Monitoring of Cell Layer Integrity with a Current-Driven Organic Electrochemical Transistor

The integrity of CaCo-2 cell barriers is investigated by organic electrochemical transistors (OECTs) in a current-driven configuration. Ion transport through cellular barriers via the paracellular pathway is modulated by tight junctions between adjacent cells. Rupturing its integrity by H2O2 is monitored by the change of the output voltage in the transfer characteristics. It is demonstrated that by operating the OECT in a current-driven configuration, the sensitive and temporal resolution for monitoring the cell barrier integrity is strongly enhanced as compared to the OECT transient response measurement. As a result, current-driven OECTs are useful tools to assess dynamic and critical changes in tight junctions, relevant for clinical applications as drug targeting and screening

Linking food web functioning and habitat diversity for an ecosystem based management: A Mediterranean lagoon case-study

We propose a modelling approach relating the functioning of a transitional ecosystem with the spatial extension of its habitats. A test case is presented for the lagoon of Venice, discussing the results in the context of the application of current EU directives. The effects on food web functioning due to changes related to manageable and unmanageable drivers were investigated. The modelling procedure involved the use of steady-state food web models and network analysis, respectively applied to estimate the fluxes of energy associated with trophic interactions, and to compute indices of food web functioning. On the long term (hundred years) temporal scale, the model indicated that the expected loss of salt marshes will produce further changes at the system level, with a lagoon showing a decrease in the energy processing efficiency. On the short term scale, simulation results indicated that fishery management accompanied by seagrass restoration measures would produce a slight transition towards a more healthy system, with higher energy cycling, and maintaining a good balance between processing efficiency and resilience. Scenarios presented suggest that the effectiveness of short term management strategies can be better evaluated when contextualized in the long term trends of evolution of a system. We also remark the need for further studying the relationship between habitat diversity and indicators of food web functioning

The obstetric syndromes: Clinical relevance of placental hormones

Preterm delivery, preeclampsia and intrauterine growth restriction are the major diseases of pregnancy. A key role in their pathogenesis is played by the placenta, which is the source of hormones and other important regulatory molecules providing the metabolic and endocrine homeostasis of the fetal-placental unit. Since obstetric syndromes are characterized by important maternal and neonatal morbidity and mortality worldwide, numerous efforts have been made over the years to prevent and treat them. Due to their complex pathogenesis, however, the therapy is poor and not very effective. Therefore, great emphasis is currently given to the prevention of these diseases through the identification of biochemical and biophysical markers, among which placental factors play a crucial role. The increasing knowledge of the role of placental molecules can indeed lead to the development of new therapeutic and diagnostic tools. © 2013 Expert Reviews Ltd

OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer

Background: Anaplastic Thyroid Cancer (ATC) is an undifferentiated and aggressive tumor that often originates from well-Differentiated Thyroid Carcinoma (DTC) through a trans-differentiation process. Epithelial-to-Mesenchymal Transition (EMT) is recognized as one of the major players of this process. OVOL2 is a transcription factor (TF) that promotes epithelial differentiation and restrains EMT during embryonic development. OVOL2 loss in some types of cancers is linked to aggressiveness and poor prognosis. Here, we aim to clarify the unexplored role of OVOL2 in ATC. Methods: Gene expression analysis in thyroid cancer patients and cell lines showed that OVOL2 is mainly associated with epithelial features and its expression is deeply impaired in ATC. To assess OVOL2 function, we established an OVOL2-overexpression model in ATC cell lines and evaluated its effects by analyzing gene expression, proliferation, invasion and migration abilities, cell cycle, specific protein localization through immunofluorescence staining. RNA-seq profiling showed that OVOL2 controls a complex network of genes converging on cell cycle and mitosis regulation and Chromatin Immunoprecipitation identified new OVOL2 target genes. Results: Coherently with its reported function, OVOL2 re-expression restrained EMT and aggressiveness in ATC cells. Unexpectedly, we observed that it caused G2/M block, a consequent reduction in cell proliferation and an increase in cell death. This phenotype was associated to generalized abnormalities in the mitotic spindle structure and cytoskeletal organization. By RNA-seq experiments, we showed that many pathways related to cytoskeleton and migration, cell cycle and mitosis are profoundly affected by OVOL2 expression, in particular the RHO-GTPase pathway resulted as the most interesting. We demonstrated that RHO GTPase pathway is the central hub of OVOL2-mediated program in ATC and that OVOL2 transcriptionally inhibits RhoU and RhoJ. Silencing of RhoU recapitulated the OVOL2-driven phenotype pointing to this protein as a crucial target of OVOL2 in ATC. Conclusions: Collectively, these data describe the role of OVOL2 in ATC and uncover a novel function of this TF in inhibiting the RHO GTPase pathway interlacing its effects on EMT, cytoskeleton dynamics and mitosis

Reconfigurable Complementary Logic Circuits with Ambipolar Organic Transistors

Ambipolar organic electronics offer great potential for simple and low-cost fabrication of complementary logic circuits on large-area and mechanically flexible substrates. Ambipolar transistors are ideal candidates for the simple and low-cost development of complementary logic circuits since they can operate as n-type and p-type transistors. Nevertheless, the experimental demonstration of ambipolar organic complementary circuits is limited to inverters. The control of the transistor polarity is crucial for proper circuit operation. Novel gating techniques enable to control the transistor polarity but result in dramatically reduced performances. Here we show high-performance non-planar ambipolar organic transistors with electrical control of the polarity and orders of magnitude higher performances with respect to state-of-art split-gate ambipolar transistors. Electrically reconfigurable complementary logic gates based on ambipolar organic transistors are experimentally demonstrated, thus opening up new opportunities for ambipolar organic complementary electronics.115Ysciescopu