Alternating Tree Automata with Qualitative Semantics

We study alternating automata with qualitative semantics over infinite binary trees: Alternation means that two opposing players construct a decoration of the input tree called a run, and the qualitative semantics says that a run of the automaton is accepting if almost all branches of the run are accepting. In this article, we prove a positive and a negative result for the emptiness problem of alternating automata with qualitative semantics. The positive result is the decidability of the emptiness problem for the case of Büchi acceptance condition. An interesting aspect of our approach is that we do not extend the classical solution for solving the emptiness problem of alternating automata, which first constructs an equivalent non-deterministic automaton. Instead, we directly construct an emptiness game making use of imperfect information. The negative result is the undecidability of the emptiness problem for the case of co-Büchi acceptance condition. This result has two direct consequences: The undecidability of monadic second-order logic extended with the qualitative path-measure quantifier and the undecidability of the emptiness problem for alternating tree automata with non-zero semantics, a recently introduced probabilistic model of alternating tree automata

Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo

BACKGROUND: Tissue plasminogen activator (tPA) exerts multiple functions in the central nervous system, depending on the partner with which it interacts. In particular, tPA acts as a positive neuromodulator of N-methyl-D-aspartate glutamatergic receptors (NMDAR). At the molecular level, it has been proposed that the pro-neurotoxicity mediated by tPA might occur through extrasynaptic NMDAR containing the GluN2D subunit. Thus, selective antagonists targeting tPA/GluN2D-containing NMDAR signaling would be of interest to prevent noxious effects of tPA. RESULTS: Here, we compared three putative antagonists of GluN2D-containing NMDAR and we showed that the new compound UBP145 ((2R*,3S*)-1-(9-bromophenan-threne-3-carbonyl)piperazine-2,3-dicarboxylic acid) is far more selective for GluN2D subunits than memantine and PPDA (phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid). Indeed, in vitro, in contrast to the two other compounds, UBP145 prevented NMDA toxicity only in neurons expressing GluN2D (ie, in cortical but not hippocampal neurons). Furthermore, in cultured cortical neurons, UBP145 fully prevented the pro-excitotoxic effect of tPA. In vivo, we showed that UBP145 potently prevented the noxious action of exogenous tPA on excitotoxic damages. Moreover, in a thrombotic stroke model in mice, administration of UBP145 prevented the deleterious effect of late thrombolysis by tPA. CONCLUSIONS: In conclusion, tPA exerts noxious effects on neurons by acting on GluN2D-containing NMDAR and pharmacological antagonists of GluN2D-containing NMDAR could be used to prevent the ability of tPA to promote neurotoxicity

Plasmodium falciparum Transcriptome Analysis Reveals Pregnancy Malaria Associated Gene Expression

gene.-exposed women than from men.These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM. These data may be very valuable for future vaccine development

An Upstream Open Reading Frame Controls Translation of var2csa, a Gene Implicated in Placental Malaria

Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue

NMDA-induced striatal brain damage and time-dependence reliability of thionin staining in rats

Excitotoxic neuronal death induced by intracerebral injection of NMDA is a widely used model for investigating the potentially neuroprotective action of pharmacological agents against brain insults involving excitotoxic processes. Surprisingly, the time-course of NMDA-induced brain damage yet has not been investigated in the rat. Answering this question clearly needs to be assessed, given that the validity of preclinical neuroprotection studies requires to be insured that brain damage has reached a plateau that corresponds to the maximal extension of neuronal death at the time the brain is removed for histological analysis. Here, we investigated the time-course of neuronal death and the time-dependence validity of thionin coloration in rats that were given an intrastriatal injection of NMDA of 50 nmol or 70 nmol. Our results show that, whatever the dose used, NMDA-induced brain damage reaches its maximal value 24-48 h after the insult. They further indicate that the volume values of brain damage as estimated by thionin coloration constitute reliable data when the brain is removed up to 48 h after injection of NMDA. However, if the brain is removed more than 48 h after the excitotoxic insult onset, there is no alternative of using other techniques, such as immunochemical or neuroimaging techniques

Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease

In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1-infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues, including the CNS, even in ART-suppressed patients. In this review, we have made Tat the center of attention for a number of reasons. First, it has been shown to be synthesized and secreted by HIV-1-infected cells in the CNS, despite the most effective suppression therapies available to date. Second, Tat has been shown to alter the functions of several host factors, disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity, dysfunction, and death. In addition, the advantages and disadvantages of ART suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined. In this review, we discuss the individual and concerted contributions of HIV-1 Tat, drug abuse, and ART with respect to damage in the CNS, and how these factors contribute to the development of HAND in HIV-1-infected patients

Recent advances of nanacarbons-MOFs composite materials and their application in photocatalysis

This article reviews the recent advances in composite materials based on nanocarbons (graphene oxide (GO), reduced graphene oxide (RGO), carbon nanotubes (CNTs)) and metal-organic frameworks (MOFs) and their application in the photocatalytic degradation of organic-inorganic pollutants and hydrogen photocatalytic production. Nanocarbons such as GO and CNTs are materials that have excellent intrinsic properties such as high electrical and thermal conductivity, chemical and thermal stability, as well as a high specific surface area. In general, the incorporation of nanocarbons in MOFs has allowed to significantly increase the photocatalytic activity of MOFs due to two factors: by increasing the specific surface area, and decreasing the recombination of the photogenerated charge carriers (electron / hole)En este artículo se revisan los avances recientes en el uso de materiales compositos utilizando nanocarbons (óxido de grafeno, óxido de grafeno reducido, nanotubos de carbono) incorporados en materiales metal-orgánicos (MOFs, por sus siglas en inglés) y su aplicación en reacciones fotocatalíticas como la degradación de contaminantes orgánicos e inorgánicos y la producción de hidrógeno. Las nanoestructuras de carbono, como el GO y CNTs son materiales que presentan excelentes propiedades intrínsecas como elevada conductividad eléctrica y térmica, así como buena estabilidad térmica y química, y alta superficie específica. En general la incorporación de los nanocarbons en los MOFs ha permitido incrementar considerablemente la actividad fotocatalitica de los MOFs, debido a que los nanocarbons se comportan como “aceptores de electrones”, separando eficientemente los portadores de carga fotogenerados (electrón/hueco) o sitios activos, disminuyendo su recombinació