only digital ReRAM and takes only 11 fJ per multiply and accumulate (MAC). Compared to an SRAM based accelerator, the energy is 430X better and latency is 34X better. Although training accuracy is degraded in the analog accelerator, several options to improve this are presented. The possible gains over a similar digital-only version of this accelerator block suggest that continued optimization of analog resistive memories is valuable. This detailed circuit and device analysis of a training accelerator may serve as a foundation for further architecture-level studies.

Inclusion of peripheral correspondences in object and pose estimation for visual servoing path-planning

This article addresses the utilization of peripheral image correspondences obtained in cameras obeying the unified model for path-planning-based visual servoing applications. The proposed approach consists of reprojecting available image correspondences onto an oriented virtual plane, which is designed to carry as many reprojections as possible from correspondences, especially those in periphery region. To realize this, a key transformation matrix is proposed and applied to spherical projections of those correspondences. After this transformation, object and pose estimation are realized via the minimization of algebraic and geometric errors by introducing appropriate parametrization and strategies. The geometric error will be defined either on the virtual plane or on the spherical surface. Minimization of error function defined on the spherical surface provides much more accurate estimation results in object structure than that of other error functions as demonstrated in simulation examples. At last, expe...

Nanofibrous peptide hydrogel elicits angiogenesis and neurogenesis without drugs, proteins, or cells

The design of materials for regenerative medicine has focused on delivery of small molecule drugs, proteins, and cells to help accelerate healing. Additionally, biomaterials have been designed with covalently attached mimics of growth factors, cytokines, or key extracellular matrix components allowing the biomaterial itself to drive biological response. While the approach may vary, the goal of biomaterial design has often centered on promoting either cellular infiltration, degradation, vascularization, or innervation of the scaffold. Numerous successful studies have utilized this complex, multicomponent approach; however, we demonstrate here that a simple nanofibrous peptide hydrogel unexpectedly and innately promotes all of these regenerative responses when subcutaneously implanted into the dorsal tissue of healthy rats. Despite containing no small molecule drugs, cells, proteins or protein mimics, the innate response to this material results in rapid cellular infiltration, production of a wide range of cytokines and growth factors by the infiltrating cells, and remodeling of the synthetic material to a natural collagen-containing ECM. During the remodeling process, a strong angiogenic response and an unprecedented degree of innervation is observed. Collectively, this simple peptide-based material provides an ideal foundational system for a variety of bioregenerative approaches.

S-Glutathionylation Influences the Property of Fibronectin

Fibronectin is a key extracellular matrix (ECM) protein that plays a role in cell growth, migration and differentiation through its engagement of cell surface receptors, known as integrins, in a spatiotemporal manner. Fibronectin is a mechanically sensitive protein displaying force-induced conformational changes that impact its multiple growth factor, integrin, and ECM protein binding domains. Fibronectin is a unique ECM protein in that it contains 4 free cysteine residues that are protected in cryptic sites, but that can be exposed under force. S-glutathionylation is a post-translational modification of cysteines that occurs in oxidative environments like the extracellular space during pathologies like cancer and fibrosis. Here, we show for the first time that fibronectin's cysteines can be glutathionylated when exposed either through chemical unfolding in its soluble form or mechanical unfolding in its fibrillar form (both on the single fiber and matrix level). Moreover, we proved that S-glutathionylation impacts the mechanical properties of fibronectin fibers. Specifically, our results reveal that glutathionylated fibronectin fibers are more extensible and less stiff compared to unmodified fibronectin. This is true for both single fibronectin fibers and fibronectin matrices. Thus S-glutathionylation of mechanically exposed cysteines on fibronectin may act as a mechanism of mechanical memory within fibronectin-rich ECMs, regulating subsequent mechanotransduction. One possible realism of this mechanism could be the enhancement fibronectin's integrin binding mechanoswitch due to fibronectin fibers being more easily stretched under lower force regimes.

Dysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion

The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment. Validation in PCa cell lines revealed that AUY922 caused marked alterations to cell morphology, and suppressed cell motility and invasion compared to vehicle or 17-AAG, concomitant with dysregulation of key extracellular matrix proteins such as fibronectin (FN1). Interestingly, while the expression of FN1 was increased by AUY922, FN1 secretion was significantly decreased. This resulted in cytosolic accumulation of FN1 protein within late endosomes, suggesting that AUY922 disrupts vesicular secretory trafficking pathways. Depletion of FN1 by siRNA knockdown markedly reduced the invasive capacity of PCa cells, phenocopying AUY922. These results highlight a novel mechanism of action for AUY922 beyond its established effects on cellular mitosis and survival and, furthermore, identifies extracellular matrix cargo delivery as a potential therapeutic target for the treatment of aggressive PCa.

Basement Membrane Defects in Genetic Kidney Diseases.

The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.

Faster Image Encryption: A Semi-Tensor Product Approach

Due to the large-scale of the images, they suffer from a long time to finish the process of encryption and decryption. In this paper, we propose a novel image-encryption algorithm to improve the performance of processing time based on the semi-tensor product (STP). The STP is a novel matrix product that works by extending the conventional matrix product in cases of unequal dimensions. In paper, we construct a small reversible key matrix by using the Kronecker product. Then, we use this key matrix to change the values of pixels in the original image by applying the semi-tensor product. As a result, the dimensions of the original image are much larger than the dimensions of the key matrix, and the amount of data that is calculated during the encryption and decryption process is effectively reduced. Meanwhile, the proposed algorithm can be used to encrypt and decrypt images of different sizes. Experiments were carried out using images of various sizes. The experimental results were compared with previous methods and the proposed method outperformed the others in terms of security and processing time.

Investment and construction project matrix as the basis of forming the highly effective organizational structure

The article covers the research results of the ways of forming the effective organizational structure for investment and construction project based on key events matrix. Current practice of investment and construction project development does not provide for project organizational structure detailed formation. Construction management plan (CMP) describes the organizational structure relatively and in general terms. Therefore, the customer confines himself only to development of staff’s schedule, and delegating the formation of organizational structure to the general contractor, what is moving the solution of this task to the construction site. A large number of participants form a spontaneous organizational structure, so the management of this structure becomes manual. This leads to the numerous adjustments to plans and construction schedules, as well as additions and changes in the technical documentation of the project. All this result in unstable work, unreasonable delays and, eventually, in quality deterioration, disruption of deadlines and rise in construction costs. This article describes the method of forming the highly effective investment and construction project’s organizational structure, which is based on the key events matrix that is the network functional model of project’s executive system. Its properties, transformation rules and the forming algorithm are described in details.

Obsolescence Mitigation in Automotive Industry using Long Term Storage Feasibility Model

The diminishing of material sources leads companies, especially industrial, to implement remedial actions to continue to serve their customers throughout the committed contractual period. Original Equipment Manufacturers face hard relations with car manufac¬turers and thousands of suppliers. The obsolescence and diminishing number of sources, specifically in electronic and IT devices, cause tough problems to OEM because of their dependency to the ever increasing number of these devices in modern cars. This is the reason why, in compliance with the IATF TS16949 standard, it is necessary to identify the costs, feasibility of implementation, as well as the success and risk chances of any obsolescence management plan. In practice, two solutions are regularly used: bridge stock and last time buy. However, the long term storage causes real management problems and cost difficulties when the supplier minimum order level is much greater than the product short term forecasts. From a technical, economical and risk assessment point of views, this paper looks at the feasibility study of long term storage based on the field situations in one of the main OEMs in the car industry. Based on a review of the literature, we identify the constraints related to the types of materials, their handling and storage conditions. By modeling the decision-makings for management of obsolescence and diminishing sources, we study the possible solutions and their consequences. The preventing actions are studied through a key matrix as a decision tool. A formal model is presented and a real automotive case is studied.

Echoes of Scripture in the Gospels by Richard B. Hays

Reviewed by: Echoes of Scripture in the Gospels by Richard B. Hays Micah D. Kiel richard b. hays, Echoes of Scripture in the Gospels (Waco, TX: Baylor University Press, 2016). Pp. xix + 504. $49.95. The word "echo" hardly provides an apt summary of the variety of ways Hays wrangles the OT into the intellectus spiritualis (pp. 348-49) of the Gospel authors. H. finds shouts, mysterious whispers, images, and songs, all in service to his more pervasive phrase, "figural reading" (e.g., 2, 347). In a short introduction, H. sets for himself a historical task, one focused on the "extant texts" rather than "conjectural reconstruction" about social location or the historical Jesus (pp. 6-7). He intends an exercise in "intertextual close reading" (p. 7). Although this reading is informed by theory, H. generally relegates such discussion to the endnotes. Many of H.'s readings depend on metalepsis, in which the quotation of or allusion to a small portion of text is made intelligible through the sense of the broader context from which it came. Hays organizes the book according to each of the evangelists, followed by a conclusion. While H. will reflect at the end on points of commonality, he teases out a unique hermeneutic and emphasis for each of the four. The clarity of his prose is impressive, as is the acuity of the figural reading he attributes to the evangelists. He never yields in attempting to demonstrate that the Scripture of Israel was the key hermeneutical matrix through which the Gospel authors fused the story of Israel with what God was doing through Jesus. Hays's interpretations are an exposition of Israel's "story" (a ubiquitous word in this book) in each Gospel, told through allusion and echo in order to give each evangelist's individual emphases. In most cases, this leads to fascinating insight into one of the Gospels. For example, H. reads Mark's call of the disciples as fishers of people (Mark 1:17) metaleptically through Jer 16:16-18 and Amos 4:1-2. This connects the call with Mark's theme of eschatological judgment and turns the story into an evocative exposition of Mark's overall eschatological agenda. H. is also instructive in his treatment of the langue of blood in Matt 27:24-5. He connects this with Zech 9:11 to suggest that the blood does not need to be associated with judgment, "but rather with cleansing … and liberation" (p. 135). These examples demonstrate the book's considerable strengths: attention to the evangelists' intentions and the ways in which echoes function through metalepsis to reveal deeper meaning and resonances. There is subtlety and depth here, achieved only through extensive awareness of Israel's Scriptures and the ways they can be reconfigured in the Gospels. Not all readers will be convinced by all of H.'s readings, but the book deserves the wide readership it certainly has already gained. There are many ways in which Hays's work could be critiqued. I am sure reviewers will ask whether repeated references to "readers" (e.g., pp. 276, 360) sufficiently describe the original reception of the Gospels. H.'s claim that Jesus embodies the God of Israel in all four Gospels will certainly spark discussion. I offer here two critiques in the spirit of dialogue that a good book such as this one inspires. First, figural readings and metalepsis are not well suited to Hays's historical claims about the evangelists' intentions. Figural reading is powerful and beautiful, but it is not externally verifiable. I demonstrate this by turning to an oration by Gregory of Nazianzus (Or. 40.10), in which he interprets Jesus' temptation in the wilderness and the dialogue between the devil and Jesus (Matt 4:5-6). The devil tells Jesus to throw himself down from [End Page 142] the pinnacle of the temple and then quotes Ps 91:11-12 about how angels will protect him. Gregory points out that the devil's quotation is selective, asking, Why do you skip the verse that follows? The very next verse (Ps 91:13) discusses the trampling of a snake, which Gregory uses metaleptically to demonstrate how Christians can triumph...

Collagen VI in healthy and diseased nervous system.

ABSTRACTCollagen VI is a major extracellular matrix protein exerting a number of functions in different tissues, spanning from biomechanical to regulatory signals in the cell survival processes, and playing key roles in maintaining the stemness or determining the differentiation of several types of cells. In the last couple of years, emerging findings on collagen VI have led to increased interest in its role in the nervous system. The role of this protein in the peripheral nervous system was intensely studied and characterized in detail. Collagen VI acts as a regulator of Schwann cell differentiation and is required for preserving peripheral nerve myelination, function and structure, as well as for orchestrating nerve regeneration after injury. Although the role and distribution of collagen VI in the peripheral nervous system is now well established, the role of this distinctive extracellular matrix component in the central nervous system, along with its links to human neurological and neurodegenerative disorders, remains an open field of investigation. In this Review, we summarize and discuss a number of recent findings related to collagen VI in the central and peripheral nervous systems. We further link these findings to different aspects of the protein that are relevant to human diseases in these compartments in order to provide a comprehensive overview of the roles of this key matrix component in the nervous system.

The influence of hyperglycemia on the remodeling of urethral connective tissue in pregnant rats

ObjectiveTo analyze the distribution and quantification of the key structural extracellular matrix components of the urethral tissue in a rat model of hyperglycemia and pregnancy. Study designA total of 120 female Wistar rats were distributed into the following four experimental groups: virgin, pregnant, hyperglycemic and hyperglycemic + pregnant groups. The urethra was harvested for histochemical, morphometric, immunohistochemical, Western blot and glycosaminoglycan analyses. All protocols were approved by the Institutional Animal Care and Use Committee of Botucatu Medical School (process number 828–2010). ResultsThe hyperglycemic + pregnant group showed significantly increased stiffness in urethral tissue. The total striated muscle was decreased, with increased deposition of collagen fibers around the muscle fibers and a change in the organization of the collagen fibrils. An increase in the relative collagen type I/III ratio and a decrease in total glycosaminoglycans were also observed. ConclusionsThis study provides the first line of experimental evidence supporting a metabolic relationship between hyperglycemia and urethral remodeling of connective tissue in pregnant rats. The different organization of the collagen fibrils and the profile of glycosaminoglycans found in urethral samples suggest that the pathology of the urethral fibromuscular system could be related to hyperglycemia-induced pelvic floor dysfunction in women, which has direct clinical implications with the possibility to develop new multidisciplinary treatments for improving the health care of these women.

Dynamic Key Matrix of Hill Cipher Using Genetic Algorithm

The matrix in Hill Cipher was designed to perform encryption and decryption. Every column and row must be inserted by integer numbers. But, not any key that can be given to the matrix used for the process. The wrong determinant result cannot be used in the process because it produces the incorrect plaintext when doing the decryption after the encryption. Genetic algorithms offer the optimized way to determine the key used for encryption and decryption on the Hill Cipher. By determining the evaluation function in the genetic algorithm, the key that fits the composition will be obtained. By implementing this algorithm, the search of the key on the Hill Cipher will be easily done without spending too much time. Genetic algorithms do well if it is combined with Hill Cipher.

Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells?

Bicuspid aortic valve (BAV) is the most common type of congenital cardiac malformation. Patients with a BAV have a predisposition for the development of thoracic aortic aneurysm (TAA). This pathological aortic dilation may result in aortic rupture, which is fatal in most cases. The abnormal aortic morphology of TAAs results from a complex series of events that alter the cellular structure and extracellular matrix (ECM) composition of the aortic wall. Because the major degeneration is located in the media of the aorta, most studies aim to unravel impaired smooth muscle cell (SMC) function in BAV TAA. However, recent studies suggest that endothelial cells play a key role in both the initiation and progression of TAAs by influencing the medial layer. Aortic endothelial cells are activated in BAV mediated TAAs and have a substantial influence on ECM composition and SMC phenotype, by secreting several key growth factors and matrix modulating enzymes. In recent years there have been significant advances in the genetic and molecular understanding of endothelial cells in BAV associated TAAs. In this review, the involvement of the endothelial cells in BAV TAA pathogenesis is discussed. Endothelial cell functioning in vessel homeostasis, flow response and signaling will be highlighted to give an overview of the importance and the under investigated potential of endothelial cells in BAV-associated TAA.

A Modifying of Hill Cipher Algorithm with 3 Substitution Caesar Cipher

The hill cipher algorithm has the uniqueness of using matrix multiplication in the process where the key used is a matrix that has weaknesses in the process of encryption and decryption. In this paper will be modified to the encryption process with caesar cipher substitution. The principle of the hill cipher algorithm using the multiplication of the 2x2 key matrix of keys is enhanced through process modification lies in the combination of initial character determination using the substitution of 3 caesar ciphers. From the results of this modification can be seen that the more the number of characters processed the time required will be longer. The magnitude of the determinant also affects time and size during the poses. A 1 character increment occurs if the initial character of the encryption process is an odd number.