Focusing on the Americas - home to 40 to 50 million Indigenous people - this book explores the history and current state of Indigenous language revitalization across this vast region. Complementary ...chapters on the USA and Canada, and Latin America and the Caribbean, offer a panoramic view while tracing nuanced trajectories of "top down" (official) and "bottom up" (grass roots) language planning and policy initiatives. Authored by leading Indigenous and non-Indigenous scholars, the book is organized around seven overarching themes: Policy and Politics; Processes of Language Shift and Revitalization; The Home-School-Community Interface; Local and Global Perspectives; Linguistic Human Rights; Revitalization Programs and Impacts; New Domains for Indigenous Languages
Providing a comprehensive, hemisphere-wide scholarly and practical source, this singular collection simultaneously fills a gap in the language revitalization literature and contributes to Indigenous language revitalization efforts.
Abstract A major obstacle in the survival and efficacy of tissue engineered transplants is inadequate oxygenation, whereby unsupportive oxygen tensions result in significant cellular dysfunction and ...death within the implant. In a previous report, we developed an innovative oxygen generating biomaterial, termed OxySite, to provide supportive in situ oxygenation to cells and prevent hypoxia-induced damage. Herein, we explored the capacity of this biomaterial to mitigate hypoxic stress in both rat and nonhuman primate pancreatic islets by decreasing cell death, supporting metabolic activity, sustaining aerobic metabolism, preserving glucose responsiveness, and decreasing the generation of inflammatory cytokines. Further, the impact of supplemental oxygenation on in vivo cell function was explored by the transplantation of islets previously co-cultured with OxySite into a diabetic rat model. Transplant outcomes revealed significant improvement in graft efficacy for OxySite-treated islets, when transplanted within an extrahepatic site. These results demonstrate the potency of the OxySite material to mitigate activation of detrimental hypoxia-induced pathways in islets during culture and highlights the importance of in situ oxygenation on resulting islet transplant outcomes.
A major hindrance in engineering tissues containing highly metabolically active cells is the insufficient oxygenation of these implants, which results in dying or dysfunctional cells in portions of ...the graft. The development of methods to increase oxygen availability within tissue-engineered implants, particularly during the early engraftment period, would serve to allay hypoxia-induced cell death. Herein, we designed and developed a hydrolytically activated oxygen-generating biomaterial in the form of polydimethylsiloxane (PDMS)-encapsulated solid calcium peroxide, PDMS-CaO2. Encapsulation of solid peroxide within hydrophobic PDMS resulted in sustained oxygen generation, whereby a single disk generated oxygen for more than 6 wk at an average rate of 0.026 mM per day. The ability of this oxygen-generating material to support cell survival was evaluated using a β cell line and pancreatic rat islets. The presence of a single PDMS-CaO2 disk eliminated hypoxia-induced cell dysfunction and death for both cell types, resulting in metabolic function and glucose-dependent insulin secretion comparable to that in normoxic controls. A single PDMS-CaO2 disk also sustained enhanced β cell proliferation for more than 3 wk under hypoxic culture conditions. Incorporation of these materials within 3D constructs illustrated the benefits of these materials to prevent the development of detrimental oxygen gradients within large implants. Mathematical simulations permitted accurate prediction of oxygen gradients within 3D constructs and highlighted conditions under which supplementation of oxygen tension would serve to benefit cellular viability. Given the generality of this platform, the translation of these materials to other cell-based implants, as well as ischemic tissues in general, is envisioned.
Liposomes with enhanced elasticity have been proven to increase the efficiency of drug transport across the skin. The understanding of the background physicochemical processes driving the liposome ...viscoelastic properties is an essential feature for the design of effective formulations involving different lipids and additive molecules. In this work we use field-cycled nuclear magnetic resonance relaxometry to analyze both the mechanical properties of liposome membranes, and their relationship with the involved molecular dynamics. Different liposomal formulations were considered. We show a correlation between the molecular dynamical regime and mesoscopic physical parameters that define the expected deformability of the vesicles. Results strongly suggest that the purity of the used lipids may influence the elastic properties of the membranes in an appreciable way. Common features in the behaviour of the involved dynamic variables were identified by comparing formulations with surfactants of similar molecular weight.
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•NMR relaxometry was used to characterize the elastic properties of liposomes.•Formulations of soybean phosphatidylcholine with different surfactants were analyzed.•The purity of used lipids strongly affects the thermal behavior of membrane elasticity.•Both elasticity and molecular diffusion are relevant for liposome deformability.•At skin temperature, the addition of surfactants does not improve deformability.
The use of immunoisolating macrodevices in islet transplantation confers the benefit of safety and translatability by containing transplanted cells within a single retrievable device. To date, there ...has been limited development and characterization of synthetic poly(ethylene glycol) (PEG)-based hydrogel macrodevices for islet encapsulation and transplantation. Herein, we describe a two-component synthetic PEG hydrogel macrodevice system, designed for islet delivery to an extrahepatic islet transplant site, consisting of a hydrogel core cross-linked with a non-degradable PEG dithiol and a vasculogenic outer layer cross-linked with a proteolytically sensitive peptide to promote degradation and enhance localized vascularization. Synthetic PEG macrodevices exhibited equivalent passive molecular transport to traditional microencapsulation materials (e.g., alginate) and long-term stability in the presence of proteases in vitro and in vivo, out to 14 weeks in rats. Encapsulated islets demonstrated high viability within the device in vitro and the incorporation of RGD adhesive peptides within the islet encapsulating PEG hydrogel improved insulin responsiveness to a glucose challenge. In vivo, the implementation of a vasculogenic, degradable hydrogel layer at the outer interface of the macrodevice enhanced vascular density within the rat omentum transplant site, resulting in improved encapsulated islet viability in a syngeneic diabetic rat model. These results highlight the benefits of the facile PEG platform to provide controlled presentation of islet-supportive ligands, as well as degradable interfaces for the promotion of engraftment and overall graft efficacy.
Tissue-engineered devices have the potential to significantly improve human health. A major impediment to the success of clinically scaled transplants, however, is insufficient oxygen transport, ...which leads to extensive cell death and dysfunction. To provide in situ supplementation of oxygen within a cellular implant, we developed a hydrolytically reactive oxygen generating material in the form of polydimethylsiloxane (PDMS) encapsulated solid calcium peroxide, termed OxySite. Herein, we demonstrate, for the first time, the successful implementation of this in situ oxygen-generating biomaterial to support elevated cellular function and efficacy of macroencapsulation devices for the treatment of type 1 diabetes. Under extreme hypoxic conditions, devices supplemented with OxySite exhibited substantially elevated beta cell and islet viability and function. Furthermore, the inclusion of OxySite within implanted macrodevices resulted in the significant improvement of graft efficacy and insulin production in a diabetic rodent model. Translating to human islets at elevated loading densities further validated the advantages of this material. This simple biomaterial-based approach for delivering a localized and controllable oxygen supply provides a broad and impactful platform for improving the therapeutic efficacy of cell-based approaches.
Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with ...cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression.
Women exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables.
The highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group.
We found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.
Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel ...fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradability and its effect on in vivo tissue responses remains underexplored. Here, the authors report a facile method to synthesize microgels crosslinked with ester‐containing junctions to afford tunable degradation kinetics. Monodisperse microgels of maleimide‐functionalized poly(ethylene‐glycol) are generated using droplet microfluidics crosslinked with thiol‐terminated, ester‐containing molecules. Tunable mechanics are achievable based on the ratio of degradable to nondegradable crosslinkers in the continuous phase. Degradation in an aqueous medium leads to microgel deformation based on swelling and a decrease in elastic modulus. Furthermore, degradation byproducts are cytocompatible and do not cause monocytic cell activation under noninflammatory conditions. These injectable microgels possess time‐dependent degradation on the order of weeks in vivo. Lastly, the evaluation of tissue responses in a subcutaneous dorsal pocket shows a dynamic type‐1 like immune response to the synthetic microgels, driven by interferon gamma (IFN‐γ ) expression, which can be moderated by tuning the degradation properties. Collectively, this study demonstrates the development of a hydrolytic microgel platform that can be adapted to desired host tissue immune responses.
Hydrolytically susceptible ethylene linkers are used for microparticle crosslinking to fabricate degradable droplet microfluidic based microgels for therapeutic delivery. The tunability and degradability conferred by the ester‐based degradation in vivo regulate the infiltration of immune cells to the implant site and the host immune polarization.
Excitotoxicity, characterized by over-activation of glutamate receptors, is a major contributor to spinal cord injury (SCI) pathophysiology, resulting in neuronal death and loss of locomotor ...function. In our previous in vitro studies, we showed that excitotoxicity induced by the glutamate analogue kainate (KA) leads to a significant reduction in the number of neurons, providing a model for SCI. Our current objective was to assess the neuroprotective role of resveratrol (RESV), a natural polyphenol, following KA-induced SCI. In vivo excitotoxicity was induced by intraspinal injection of KA immediately followed by RESV administration to Balb/C adult male mice. In neonatal mouse spinal cord preparations, excitotoxicity was transiently induced by bath-applied KA, either with or without RESV. KA administration resulted in a significant deterioration in hindlimb motor coordination and balance during locomotion, which was partially reverted by RESV. Additionally, RESV preserved neurons in both dorsal and ventral regions. Sirtuin 2 (SIRT2) immunoreactive signal was increased by RESV, while the selective SIRT1 inhibitor 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX-527) attenuated RESV neuroprotective effects. These findings suggest that RESV attenuation of excitotoxic-induced neuronal loss and locomotor deficits is mediated, at least in part, through the activation of SIRT1, potentially involving SIRT2 as well. Indeed, our results highlight the potential use of RESV to enhance neuroprotective strategies for SCI.
Resveratrol improved locomotion after in vivo spinal excitotoxic damage and promoted neuronal cell survival after kainate spinal injury, at least in part, through the activation of SIRT1, potentially involving SIRT2 as well. These findings may have an important relevance and highlight the potential use of this natural polyphenol to enhance neuroprotective strategies for SCI. Display omitted
•RESV partially restores locomotion after in vivo spinal excitotoxic damage.•RESV promotes neuronal cell survival after kainate spinal injury.•RESV neuroprotection involves SIRT1 modulation.
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