Caspase activation precedes and leads to tangles

Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death(1,2), severe cytological abnormalities(3), and markers of caspase activation and apoptosis(4–6), leading to the idea that tangles cause neurodegeneration in Alzheimer’s disease and tau-related frontotemporal dementia. However, using in vivo multiphoton imaging to observe tangles and activation of executioner caspases in living tau transgenic mice (Tg4510 strain), we find the opposite: caspase activation occurs first, and precedes tangle formation by hours to days. New tangles form within a day. After a new tangle forms, the neuron remains alive and caspase activity seems to be suppressed. Similarly, introduction of wild-type 4-repeat tau (Tau-4R) into wild-type animals triggered caspase activation, tau truncation and tau aggregation. Adeno-associated virus-mediated expression of a construct mimicking caspase-cleaved tau into wild-type mice led to the appearance of intracellular aggregates, tangle-related conformational- and phospho-epitopes, and the recruitment of full-length endogenous tau to the aggregates. On the basis of these data, we propose a new model in which caspase activation cleaves tau to initiate tangle formation, then truncated tau recruits normal tau to misfold and form tangles. Because tangle-bearing neurons are long-lived, we suggest that tangles are ‘off pathway’ to acute neuronal death. Soluble tau species, rather than fibrillar tau, may be the critical toxic moiety underlying neurodegeneration

Populist Mobilization: A New Theoretical Approach to Populism*

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112280/1/j.1467-9558.2011.01388.x.pd

Chromo- and Fluorogenic Organometallic Sensors

Compounds that change their absorption and/or emission properties in the presence of a target ion or molecule have been studied for many years as the basis for optical sensing. Within this group of compounds, a variety of organometallic complexes have been proposed for the detection of a wide range of analytes such as cations (including H+), anions, gases (e.g. O 2, SO2, organic vapours), small organic molecules, and large biomolecules (e.g. proteins, DNA). This chapter focuses on work reported within the last few years in the area of organometallic sensors. Some of the most extensively studied systems incorporate metal moieties with intense long-lived metal-to-ligand charge transfer (MLCT) excited states as the reporter or indicator unit, such as fac-tricarbonyl Re(I) complexes, cyclometallated Ir(III) species, and diimine Ru(II) or Os(II) derivatives. Other commonly used organometallic sensors are based on Pt-alkynyls and ferrocene fragments. To these reporters, an appropriate recognition or analyte-binding unit is usually attached so that a detectable modification on the colour and/or the emission of the complex occurs upon binding of the analyte. Examples of recognition sites include macrocycles for the binding of cations, H-bonding units selective to specific anions, and DNA intercalating fragments. A different approach is used for the detection of some gases or vapours, where the sensor's response is associated with changes in the crystal packing of the complex on absorption of the gas, or to direct coordination of the analyte to the metal centre

Category-specific naming impairment in temporal lobe epilepsy through cortical electrical stimulation: Case report

Current studies based on specific naming subcategories are scarce and specially if they are combined with cortical electrical stimulation mapping (CES). Most researchers use generic categories of objects that have not shown to be useful for epileptic patients. The present study explores the ability to retrieve words with the aim of naming entities through CES during surgery of a patient with left temporal lobe epilepsy (TLE) prior to anterior temporal lobectomy (ATL). During the CES we observed alterations in the naming of faces, living things (LTh) and parts of the body, with conservation of non-living things (NLTh). CES allowed the identification and prediction of regions at risk of being resected. This result shows that the naming deficits are selective and can be used as indicators and predictors of post-operative cognitive dysfunction in TLE since the regions involved in this function are associated with the pole and inferior and medial temporal gyrus. Resumen: Actualmente los estudios de subcategorías en la denominación son escasos y más cuando se combinan con estimulación eléctrica cortical directa (EEC). La mayoría usa objetos que no han mostrado ser específicos en epilepsia del lóbulo temporal (ELT). El presente estudio explora la recuperación de las palabras con el objetivo de nombrar entidades (denominación) a través de la EEC durante la cirugía de una paciente con ELT-izquierdo previo a la lobectomía temporal anterior (LTA) Durante la estimulación se observaron alteraciones en la denominación de rostros, seres vivos (SV) animados y partes del cuerpo, con conservación de los seres no vivos (SNV). La EEC permitió identificar y predecir las regiones con riesgo de ser resecadas. Este resultado muestra que las alteraciones en la denominación son selectivas por lo que pueden emplearse como predictores de disfunción cognitiva postquirúrgica, ya que esta función depende de polo y giro temporal inferior y medial. Keywords: Naming, Cortical electrical stimulation mapping, Language, Temporal lobe epilepsy, Palabras clave: Denominación, Estimulación eléctrica cortical directa, Lenguaje, Epilepsia del lóbulo tempora