Short-term alterations in hippocampal glutamate transport system caused by one-single neonatal seizure episode: Implications on behavioral performance in adulthood

AbstractImpairment in the activity and expression of glutamate transporters has been found in experimental models of epilepsy in adult animals. However, there are few studies investigating alterations on glutamate transporters caused by epilepsy in newborn animals, especially in the early periods after seizures. In this study, alterations in the hippocampal glutamate transporters activity and immunocontent were investigated in neonatal rats (7 days old) submitted to kainate-induced seizures model. Glutamate uptake, glutamate transporters (GLT-1, GLAST, EAAC1) and glutamine synthetase (GS) were assessed in hippocampal slices obtained 12h, 24h, 48h, 72h and 60 days after seizures. Immunoreactivity for hippocampal GFAP, NeuN and DAPI were assessed 24h after seizure. Behavioral analysis (elevated-plus maze and inhibitory avoidance task) was also investigated in the adult animals (60 days old). The decrease on glutamate uptake was observed in hippocampal slices obtained 24h after seizures. The immunocontent of GLT-1 increased at 12h and decreased at 24h (+62% and −20%, respectively), while GLAST increased up to 48h after seizures. No alterations were observed for EAAC1 and GS. It should be mentioned that there were no long-term changes in tested glutamate transporters at 60 days after kainate treatment. GFAP immunoreactivity increased in all hippocampal subfields (CA1, CA3 and dentate gyrus) with no alterations in NeuN and DAPI staining. In the adulthood, kainate-treated rats showed anxiety-related behavior and lower performance in the inhibitory avoidance task. Our findings indicate that acute modifications on hippocampal glutamate transporters triggered by a single convulsive event in early life may play a role in the behavioral alterations observed in adulthood

Serum levels of S100B and NSE proteins in Alzheimer's disease patients

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease is the most common dementia in the elderly, and the potential of peripheral biochemical markers as complementary tools in the neuropsychiatric evaluation of these patients has claimed further attention.</p> <p>Methods</p> <p>We evaluated serum levels of S100B and neuron-specific enolase (NSE) in 54 mild, moderate and severe Alzheimer's disease (AD) patients and in 66 community-dwelling elderly. AD patients met the probable NINCDS-ADRDA criteria. Severity of dementia was ascertained by the Clinical Dementia Rating (CDR) scale, cognitive function by the Mini Mental State Examination (MMSE), and neuroimage findings with magnetic resonance imaging. Serum was obtained from all individuals and frozen at -70°C until analysis.</p> <p>Results</p> <p>By comparing both groups, serum S100B levels were lower in AD group, while serum NSE levels were the same both groups. In AD patients, S100B levels were positively correlated with CDR scores (rho = 0.269; p = 0.049) and negatively correlated with MMSE scores (rho = -0.33; <it>P </it>= 0.048). NSE levels decreased in AD patients with higher levels of brain atrophy.</p> <p>Conclusions</p> <p>The findings suggest that serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in AD.</p

Upstream and downstream process development of a Vero cell-based yellow fever vaccine

Yellow fever (YF) is a lethal viral disease that is endemic in some tropical regions of South America, Central America and Africa. An attenuated vaccine produced in embryonated eggs is available since the 1930’s and is known to be highly effective and safe. However, after large vaccination campaigns in the 2000’s, reports of rare, but serious adverse events have stimulated Biomanguinhos/FIOCRUZ, who produces the current attenuated 17DD vaccine, to develop a new, inactivated vaccine. Over the last years, through a partnership of the Federal University of Rio de Janeiro and Biomanguinhos/FIOCRUZ, both upstream and downstream processes were developed. The upstream process was established based on Vero cell cultivation on microcarriers in serum-free medium, using stirred-tank bioreactors. The first studies were carried out in spinner flasks to select the microcarrier type and the serum-free medium. Also, statistical DOE tools were used to study the infection step, varying the moiety of infection and the time of infection. This process was then scale-up to stirred-tank bioreactors and further optimized regarding microcarrier concentration, stepwise medium addition, dissolved oxygen level/sparging intensity, impeller configuration and time of harvest. The final upstream process that was established results in virus titers of 10^8 pfu/mL within a time frame 144h post inoculation of the cells in the bioreactor. The downstream process was designed priorizing chromatographic techniques, aiming at achieving high purity levels and extensive removal of process-related critical contaminants, such as DNA and host-cell proteins (HCP), as preconized by the regulatory authorities. For the capture step, both cation- and anion-exchange chromatographies were evaluated. A Q membrane adsorber process was selected and the best operational conditions in terms of pH, temperature, buffers and washing strategies were determined. For the second purification step, three techniques were evaluated: multimodal chromatography, ultrafiltration/diafiltration, and hydrophobic interaction chromatography using a HIC membrane adsorber. The multimodal resin showed the best results, and operational conditions of this step were further optimized. The final 2-step yellow-fever virus purification process resulted in an overall yield of 52% and residual HCP of 350 ppm (0.05%). Residual DNA was 1.2 ng per dose, considering the dose established based on animal studies, and is in agreement with the limit recommended by the World Health Organization (\u3c10 ng/dose). Electrophoretic analysis (SDS-PAGE) of the purified samples showed a band corresponding to 96% of identified proteins with molecular mass of 56 kDa, which is the expected mass for the virus envelope protein (E). Anti-E Western blot (WB) showed a single band, confirming the identity of the samples. No band was revealed in the anti-HCP blot, confirming the low HCP levels quantified. The developed process allows the production of a new, high-purity yellow-fever vaccine through a scalable technology, which is better suited than egg-based technology to meet emergency demands in case of epidemics and is useful in the current scenario of increasing worldwide demand YF vaccine

Increase in serum S100B protein level after a swimming

Catalogue Data Abstract/Résumé Physical activity has been shown to be a beneficial stimulus to the central and peripheral nervous systems. The S100B is a cytokine physiologically produced and released predominantly by astrocytes on the central nervous system (CNS). In order to study the possible influence of a nonimpact exercise on S100B serum levels, we measured this protein serum level after a 7,600-meter swimming race. We observed an increase in S100B levels in athletes post-race compared with their baseline values, pointing to a potential acute influence of physical exercise on serum S100B levels not related with CNS injury. We discuss this result and emphasize the possible central and peripheral origins of S100B serum levels. Les bénéfices de l&apos;activité physique sur les systèmes nerveux central et périphérique ne sont plus à prouver. Les S100B sont des cytokines produites physiologiquement et surtout libérées par les astrocytes du système nerveux central (CNS). Pour étudier l&apos;effet potentiel d&apos;une activité physique sans impact, nous avons mesuré les concentrations sériques de cette protéin

MARTA: A high-energy cosmic-ray detector concept with high-accuracy muon measurement

A new concept for the direct measurement of muons in air showers is presented. The concept is based on resistive plate chambers (RPCs), which can directly measure muons with very good space and time resolution. The muon detector is shielded by placing it under another detector able to absorb and measure the electromagnetic component of the showers such as a water-Cherenkov detector, commonly used in air shower arrays. The combination of the two detectors in a single, compact detector unit provides a unique measurement that opens rich possibilities in the study of air showers.Comment: 11 page

A Double-Blind, Randomized, Placebo-Controlled 4-Week Study on the Efficacy and Safety of the Purinergic Agents Allopurinol and Dipyridamole Adjunctive to Lithium in Acute Bipolar Mania

The therapeutics for Bipolar Disorders (BD) is still far from adequate and new options with improved effectiveness, safety and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting at the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania

Glycolysis-Derived Compounds From Astrocytes That Modulate Synaptic Communication

Based on the concept of the tripartite synapse, we have reviewed the role of glucose-derived compounds in glycolytic pathways in astroglial cells. Glucose provides energy and substrate replenishment for brain activity, such as glutamate and lipid synthesis. In addition, glucose metabolism in the astroglial cytoplasm results in products such as lactate, methylglyoxal, and glutathione, which modulate receptors and channels in neurons. Glucose has four potential destinations in neural cells, and it is possible to propose a crossroads in “X” that can be used to describe these four destinations. Glucose-6P can be used either for glycogen synthesis or the pentose phosphate pathway on the left and right arms of the X, respectively. Fructose-6P continues through the glycolysis pathway until pyruvate is formed but can also act as the initial compound in the hexosamine pathway, representing the left and right legs of the X, respectively. We describe each glucose destination and its regulation, indicating the products of these pathways and how they can affect synaptic communication. Extracellular L-lactate, either generated from glucose or from glycogen, binds to HCAR1, a specific receptor that is abundantly localized in perivascular and post-synaptic membranes and regulates synaptic plasticity. Methylglyoxal, a product of a deviation of glycolysis, and its derivative D-lactate are also released by astrocytes and bind to GABAA receptors and HCAR1, respectively. Glutathione, in addition to its antioxidant role, also binds to ionotropic glutamate receptors in the synaptic cleft. Finally, we examined the hexosamine pathway and evaluated the effect of GlcNAc-modification on key proteins that regulate the other glucose destinations

Quantum discord determines the interferometric power of quantum states

Quantum metrology exploits quantum mechanical laws to improve the precision in estimating technologically relevant parameters such as phase, frequency, or magnetic fields. Probe states are usually tailored to the particular dynamics whose parameters are being estimated. Here we consider a novel framework where quantum estimation is performed in an interferometric configuration, using bipartite probe states prepared when only the spectrum of the generating Hamiltonian is known. We introduce a figure of merit for the scheme, given by the worst-case precision over all suitable Hamiltonians, and prove that it amounts exactly to a computable measure of discord-type quantum correlations for the input probe. We complement our theoretical results with a metrology experiment, realized in a highly controllable room-temperature nuclear magnetic resonance setup, which provides a proof-of-concept demonstration for the usefulness of discord in sensing applications. Discordant probes are shown to guarantee a nonzero phase sensitivity for all the chosen generating Hamiltonians, while classically correlated probes are unable to accomplish the estimation in a worst-case setting. This work establishes a rigorous and direct operational interpretation for general quantum correlations, shedding light on their potential for quantum technology

Observation of time-invariant coherence in a nuclear magnetic resonance quantum simulator

The ability to live in coherent superpositions is a signature trait of quantum systems and constitutes an irreplaceable resource for quantum-enhanced technologies. However, decoherence effects usually destroy quantum superpositions. It has been recently predicted that, in a composite quantum system exposed to dephasing noise, quantum coherence in a transversal reference basis can stay protected for indefinite time. This can occur for a class of quantum states independently of the measure used to quantify coherence, and requires no control on the system during the dynamics. Here, such an invariant coherence phenomenon is observed experimentally in two different setups based on nuclear magnetic resonance at room temperature, realising an effective quantum simulator of two- and four-qubit spin systems. Our study further reveals a novel interplay between coherence and various forms of correlations, and highlights the natural resilience of quantum effects in complex systems