Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens), cell adhesion (fibronectin), muscle development (myosins and melusin) and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB) is upregulated in LGMD2A muscle samples, it could be hypothesized that β-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1). Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies

Brain rhythms alterations and their effect in functional networks: A simultaneous EEG/fMRI study in Fixation-off epilepsy

Fixation-off sensitivity (FOS) denotes the forms of EEG abnormalities, which are elicited by elimination of central vision or fixation. The phenomenon seems to depend on variables that modulate the alpha rhythm, however, the cerebral mechanisms underlying FOS remain unclear [1]. The scarce previous fMRI findings related to FOS have shown activation in extrastriate cortex [2] and also in frontal areas [3][4]. On the other hand, simultaneous EEG-fMRI technique has been used to assess the relationship between spontaneous power fluctuations of electrical rhythms and associated fMRI signal modulations. These studies have identified that lateral frontoparietal networks show a negative correlation with alpha band in healthy subjects. This neuroanatomical pattern is related to attentional processes and cognitive resources. Moreover, a sub-beta band (17-23 Hz) has been identified with posterior cingulate, temporoparietal junction and dorso-medial prefrontal cortex activations, which correspond to the DMN [5][6].

Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy

Fixation-off sensitivity (FOS) denotes the forms of epilepsy elicited by elimination of fixation. FOS-IGE patients are rare cases [1]. In a previous work [2] we showed that two FOS-IGE patients had different altered EEG rhythms when closing eyes; only beta band was altered in patient 1 while theta, alpha and beta were altered in patient 2. In the present work, we explain the relationship between the altered brain rhythms in these patients and the disruption in functional brain networks.

Reintroducción del altramuz endémico valenciano Lupinus mariaejosephae mediante la inoculación de cepas seleccionadas de bacterias del género Bradyrhizobium

Lupinus mariae-josephae es un altramuz endémico de la provincia de Valencia de reciente descubrimiento para la ciencia. Se conocen solo 4 poblaciones, algunas con miles de individuos pero todas ellas con grandes fluctuaciones interanuales, tanto demográficas como de éxito reproductivo. Es por ello que está incluida en el Catálogo Valenciano de Especies de Flora Amenazadas como "Especie Vulnerable". Con finalidad conservacionista se realizó una reintroducción de la especie dentro de su área de distribución conocida. Para ello, se sembraron semillas del altramuz valenciano en 3 grupos (tratamientos) diferentes, 2 de ellos inoculados con sendas cepas de una bacteria simbionte fijadora de nitrógeno atmosférico del género Bradyrhizobium; al tercero no se le inoculó ninguna bacteria. La bacteria, específica de esta leguminosa, y las cepas, fueron aisladas, estudiadas y seleccionadas en investigaciones anteriores. Al final del ciclo biológico de la especie se valoró el éxito en la supervivencia y el éxito reproductivo encontrando resultados óptimos sobre todo para una de las cepas utilizadas (LmjC) que previamente ya había demostrado un comportamiento eficiente en condiciones controladas. Estos resultados serán de gran ayuda para el futuro establecimiento de nuevas poblaciones del altramuz valenciano, con la posible mejora de su estatus de amenaza.

Conservation of endangered Lupinus mariae-josephae in its natural habitat by inoculation with selected, native Bradyrhizobium strains

Lupinus mariae-josephae is a recently discovered endemism that is only found in alkaline-limed soils, a unique habitat for lupines, from a small area in Valencia region (Spain). In these soils, L. mariae-josephae grows in just a few defined patches, and previous conservation efforts directed towards controlled plant reproduction have been unsuccessful. We have previously shown that L. mariae-josephae plants establish a specific root nodule symbiosis with bradyrhizobia present in those soils, and we reasoned that the paucity of these bacteria in soils might contribute to the lack of success in reproducing plants for conservation purposes. Greenhouse experiments using L. mariae-josephae trap-plants showed the absence or near absence of L. mariae-josephae-nodulating bacteria in ‘‘terra rossa’’ soils of Valencia outside of L. mariaejosephae plant patches, and in other ‘‘terra rossa’’ or alkaline red soils of the Iberian Peninsula and Balearic Islands outside of the Valencia L. mariae-josephae endemism region. Among the bradyrhizobia able to establish an efficient symbiosis with L. mariae-josephae plants, two strains, LmjC and LmjM3 were selected as inoculum for seed coating. Two planting experiments were carried out in consecutive years under natural conditions in areas with edapho-climatic characteristics identical to those sustaining natural L. mariae-josephae populations, and successful reproduction of the plant was achieved. Interestingly, the successful reproductive cycle was absolutely dependent on seedling inoculation with effective bradyrhizobia, and optimal performance was observed in plants inoculated with LmjC, a strain that had previously shown the most efficient behavior under controlled conditions. Our results define conditions for L. mariae-josephae conservation and for extension to alkaline-limed soil habitats, where no other known lupine can thrive.