Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin.

Despite expanding knowledge regarding the role of astroglia in regulating neuronal function, little is known about regional or functional subgroups of brain astroglia and how they may interact with neurons. We use an astroglia-specific promoter fragment in transgenic mice to identify an anatomically defined subset of adult gray matter astroglia. Using transcriptomic and histological analyses, we generate a combinatorial profile for the in vivo identification and characterization of this astroglia subpopulation.

Mutant Huntingtin Disrupts the Nuclear Pore Complex.

Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs).

c9orf72 Disease-Related Foci Are Each Composed of One Mutant Expanded Repeat RNA.

The chromosome 9 open reading frame 72 (c9orf72) gene contains a hexanucleotide (GGGGCC) repeat expansion responsible for many cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mutant intronic RNA forms "foci" within nuclei, but the connection between transcript expression, foci, and biochemical disease mechanisms is unclear. Knowing the absolute numbers of cellular RNAs, in any system, is important for understanding the molecular mechanisms of natural physiology, disease, and drug action.

Generation of GFAP::GFP astrocyte reporter lines from human adult fibroblast-derived iPS cells using zinc-finger nuclease technology.

Astrocytes are instrumental to major brain functions, including metabolic support, extracellular ion regulation, the shaping of excitatory signaling events and maintenance of synaptic glutamate homeostasis. Astrocyte dysfunction contributes to numerous developmental, psychiatric and neurodegenerative disorders. The generation of adult human fibroblast-derived induced pluripotent stem cells (iPSCs) has provided novel opportunities to study mechanisms of astrocyte dysfunction in human-derived cells.

Overview of current and alternative therapies for idiopathic membranous nephropathy.

Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, which is characterized by edema, hypoalbuminemia, hyperlipidemia, lipiduria, and proteinuria. Determination of idiopathic membranous nephropathy (IMN) disease progression risk is important for guiding initial therapy, with immunosuppressive therapy being reserved for high-risk patients. Because IMN may spontaneously remit in approximately 30% of patients, it is important to carefully select which patients should begin immunosuppressive therapy so as to maximize clinical benefit while limiting toxicity.

RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.

A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72 gene is the most common genetic abnormality in familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The function of the C9ORF72 protein is unknown, as is the mechanism by which the repeat expansion could cause disease. Induced pluripotent stem cell (iPSC)-differentiated neurons from C9ORF72 ALS patients revealed disease-specific (1) intranuclear GGGGCCexp RNA foci, (2) dysregulated gene expression, (3) sequestration of GGGGCCexp RNA binding protein ADARB2, and (4) susceptibility to excitotoxicity.

Role of interleukin-1 inhibitors in the management of gout.

Interleukin-1 (IL-1) inhibitors potentially have a role as antiinflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or glucocorticoids, for acute attacks. Additionally, IL-1 inhibitors may also help patients with polyarticular and tophaceous gout by making them less vulnerable to breakthrough attacks during initiation of chronic urate-lowering treatment, the mainstay of gout therapy. Because evidence highlights the role of proinflammatory cytokine IL-1 in the inflammation process during an acute gouty attack, IL-1 inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory diseases, providing support for its potential role in the inflammatory process of gout.

Specification of neural cell fate and regulation of neural stem cell proliferation by microRNAs.

In the approximately 20 years since microRNAs (miRNAs) were first characterized, they have been shown to play important roles in diverse physiologic functions, particularly those requiring coordinated changes in networks of signaling pathways. The ability of miRNAs to silence expression of multiple gene targets hints at complex connections that research has only begun to elucidate. The nervous system, particularly the brain, and its progenitor cells offer opportunities to examine miRNA function due to the myriad different cell types, numerous functionally distinct regions, and fluidly dynamic connections between them.