Anti-peptide aptamers recognize amino acid sequence and bind a protein epitope.

In vitro selection of nucleic acid binding species (aptamers) is superficially similar to the immune response. Both processes produce biopolymers that can recognize targets with high affinity and specificity. While antibodies are known to recognize the sequence and conformation of protein surface features (epitopes), very little is known about the precise interactions between aptamers and their epitopes. Therefore, aptamers that could recognize a particular epitope, a peptide fragment of human immunodeficiency virus type I Rev, were selected from a random sequence RNA pool. Several of the selected RNAs could bind the free peptide more tightly than a natural RNA ligand, the Rev-binding element. In accord with the hypothesis that protein and nucleic acid binding cusps are functionally similar, interactions between aptamers and the peptide target could be disrupted by sequence substitutions. Moreover, the aptamers appeared to be able to bind peptides with different solution conformations, implying an induced fit mechanism for binding. Just as anti-peptide antibodies can sometimes recognize the corresponding epitope when presented in a protein, the anti-peptide aptamers were found to specifically bind to Rev.

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Despite considerable evidence that ethanol can enhance chloride flux through the gamma-aminobutyric acid type A (GABA/A/) receptor-channel complex in several central neuron types, the effect of ethanol on hippocampal GABAergic systems is still controversial. Therefore, we have reevaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolation of the various components of excitatory and inhibitory synaptic potentials, using intracellular current- and voltage-clamp recording methods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynaptic potentials/currents (IPSP/Cs) containing both GABA/A/ and GABA/B/ components. However, after selective pharmacological blockade of the GABA/B/ component of the IPSP (GABA/B/-IPSP/C) by CGP-35348, low concentrations of ethanol (22-66 mM) markedly enhanced the peak amplitude, and especially the area, of the GABA/A/ component (GABA/A/-IPSP/C) in most CA1 pyramidal neurons. Ethanol had no significant effect on the peak amplitude or area of the pharmacologically isolated GABA/B/-inhibitory postsynaptic current (IPSC). These results provide new data showing that activation of GABAB receptors can obscure ethanol enhancement of GABA/A/ receptor function in hippocampus and suggest that similar methods of pharmacological isolation might be applied to other brain regions showing negative or mixed ethanol-GABA interactions.

A molecular anchor for stabilizing triple-helical DNA.

Molecular modeling has been used to predict that 2,6-disubstituted amidoanthraquinones, and not the 1,4 series, should preferentially interact with and stabilize triple-stranded DNA structures over duplex DNA. This is due to marked differences in the nature of chromophore-base stacking and groove accessibility for the two series. A DNA foot-printing method that monitors the extent of protection from DNase I cleavage on triplex formation has been used to examine the effects of a number of synthetic isomer compounds in the 1,4 and 2,6 series. The experimental results are in accord with the predicted behavior and confirm that the 1,4 series bind preferentially to double- rather than triple-stranded DNA, whereas the isomeric 2,6 derivatives markedly favor binding to triplex DNA.

Proactive and reactive inhibition during overt and covert actions. An electrical neuroimaging study.

Response inhibition is the ability to suppress inadequate but automatically activated, prepotent or ongoing response tendencies. In the framework of motor inhibition, two distinct operating strategies have been described: “proactive” and “reactive” control modes. In the proactive modality, inhibition is recruited in advance by predictive signals, and actively maintained before its enactment. Conversely, in the reactive control mode, inhibition is phasically enacted after the detection of the inhibitory signal. To date, ample evidence points to a core cerebral network for reactive inhibition comprising the right inferior frontal gyrus (rIFG), the presupplementary motor area (pre-SMA) and the basal ganglia (BG). Moreover, fMRI studies showed that cerebral activations during proactive and reactive inhibition largely overlap. These findings suggest that at least part of the neural network for reactive inhibition is recruited in advance, priming cortical regions in preparation for the upcoming inhibition. So far, proactive and reactive inhibitory mechanisms have been investigated during tasks in which the requested response to be stopped or withheld was an “overt” action execution (AE) (i.e., a movement effectively performed). Nevertheless, inhibitory mechanisms are also relevant for motor control during “covert actions” (i.e., potential motor acts not overtly performed), such as motor imagery (MI). MI is the conscious, voluntary mental rehearsal of action representations without any overt movement. Previous studies revealed a substantial overlap of activated motor-related brain networks in premotor, parietal and subcortical regions during overtly executed and imagined movements. Notwithstanding this evidence for a shared set of cerebral regions involved in encoding actions, whether or not those actions are effectively executed, the neural bases of motor inhibition during MI, preventing covert action from being overtly performed, in spite of the activation of the motor system, remain to be fully clarified. Taking into account this background, we performed a high density EEG study evaluating cerebral mechanisms and their related sources elicited during two types of cued Go/NoGo task, requiring the execution or withholding of an overt (Go) or a covert (MI) action, respectively. The EEG analyses were performed in two steps, with different aims: 1) Analysis of the “response phase” of the cued overt and covert Go/NoGo tasks, for the evaluation of reactive inhibitory control of overt and covert actions. 2) Analysis of the “preparatory phase” of the cued overt and covert Go/NoGo EEG datasets, focusing on cerebral activities time-locked to the preparatory signals, for the evaluation of proactive inhibitory mechanisms and their related neural sources. For these purposes, a spatiotemporal analysis of the scalp electric fields was applied on the EEG data recorded during the overt and covert Go/NoGo tasks. The spatiotemporal approach provide an objective definition of time windows for source analysis, relying on the statistical proof that the electric fields are different and thus generated by different neural sources. The analysis of the “response phase” revealed that key nodes of the inhibitory circuit, underpinning inhibition of the overt movement during the NoGo response, were also activated during the MI enactment. In both cases, inhibition relied on the activation of pre-SMA and rIFG, but with different temporal patterns of activation in accord with the intended “covert” or “overt” modality of motor performance. During the NoGo condition, the pre-SMA and rIFG were sequentially activated, pointing to an early decisional role of pre-SMA and to a later role of rIFG in the enactment of inhibitory control of the overt action. Conversely, a concomitant activation of pre-SMA and rIFG emerged during the imagined motor response. This latter finding suggested that an inhibitory mechanism (likely underpinned by the rIFG), could be prewired into a prepared “covert modality” of motor response, as an intrinsic component of the MI enactment. This mechanism would allow the rehearsal of the imagined motor representations, without any overt movement. The analyses of the “preparatory phase”, confirmed in both overt and covert Go/NoGo tasks the priming of cerebral regions pertaining to putative inhibitory network, reactively triggered in the following response phase. Nonetheless, differences in the preparatory strategies between the two tasks emerged, depending on the intended “overt” or “covert” modality of the possible incoming motor response. During the preparation of the overt Go/NoGo task, the cue primed the possible overt response programs in motor and premotor cortex. At the same time, through preactivation of a pre-SMA-related decisional mechanism, it triggered a parallel preparation for the successful response selection and/or inhibition during the subsequent response phase. Conversely, the preparatory strategy for the covert Go/NoGo task was centred on the goal-oriented priming of an inhibitory mechanism related to the rIFG that, being tuned to the instructed covert modality of the motor performance and instantiated during the subsequent MI enactment, allowed the imagined response to remain a potential motor act. Taken together, the results of the present study demonstrate a substantial overlap of cerebral networks activated during proactive recruitment and subsequent reactive enactment of motor inhibition in both overt and covert actions. At the same time, our data show that preparatory cues predisposed ab initio a different organization of the cerebral areas (in particular of the pre-SMA and rIFG) involved with sensorimotor transformations and motor inhibitory control for executed and imagined actions. During the preparatory phases of our cued overt and covert Go/NoGo tasks, the different adopted strategies were tuned to the “how” of the motor performance, reflecting the intended overt and covert modality of the possible incoming action.

Integral elastic, electronic-state, ionization, and total cross sections for electron scattering with furfural

We report absolute experimental integral cross sections (ICSs) for electron impact excitation of bands of electronic-states in furfural, for incident electron energies in the range 20-250 eV. Wherever possible, those results are compared to corresponding excitation cross sections in the structurally similar species furan, as previously reported by da Costa et al. [Phys. Rev. A 85, 062706 (2012)] and Regeta and Allan [Phys. Rev. A 91, 012707 (2015)]. Generally, very good agreement is found. In addition, ICSs calculated with our independent atom model (IAM) with screening corrected additivity rule (SCAR) formalism, extended to account for interference (I) terms that arise due to the multi-centre nature of the scattering problem, are also reported. The sum of those ICSs gives the IAM-SCAR+I total cross section for electron-furfural scattering. Where possible, those calculated IAM-SCAR+I ICS results are compared against corresponding results from the present measurements with an acceptable level of accord being obtained. Similarly, but only for the band I and band II excited electronic states, we also present results from our Schwinger multichannel method with pseudopotentials calculations. Those results are found to be in good qualitative accord with the present experimental ICSs. Finally, with a view to assembling a complete cross section data base for furfural, some binary-encounter-Bethe-level total ionization cross sections for this collision system are presented. (C) 2016 AIP Publishing LLC.

Comparación de las macroalgas epizóicas de la madreperla Pinctada mazatlanica (Hanley 1856) con las de fondos rocosos en la bahía de La Paz, Baja California Sur, México

El presente estudio describe la comunidad de macroalgas epizóicas de Pinctada mazatlanica y la compara con la del substrato rocoso. Colectamos un total de 36 muestras de la comunidad de macroalgas, 18 muestras sobre ostras y otras tantas sobre substrato rocoso en la Península San Juan Nepomuceno, bahía de La Paz, México. Las algas fueron colectadas mediante buceo SCUBA raspando las distintas superficies (25 cm2 de substrato rocoso). El tamaño de muestra fue ajustado por curva de acumulación de especies y expresado con un modelo polinomial. Comparamos las comunidades de algas con análisis multivariantes de similitud basados en el índice de Bray-Curtis, entre substratos, diferentes alturas de ostras perleras y profundidades. Encontramos 27 especies de algas epizóicas (15.4% Clorophyta, 3.8% Phaeophyta y 80.8% Rhodophyta) con una disimilitud de 71.16% con respecto al substrato rocoso. El dendrograma mostró tres agrupaciones de macroalgas en P. mazatlanica. El primero caracterizado por Chondria, Jania, Herposiphonia tenella y Gracilaria. El segundo compuesto por Jania, Polysiphonia acuminata, P. decusata y Spyridia filamentosa. El tercero constituido por Polysiphonia sp., Jania, Herposiphonia tenella, Ceramium canouii y Amphiroa sp. Estas agrupaciones y los talos filamentosos de las algas epizóicas corresponden a estados iniciales de sucesión.

De Gaulle and Europe: Historical Revision and Social Science Theory. Program for the Study of Germany and Europe Working Paper Series 8.5

The thousands of books and articles on Charles de Gaulle's policy toward European integration, whether written by historians, social scientists, or commentators, universally accord primary explanatory importance to the General's distinctive geopolitical ideology. In explaining his motivations, only secondary significance, if any at all, is attached to commercial considerations. This paper seeks to reverse this historiographical consensus by examining the four major decisions toward European integration during de Gaulle's presidency: the decisions to remain in the Common Market in 1958, to propose the Foucher Plan in the early 1960s, to veto British accession to the EC, and to provoke the "empty chair" crisis in 1965-1966, resulting in the "Luxembourg Compromise." In each case, the overwhelming bulk of the primary evidence-speeches, memoirs, or government documents-suggests that de Gaulle's primary motivation was economic, not geopolitical or ideological. Like his predecessors and successors, de Gaulle sought to promote French industry and agriculture by establishing protected markets for their export products. This empirical finding has three broader implications: (1) For those interesred in the European Union, it suggests that regional integration has been driven primarily by economic, not geopolitical considerations--even in the "least likely" case. (2) For those interested in the role of ideas in foreign policy, it suggests that strong interest groups in a democracy limit the impact of a leader's geopolitical ideology--even where the executive has very broad institutional autonomy. De Gaulle was a democratic statesman first and an ideological visionary second. (3) For those who employ qualitative case-study methods, it suggests that even a broad, representative sample of secondary sources does not create a firm basis for causal inference. For political scientists, as for historians, there is in many cases no reliable alternative to primary-source research.

An Assessment of US Progress towards its Pledge on Climate Change Mitigation. CEPS ECP Report No. 12, 15 October 2012

In 2009, President Obama pledged that, by 2020, the United States would achieve reductions in greenhouse gas emissions of 17% from 2005 levels. With the failure of Congress to adopt comprehensive climate legislation in 2010, the feasibility of the pledge was put in doubt. However, we find that the United States is near to reaching this goal: the country is currently on course to achieve reductions of 16.3% from 2005 levels in 2020. Three factors contribute to this outcome: greenhouse gas regulations under the Clean Air Act, secular trends including changes in relative fuel prices and energy efficiency and sub-national efforts. Perhaps even more surprising, domestic emissions are probably lower than would have been the case if the Waxman-Markey cap-and-trade proposal had become law in 2010. At this point, however, the United States is expected to fail to meet its financing commitments under the Copenhagen Accord for 2020.

Plasticité du cortex visuel: «homéodynamie» des connexions neuronales et modèle d’effets d’antidépresseurs

Les informations sensorielles sont traitées dans le cortex par des réseaux de neurones co-activés qui forment des assemblées neuronales fonctionnelles. Le traitement visuel dans le cortex est régit par différents aspects des caractéristiques neuronales tels que l’aspect anatomique, électrophysiologique et moléculaire. Au sein du cortex visuel primaire, les neurones sont sélectifs à divers attributs des stimuli tels que l’orientation, la direction, le mouvement et la fréquence spatiale. Chacun de ces attributs conduit à une activité de décharge maximale pour une population neuronale spécifique. Les neurones du cortex visuel ont cependant la capacité de changer leur sélectivité en réponse à une exposition prolongée d’un stimulus approprié appelée apprentissage visuel ou adaptation visuelle à un stimulus non préférentiel. De ce fait, l’objectif principal de cette thèse est d’investiguer les mécanismes neuronaux qui régissent le traitement visuel durant une plasticité induite par adaptation chez des animaux adultes. Ces mécanismes sont traités sous différents aspects : la connectivité neuronale, la sélectivité neuronale, les propriétés électrophysiologiques des neurones et les effets des drogues (sérotonine et fluoxétine). Le modèle testé se base sur les colonnes d’orientation du cortex visuel primaire. La présente thèse est subdivisée en quatre principaux chapitres. Le premier chapitre (A) traite de la réorganisation du cortex visuel primaire suite à une plasticité induite par adaptation visuelle. Le second chapitre (B) examine la connectivité neuronale fonctionnelle en se basant sur des corrélations croisées entre paires neuronales ainsi que sur des corrélations d’activités de populations neuronales. Le troisième chapitre (C) met en liaison les aspects cités précédemment (les effets de l’adaptation visuelle et la connectivité fonctionnelle) aux propriétés électrophysiologiques des neurones (deux classes de neurones sont traitées : les neurones à décharge régulière et les neurones à décharge rapide ou burst). Enfin, le dernier chapitre (D) a pour objectif l’étude de l’effet du couplage de l’adaptation visuelle à l’administration de certaines drogues, notamment la sérotonine et la fluoxétine (inhibiteur sélectif de recapture de la sérotonine). Méthodes En utilisant des enregistrements extracellulaires d’activités neuronales dans le cortex visuel primaire (V1) combinés à un processus d’imagerie cérébrale optique intrinsèque, nous enregistrons l’activité de décharge de populations neuronales et nous examinons l’activité de neurones individuels extraite des signaux multi-unitaires. L’analyse de l’activité cérébrale se base sur différents algorithmes : la distinction des propriétés électrophysiologiques des neurones se fait par calcul de l’intervalle de temps entre la vallée et le pic maximal du potentiel d’action (largeur du potentiel d’action), la sélectivité des neurones est basée sur leur taux de décharge à différents stimuli, et la connectivité fonctionnelle utilise des calculs de corrélations croisées. L’utilisation des drogues se fait par administration locale sur la surface du cortex (après une craniotomie et une durotomie). Résultats et conclusions Dans le premier chapitre, nous démontrons la capacité des neurones à modifier leur sélectivité après une période d’adaptation visuelle à un stimulus particulier, ces changements aboutissent à une réorganisation des cartes corticales suivant un patron spécifique. Nous attribuons ce résultat à la flexibilité de groupes fonctionnels de neurones qui étaient longtemps considérés comme des unités anatomiques rigides. En effet, nous observons une restructuration extensive des domaines d’orientation dans le but de remodeler les colonnes d’orientation où chaque stimulus est représenté de façon égale. Ceci est d’autant plus confirmé dans le second chapitre où dans ce cas, les cartes de connectivité fonctionnelle sont investiguées. En accord avec les résultats énumérés précédemment, les cartes de connectivité montrent également une restructuration massive mais de façon intéressante, les neurones utilisent une stratégie de sommation afin de stabiliser leurs poids de connectivité totaux. Ces dynamiques de connectivité sont examinées dans le troisième chapitre en relation avec les propriétés électrophysiologiques des neurones. En effet, deux modes de décharge neuronale permettent la distinction entre deux classes neuronales. Leurs dynamiques de corrélations distinctes suggèrent que ces deux classes jouent des rôles clés différents dans l’encodage et l’intégration des stimuli visuels au sein d’une population neuronale. Enfin, dans le dernier chapitre, l’adaptation visuelle est combinée avec l’administration de certaines substances, notamment la sérotonine (neurotransmetteur) et la fluoxétine (inhibiteur sélectif de recapture de la sérotonine). Ces deux substances produisent un effet similaire en facilitant l’acquisition des stimuli imposés par adaptation. Lorsqu’un stimulus non optimal est présenté en présence de l’une des deux substances, nous observons une augmentation du taux de décharge des neurones en présentant ce stimulus. Nous présentons un modèle neuronal basé sur cette recherche afin d’expliquer les fluctuations du taux de décharge neuronale en présence ou en absence des drogues. Cette thèse présente de nouvelles perspectives quant à la compréhension de l’adaptation des neurones du cortex visuel primaire adulte dans le but de changer leur sélectivité dans un environnement d’apprentissage. Nous montrons qu’il y a un parfait équilibre entre leurs habiletés plastiques et leur dynamique d’homéostasie.

Strong governments, weak banks. CEPS Policy Brief No. 305, 25 November 2013

Banks in the northern eurozone have capital ratios that are, on average, less than half of the capital ratios of banks in the eurozone’s periphery. The authors explain this by the fact that northern eurozone banks profit from the financial solidity of their governments and follow business strategies aimed at issuing too much subsidised debt. In doing so, they weaken their balance sheets and become more fragile – less able to withstand future shocks. Paradoxically, financially strong governments breed fragile banks. The opposite occurs in countries with financially weak governments. In these countries banks are forced to strengthen themselves because they are unable to rely on their governments. As a result they have significantly more capital and reserves than banks in the northern eurozone. Recommendations More than in the south, the governments of northern Europe should stand up and force the banks to issue more equity. This should go much further than what is foreseen in the Basel III accord. If the experience of the southern eurozone countries is any guide, banks in the north of the eurozone should at least double the capital and the reserves as a percentage of their balance sheets. Failure to do so risks destroying the financial solidity of the northern European governments when, in the future, negative shocks force these governments to come to the rescue of their undercapitalised banks. The new responsibilities entrusted to the European Central Bank as the single supervisor in the eurozone create a unique opportunity for that institution to change the regulatory and supervisory culture in the eurozone – one that has allowed the large banks to continue living dangerously, with insufficient capital.

Time to Set Banking Regulation Right. CEPS Paperbacks. March 2012

Excessive leverage and risk-taking by large international banks were the main causes of the 2008-09 financial crisis and the ensuing sharp drop in economic activity and employment. World leaders and central bankers promised that it would not happen again and, to this end, undertook to overhaul banking regulation, first and foremost by rectifying Basel prudential rules. This study argues that the new Basel III Accord and the ensuing EU Capital Requirements Directive IV fail to correct the two main shortcomings of international prudential rules: 1) reliance on banks’ risk management models for the calculation of capital requirements and 2) the lack of accountability by supervisors. Accordingly, the authors propose the calculation of capital requirements without risk adjustment and creation of a system of mandated action by supervisors modelled on the US framework of Prompt Corrective Action (PCA). They also recommend that banks should be required to issue large amounts of debentures that are convertible into equity in order to strengthen market discipline on management and shareholders.

Ukraine on the edge. EPC Commentary, 24 April 2014

During the past six months Ukraine has been through a revolution, its Crimean peninsula has been annexed by Russia and its territorial integrity continues to be challenged. With ongoing unrest in three Eastern regions, a peace deal recently agreed in Geneva hangs by a thread as pro-Russian separatists continue to occupy numerous public buildings and international actors remain divided over how long to wait for Russia to implement the accord before placing new sanctions. While the West accuses Russia of provoking and influencing the unrest, Russia points the finger at Ukraine’s interim leadership which it claims is illegal and “fascist”.

The UN General Assembly Vote: Upgrading the Status of Palestine and Its Implications for a Possible Role of the ICC. IES Policy Brief Issue 2013/06 • June 2013

On 29 November 2012, the General Assembly of the United Nations (UN) voted overwhelmingly to accord Palestine ‘Non-Member Observer State’ Status in the UN. In the first part of this Policy Brief, the implications of upgrading the status of Palestine with regard to the possible role of the International Criminal Court (ICC) will be assessed. In April 2012, the Office of the Prosecutor of the ICC declined to accept jurisdiction for acts committed on the territory of Palestine since 1 July 2002, justifying its decision based on the fact that Palestine had, at the time, only the status of an ‘Observer Entity’ at the UN. Subsequently, it will be analysed if the Palestinian pursuit of its cause before the ICC can be considered as an effective lawfare strategy or rather as a poisoned chalice.

De Gaulle and Europe: Historical Revision and Social Science Theory. CES Germany & Europe Working Papers, No. 08.5, 1998

The thousands of books and articles on Charles de Gaulle's policy toward European integration, whether written by historians, political scientists, or commentators, universally accord primary explanatory importance to the General's distinctive geopolitical ideology. In explaining his motivations, only secondary significance, if any at all, is attached to commercial considerations. This paper seeks to reverse this historiographical consensus by the four major decisions toward European integration taken under de Gaulle's Presidency: the decisions to remain in the Common Market in 1958, to propose the Fouchet Plan in the early 1960s, to veto British accession to the EC, and to provoke the "empty chair" crisis in 1965-1966, resulting in Luxembourg Compromise. In each case, the overwhelming bulk of the primary evidence speeches, memoirs, or government documents suggests that de Gaulle's primary motivation was economic, not geopolitical or ideological. Like his predecessors and successors, de Gaulle sought to promote French industry and agriculture by establishing protected markets for their export products. This empirical finding has three broader implications: (1) For those interested in the European Union, it suggests that regional integration has been driven primarily by economic, not geopolitical considerations even in the least likely case. (2) For those interested in the role of ideas in foreign policy, it suggests that strong interest groups in a democracy limit the impact of a leaders geopolitical ideology even where the executive has very broad institutional autonomy. De Gaulle was a democratic statesman first and an ideological visionary second. (3) For those who employ qualitative case-study methods, it suggests that even a broad, representative sample of secondary sources does not create a firm basis for causal inference. For political scientists, as for historians, there is in many cases no reliable alternative to primary source research.

The nuclear deal with Iran: Le moment suprême? CEPS Commentary, 16 July 2015

More than two years in the making, the agreement concluded by China, the EU, France, Germany, Russia, the UK and the US with Iran to prevent the ‘weaponisation’ of the latter’s nuclear programme is a big deal. But, cautions Steven Blockmans in this CEPS Commentary, it is not the silver bullet to the normalisation of relations. Implementation will be a tortuous process, fraught with suspicion and friction. Although Europe has been called upon to seize the moment and to shift to a relationship with Iran based on engagement, not containment, the EU and its member states would be better advised not to move beyond their nuclear focus too quickly, but rather to show a sense of duty and loyal cooperation with their international partners by supporting the effective execution of the accord.