Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold

Alexandros G.Sfakianakis shared this article with you from Inoreader Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation

Alexandros G.Sfakianakis shared this article with you from Inoreader Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology] Μέσω JBC Papers in Press ST6Gal-I, an enzyme upregulated in numerous malignancies, adds α2-6-linked sialic acids to select membrane receptors, thereby modulating receptor signaling and cell phenotype. In this study, we investigated ST6Gal-I's role in epithelial to mesenchymal transition (EMT) using the Suit2 pancreatic cancer cell line, which has low endogenous ST6Gal-I and limited metastatic potential, along with two metastati c Suit2-derived subclones, S2-013 and S2-LM7AA, which have upregulated ST6Gal-I. RNA-Seq results suggested that the metastatic subclones had greater activation of EMT-related gene networks than parental Suit2 cells, and forced overexpression (OE) of ST6Gal-I in the Suit2 line was sufficient to activate EMT pathways. Accordingly, we evaluated expression of EMT markers and cell invasiveness (a key phenotypic feature of EMT) in Suit2 cells with or without ST6Gal-I OE, as well as S2-013 and S2-LM7AA cells with or without ST6Gal-I knockdown (KD). Cells with high ST6Gal-I expression displayed enrichment in mesenchymal markers (N-cadherin, slug, snail, fibronectin) and cell invasiveness, relative to ST6Gal-I-low cells. Contrarily, epithelial markers (E-cadherin, occludin) were suppressed in ST6Gal-I-high cells. To gain mechanistic insight into ST6Gal-I's role in EMT, we examined the activity of EGFR, a known EMT driver. ST6Gal-I-high cells had greater α2-6 sialylation and activation of EGFR than ST6Gal-I-low cells. The EGFR inhibitor, erlotinib, neutralized ST6Gal-I-dependent differences in EGFR activation, mesenchymal marker expression and invasiveness in Suit2 and S2-LM7AA, but not S2-013, lines. Collectively, these results advance our understanding of ST6Gal-I's tumor-promoting function by highlighting a role for ST6Gal-I in EMT, which may be mediated, at least in part, by α2-6-sialylated EGFR. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology] Μέσω JBC Papers in Press The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and d endritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of human RGS14. Here we report that RGS14 encoding LR or RQ profoundly impacts protein functions in hippocampal neurons. RGS14 membrane localization is regulated by binding Gαi-GDP, whereas RGS14 nuclear export is regulated by Exportin 1 (XPO1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit LTP. Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to Gαi1, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and syna ptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

From pathogen to a commensal: modification of the Microbacterium nematophilum-Caenorhabditis elegans interaction during chronic infection by the absence of host insulin signalling [RESEARCH ARTICLE]

Alexandros G.Sfakianakis shared this article with you from Inoreader From pathogen to a commensal: modification of the Microbacterium nematophilum-Caenorhabditis elegans interaction during chronic infection by the absence of host insulin signalling [RESEARCH ARTICLE] Μέσω Biology Open current issue Maria Gravato-Nobre, Jonathan Hodgkin, and Petros Ligoxygakis The nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and vigour. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, the long-lived daf-2 mutant was resi stant to chronic infection, showing reduced colonisation and higher vigour. In fact, UV336 interaction with daf-2 resulted in a host lifespan extension beyond OP50, the Escherichia coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Our results indicate that the interaction between host genotype and strain-specific bacteria determines longevity and health for C. elegans. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

De-Ritis Ratio Is Associated with Mortality after Cardiac Arrest

Alexandros G.Sfakianakis shared this article with you from Inoreader De-Ritis Ratio Is Associated with Mortality after Cardiac Arrest Μέσω Hindawi Publishing Corporation Introduction. The aim of our study was to explore the associations of the aspartate transaminase/alanine transaminase (De-Ritis) ratio with outcomes after cardiac arrest (CA). Methods. This retrospective study included 374 consecutive adult cardiac arrest patients. Information on the study population was obtained from the Dryad Digital Repository. Patients were divided into tertiles based on their De-Ritis ratio. The logistic regression hazard analysis was used to assess the independent relationship between the De-Ritis ratio and mortality. The Kaplan-Meier method and log-rank test were used to estimate the survival of different groups. Receiver operating characteristic (ROC) curve analysis was utilized to compare the prognostic ability of biomarkers. A model combining the De-Ritis ratio was established, and its performance was evaluated using the Akaike information criterion (AIC). Results. Of the 374 patients who were included in the study, 194 patients (51.9%) died in the intensive care unit (ICU), 213 patients (57.0%) died during hospitalization, and 226 patients (60.4%) had an unfavorable neurologic outcome. Logistic regression analysis including potentially confounding factors showed that the De-Ritis ratio was independently associated with mortality, yielding a more than onefold risk of ICU mortality (OR 1.455; 95% CI 1.088-1.946; ) and hospital mortality (OR 1.378; 95% CI 1.031-1.842; ). Discriminatory performance assessed by ROC curves showed an area under the curve of 0.611 (95% CI 0.553-0.668) for ICU mortality and 0.625 (0.567-0.682) for hospital mortality. Further, the likelihood ratio test (LRT) analysis showed that the model combining the De-Ritis ratio had a smaller AIC and higher likelihood ratio score than the model without the De-Ritis ratio. The Kaplan-Meier curves sho wed that the CA patients in the De-Ritis ratio tertile 3 group clearly had a significantly higher incidence of ICU mortality ().Conclusion. An elevated De-Ritis ratio on admission was significantly associated with ICU mortality and hospital mortality after CA. Assessment of the De-Ritis ratio might help identify groups at high risk for mortality. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cervical Cancer Screening Guidelines in the Postvaccination Era: Review of the Literature

Alexandros G.Sfakianakis shared this article with you from Inoreader Cervical Cancer Screening Guidelines in the Postvaccination Era: Review of the Literature Μέσω Hindawi Publishing Corporation Cervical cancer is relatively rare in high-income countries, where organized screening programs are in place, as well as opportunistic ones. As the human papillomavirus (HPV) vaccination rates increase, the prevalence of cervical precancers and cancers is going to decrease rapidly very soon, even if, in the most optimistic scenario, it is unlikely that optimal vaccination coverage will be achieved. Then, the optimal screening paradigm for cervical cancer prevention in the postvaccination era is still debated. Screening guidelines are being developed with the aim of reducing the number of tests a woman needs during her lifetime, in order to receive the maximum benefit from screening, while decreasing potential harms that may result with the use of a screening strategy (overdiagnosis, overtreatment, anxiety, and c osts). With this purpose in mind, new management guidelines for cervical cancer screening abnormalities are recommendations based on risks, not on results. This review aims to summarize the process that led to the introduction of the HPV DNA test in screening programs and the different screening strategies. Moreover, it aims to introduce the new risk-based guidelines for the future, where full HPV genotyping can resize the risk on the basis of specific high-risk genotypes. In the same way, the data regarding HPV vaccination could be introduced as soon as women vaccinated with the nonavalent vaccine reach the screening age, with the recommendation of a prolonged screening interval. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.