Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall structure and elastic fiber integrity were normal in resistance/muscular arteries (renal, mesenteric, and saphenous). Elastin cross-linking and total elastin content were unchanged in large or small arteries, whereas elastic fiber architecture was abnormal in large vessels. While the E57K mutation did not affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of mutant animals compared to wild-type arteries but equivalent in mesenteric arteries. We found a differential role of FBLN4 in elastic fiber assembly, where it functions mainly in large conduit arteries. These results suggest that elastin assembly has different requirements depending on vessel type. Normal levels of elastin cross-links in mutant tissue call into question FBLN4\u27s suggested role in mediating lysyl oxidase-elastin interactions. Future studies investigating tissuespecific elastic fiber assembly may lead to novel therapeutic interventions for ARCL1B and other disorders of elastic fiber assembly. 2017 © The Authors, some rights reserved

Sterilization of lung matrices by supercritical carbon dioxide

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO(2)) that can achieve a sterility assurance level 10(−6) in decellularized lung matrix. The effects of ScCO(2) treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO(2) did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO(2), indicating that ScCO(2) produces a matrix that is stable during storage. The current study's results indicate that ScCO(2) can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes

Fluency and Sound System Disorder: What to Do?

Stuttering is a complex disorder that requires a multi-dynamic approach and becomes increasingly more complex when a comorbidity is present; therefore, this poster will present the available data on the comorbidity of fluency and sound system disorders in preschool aged children. Specifically, this poster will provide background information relating to the epidemiology of stuttering in terms of onset, speech characteristics, predictive factors, and current evidence-based practice. Background information pertaining to a sound system disorder and common therapeutic approaches will be discussed as well. Research regarding current clinical practice when treating both disorders and the efficacy behind treating both at the same time will be provided. Lastly, this poster will discuss the efficacy behind treating both disorders in young children.https://griffinshare.fontbonne.edu/slp-posters/1018/thumbnail.jp

Antiferromagnetic Dimers of Ni(II) in the S=1 Spin-Ladder Na_2Ni_2(C_2O_4)_3(H_2O)_2

We report the synthesis, crystal structure and magnetic properties of the S=1 2-leg spin-ladder compound Na_2Ni_2(C_2O_4)_3(H_2O)_2. The magnetic properties were examined by magnetic susceptibility and pulsed high field magnetization measurements. The magnetic excitations have been measured in high field high frequency ESR. Although the Ni(II) ions form structurally a 2-leg ladder, an isolated dimer model consistently describes the observations very well. The analysis of the temperature dependent magnetization data leads to a magnetic exchange constant of J=43 K along the rungs of the ladder and an average value of the g-factor of 2.25. From the ESR measurements, we determined the single ion anisotropy to D=11.5 K. The validity of the isolated dimer model is supported by Quantum Monte Carlo calculations, performed for several ratios of interdimer and intradimer magnetic exchange and taking into account the experimentally determined single ion anisotropy. The results can be understood in terms of the different coordination and superexchange angles of the oxalate ligands along the rungs and legs of the 2-leg spin ladder.Comment: 8 pages, 10 figure

Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice

Elastic fibers provide tissues with elasticity which is critical to the function of arteries, lungs, skin, and other dynamic organs. Loss of elasticity is a major contributing factor in aging and diseases. However, the mechanism of elastic fiber development and assembly is poorly understood. Here, we show that lack of fibulin-4, an extracellular matrix molecule, abolishes elastogenesis. fibulin-4(−/−) mice generated by gene targeting exhibited severe lung and vascular defects including emphysema, artery tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages. All the homozygous mice died perinatally. The earliest abnormality noted was a uniformly narrowing of the descending aorta in fibulin-4(−/−) embryos at embryonic day 12.5 (E12.5). Aorta tortuosity and irregularity became noticeable at E15.5. Histological analysis demonstrated that fibulin-4(−/−) mice do not develop intact elastic fibers but contain irregular elastin aggregates. Electron microscopy revealed that the elastin aggregates are highly unusual in that they contain evenly distributed rod-like filaments, in contrast to the amorphous appearance of normal elastic fibers. Desmosine analysis indicated that elastin cross-links in fibulin-4(−/−) tissues were largely diminished. However, expression of tropoelastin or lysyl oxidase mRNA was unaffected in fibulin-4(−/−) mice. In addition, fibulin-4 strongly interacts with tropoelastin and colocalizes with elastic fibers in culture. These results demonstrate that fibulin-4 plays an irreplaceable role in elastogenesis

Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1

Editorial Análisis de casos Reforma agraria y lucha por la tierra en América Latina La Reforma Agraria en América Latina: una revolución frustrada Plinio Arruda Sampaio A Nova Questão Agrária e a Reinvenção do Campesinato: o caso do MST Carlos Walter Porto-Gonçalves El movimiento campesino en el Paraguay: conflictos, planteamientos y desafíos Tomás Palau Viladesau Movimientos campesinos e indígenas en México: la lucha por la tierra Luciano Concheiro Bórquez y Sergio Grajales Ventura Las luchas campesinas en Colombia en los albores del siglo XXI: de la frustración a la esperanza Isaías Tobasura Acuña Documentos O que precisa ser feito para mudar a vida do povo! Comunicado del Frente Nacional Campesino Ezequiel Zamora de Venezuela Cronología del conflicto La geografía política del conflicto social en América Latina José Seoane y Clara Algranati Región Sur Los sindicatos uruguayos ante el primer gobierno de izquierda Luis Senatore y Jaime Yaffé • Argentina • Brasil • Chile • Paraguay • Uruguay Región Andina Quito en abril: los forajidos derrotan al coronel Mario Unda • Bolivia • Colombia • Ecuador • Perú • Venezuela Región Norte La Guatemala de la resistencia y de la esperanza: las jornadas de lucha contra el CAFTA Simona Violetta Yagenova • Costa Rica • El Salvador • Guatemala • Honduras • México • Nicaragua • Panamá • Puerto Rico • República Dominicana Debates Territorio y movimientos sociales O retorno do território Apresentação por Maria Adélia Aparecida de Souza Milton Santos Outros territórios, outros mapas Ana Clara Torres Ribeiro Movimentos socioterritoriais e movimentos socioespaciais Bernardo Mançano Fernandes Territorios en disputa: iniciativas productivas y acción política en Mosconi, Argentina Norma Giarracca y Juan Wahren Sarjam [Vocablo en lengua aymara que significa ándate] Jorge A. Sainz Cardon

Recipient‐derived EDA fibronectin promotes cardiac allograft fibrosis

Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long‐term allograft survival. While initiating elements of anti‐allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A‐containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN‐deficient (EDA −/− ) and wild‐type (WT) mice. While EDA −/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA −/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra‐graft expression of pro‐fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T‐helper lineages. Conditions supporting regulatory T‐cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient‐derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft‐protective, may drive production of ECM molecules which enhance deleterious remodelling responses. Thus, EDA cFN may be a therapeutic target for ameliorating fibrosis associated with chronic cardiac allograft rejection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90405/1/3010_ftp.pd

Parents’ Perspectives about Tele-Intervention Services for their Children who are Deaf or Hard of Hearing

Purpose: In the first of a two-part survey series, this cross-sectional survey study explored parent perceptions of tele-intervention (TI) services for their young children who are deaf or hard of hearing. Using Likert rating scales, the survey queried parent confidence in understanding their child’s language development, perceptions of the coaching and support they received, the parent-professional partnership, and overall views and recommendations. Data were collected March-May 2020, not realizing the survey release would coincide with the Covid-19 pandemic and the influx of unexpected virtual services. For this reason, data were stratified between those who had received TI services for more than versus less than three months. Responses for in-person services were also evaluated for additional context. Methods: Responses from 48 participants who received TI and 18 participants who received in-person services (n=66) were analyzed using descriptive statistics. Cronbach’s alpha showed high internal consistency for all Likert scales; items of each subscale were sum-scored to examine relationships across queried areas of service delivery. Results: Ninety-six percent of all respondents were highly or mostly satisfied with their TI services and 90% would definitely or probably recommend TI to other families. Overall positive findings were found across Likert scale queries, with no differences between parent perceptions of TI and in-person services, nor between TI for more than versus less than three months. However, findings also highlighted areas in which TI and in-person providers could improve intervention effectiveness, including coaching and supports to optimize parent confidence in understanding and facilitating their child’s language and communication goals. Conclusions: Parent perceptions of the TI delivery model were favorable. Implications and recommendations for both TI and in-person providers are discussed