Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes

Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition to desmoglein-3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of cell-cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in cells treated with autoantibodies compared to those treated with normal antibodies. The apoptotic process induced by IgG autoantibodies was characterized by caspase-3 activation, Bcl-2 depletion and Bax expression. The present report demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries

Background: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seednetwork of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development. Methodology/Principal Findings: Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina. Conclusions/Significance: We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will facilitate the use of prior biological knowledge to develop rational systems-based hypotheses

Contribución al conocimiento de los depósitos detríticos pleistocenos de los montes Vascos-Pirineos Occidentales y su relación con formaciones edáficas surpirenaicas

Se estudian las formas y distribución de los óxidos de hierro en diversos coluviones del piedemonte septentrional de las sierras de Aralar y Aizkorri y del área periglaciar de la Cuenca de Pamplona comparándolas con las del complejo de morrenas y terrazas del Aragón. Para valorar el grado de alteración de los sedimentos y utilizarlo como criterio cronológico de correlación se han definido como indicadores las relaciones representativas de las proporciones de hierro libre, silicatado y cristalino en la fracción inferior a 2 mm. No existe relación alguna entre el contenido total de hierro y la edad de los depósitos, mientras que el hierro amorfo o de baja cristalinidad tiende a valores altos en los sedimentos recientes. En cambio, la proporción que representa el hierro cristalino se incrementa con la edad de la formación. El intervalo 40-50% de la fracción (Fed-Feo)Aralar eta Aizkorri mendizerretako ipar behealdeko eta Iruñerriko glaziar inguruko burdin oxidoen forma eta banaketa aztertzen dira, Aragoiko morrena eta terraza multzoarekin alderatuz. Sedimentuen aldaketa-maila baloratu ahal izateko eta koerlazio-irizpide kronologiko gisa erabiltzearren, 2 mm-z beheitiko frakzioan aurkituriko burdina libre, silikatado eta kristalinoen proportzioen erlazio adierazgarriak hartu dira adierazletzat. Ez da inolako erlaziorik burdin eduki osoaren eta depositoaren adinaren artean, burdina amorfo edo kristalinitate gutxikoak balore altuetara jotzen du sedimentu berriagoetan. Burdina kristalinoaren proportzioa, ordea, gorantza doa adinaren arabera. (Fed-Feo)Dans cette étude on analyse les formes et la distribution des oxydes de fer dans plusieurs colluvions du pied de montagne septentrional des chaînes d'Aralar et d'Aizkorri et de la zone périglaciaire du Bassin de Pamplona, en les comparant avec ceux existant sur l'ensemble des morraines et des terraces de l'Aragon. Pour déterminer le degré d'altération des sédiments et pour l'utiliser comme critère chronologique de conrrélation, nous avons choisi comme indicateurs les rapports représentatifs des proportions de fer libre, de silicate et de critallin dans la fraction inférieure à 2 mm. Il n'y aucun rapport entre le contenu total en fer et l'âge des dépôts, tandis que le fer amorphe ou de basse cristallité présente des valeurs élevées dans les sédiments récents. Par contre, la proportion de fer cristallin augmente avec l'âge de la formation. L'intervalle 40-50% de la fraction (Fed-Feo