Mild cognitive impairment subtypes: An MEG study

Previous studies of the dementia continuum have characterized the early disruption of the brain oscillatory activity at the stage of Mild cognitive impairment (MCI). Reduction in power in posterior regions in the alpha band has been one of the landmarks of the Alzheimer Disease accompanied by the anteriorization of the theta band power. However, little is known about the neurophysiological differences between single and multidomain MCI patients.Our goal is to study the differences in oscillatory magnetic activity between amnestic single and multidomain MCI. This will allow us to test whether the effect of the impairment in a single cognitive domain or in a more widespread functional impairment can be reflected in specific neurophysiological profiles.

Classifying GABAergic interneurons with semi-supervised projected model-based clustering

Objectives: A recently introduced pragmatic scheme promises to be a useful catalog of interneuron names.We sought to automatically classify digitally reconstructed interneuronal morphologies according tothis scheme. Simultaneously, we sought to discover possible subtypes of these types that might emergeduring automatic classification (clustering). We also investigated which morphometric properties weremost relevant for this classification.Materials and methods: A set of 118 digitally reconstructed interneuronal morphologies classified into thecommon basket (CB), horse-tail (HT), large basket (LB), and Martinotti (MA) interneuron types by 42 of theworld?s leading neuroscientists, quantified by five simple morphometric properties of the axon and fourof the dendrites. We labeled each neuron with the type most commonly assigned to it by the experts. Wethen removed this class information for each type separately, and applied semi-supervised clustering tothose cells (keeping the others? cluster membership fixed), to assess separation from other types and lookfor the formation of new groups (subtypes). We performed this same experiment unlabeling the cells oftwo types at a time, and of half the cells of a single type at a time. The clustering model is a finite mixtureof Gaussians which we adapted for the estimation of local (per-cluster) feature relevance. We performedthe described experiments on three different subsets of the data, formed according to how many expertsagreed on type membership: at least 18 experts (the full data set), at least 21 (73 neurons), and at least26 (47 neurons).Results: Interneurons with more reliable type labels were classified more accurately. We classified HTcells with 100% accuracy, MA cells with 73% accuracy, and CB and LB cells with 56% and 58% accuracy,respectively. We identified three subtypes of the MA type, one subtype of CB and LB types each, andno subtypes of HT (it was a single, homogeneous type). We got maximum (adapted) Silhouette widthand ARI values of 1, 0.83, 0.79, and 0.42, when unlabeling the HT, CB, LB, and MA types, respectively,confirming the quality of the formed cluster solutions. The subtypes identified when unlabeling a singletype also emerged when unlabeling two types at a time, confirming their validity. Axonal morphometricproperties were more relevant that dendritic ones, with the axonal polar histogram length in the [pi, 2pi) angle interval being particularly useful.Conclusions: The applied semi-supervised clustering method can accurately discriminate among CB, HT, LB, and MA interneuron types while discovering potential subtypes, and is therefore useful for neuronal classification. The discovery of potential subtypes suggests that some of these types are more heteroge-neous that previously thought. Finally, axonal variables seem to be more relevant than dendritic ones fordistinguishing among the CB, HT, LB, and MA interneuron types.

Mecanismos implicados en las etapas iniciales de infección en la cancrosis de los cítricos provocada por Xanthomonas citri subsp. citri

La cancrosis o chancro bacteriano de los cítricos (CBC) causada por Xanthomonas citri subsp. citri (Xcc) y X. fuscans subsp. aurantifolii, afecta a un gran número de especies dentro de la familia de las rutáceas, especialmente cítricos. Esta enfermedad produce graves pérdidas económicas allí donde está presente, principalmente porque la comercialización de cítricos desde las zonas afectadas hacía zonas libres de cancrosis, está sujeta a fuertes medidas cuarentenarias. La cancrosis se encuentra distribuida a nivel mundial pero no se ha localizado ni en la Unión Europea ni en ningún área del Mediterráneo. Se han descrito tres tipos de cancrosis en función de la gama de huésped y de las características fenotípicas y genotípicas de las bacterias que las producen. La más extendida es la cancrosis tipo A producida por Xcc, dentro de la cual se distinguen los subtipos Aw y A*, originarios de Florida y Sudeste Asiático, respectivamente, que de forma natural solo son capaces de producir enfermedad en lima mejicana. En este trabajo se presentan estudios sobre mecanismos implicados en las primeras etapas de la infección, como la quimiotaxis y formación de biopelículas, en la cancrosis de los cítricos. La quimiotaxis es el proceso por el cual las bacterias se dirigen hacia zonas favorables para su supervivencia y desarrollo. Los perfiles quimiotácticos obtenidos frente a distintas fuentes de carbono, así como los estudios en relación al contenido de proteínas aceptoras de grupos metilo (MCPs), permitieron agrupar a las cepas de Xanthomonas estudiadas en este trabajo, de acuerdo a la enfermedad producida y a su gama de huésped. Todas las cepas mostraron quimiotaxis positiva frente a extractos de hoja y apoplasto de diferentes especies, sin embargo, Xcc 306, X. alfalfae subsp. citrumelonis (Xac) y X. campestris pv. campestris (Xc) manifestaron respuestas más específicas frente a extractos de apoplasto de hojas de naranjo dulce, lima y col china, respectivamente. Dicho resultado nos permite asociar el mecanismo de quimiotaxis con la capacidad de las cepas de Xanthomonas para colonizar estos huéspedes de forma específica. Las cepas estudiadas fueron capaces de realizar movimiento tipo swimming, twitching y sliding en distintos medios, siendo el movimiento swimming el único en el que se encontraron diferencias entre las cepas de Xcc con distinta gama de huésped. En este trabajo se ha estudiado además la formación de biopelículas en superficies bióticas y abióticas, un mecanismo importante tanto para la supervivencia en superficie vegetal como para el desarrollo de la infección. Las cepas de Xanthomonas estudiadas fueron capaces de formar biopelículas in vitro, siendo mayor en un medio que simula el apoplasto y que contiene una baja concentración de nutrientes en comparación con medios que contenían alta concentración de nutrientes. La formación de biopelículas en superficie vegetal se encontró relacionada, en las cepas patógenas de cítricos, con la capacidad para infectar un tejido o huésped determinado. Se han caracterizado algunos de los componentes de la matriz extracelular producida por Xcc, que compone hasta un 90% de las bipoelículas. Entre ellos destaca el ADN extracelular, que tiene un papel como adhesina en las primeras etapas de formación de biopelículas y estructural en biopelículas maduras. Además, se han identificado el pilus tipo IV como componente importante en las biopelículas, que también participa en motilidad. Finalmente, se han realizado estudios sobre la expresión de genes implicados en motilidad bacteriana y formación de biopelículas que han confirmado las diferencias existentes entre cepas de Xcc de amplia y limitada gama de huésped, así como el papel que juegan elementos como el pilus tipo IV o el flagelo en estos procesos. ABSTRACT Xanthomonas citri subsp. citri (Xcc) and X. fuscans subsp. aurantifolii are the causal agents of Citrus Bacterial Canker (CBC) which is one of the most important citrus diseases. CBC affects all Citrus species as well as other species from Rutaceae family. CBC produces strong economic losses; furthermore the commercialization of plants and fruits is restricted from infested to citrus canker free areas. The disease is worldwide distributed in tropical and subtropical areas, however it is not present in the European Union. Three types of CBC have been described according to the host range and phenotypic and genotypic characteristics. CBC type A caused by Xcc is he widest distributed. Within CBC A type two subtypes Aw and A* were described from Florida and Iran respectively, both infecting only Mexican lime. Herein mechanisms connected to early events in the citrus bacterial canker disease such as chemotaxis and biofilm formation, were studied. Chemotaxis allows bacteria to move towards the more suitable environments for its survival, host colonization and infection. Studies performed on citrus pathogenic Xanthomonas and X. campestris pv. campestris (Xc), a crucifer pathogen, have shown different chemotactic profiles towards carbon compound as well as different MCPs profile, which clustered strains according to host range and disease caused. Every strain showed positive chemotaxis toward leaf extracts and apoplastic fluids from sweet orange, Mexican lime and Chinese cabbage leaves. However, a more specific response was found for strains Xcc 306, X. alfalfae subsp. citrumelonis and Xc towards sweet orange, Mexican lime and Chinese cabbage apoplastic fluids, respectively. These results relate chemotaxis with the higher ability of those strains to specifically colonize their proper host. Xanthomonas strains studied were able to perform swimming, sliding and twitching motilities. The ability to swim was variable among CBC strains and seemed related to host range. Biofilm formation is an important virulence factor for Xcc because it allows a better survival onto the plant surface as well as facilitates the infection process. The studied Xanthomonas strains were able to form biofilm in vitro, on both nutrient rich and apoplast mimicking media, furthermore the biofilm formation by all the strains was higher in the apoplast mimicking media. The ability to form biofilm in planta by Xcc and Xac strains was dependent of the host and the tissue colonized. The wide host range CBC strain was able to form biofilm onto several citrus leaves and fruits, however the limited host range CBC strain produced biofilm solely onto Mexican lime leaves and fruits. Furthermore Xac strain, which solely infects leaves of young plants, was not able to develop biofilms on fruits. Some components of the extracellular matrix produced by Xcc strains have been characterized. Extracellular DNA acted as an adhesin at the very early stages of biofilm formation and as structural component of mature biofilm for citrus pathogenic Xanthomonas. Furthermore type IV pilus has been identified as a component of the extracellular matrix in biofilm and motility. Transcriptional studies of genes related with biofilm formation and motility have confirmed the differential behavior found among wide and limited host range CBC strains as well as the role of type IV pili and flagellum on those processes.