A Role for Xanthurenic Acid in the Control of Brain Dopaminergic Activity

Xanthurenic acid (XA) is a metabolite of the kynurenine pathway (KP) synthetized in the brain from dietary or microbial tryptophan that crosses the blood-brain barrier through carrier-mediated transport. XA and kynurenic acid (KYNA) are two structurally related compounds of KP occurring at micromolar concentrations in the CNS and suspected to modulate some pathophysiological mechanisms of neuropsychiatric and/or neurodegenerative diseases. Particularly, various data including XA cerebral distribution (from 1 µM in olfactory bulbs and cerebellum to 0.1–0.4 µM in A₉ and A₁₀), its release, and interactions with G protein-dependent XA-receptor, glutamate transporter and metabotropic receptors, strongly support a signaling and/or neuromodulatory role for XA. However, while the parent molecule KYNA is considered as potentially involved in neuropsychiatric disorders because of its inhibitory action on dopamine release in the striatum, the effect of XA on brain dopaminergic activity remains unknown. Here, we demonstrate that acute local/microdialysis-infusions of XA dose-dependently stimulate dopamine release in the rat prefrontal cortex (four-fold increase in the presence of 20 µM XA). This stimulatory effect is blocked by XA-receptor antagonist NCS-486. Interestingly, our results show that the peripheral/intraperitoneal administration of XA, which has been proven to enhance intra-cerebral XA concentrations (about 200% increase after 50 mg/kg XA i.p), also induces a dose-dependent increase of dopamine release in the cortex and striatum. Furthermore, our in vivo electrophysiological studies reveal that the repeated/daily administrations of XA reduce by 43% the number of spontaneously firing dopaminergic neurons in the ventral tegmental area. In the substantia nigra, XA treatment does not change the number of firing neurons. Altogether, our results suggest that XA may contribute together with KYNA to generate a KYNA/XA ratio that may crucially determine the brain normal dopaminergic activity. Imbalance of this ratio may result in dopaminergic dysfunctions related to several brain disorders, including psychotic diseases and drug dependence.     

Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma

Over the past two decades, the natural history of multiple myeloma (MM) has evolved dramatically, owing primarily to novel agents targeting MM in the bone marrow microenvironment (BMM) pathways. However, the mechanisms of resistance acquisition remain a mystery and are poorly understood. Autophagy and apoptosis are tightly controlled processes and play a critical role in the cell growth, development, and survival of MM. Genetic instability and abnormalities are two hallmarks of MM. During MM progression, plasma malignant cells become genetically unstable and activate various signaling pathways, resulting in the overexpression of abnormal proteins that disrupt autophagy and apoptosis biological processes. Thus, achieving a better understanding of the autophagy and apoptosis processes and the proteins that crosslinked both pathways, could provide new insights for the MM treatment and improve the development of novel therapeutic strategies to overcome resistance. This review presents a sufficient overview of the roles of autophagy and apoptosis and how they crosslink and control MM progression and drug resistance. Potential combination targeting of both pathways for improving outcomes in MM patients also has been addressed.     

Optimized Discrete Control Law for Quadrotor Stabilization: Experimental Results

This paper deals with the real-time stabilization of a Quadrotor mini helicopter applying a discrete optimal control. A discrete control strategy is better adapted to be executed in a micro-controller, therefore better results are expected with respect to continuous case. Furthermore, the optimal control law allows to helicopter to save energy and then increase its time of flight. The discrete optimal control law is synthesized considering an infinite horizon together with an exact linearization of the nonlinear dynamics of flying vehicle. At the end of this procedure the optimal control law obtained through an exact linearization is simple and easier to tune compared to the optimal strategy where the exact linearization is not performed. Taking into account the obtained experimental results, the proposed control technique produces an appropriate stabilization of the mini UAV.     

Physical,structural and optical studies on magnesium borate glasses doped with dysprosium ion

Intense visible emissions from dysprosium(Dy3+) ions doped glasses became prospective for diverse technological applications. In this paper, physical, optical and structural properties of magnesium borate glasses doped with varied concentrations of Dy_2 O_3 were examined. Such glasses were synthesised by melt quenching method and characterized at room temperature using several analytical techniques.Luminescence and absorption spectra(in the visible region) of as-quenched samples were used to evaluate the physical and optical properties. XRD pattern confims the amorphous state of as-quenched samples. The Fourier transform infrared(FTIR) spectra of glasses reveal various bonding vibrations assigned to different functional groups. UV-vis-NIR spectra disclose eight absorption bands accompanied by a band for hypersensitive transition positioned at 1260 nm(~6 H_(15/2)→~6 F_(11/2)). The values of direct and indirect optical energy band gap of the studied glasses are decreased with the increase of Dy~(3+) ion contents. The photoluminescence spectra of all glasses under the excitation of 380 nm display two prominent emission bands centred at 497 nm(~4 F_(9/2)→~6 H_(15/2), blue) and 587 nm(~4 F_(9/2) →~6 H_(13/2), green).The achieved intense luminescence from the proposed glass composition may be beneficial for solidstate laser applications.