1,721,233 research outputs found
The Peroxisome Proliferator-activated Receptor γ (PPARγ) Controls Natural Protective Mechanisms against Lipid Peroxidation in Amyotrophic Lateral Sclerosis
Get PDFRecent evidence highlights the peroxisome proliferator-activated receptors (PPARs) as critical neuroprotective factors in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To gain new mechanistic insights into the role of these receptors in the context of ALS, here we investigated how PPAR transcriptional activity varies in hSOD1(G93A) ALS transgenic mice. We demonstrate that PPARγ-driven transcription selectively increases in the spinal cord of symptomatic hSOD1(G93A) mice. This phenomenon correlates with the up-regulation of target genes, such as lipoprotein lipase and glutathione S-transferase α-2, which are implicated in scavenging lipid peroxidation by-products. Such events are associated with enhanced PPARγ immunoreactivity within motor neuronal nuclei. This observation, and the fact that PPARγ displays increased responsiveness in cultured hSOD1(G93A) motor neurons, points to a role for this receptor in neutralizing deleterious lipoperoxidation derivatives within the motor cells. Consistently, in both motor neuron-like cultures and animal models, we report that PPARγ is activated by lipid peroxidation end products, such as 4-hydroxynonenal, whose levels are elevated in the cerebrospinal fluid and spinal cord from ALS patients. We propose that the accumulation of critical concentrations of lipid peroxidation adducts during ALS progression leads to the activation of PPARγ in motor neurons. This in turn triggers self-protective mechanisms that involve the up-regulation of lipid detoxification enzymes, such as lipoprotein lipase and glutathione S-transferase α-2. Our findings indicate that anticipating natural protective reactions by pharmacologically modulating PPARγ transcriptional activity may attenuate neurodegeneration by limiting the damage induced by lipid peroxidation derivatives
A Pressure-Polish Setup to Fabricate Patch Pipettes Yielding Low Access Resistance and Efficient Intracellular Perfusion
No full textWhen performing whole-cell configuration recordings, it is important to minimize series resistance, to reduce time constant of charging the cell membrane capacitance and error in membrane potential control. To this goal, it was improved an existing method widening the patch pipette shank, through the calibrated combination of heat and air pressure. The heat was produced by passing current in a filament shaped appropriately to ensure an homogeneous heating of the pipette shank. The pressurized air was applied to the lumen of a pipette, pulled from a borosilicate glass microcap, via the pressure port of a modified commercial holder. The pipette reshaping was viewed on a LCD monitor, connected to a contrast-intensified CCD camera, coupled to a modified bright-field stereomicroscope. By appropriately regulating timing of air pressure and heating application, the pipette shank was widened as desired, independently by the tip opening diameter. The methods illustrated here to fabricate and use the patch pipettes, using just one glass type, allowed to seal on a wide variety of cell types, isolated from different amphibian, reptilian, fish, and mammalian tissues, and on artificial membranes made with many different lipid mixtures. The access resistance yielded by pressure polished pipettes resulted ~4-fold smaller than the one attained with conventional pipettes; besides improving the electrical recordings, this minimized intracellular ion accumulation or depletion as well. Enlarged shank geometry allowed fast intracellular perfusion, as shown by fluorescence imaging, also via pulled quartz or plastic tubes, that could be inserted very close to the pipette tip
Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases
Get PDFRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia
S-InTime: A social cloud analytical service oriented system
No full textSocial Networking activities raise multiple challenges for the evolution of Service Oriented Systems Engineering. The purpose of this research work is to demonstrate how a specific core technology and cloud platform with micro-services can be designed and used for performing data-intensive computations and implementing services in a real case of social analytics. In detail, we face the challenges of real-time data-intensive processing with the systematic application of in-memory view-based information modeling & computation, which is based on different types of non-materialized views without pre-aggregation of data. Finally, our study presents and compares design alternatives for these mappings, and demonstrates their effective application for implementing a large set of social analytics service types, with particular reference to the case of streaming sources of twitter data. A prototype of this system was experimented in the contest of a specific kind of social event, a permanent exhibition of Artworks, where the system collected and analyzed in real-time the tweets issued in an entire region, including exhibition sites, and continuously updated analytical dashboards placed in one of the exhibition rooms. © 2016 Elsevier B.V
Biophysical characterization of antimicrobial peptides activity: From in vitro to ex vivo techniques
No full textAntimicrobial peptides (AMPs) are evolutionarily conserved components of the innate immune defense system of many living organisms varying from prokaryotes to eukaryotes, including humans. Due to their broad-spectrum activity and low level of induced resistance, these short aminoacid sequences represent a novel class of potential antimicrobial agents. Besides the development of anti-bacterial drugs, AMPs constitute ideal molecular models for the design of molecules with wide-ranging nanomedical applications, such as anti-tumorigenic agents and pharmacological tools to cure channelopaties. Several techniques are currently used to shed light on the mechanisms of action of AMPs, ranging from the characterization of the interaction between peptides and biomimetic membranes and/or intracellular targets, to the study of AMPs effects on pathogens, living cells and tissues. Comprehensive and multiscale studies are crucial to design new AMPs and to identify molecules that can boost their activity. In this minireview we summarize the most recent achievements in AMP-characterization, with a special emphasis on the integration of biophysical approaches, which can synergistically help to bridge the gap between in vitro and ex vivo investigations. © 2013 Bentham Science Publishers
Adult neurogenesis in the rat olfactory bulb
No full textIn adult animals, neurons generated within the subventricular zone
(SVZ), following the rostral migratory stream (RMS), reach the
olfactory bulb (OB), where they apparently give rise to interneurons.
In fact, there has never been a functional demonstration
that these cells are true neurons. Filling this gap has been impeded
largely by the inability to distinguish between newly generated cells
(NGC) in living brain tissue using conventional approaches. We
have solved this problem combining retrovirus-mediated genetransfer
and patch-clamp electrophysiology. The viral vector,
including a gene for GFP, was injected into the SVZ. After 2 weeks,
GFP+ cells resembling periglomerular cells (PG) were observed in
the OB. Using a whole-cell patch-clamp technique, we recorded
action potentials from NGC in response to the injection of
depolarizing currents, and we have isolated and characterized
Na+ and K+ currents. About 95% of the NGC were PG cells; the
remaining ended their migration between internal plexiform
and mitral cell layers, and were identified as short-axon cells. The
progressive maturation of NGC has been characterized in time and
space along the RMS. When in the RMS, the cells show only a
weak delayed rectifier K+-current, to which an A-current is added
when the OB is reached. The mature cells lose the delayed rectifier
K+-current, and only display A- and Na+-currents. Finally, by
recording action potentials and excitatory synaptic currents in
response to stimulation of the olfactory nerve, for the first time we
have demonstrated that the NGC fully integrate into the bulbar
circuitry, establishing functional synaptic contacts
N-Haloamidines. VI. Reaction of N-chloro-N'-benzenesulfonylbenzamidines with enamines
No full textThe reaction between N-chloro-N'-benzenesulfonylbenzamidines and ß,ß-disubstituted enamines affords N-(benzenesulfonyl)-N'- [(2-chloro-2-substituted-l-amino)-propyl]-benzamidines. When both ß-substi tuents are methyl groups the open chain adducts have been isolated and characterized; whereas, when one of the two substituents is a phenyl group, they have been characterized only by PMR because of the easy cyclization to 1-benzenesulfonyl-4, 5-dihydroimidazoles
Characterization of Zebrafish Green Cone Photoresponse Recorded with Pressure-Polished Patch Pipettes, Yielding Efficient Intracellular Dialysis.
No full textThe phototransduction enzymatic cascade in cones is less understood than in rods, and the zebrafish is an ideal model with which to investigate vertebrate and human vision. Therefore, here, for the first time, the zebrafish green cone photoresponse is characterized also to obtain a firm basis for evaluating how it is modulated by exogenous molecules. To this aim, a powerful method was developed to obtain long-lasting recordings with low access resistance, employing pressure-polished patch pipettes. This method also enabled fast, efficient delivery of molecules via a perfusion system coupled with pulled quartz or plastic perfusion tubes, inserted very close to the enlarged pipette tip. Sub-saturating flashes elicited responses in different cells with similar rising phase kinetics but with very different recovery kinetics, suggesting the existence of physiologically distinct cones having different Ca2+ dynamics. Theoretical considerations demonstrate that the different recovery kinetics can be modelled by simulating changes in the Ca2+-buffering capacity of the outer segment. Importantly, the Ca2+-buffer action preserves the fast response rising phase, when the Ca2+-dependent negative feedback is activated by the light-induced decline in intracellular Ca2+
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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