Lyso-IP: Uncovering Pathogenic Mechanisms of Lysosomal Dysfunction
By Emma Sherrell onPublished: Future applications of rapid lysosomal isolation techniques are likely to greatly enhance our understanding of lysosomal dysfunction in rare and common neurodegeneration causes.
Modelling human brain-wide pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits
By savannah onIn parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model may open new research avenues in the field of brain aging and neurodegeneration.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
By savannah onThe authors increased Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders. View original preprint.
Is Gauchian genotyping of GBA1 variants reliable?
By Emma Sherrell onPreprint: The authors evaluated Gauchian in 90 Sanger-sequenced patients with GD and five GBA1 heterozygotes using the software tool Gauchian to identify GBA1 variants from whole genome sequencing. While Gauchian genotyped most patients correctly, this limits Gauchian's utility in variant screening and precluding its use in diagnostics.
Targeted detection of SNCA CNVs in SOX10+ nuclei from oligodendrocytes containing alpha-synuclein inclusions isolated from human post-mortem brain
By savannah onThe protocol is optimized to detect SOX10, a nuclear oligodendrocyte marker, and alpha-synuclein inclusions, which are frequently retained at the perinucleus in MSA (the so-called Papp-Lantos inclusions). This protocol also describes its use in affected PD and MSA brain regions such as the putamen, substantia nigra (SN), and cerebellum.
Section 3: Libraries quality control (QC)
By savannah onThis protocol details quality control of libraries and should be performed after Section 2: NGS library preparation for sequencing.
Section 2: NGS library preparation for sequencing
By savannah onThis protocol details NGS library preparation for sequencing and should be performed after Section 1: Enzymatic DNA Fragmentation (Manually).
Population fraction of Parkinson’s disease attributable to preventable risk factors
By Emma Sherrell onPublished: The team identified repeated blows to head in sports/combat as a potential new risk factor. 23% of PD cases in females were attributable to pesticides/herbicides exposure, and 30% of PD in males were attributable to pesticides/herbicides, military-related chemical exposures, and repeated blows to the head, and therefore could have potentially been prevented. View original preprint.
Section 1: Enzymatic DNA Fragmentation (Manually)
By savannah onThis protocol details manual enzymatic DNA Fragmentation prior to Section 2: NGS library preparation for sequencing.
Manual isolation of nuclei from human brain using CellRaft device and single nucleus Whole Genome Amplification
By savannah onProtocol for manual nuclear isolation from human brain tissue using Cell Raft device for single cell Whole Genome Amplification Protocol for manual nuclear isolation from human brain tissue using Cell Raft device for single cell Whole Genome Amplification
PyRates—A code-generation tool for modeling dynamical systems in biology and beyond
By Emma Sherrell onPublished: The main purpose of the paper is to demonstrate how these three tools can support the computational/mathematical modeling of neural systems with a variety of numerical methods that are well tested and documented. Thus, the authors present a powerful tool kit for computational/mathematical approaches to studying the dynamics and functions of complex neural systems such as the basal ganglia. View original preprint.
Single-cell Whole Genome Amplification (scWGA) of human post-mortem brain samples isolated by Laser Capture Microdissection (LCM)
By savannah onThis protocol uses Laser Capture Microdissection (LCM) technology on human post-mortem brain tissue slides with rapid Giemsa staining to isolate single nuclei for Single-cell Whole Genome Amplification (scWGA) in order to do low coverage (<1x) single-cell whole genome sequencing to detect mega-base somatic Copy Number Variations (CNVs).
ICC confocal images: Protein aggregation and calcium dysregulation are the earliest hallmarks of familial Parkinson’s disease in human midbrain dopaminergic neurons
By savannah onOur differentiation paradigm generates an efficient model for studying disease mechanisms in PD, and highlights that protein misfolding to generate intraneuronal oligomers is one of the earliest critical events driving disease in human neurons, rather than a late-stage hallmark of the disease.
RASP: Optimal single fluorescent puncta detection in complex cellular backgrounds
By savannah onPreprint: This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments with a sensitivity down to the level of the single protein.
TX2P – Transcript to protein
By savannah onTX2P allows for automated integration of mass spectometry data in long-read RNA-sequencing workflow. It does so by predicting open reading frames for each transcripts within an input GTF/GFF file, translates it into peptide sequences and then searches for those predicted proteins in mass spec datasets using MetaMorpheus.
Gavage – food supplementation for stalled weight gain in mice
By Emma Sherrell onFeeding protocol for Ndufs2fl/fl mice,
Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson’s disease
By Emma Sherrell onPublished: To understand PD-associated sleep-wake abnormalities, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. View original preprint.
State-dependent GABAergic regulation of striatal spiny projection neuron excitability: NEURON + Python model of striatal projection neurons
By Emma Sherrell onThis repository contains a NEURON + Python model of striatal projection neurons (or SPNs) designed to simulate the interaction between GABAergic and glutamatergic synaptic inputs.
Preparation of tissue for Ribo-Tag/RNAseq analysis
By Emma Sherrell onThis protocols describes the RiboTag virus vectors injected into mouse brain, tissue dissection, immunoprecipitation and RNA extraction for RNAseq.
Sleep-wake recording in Dan Lab
By Emma Sherrell onSurgery and setups for recording 24-hour natural sleep/wake cycles in mice.