Dose optimization for long-term rAAV-mediated RNA interference in the nigrostriatal projection neurons

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Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a kinase and GTPase, and PD-linked mutations are known to influence both enzymatic acti ...

National Academy of Sciences2020

Single-Cell Tracing Dissects Regulation of Maintenance and Inheritance of Transcriptional Reinduction Memory

Sebastian Maerkl, Johannes Becker

Transcriptional memory of gene expression enables adaptation to repeated stimuli across many organisms. However, the regulation and heritability of transcriptional memory in single cells and through divisions remains poorly understood. Here, we combined mi ...

2020

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

Srikanth Ramaswamy, Vignayanandam Ravindernath Muddapu

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). Although many mechanisms have been suggested, a decisive root cause of this cell loss is ...

2019

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment

Laurent Keller, Pierre Gönczy, Frédéric Schütz, Alexandra Bezler, Raffaella Conconi

RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by ...

2019

Classification of degenerative parkinsonism subtypes by support-vector-machine analysis and striatal I-123-FP-CIT indices

Dimitri Nestor Alice Van De Ville, Maria Giulia Preti

ObjectivesTo provide an automated classification method for degenerative parkinsonian syndromes (PS) based on semiquantitative I-123-FP-CIT SPECT striatal indices and support-vector-machine (SVM) analysis.Methods(123)I-FP-CIT SPECT was performed at a singl ...

Springer2019

The dopaminergic VTA - basal amygdala projection contributes to signal aversive state in fear memory

Wei Tang

Dopamine released from midbrain neurons is an important neuromodulatory signal during associative learning in many forebrain circuits. One model of associative learning is auditory cued fear learning, during which an innocuous sensory percept like a tone ( ...

EPFL2018

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of accumbal dopamine D1 receptors

Maria del Carmen Sandi Perez, Carlos Canto Alvarez, Olivia Zanoletti, Jocelin Grosse, Michael van der Kooij, Fiona Hollis, Laura Lozano Montes, Marie-Isabelle Guillot de Suduiraut, Ioannis Zalachoras, Sonia Abad Florensa

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines’ effects in social competition are not understood. Convergi ...

Nature Publishing Group2018

Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Andrej Benjak, Nina Theres Odermatt

Tight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, ...

Nature Research2018

Quantitative single cell dynamics of signaling and transcriptional response in mammalian cells

Onur Tidin

Cells live in ever-changing environments, thereby facing a variety of dynamic environmental signals. Environmental stimuli elicit intracellular responses through signaling pathways, which converge on transcriptional activation or repression of target genes ...

EPFL2018

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