Interactions between Primary Neurons and Graphene Films with Different Structure and Electrical Conductivity

Graphene-based materials represent a useful tool for the realization of novel neural interfaces. Several studies have demonstrated the biocompatibility of graphene-based supports, but the biological interactions between graphene and neurons still pose open questions. In this work, the influence of graphene films with different characteristics on the growth and maturation of primary cortical neurons is investigated. Graphene films are grown by chemical vapor deposition progressively lowering the temperature range from 1070 to 650 °C to change the lattice structure and corresponding electrical conductivity. Two graphene-based films with different electrical properties are selected and used as substrate for growing primary cortical neurons: i) highly crystalline and conductive (grown at 1070 °C) and ii) highly disordered and 140-times less conductive (grown at 790 °C). Electron and fluorescence microscopy imaging reveal an excellent neuronal viability and the development of a mature, structured, and excitable network onto both substrates, regardless of their microstructure and electrical conductivity. The results underline that high electrical conductivity by itself is not fundamental for graphene-based neuronal interfaces, while other physico–chemical characteristics, including the atomic structure, should be also considered in the design of functional, bio-friendly templates. This finding widens the spectrum of carbon-based materials suitable for neuroscience applications

PGC-1α induced browning promotes involution and inhibits lactation in mammary glands

The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unknown. First, we show that PGC-1α is highly expressed during puberty and involution, but nearly disappeared in pregnancy and lactation. Then, taking advantage of a newly generated transgenic mouse model with a stable and specific overexpression of PGC-1α in mammary glands, we demonstrate that the re-expression of this coactivator during the lactation stage leads to a precocious regression of the mammary glands. Thus, we propose that PGC-1α action is non-essential during pregnancy and lactation, whereas it is indispensable during involution. The rapid preadipocyte–adipocyte transition, together with an increased rate of apoptosis promotes a premature mammary glands involution that cause lactation defects and pup growth retardation. Overall, we provide new insights in the comprehension of female reproductive cycles and lactation deficiency, thus opening new roads for mothers that cannot breastfeed

Dabrafenib and trametinib activity in a patient with BRAF V600E mutated and microsatellite instability high (MSI-H) metastatic endometrial cancer

BACKGROUND: Targeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies. CASE PRESENTATION: We report herein the case of a heavily pre-treated patient with recurrent microsatellite instability high (MSI-H) BRAF V600E mutated endometrial adenocarcinoma, which was successfully treated with the V600E targeting agent dabrafenib. After developing resistance to this agent, the MEK targeting agent trametinib was added to dabrafenib achieving again a therapeutic response. CONCLUSIONS: This case shows that dabrafenib both as monotherapy and when combined with trametinib may exert significant therapeutic activity in heavily pretreated BRAF V600E mutated endometrial adenocarcinoma, and highlight potential benefits of personalized treatment in this disease

Deciphering the nuclear bile acid receptor FXR paradigm

Originally called retinoid X receptor interacting protein 14 (RIP14), the farnesoid X receptor (FXR) was renamed after the ability of its rat form to bind supra-physiological concentrations of farnesol. In 1999 FXR was de-orphanized since primary bile acids were identified as natural ligands. Strongly expressed in the liver and intestine, FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of conditions such as cholestasis, fatty liver disease, cholesterol gallstone disease, intestinal inflammation and tumors. Furthermore, given the importance of FXR in the gut-liver axis feedbacks regulating lipid and glucose homeostasis, FXR modulation appears to have great input in diseases such as metabolic syndrome and diabetes. Exciting results from several cellular and animal models have provided the impetus to develop synthetic FXR ligands as novel pharmacological agents. Fourteen years from its discovery, FXR has gone from bench to bedside; a novel nuclear receptor ligand is going into clinical use

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

In pres

A Fixed-Wing Biplane MAV for Low Speed Missions

Practical MAVs missions, such as outdoor urban environment recognitions, simultaneously require a capability of both dashing to escape enemy fire and slowly loitering over a target in order to capture and transmit clear images to a ground station. Since an MAV intrinsically offers better payload and endurance capabilities than a rotorcraft of an equal size, fixed-wing MAVs can be considered as promising platforms to start with. The objective of this study is to investigate the possibility of developing a fixed-wing MAV which can both perform rapid translations and low-speed flights through urban canyons. Alow-speed wind tunnel testing is conducted to compare several powered configurations including monoplane, biplane and tandem wing combinations. The testing also focuses on wing-propeller interactions. Results indicate that a positive stagger biplane configuration powered by counter-rotating propellers placed in pusher position provides the best trade-off between a high-speed performance and a low-speed capability with a limited electric consumption. Consequently, a 30 cm span MAV biplane prototype, named TYTO-30, has been designed and built. TYTO-30 is equipped with a 110g-payload which includes a video camera, navigation and autopilot system and has been flight tested successfully

Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia

Key Points LAPTM5 c403t and HCLS1g496a are potentially novel contributors for the genetic predisposition to familial WM. LAPTM5 c403t and HCLS1g496a represent possible candidates for screening in familial WM

Nkx3.2 Promotes Primary Chondrogenic Differentiation by Upregulating Col2a1 Transcription

Background: The Nkx3.2 transcription factor promotes chondrogenesis by forming a positive regulatory loop with a crucial chondrogenic transcription factor, Sox9. Previous studies have indicated that factors other than Sox9 may promote chondrogenesis directly, but these factors have not been identified. Here, we test the hypothesis that Nkx3.2 promotes chondrogenesis directly by Sox9-independent mechanisms and indirectly by previously characterized Sox9-dependent mechanisms. Methodology/Principal Findings: C3H10T1/2 pluripotent mesenchymal cells were cultured with bone morphogenetic protein 2 (BMP2) to induce endochondral ossification. Overexpression of wild-type Nkx3.2 (WT-Nkx3.2) upregulated glycosaminoglycan (GAG) production and expression of type II collagen a1 (Col2a1) mRNA, and these effects were evident before WT-Nkx3.2-mediated upregulation of Sox9. RNAi-mediated inhibition of Nkx3.2 abolished GAG production and expression of Col2a1 mRNA. Dual luciferase reporter assays revealed that WT-Nkx3.2 upregulated Col2a1 enhancer activity in a dose-dependent manner in C3H10T1/2 cells and also in N1511 chondrocytes. In addition, WT-Nkx3.2 partially restored downregulation of GAG production, Col2 protein expression, and Col2a1 mRNA expression induced by Sox9 RNAi. ChIP assays revealed that Nkx3.2 bound to the Col2a1 enhancer element. Conclusions/Significance: Nkx3.2 promoted primary chondrogenesis by two mechanisms: Direct and Sox9-independen