Versatile and non-cytotoxic GelMA-xanthan gum biomaterial ink for extrusion-based 3D bioprinting

Extrusion-based 3D bioprinting allows the 3D printing of bioinks, composed of cells and biomaterials, to mimic the complex 3D hierarchical structure of native tissues. Successful 3D bioprinting requires bioinks with specific properties, such as biocompatibility, printability, and biodegradability according to the desired application. In the present work, we aimed at developing a new versatile blend of gelatin methacryloyl-xanthan gum (GelMA-XG) suitable for extrusion-based 3D bioprinting with a straightforward process. To this end, we first optimized the process of gelatin methacryloyl (GelMA) synthesis by investigating the impact of different buffer solutions on the degree of functionalization, swelling degree, and degradation rate. The addition of xanthan gum (XG) enabled further tuning of biodegradability and an improvement of GelMA printability. Specifically, an optimal concentration of XG was found through rheological characterization and printability tests. The optimized blend showed enhanced printability and improved shape fidelity as well as its degradation products turned out to be non-cytotoxic, thus laying the foundation for cell-based applications. In conclusion, our newly developed biomaterial ink is a promising candidate for extrusion-based 3D bioprinting

Aerosol Jet Printing of a Benzocyclobutene-Based Ink as Adhesive Material for Wafer Bonding Application

Aerosol jet printing (AJP) is an emerging additive manufacturing technology that is gaining increasing attention in the electronic field. Several studies have been carried out on the AJP of conductive, semiconductive, and dielectric polymers for electronic applications. However, wafer bonding is an application that is still uncovered by literature. Therefore, in this work, the AJP of benzocyclobutene (BCB) as a polymeric adhesive for wafer bonding is presented for the first time. A thorough characterization of the processing parameters is carried out to identify the most ideal conditions for printing at a relatively high speed. Then, square patterns are printed, proving the versatility of the AJP technology in terms of the reachable thickness of the deposited BCB patterns. Complex patterns with a resolution of approximate to 60 mu m are also printed. The bonding properties of the BCB are characterized from a morphological and mechanical point of view. In particular, the shear strength of the BCB coatings deposited with AJP is approximate to 39 MPa and it is comparable with the shear strength of BCB coating deposited by spin-coating. Consequently, AJP represents a valid alternative for the deposition of polymeric adhesive for wafer bonding

Exploring the endocannabinoidome in genetically obese (ob/ob) and diabetic (db/db) mice: Links with inflammation and gut microbiota

Background: Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes. Results: The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice. Conclusions: The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations

Impact of recycling and lateral sediment input on grain size fining trends – implications for reconstructing tectonic and climate forcings in ancient sedimentary systems

Grain size trends in basin stratigraphy are thought to preserve a rich record of the climatic and tectonic controls on landscape evolution. Stratigraphic models assume that over geological timescales, the downstream profile of sediment deposition is in dynamic equilibrium with the spatial distribution of tectonic subsidence in the basin, sea level and the flux and calibre of sediment supplied from mountain catchments. Here, we demonstrate that this approach in modelling stratigraphic responses to environmental change is missing a key ingredient: the dynamic geomorphology of the sediment routing system. For three large alluvial fans in the Iglesia basin, Argentine Andes we measured the grain size of modern river sediment from fan apex to toe and characterise the spatial distribution of differential subsidence for each fan by constructing a 3D model of basin stratigraphy from seismic data. We find, using a self-similar grain size fining model, that the profile of grain size fining on all three fans cannot be reproduced given the subsidence profile measured and for any sediment supply scenario. However, by adapting the self-similar model, we demonstrate that the grain size trends on each fan can be effectively reproduced when sediment is not only sourced from a single catchment at the apex of the system, but also laterally, from tributary catchments and through fan surface recycling. Without constraint on the dynamic geomorphology of these large alluvial systems, signals of tectonic and climate forcing in grain size data are masked and would be indecipherable in the geological record. This has significant implications for our ability to make sensitive, quantitative reconstructions of external boundary conditions from the sedimentary record

E-Cadherin Destabilization Accounts for the Pathogenicity of Missense Mutations in Hereditary Diffuse Gastric Cancer

E-cadherin is critical for the maintenance of tissue architecture due to its role in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary Diffuse Gastric Cancer (HDGC) and missense mutations represent a clinical burden, due to the uncertainty of their pathogenic role. In vitro and in vivo, most mutations lead to loss-of-function, although the causal factor is unknown for the majority. We hypothesized that destabilization could account for the pathogenicity of E-cadherin missense mutations in HDGC, and tested our hypothesis using in silico and in vitro tools. FoldX algorithm was used to calculate the impact of each mutation in E-cadherin native-state stability, and the analysis was complemented with evolutionary conservation, by SIFT. Interestingly, HDGC patients harbouring germline E-cadherin destabilizing mutants present a younger age at diagnosis or death, suggesting that the loss of native-state stability of E-cadherin accounts for the disease phenotype. To elucidate the biological relevance of E-cadherin destabilization in HDGC, we investigated a group of newly identified HDGC-associated mutations (E185V, S232C and L583R), of which L583R is predicted to be destabilizing. We show that this mutation is not functional in vitro, exhibits shorter half-life and is unable to mature, due to premature proteasome-dependent degradation, a phenotype reverted by stabilization with the artificial mutation L583I (structurally tolerated). Herein we report E-cadherin structural models suitable to predict the impact of the majority of cancer-associated missense mutations and we show that E-cadherin destabilization leads to loss-of-function in vitro and increased pathogenicity in vivo

Contamination Control and Assay Results for the Majorana Demonstrator Ultra Clean Components

The MAJORANA DEMONSTRATOR is a neutrinoless double beta decay experiment utilizing enriched Ge-76 detectors in 2 separate modules inside of a common solid shield at the Sanford Underground Research Facility. The DEMONSTRATOR has utilized world leading assay sensitivities to develop clean materials and processes for producing ultra-pure copper and plastic components. This experiment is now operating, and initial data provide new insights into the success of cleaning and processing. Post production copper assays after the completion of Module 1 showed an increase in U and Th contamination in finished parts compared to starting bulk material. A revised cleaning method and additional round of surface contamination studies prior to Module 2 construction have provided evidence that more rigorous process control can reduce surface contamination. This article describes the assay results and discuss further studies to take advantage of assay capabilities for the purpose of maintaining ultra clean fabrication and process design.Comment: Proceedings of Low Radioactivity Techniques (LRT May 2017, Seoul