BACKGROUND The analysis of coverage depth in next-generation sequencing data allows the detection of gene dose alterations. We explore the frequency of such structural events in a Spanish cohort of sporadic PD cases. METHODS Gene dose alterations were detected with the eXome-Hidden Markov Model (XHMM) software from depth of coverage in resequencing data available for 38 Mendelian and other ri...

Reactive α-dicarbonyls (α-DCs), like methylglyoxal (MGO), accumulate with age and have been implicated in aging and various age-associated pathologies, such as diabetic complications and neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Evolutionarily conserved glyoxalases are responsible for α-DC detoxification; however, their core biochemical regulation has remained uncle...

Parkinson's disease (PD) is one of the major causes of parkinsonism syndrome. Its characteristic motor symptoms are attributable to dopaminergic neurons loss in the midbrain. Genetic advances have highlighted underlying molecular mechanisms and provided clues to potential therapies. However, most of the studies focusing on the genetic component of PD have been performed on American, European an...

Parkinson's disease can be caused by rare familial genetic mutations, but in most cases it is likely to result from an interaction between multiple genetic and environmental risk factors. Over recent years, many variants in a growing number of genes involved in the pathogenesis of Parkinson's disease have been identified. Mutations in several genes have been shown to cause familial parkinsonism...

The purpose of this paper is to survey some recent results in the theory of “p-adic cohomology”, by which we will mean several different (but related) things: the de Rham or p-adic étale cohomology of varieties over p-adic fields, or the rigid cohomology of varieties over fields of characteristic p > 0. Our goal is to update Illusie’s beautiful 1994 survey [I] by reporting on some of the many i...

Given noisy signal, its nite discrete wavelet transform is an estimator of signal's wavelet expansion coeecients. An appropriate thresholding of coeecients for further reconstruction of de-noised signal plays a key-role in the wavelet decomposition/reconstruction procedure. DJ1] proposed a global threshold = p 2 logn and showed that such a threshold asymptotically reduces the expected risk of t...

The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was iden...

Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that were shown to functionally interact by yet unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Thus, parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induce...

Transcription activator-like effector nucleases (TALENs) have become powerful tools for targeted genome editing. Here we demonstrate efficient targeted mutagenesis in medaka (Oryzias latipes), which serves as an excellent vertebrate model for genetics and genomics. We designed and constructed a pair of TALENs targeting the medaka DJ-1 gene, a homolog of human DJ-1 (PARK7). These TALENs induced ...