High-Mobility Few-Layer Graphene Field Effect Transistors Fabricated on Epitaxial Ferroelectric Gate Oxides

The carrier mobility \mu of few-layer graphene (FLG) field-effect transistors increases ten-fold when the SiO_2 substrate is replaced by single-crystal epitaxial Pb(Zr_0.2Ti_0.8)O_3 (PZT). In the electron-only regime of the FLG, \mu reaches 7x10^4 cm^2/Vs at 300K for n = 2.4x10^12/cm^2, 70% of the intrinsic limit set by longitudinal acoustic (LA) phonons; it increases to 1.4x10^5 cm^2/Vs at low temperature. The temperature-dependent resistivity \rho(T) reveals a clear signature of LA phonon scattering, yielding a deformation potential D = 7.8+/-0.5 eV.Comment: 5 pages, 4 figure

Role of RGS14(414) in object recognition memory and regulation of synaptic plasticity in perirhinal cortex

Participation of perirhinal and frontal cortices in processing of object recognition memory has long been recognized, however, recently our laboratory extended this to area V2 of visual cortex. We observed that RGS14414-mediated activation of area V2 neurons leads to an enormous increase in object recognition memory. This memory enhancement was of such extent that it converted short term memory of 45 minutes into long lasting long-term memory that could be traced even after many months. Here, we have tested the memory enhancer effect of RGS14414 in perirhinal cortex, an area intimately involved in processing of object memory. A relationship of behavioral performance of RGS14414-treated rats with electrophysiological synaptic plasticity was investigated. Stimulation of perirhinal cortex with RGS14414 produced an equally robust increase in object recognition memory as was observed in area V2. Further, we found that RGS14414-mediated activation of perirhinal cortex, (i) blocked the depotentiation induced by 1Hz stimulation during 10min; (ii) blocked the LTP induced by 20Hz stimulation while showed no effect at 100Hz stimulation; and (iii) reduced the LTD induced by the application of 20µM carbachol, a cholinergic receptor agonist, during 10min, however no effect was observed at a higher concentration (50µM). Furthermore, we also observed that phosphorylated isoforms of AMPA receptor 1 and 2 (iGluR1 & iGluR2) were significantly reduced. Thus, our results indicate that iGluRs reflects the level of synaptic plasticity (LTP and LTD) observed in RGS-animals but lack this correlation with enhanced memory behavior. This work was supported by projects from MINECO, Junta de Andalucía y NIH.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Magnetic anisotropy modulation of magnetite in Fe3O4/BaTiO3(100) epitaxial structures

Temperature dependent magnetometry and transport measurements on epitaxial Fe3O4 films grown on BaTiO3(100) single crystals by molecular beam epitaxy show a series of discontinuities, that are due to changes in the magnetic anisotropy induced by strain in the different crystal phases of BaTiO3. The magnetite film is under tensile strain at room temperature, which is ascribed to the lattice expansion of BaTiO3 at the cubic to tetragonal transition, indicating that the magnetite film is relaxed at the growth temperature. From the magnetization versus temperature curves, the variation in the magnetic anisotropy is determined and compared with the magnetoelastic anisotropies. These results demonstrate the possibility of using the piezoelectric response of BaTiO3 to modulate the magnetic anisotropy of magnetite films.Comment: 4 pages, 4 figure

Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts both as an extracellular ligand for endothelial differentiation gene receptor family and as an intracellular second messenger. Cellular levels of S1P are low and tightly regulated by sphingosine kinase (SPK). Recent studies have suggested that eNOS pathway may function as a downstream target for the biological effects of receptor-mediated S1P. Here we have studied the possible interplay between intracellular SIP generation and the eNOS activation pathway. S1P causes an endothelium-dependent vasorelaxation in rat aorta that is PTX sensitive, inhibited by L-NAME that involves eNOS phosphorylation, and mainly dependent on hsp90. When rat aorta rings were incubated with the SPK inhibitor DL-threo-dihydrosphingosine (DTD), there was a concentration-dependent reduction of Ach-induced vasorelaxation, implying a consistent contribution of sphingolipid pathway through intracellular sphingosine release and phosphorylation. Co-immunoprecipitation experiments consistently showed increased association of hsp90 with eNOS after exposure of cells to S1P as well to BK or calcium ionophore A-23187. Interestingly, as opposite to A-23187, BK and S1P effect were significantly inhibited by pretreatment with the SPK inhibitor DTD. In conclusion, our data demonstrate that an interplay exists among eNOS, hsp90, and intracellularly generated S1P where eNOS coupling to hsp90 is a major determinant for NO release as confirmed by our functional and molecular studies

Heart Rate Variability Analysis Guided by Respiration in Major Depressive Disorder

In this study a Heart Rate Variability (HRV) analysis guided by respiration to evaluate different patterns of Autonomic Nervous System (ANS) in response to a cognitive stressor between Major Depressive Disorder (MDD) and control (CT) subjects is presented. Cardiorespiratory Time Frequency Coherence (TFC) reveals the local coupling of HRV and respiration signal which is essential and usually not included in estimation of ANS measures derived by HRV. Parasympathetic activity of ANS is measured as the power at the frequencies where TFC between HRV and respiration is significant, whereas sympathetic dominance is measured as the normalized power in the low frequency band [0.04,0.15] Hz of HRV excluding the power of those frequencies related to respiration. Results showed significantly lower (p <; 0.05) sympathetic dominance in MDD with respect to CT subjects during stress, suggesting that ANS reactivity as response to stress stimuli is lower in MDD patients. The study of ANS reactivity to a stressor may serve as a biomarker useful for the early diagnosis and monitoring of MDD patients

MiR-1227 targets SEC23A to regulate the shedding of large extracellular vesicles

Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show that miR-1227, which is enriched in prostate cancer EVs, compared to the cell of origin, but not in EVs derived from prostate benign epithelial cells, induces the shedding of large EVs (such as large oncosomes), while inhibiting the shedding of small EVs (such as exosomes). RNA sequencing from cells stably expressing miR-1227, a modified RISCTRAP assay that stabilizes and purifies mRNA-miR-1227 complexes for RNA sequencing, and in silico target prediction tools were used to identify miR-1227 targets that may mediate this alteration in EV shedding. The COPII vesicle protein SEC23A emerged and was validated by qPCR, WBlot, and luciferase assays as a direct target of miR-1227. The inhibition of SEC23A was sufficient to induce the shedding of large EVs. These results identify a novel mechanism of EV shedding, by which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Cultured circulating tumor cells and their derived xenografts for personalized oncology

AbstractRecent cancer research has demonstrated the existence of circulating tumor cells (CTCs) in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells