- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Pregnancy-related medical research
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Thermal Regulation in Medicine
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Anesthesia and Neurotoxicity Research
- Neuropeptides and Animal Physiology
- Epilepsy research and treatment
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
- Neurotransmitter Receptor Influence on Behavior
- Growth Hormone and Insulin-like Growth Factors
- Ion channel regulation and function
- Neurogenetic and Muscular Disorders Research
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Amyotrophic Lateral Sclerosis Research
- Spinal Dysraphism and Malformations
Ionis Pharmaceuticals (United States)
2016-2024
Johnson & Johnson (United States)
2002-2009
Johnson & Johnson (Israel)
2009
University of Miami
2005
Silesian University of Technology
2004
Lund University
1995-2000
Lactic acid is a well known metabolic by-product of intense exercise, particularly under anaerobic conditions. Lactate also key source energy and an important substrate, it has been hypothesized to be signaling molecule directing activity. Here we show that GPR81, orphan G-protein-coupled receptor highly expressed in fat, fact sensor for lactate. activates GPR81 its physiological concentration range 1–20 mm suppresses lipolysis mouse, rat, human adipocytes as differentiated 3T3-L1 cells....
Laser capture microdissection in combination with microarrays allows for the expression analysis of thousands genes selected cells. Here we describe single-cell gene profiling CA1 neurons rat hippocampus using a laser capture, T7 RNA amplification, and cDNA microarray analysis. Subsequent cluster data identified two different cell types: pyramidal an interneuron. Cluster also revealed differences among neurons, indicating that even single type vivo is not homogeneous population cells at...
We describe a sensor capable of detecting single DNA molecules. The is based on nanopore prepared in polymer film by latent ion track-etching technique. For this purpose, foil was penetrated heavy total kinetic energy 2.2 GeV, followed preferential etching the track. molecules were detected as they blocked current flow during translocation through nanopore, driven an electric field. nanopores are highly stable and their dimensions adjustable controlling conditions. DNA, conical with opening...
Chronic and elevated levels of the antiviral cytokine IFN-α in brain are neurotoxic. This is best observed patients with genetic cerebral interferonopathies such as Aicardi-Goutières syndrome. Cerebral typically manifest early childhood lead to debilitating disease premature death. There no cure for these diseases existing treatments largely aimed at managing symptoms. Thus, an effective therapeutic strategy urgently needed. Here, we investigated effect antisense oligonucleotides targeting...
Both relaxin-3 and its receptor (GPCR135) are expressed predominantly in brain regions known to play important roles processing sensory signals. Recent studies have shown that is involved the regulation of stress feeding behaviors. The mechanisms underlying involvement relaxin-3/GPCR135 stress, feeding, other potential functions remain be studied. Because also activates relaxin (LGR7), which brain, selective GPCR135 agonists antagonists crucial study physiological vivo. Previously, we...
Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However, ASO pharmacokinetic (PK) pharmacodynamic (PD) properties remain poorly understood in IT compartment. We applied multimodal imaging techniques elucidate PK PD unlabeled, radioactively labeled, or fluorescently labeled ASOs targeting ubiquitously expressed neuron-specific RNAs. Following lumbar bolus injection rats, all spread...
Prokineticins 1 and 2 (PK1 PK2) have been recently identified from humans other mammals play multiple functional roles. PK proteins are ligands for two G protein-coupled receptors, receptor (PKR1) (PKR2). Here, we report the molecular cloning pharmacological characterization of an alternatively spliced product PK2 gene encoding 21 additional amino acids compared with PK2, designated PK2L (for long form). mRNA is broadly expressed, as PK2. However, expression lower in brain, undetectable...
Glioblastoma, aggressive primary brain tumors with a dismal prognosis, promote the recruitment of microglia, resident innate immune cells, and ultimately their activation toward tumor-supportive phenotype that increases gliomal proliferation invasion capability. Here, we report upon stimulation by glioma microglia transit via reactive state holding anti-tumoral properties coupled to reduced DNMT3A chromatin occupancy DNA demethylation microglial pro-inflammatory gene expressions. We find...
Abstract Transient global ischaemia induces the expression of immediate early genes. Using in situ hybridization, c‐ fos, fosB, fra‐1, fra‐2 , jun and junB was studied after 15 min normothermic hypothermia (33°C) transient forebrain rat, induced by common carotid occlusion combined with systemic hypotension. Two phases induction genes were observed. The phase, peaking at 1–2 h reperfusion, dominated marked dentate gyrus. second maximal 12–36 observed particularly vulnerable CA1 CA3 regions....
Microglia are multifunctional cells that key players in brain development and homeostasis. Recent years have seen tremendous growth our understanding of the role microglia play neurodegeneration, CNS injury, developmental disorders. Given show diverse functional phenotypes, there is a need for more precise tools to characterize microglial states. Here, we experimentally define gene modules as foundation describing states.In an effort develop comprehensive classification scheme, profiled...
A novel bioactive form of neurotensin post-translationally modified at a Glu residue was isolated from porcine intestine. Purification the peptide guided by detection intracellular Ca2+ release in SK-N-SH neuroblastoma cells. Using high resolution accurate mass analysis on an ion trap Fourier transform spectrometer, post-translational modification identified as arginine linked to gamma-carboxyl via isopeptide bond, and we named newly "arginylated neurotensin" (R-NT,...
Functional alterations in striatal projection neurons play a critical role the development of motor symptoms Parkinson's disease (PD), but their molecular adaptation to dopamine depletion remains poorly understood. In particular, type and extent regulation postsynaptic signal transduction pathways that determine responsiveness incoming stimuli, are currently unknown. Using cell-type-specific transcriptome analyses rodent model chronic depletion, we identified large-scale gene expression...
Generating gene-expression profiles from laser-captured cells requires the successful combination of laser-capture microdissection, RNA extraction, amplification, and microarray analysis. To permit single-cell profiling, amplification method has to be sufficiently powerful bridge gap between amount available a single cell what is required by microarray, that spans 5 6 orders magnitude. This chapter focuses on using two-round T7 method. The protocols described are adapted for material have...