Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The re

LGBTQ Caregiver Acceptance Scale (LCAS): Development and Validation With a Latinx Sample

Caregiver acceptance and rejection is crucial to the well-being of lesbian, gay, bisexual, transgender, and queer (LGBTQ) people. Research shows that caregivers are affected by having an LGBTQ child/family member, yet studies have neglected to capture the experiences of Latinx caregivers. We present the development and initial validation of the LGBTQ Caregiver Acceptance Scale (LCAS) with a Latinx sample. We developed items based on a review of the literature, expert feedback (N = 9), and community member feedback (N = 9; Study 1). We then assessed the factor structure through exploratory factor analysis (EFA) in a sample of 215 Latinx caregivers of LGBTQ people (Study 2). The final LCAS consists of 40 items and six dimensions of Latinx caregivers\u27 acceptance and rejection of their LGBTQ child/family member: Outness, Caregiver Acceptance, Concealment, Respeto, Attitudes Toward Queer Parenting, and Supportive Actions. Convergent and divergent validity was performed to compare the LCAS to other constructs of caregiver acceptance and rejection, family conflict and cohesion, and attitudes toward the LGBTQ community. As hypothesized, all subscale scores and total score were found to be significantly correlated with the constructs used for comparison. This validated measure of LGBTQ-specific acceptance and rejection among caregivers provides a rich opportunity to understand family processes and help inform evidence-based interventions. We provide implications for clinicians working with Latinx caregivers of LGBTQ youth

Gβγ is a negative regulator of AP-1 mediated transcription

Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both G alpha and G beta gamma subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the G beta gamma subunit. Here, we show that co-expression of the G beta gamma dimer decreased phorbol 12-myristate 13-acetate (PMA)-stimulated AP-1 gene reporter activity in HEK293 cells as well as the AP-1 dependent gonadotropin-releasing hormone-stimulated human follicle-stimulating hormone beta reporter activity in L beta T2 gonadotrope cells. Further, we identify Fos transcription factors as novel interactors of the G beta 1 subunit, using protein fragment complementation assays, as well as co-immunoprecipitation in vivo and in vitro. Fos proteins dimerize with Jun proteins to form activator protein-1 (AP-1) transcription factor complexes, which regulate target gene expression. G beta gamma did not interfere with the dimerization of Fos and Jun or their ability to bind DNA. Rather, G beta gamma co-localized with the AP-1 complex in the nucleus and recruited histone deacetylases (HDACs) to inhibit AP-1 transcriptional activity. Our data indicate a novel role for G beta gamma subunits as transcriptional regulators. (C) 2010 Elsevier Inc. All rights reserved

Reconstructing the environmental conditions around the Silurian Ireviken Event using the carbon isotope composition of bulk and palynomorph organic matter

The carbon isotope composition (δ13C) of bulk organic matter and two palynomorph groups (scolecodonts and chitinozoans) from the Llandovery-Wenlock strata of Gotland (E Sweden) are compared to gain knowledge about carbon cycling in the Silurian (sub)tropical shelf environment. The δ13C values of the palynomorphs are mostly lower than the δ13C values of the bulk organic matter, and the δ13C values of the benthic scolecodonts are lower than those of the planktonic chitinozoans. While the difference between bulk and palynomorph δ13C may be in part a function of trophic state, the lower values of the scolecodonts relative to those of chitinozoans, which are assumed to live in the well-mixed water column, might imply an infaunal mode of life for the polychaetes that carried the scolecodonts. Lower δ13C for the scolecodonts in the middle of the section may represent variations in primary marine productivity (supported by acritarch abundance data), oxidation of organic matter in the bottom waters, or genera effects. In general, however, trends between the three data sets are parallel, indicating similarities in the low frequency, environmentally forced controls. The δ13C data show a decreasing trend from the base of the section, up to a horizon well below the base of the Upper Visby Formation. At this level, and therefore probably several 10 kyr before the δ13C increase in the carbonates, the δ13C organic values increase by ~1‰. This perhaps is an expression of a changed composition of the bulk organic matter associated with the extinction events prior to the Llandovery-Wenlock boundary

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte-like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte-like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte-like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Whole exome sequencing of rare aggressive breast cancer histologies

Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression