Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation

Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1−/−-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter. Mutant Adktm1−/−-Tg(UbiAdk) mice were characterized by increased brain ADK activity and constitutive overexpression of transgenic ADK throughout the brain, with particularly high levels in hippocampal pyramidal neurons. This ADK overexpression was associated with increased baseline levels of locomotion. Most importantly, two-thirds of the mutant mice analysed exhibited spontaneous seizure activity in the hippocampus and cortex. This was the direct consequence of transgene expression, since this seizure activity could be prevented by systemic application of the ADK inhibitor 5-iodotubercidin. Intrahippocampal injection of kainate in the mutant mice resulted in astrogliosis to the same extent as that observed in wild-type mice despite the absence of endogenous astrocytic ADK. Therefore, KASE-induced upregulation of endogenous ADK in wild-type mice is a consequence of astrogliosis. However, seizures in kainic acid-injected mutants displayed increased intra-ictal spike frequency compared with wild-type mice, indicating that, once epilepsy is established, increased levels of ADK aggravate seizure severity. We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epileps

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

PSSA-2, a Membrane-Spanning Phosphoprotein of Trypanosoma brucei, Is Required for Efficient Maturation of Infection

The coat of Trypanosoma brucei consists mainly of glycosylphosphatidylinositol-anchored proteins that are present in several million copies and are characteristic of defined stages of the life cycle. While these major components of the coats of bloodstream forms and procyclic (insect midgut) forms are well characterised, very little is known about less abundant stage-regulated surface proteins and their roles in infection and transmission. By creating epitope-tagged versions of procyclic-specific surface antigen 2 (PSSA-2) we demonstrated that it is a membrane-spanning protein that is expressed by several different life cycle stages in tsetse flies, but not by parasites in the mammalian bloodstream. In common with other membrane-spanning proteins in T. brucei, PSSA-2 requires its cytoplasmic domain in order to exit the endoplasmic reticulum. Correct localisation of PSSA-2 requires phosphorylation of a cytoplasmic threonine residue (T305), a modification that depends on the presence of TbMAPK4. Mutation of T305 to alanine (T305A) has no effect on the localisation of the protein in cells that express wild type PSSA-2. In contrast, this protein is largely intracellular when expressed in a null mutant background. A variant with a T305D mutation gives strong surface expression in both the wild type and null mutant, but slows growth of the cells, suggesting that it may function as a dominant negative mutant. The PSSA-2 null mutant exhibits no perceptible phenotype in culture and is fully competent at establishing midgut infections in tsetse, but is defective in colonising the salivary glands and the production of infectious metacyclic forms. Given the protein's structure and the effects of mutation of T305 on proliferation and localisation, we postulate that PSSA-2 might sense and transmit signals that contribute to the parasite's decision to divide, differentiate or migrate

00 [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Cognitive Interference in Sports – Validation of a German Version of the Thoughts Occurrence Questionnaire Sport (TOQS)

Konzentration ist für die sportliche Leistungserbringung wesentlich. Die Störung der Konzentration durch eigene Gedanken wird als kognitive Interferenz bezeichnet. Im englischsprachigen Raum wird diese Interferenz mit dem Thought Occurence Questionnaire Sport (TOQS; Hatzigeorgiadis & Biddle, 2000) erfasst. Die vorliegende Arbeit validiert eine deutsche Version (TOQS-D) an zwei Stichproben bestehend aus insgesamt 348 Sporttreibenden (56 % männlich, MAlter = 25, SDAlter = 6, 61 % Teamsportarten, 53 % Mitglied im Schweizer Nationalkader). Eine explorative Faktorenanalyse (Stichprobe 1) sowie eine konfirmatorische Faktorenanalyse (Stichprobe 2) bestätigen die Struktur der Originalversion mit drei interkorrelierenden Faktoren: Leistungssorgen, aufgabenirrelevante Gedanken und Fluchtgedanken. Die Skala hat gute Reliabilitätswerte (interne Konsistenz: α = .89; Retestreliabilität: r = .82). Zudem zeigt der TOQS-D die erwartete konvergente Validität (Konzentrationsstörungen, Wettkampfangst), divergente Validität (Achtsamkeit) und Kriteriumsvalidität (Selbsteinschätzung der sportlichen Leistung). Mit dem TOQS-D liegt damit ein geeignetes Instrument vor, dessen Einsatzmöglichkeiten in Praxis und Forschung abschließend diskutiert werden.Concentration is essential for athletic performance. The disturbance of concentration by thoughts is called cognitive interference. In English-speaking countries, this interference is assessed with the Thought Occurrence Questionnaire for Sport (TOQS; Hatzigeorgiadis & Biddle, 2000). The present study validated a German version (TOQS-D) on two samples consisting of a total of 348 athletes (56 % male, Mage = 25, SDage = 6, 61 % team sports, 53 % national team members). An exploratory factor analysis (Sample 1) and a confirmatory factor analysis (Sample 2) confirmed the structure of the original version with three correlated factors: performance worries, task-irrelevant thoughts, and thoughts of escape. The scale has good reliability scores (internal consistency: α = .89; test–retest reliability: r = .82). In addition, the TOQS-D shows the expected convergent (concentration disruption, competition anxiety), divergent (mindfulness), and criterion validity (self-assessment of athletic performance). The TOQS-D can be considered an appropriate questionnaire, and its applications in practice and research is discussed

Kognitive Interferenz im Sport - Validierung einer deutschsprachigen Version des „Thoughts Occurence Questionnaires Sport“ (TOQS)

Konzentration ist für die sportliche Leistungserbringung wesentlich. Die Störung der Konzentration durch eigene Gedanken wird als kognitive Interferenz bezeichnet. Im englischsprachigen Raum wird diese Interferenz mit dem Thought Occurence Questionnaire Sport (TOQS; Hatzigeorgiadis & Biddle, 2000) erfasst. Die vorliegende Arbeit validiert eine deutsche Version (TOQS-D) an zwei Stichproben bestehend aus insgesamt 348 Sporttreibenden (56 % männlich, MAlter = 25, SDAlter = 6, 61 % Teamsportarten, 53 % Mitglied im Schweizer Nationalkader). Eine explorative Faktorenanalyse (Stichprobe 1) sowie eine konfirmatorische Faktorenanalyse (Stichprobe 2) bestätigen die Struktur der Originalversion mit drei interkorrelierenden Faktoren: Leistungssorgen, aufgabenirrelevante Gedanken und Fluchtgedanken. Die Skala hat gute Reliabilitätswerte (interne Konsistenz: α = .89; Retestreliabilität: r = .82). Zudem zeigt der TOQS-D die erwartete konvergente Validität (Konzentrationsstörungen, Wettkampfangst), divergente Validität (Achtsamkeit) und Kriteriumsvalidität (Selbsteinschätzung der sportlichen Leistung). Mit dem TOQS-D liegt damit ein geeignetes Instrument vor, dessen Einsatzmöglichkeiten in Praxis und Forschung abschließend diskutiert werden

Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation

Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1−/−-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter. Mutant Adktm1−/−-Tg(UbiAdk) mice were characterized by increased brain ADK activity and constitutive overexpression of transgenic ADK throughout the brain, with particularly high levels in hippocampal pyramidal neurons. This ADK overexpression was associated with increased baseline levels of locomotion. Most importantly, two-thirds of the mutant mice analysed exhibited spontaneous seizure activity in the hippocampus and cortex. This was the direct consequence of transgene expression, since this seizure activity could be prevented by systemic application of the ADK inhibitor 5-iodotubercidin. Intrahippocampal injection of kainate in the mutant mice resulted in astrogliosis to the same extent as that observed in wild-type mice despite the absence of endogenous astrocytic ADK. Therefore, KASE-induced upregulation of endogenous ADK in wild-type mice is a consequence of astrogliosis. However, seizures in kainic acid-injected mutants displayed increased intra-ictal spike frequency compared with wild-type mice, indicating that, once epilepsy is established, increased levels of ADK aggravate seizure severity. We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epileps