Redox sensitivity of tyrosine hydroxylase activity and expression in dopaminergic dysfunction

Oxidant molecules generated during neuronal metabolism appear to play a significant role in the processes of aging and neurodegeneration. Increasing experimental evidence suggests the noteworthy relevance of the intracellular reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production, conferring on them a high vulnerability to free radical damage, one of the major causes of selective DA-ergic neuron dysfunction and degeneration related to neurological disorders such as Parkinson’s disease. Tyrosine hydroxylase (tyrosine 3-monooxygenase; E.C. 1.14.16.2; TH) activity represents the rate-limiting biochemical event in DA synthesis. TH activity, metabolism and expression are finely tuned by several regulatory systems in order to maintain a crucial physiological condition in which DA synthesis is closely coupled to its secretion. Alterations of these regulatory systems of TH functions have indeed been thought to be key events in the DA-ergic degeneration. TH has seven cysteine residues presenting thiols. Depending on the oxido-reductive (redox) status of the cellular environment, thiols exist either in the reduced form of free thiols or oxidized to disulfides. The formation of disulfides in proteins exerts critical regulatory functions both in physiological and in pathological conditions when oxidative stress is sustained. Several reports have recently shown that redox state changes of thiol residues, as consequence of an oxidative injury, can directly or indirectly affect the TH activity, metabolism and expression. The major focus of this review, therefore, is to report recent evidence on the redox modulation of TH activity and expression, and to provide an overview of a cellular phenomenon that might represent a target for new therapeutic strategies against the DA-ergic neurodegenerative disorders.peer-reviewe

Bombay hypertopologies

[EN] Recently it was shown that, in a metric space, the upper Wijsman convergence can be topologized with the introduction of a new far-miss topology. The resulting Wijsman topology is a mixture of the ball topology and the proximal ball topology. It leads easily to the generalized or g-Wijsman topology on the hyperspace of any topological space with a compatible LO-proximity and a cobase (i.e. a family of closed subsets which is closed under finite unions and which contains all singletons). Further generalization involving a topological space with two compatible LO-proximities and a cobase results in a new hypertopology which we call the Bombay topology. The generalized locally finite Bombay topology includes the known hypertopologies as special cases and moreover it gives birth to many new hypertopologies. We show how it facilitates comparison of any two hypertopologies by proving one simple result of which most of the existing results are easy consequences.Di Maio, G.; Meccariello, E.; Naimpally, S. (2003). Bombay hypertopologies. Applied General Topology. 4(2):421-444. doi:10.4995/agt.2003.2042.SWORD4214444

Graph topologies on closed multifunctions

[EN] In this paper we study function space topologies on closed multifunctions, i.e. closed relations on X x Y using various hypertopologies. The hypertopologies are in essence, graph topologies i.e topologies on functions considered as graphs which are subsets of X x Y . We also study several topologies, including one that is derived from the Attouch-Wets filter on the range. We state embedding theorems which enable us to generalize and prove some recent results in the literature with the use of known results in the hyperspace of the range space and in the function space topologies of ordinary functions.Di Maio, G.; Meccariello, E.; Naimpally, S. (2003). Graph topologies on closed multifunctions. Applied General Topology. 4(2):445-465. doi:10.4995/agt.2003.2044.SWORD4454654

Development of a new expendable probe for the study of pelagic ecosystems from voluntary observing ships

Physical and biological processes of the marine ecosystem have a high spatial and temporal variability, whose study is possible only through high resolution and synoptic observations. The Temperature and Fluorescence Launchable Probe was charted in order to answer to the claim of a cost effective temperature and fluorescence expendable profiler, to be used in ships of opportunity. The development of the expendable fluorometer has followed similar concepts of the XBT (a wire conducting the signal to a computer card), but differently from the latter it was developed with an electronic system which can be improved and adapted to several variables measure channels. To reach the aim of a low-cost probe, were utilized commercial components:a glass bulb temperature resistor for the temperature measurement, blue LEDs, a photodiode and available selective glass filters, for the fluorescence measurement. The measurement principle employed to detect phytoplankton’s biomass is the active fluorescence. This method is an in vivo chlorophyll estimation, that can get the immediate biophysical reaction of phytoplankton inside the aquatic environment; it is a non-disruptive method which gives real time estimation and avoids the implicit errors due to the manipulation of samples. The possibility of using a continuous profiling probe, with an active fluorescence measurement, is very important in real time phytoplankton’s study; it is the best way to follow the variability of sea productivity. In fact, because of the high time and space variability of phytoplankton, due to its capability to answer in a relatively short time to ecological variations in its environment and because of its characteristic patchiness, there isn’t a precise quantitative estimation of the biomass present in the Mediterranean Sea.L'articolo è disponibile sul sito dell'editore http://publications.copernicus.org

Serafino Zappacosta: An Enlightened Mentor and Educator.

With this article, the authors aim to honor the memory of Serafino Zappacosta, who had been their mentor during the early years of their career in science. The authors discuss how the combination of Serafino Zappacosta's extraordinary commitment to teaching and passion for science created a fostering educational environment that led to the creation of the "Ruggero Ceppellini Advanced School of Immunology." The review also illustrates how the research on the MHC and the inspirational scientific context in the Zappacosta's laboratory influenced the authors' early scientific interests, and subsequent professional work as immunologists

Electrostatic and Structural Bases of Fe2+ Translocation through Ferritin Channels

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe(2+)-loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe(2+) uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe(2+) through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H' protein and some of its variants as case studies. We describe the structural features that determine Fe(2+) translocation with atomistic detail, and we propose a putative mechanism for Fe(2+) transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin

5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

The activity of voltage-gated K(+) channels (Kv) can be dynamically modulated by several events, including neurotransmitter stimulated biochemical cascades mediated by G protein-coupled receptors such as 5-HT2 receptors (5-HT2Rs). Activation of 5-HT2A/CR inhibits the Shaker-like K(+) channels Kv1.1 and Kv1.2, and this modulation involves the dual coordination of both RPTPα and distinct tyrosine kinases coupled to this receptor; 5-HT2Rs-mediated modulation of Kv channels controls glutamate release onto prefrontal cortex neurons that might play critical roles in neurophysiological, neurological, and psychiatric conditions. Noticeably, hallucinogens modulate Kv channel activity, acting at 5-HT2R. Hence, comprehensive knowledge of 5-HT2R signaling through modulation of distinct K(+) channels is a pivotal step in the direction that will enable scientists to discover novel 5-HT functions and dysfunctions in the brain and to identify original therapeutic targets.peer-reviewe

Preferential modulation of the lateral habenula activity by serotonin-2A rather than -2C receptors: Electrophysiological and neuroanatomical evidence

Aims: Serotonergic (5-HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5-HT receptors (5-HTRs) involved, the 5-HT2CR seems to play a pivotal role. Yet, the role of 5-HT2ARs in the control of the LHb neuronal activity is completely unknown. Methods: Single-cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5-HT2CR and 5-HT2AR with Ro 60-0175 and SB242084, TCB-2 and MDL11939, respectively. The expression of both receptors in the LHb was confirmed using immunohistochemistry. Results: Cumulative doses (5-640 \uce\ubcg/kg, iv) of Ro 60-0175 and TCB-2 affected the activity of 34% and 63% of the LHb recorded neurons, respectively. LHb neurons were either inhibited at low doses or excited at higher doses of the 5-HT2A/CR agonists. SB242084 or MDL11939 (both at 200 \uce\ubcg/kg, iv) did not modify neuronal firing when injected alone, but reverted the bidirectional effects of Ro 60-0175 or TCB-2, respectively. 5-HT2CRs and 5-HT2ARs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5-HT2ARs are expressed by the majority of LHb astrocyte cells. Conclusions: Peripheral administration of 5-HT2AR agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5-HT2CR activation