Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain

The aim of this study was to evaluate glucose-bearing niosomes as a brain targeted delivery system for the vasoactive intestinal peptide (VIP). To this end, VIP/125I-VIP-loaded glucose-bearing niosomes were intravenously injected to mice. Brain uptake was determined by measuring the radioactivity of 125I-labeled VIP using gamma-counting, after intravenous administration of VIP in solution or encapsulated in glucose-bearing niosomes or in control niosomes. VIP integrity was assessed by reversed-phase HPLC analysis of brain extracts. Distribution of 125I-VIP derived radioactivity was examined from serial brain slices. HPLC analysis confirmed the presence of intact VIP in brain after administration of VIP-loaded niosomes, but not after administration of VIP solution. Encapsulation within glucose-bearing niosomes mainly allowed a significantly higher VIP brain uptake compared to control niosomes (up to 86%, 5min after treatment). Brain distribution of intact VIP after injection of glucose-bearing niosomes, indicated that radioactivity was preferentially located in the posterior and the anterior parts of the brain, whereas it was homogeneously distributed in the whole brain after the administration of control vesicles. In conclusion, this novel vesicular formulation of VIP delivers intact VIP to particular brain regions in mice. Glucose-bearing vesicles might be therefore a novel tool to deliver drugs across the blood-brain barrier (BBB)

Effects of the vasoactive intestinal peptide (VIP) and related peptides on glioblastoma cell growth in vitro

The growth rate of numerous cancer cell lines is regulated in part by actions of neuropeptides of the vasoactive intestinal peptide (VIP) family, which also includes pituitary adenylate cyclase-activating peptide (PACAP), glucagon, and peptide histidine/isoleucine (PHI). The aim of this work was to investigate the effect of these peptides on the growth of the rat glioblastoma cell line C6 in vitro. We also sought to determine which binding sites were correlated with the effects observed. Proliferation studies performed by means of a CyQuant trade mark assay showed that VIP and PACAP strongly stimulated C6 cell proliferation at most of the concentrations tested, whereas PHI increased cell proliferation only when associated with VIP. Two growth hormone-releasing factor (GRF) derivatives and the VIP antagonist hybrid peptide neurotensin-VIP were able to inhibit VIP-induced cell growth stimulation, even at very low concentrations. Binding experiments carried out on intact cultured C6 cells, using 125I-labeled VIP and PACAP as tracers, revealed that the effects of the peptides on cell growth were correlated with the expression on C6 cells of polyvalent high-affinity VIP-PACAP binding sites and of a second subtype corresponding to very high-affinity VIP-selective binding species. The latter subtype, which interacted poorly with PACAP with a 10,000-fold lower affinity than VIP, might mediate the antagonist effects of neurotensin- VIP and of both GRF derivatives on VIP-induced cell growth stimulation

Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats

The aim of this work was to study in rats the nasal route for the brain delivery of the vasoactive intestinal peptide (VIP) neuropeptide. After evaluating VIP stability in solutions obtained from nasal washes, the effect of formulation parameters (pH 4-9, 0-1% (w/v) lauroylcarnitine (LC), hypo- or isoosmolality) on the brain uptake of intranasally administered VIP (10(-8)M)/125I-VIP (300,000 cpm/ml) was studied, using an in situ perfusion technique. Brain radioactivity distribution was assessed by quantitative autoradiographic analysis. Results were compared to intravenously administered VIP. With a hypotonic formulation at pH 4 containing 0.1% LC and 1% bovine serum albumin, VIP stability was satisfactory and loss by adsorption was minimal. Using this formulation, around 0.11% of initial radioactivity was found in the brain after 30 min perfusion and was located in the olfactory bulbs, the midbrain and the cerebellum. HPLC analysis of brain and blood extracts demonstrated the presence of intact VIP in brain and its complete degradation in the blood compartment. By intravenous administration, no intact VIP was found either in brain or in blood. In conclusion, intact VIP could be delivered successfully to the brain using the intranasal route for administration

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

Searches for the Violation of Pauli Exclusion Principle at LNGS in VIP(-2) experiment

The VIP (Violation of Pauli exclusion principle) experiment and its follow-up experiment VIP-2 at the Laboratori Nazionali del Gran Sasso (LNGS) search for X-rays from Cu atomic states that are prohibited by the Pauli Exclusion Principle (PEP). The candidate events, if they exist, will originate from the transition of a $2p$ orbit electron to the ground state which is already occupied by two electrons. The present limit on the probability for PEP violation for electron is 4.7 $\times10^{-29}$ set by the VIP experiment. With upgraded detectors for high precision X-ray spectroscopy, the VIP-2 experiment will improve the sensitivity by two orders of magnitude.Comment: 5 pages, 3 figures, 1 table. Conference proceedings for oral presentation at TAUP 2015, Torin

RIDWAN KAMIL AND TRI RISMAHARINI: LOCAL AND IDEAL LEADERSHIP MODELS IN THE MILLENNIAL ERA

This study discusses the ideal of local leadership models in the millennial era. This research is library research, which collects and analyzes documents, both written documents, pictures and electronics as well as books that discuss leadership, journals and research that have been conducted relating to ideal leadership in millennial generation era. In the millennial era, effective governance will be realized if the leader can meet the qualifications as a credible leader, has the ability, intelligence, and vision far ahead. A good leader must have integrity, honesty, and loyalty for the interests of the people. Millennial leadership needs to support the spirit of independence and entrepreneurship of the millennial generation

Two-dimensional solar spectropolarimetry with the KIS/IAA Visible Imaging Polarimeter

Spectropolarimetry at high spatial and spectral resolution is a basic tool to characterize the magnetic properties of the solar atmosphere. We introduce the KIS/IAA Visible Imaging Polarimeter (VIP), a new post-focus instrument that upgrades the TESOS spectrometer at the German VTT into a full vector polarimeter. VIP is a collaboration between the KIS and the IAA. We describe the optical setup of VIP, the data acquisition procedure, and the calibration of the spectropolarimetric measurements. We show examples of data taken between 2005 and 2008 to illustrate the potential of the instrument. VIP is capable of measuring the four Stokes profiles of spectral lines in the range from 420 to 700 nm with a spatial resolution better than 0.5". Lines can be sampled at 40 wavelength positions in 60 s, achieving a noise level of about 2 x 10E-3 with exposure times of 300 ms and pixel sizes of 0.17" x 0.17" (2 x 2 binning). The polarization modulation is stable over periods of a few days, ensuring high polarimetric accuracy. The excellent spectral resolution of TESOS allows the use of sophisticated data analysis techniques such as Stokes inversions. One of the first scientific results of VIP presented here is that the ribbon-like magnetic structures of the network are associated with a distinct pattern of net circular polarization away from disk center. VIP performs spectropolarimetric measurements of solar magnetic fields at a spatial resolution that is only slightly worse than that of the Hinode spectropolarimeter, while providing a 2D field field of view and the possibility to observe up to four spectral regions sequentially with high cadence. VIP can be used as a stand-alone instrument or in combination with other spectropolarimeters and imaging systems of the VTT for extended wavelength coverage.Comment: 10 pages, 8 figures, accepted by Astronomy and Astrophysics v2: figures updated with improved qualit

A collaborative platform for integrating and optimising Computational Fluid Dynamics analysis requests

A Virtual Integration Platform (VIP) is described which provides support for the integration of Computer-Aided Design (CAD) and Computational Fluid Dynamics (CFD) analysis tools into an environment that supports the use of these tools in a distributed collaborative manner. The VIP has evolved through previous EU research conducted within the VRShips-ROPAX 2000 (VRShips) project and the current version discussed here was developed predominantly within the VIRTUE project but also within the SAFEDOR project. The VIP is described with respect to the support it provides to designers and analysts in coordinating and optimising CFD analysis requests. Two case studies are provided that illustrate the application of the VIP within HSVA: the use of a panel code for the evaluation of geometry variations in order to improve propeller efficiency; and, the use of a dedicated maritime RANS code (FreSCo) to improve the wake distribution for the VIRTUE tanker. A discussion is included detailing the background, application and results from the use of the VIP within these two case studies as well as how the platform was of benefit during the development and a consideration of how it can benefit HSVA in the future