1,720,976 research outputs found
Heterologeous expression of a glial Kir channel (KCNJ10) in a neuroblastoma spinal cord (NSC-34) cell line.
No full textHeterologeous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K(+) channels (Kir channels) are potential candidate proteins to hyperpolarise neuronal cell membranes. However, heterologeous expression of inwardly-rectifying K(+) channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K(+) currents as well as hyperpolarisation of the cell membrane was observed in Kir4.1-transfected cells. Na(+) inward currents, observed in NSC34 controls, were absent in Kir4.1-EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologeous expression of a weakly inward-rectifying K(+) channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more glial-like phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms
Heterologeous expression of a glial Kir channel (KCNJ10) in a neuroblastoma spinal cord (NSC-34) cell line.
No full textHeterologeous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K(+) channels (Kir channels) are potential candidate proteins to hyperpolarise neuronal cell membranes. However, heterologeous expression of inwardly-rectifying K(+) channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K(+) currents as well as hyperpolarisation of the cell membrane was observed in Kir4.1-transfected cells. Na(+) inward currents, observed in NSC34 controls, were absent in Kir4.1-EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologeous expression of a weakly inward-rectifying K(+) channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more glial-like phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms
Co-enrichment of Kir4.1 and AQP4 channels in spinal cord astrocytes suggests coupling of K+ flux and water transport: swelling experiments using transgenic mouse technology and time lapse 2-photon laser microscopy
No full textCo-enrichment of Kir4.1 and AQP4 channels in spinal cord astrocytes suggests coupling of K+ flux and water transport: swelling experiments using transgenic mouse technology and time lapse 2-photon laser microscopy
No full textMitofusin 2 gene mutation (R94Q) causing severe early-onset axonal polyneuropathy (CMT2A)
No full textCharcot-Marie-Tooth disease (CMT) has been classified into two types: demyelinating forms (CMT1) and axonal forms (CMT2). Mutations in the CMT2A locus have been linked to the KIF1B and the mitofusin 2 (MFN2) genes. Here, we report a German patient with CMT2 with an underlying spontaneous mutation (c.281G -> A) in the MFN2 gene. Clinically, the patient presented with early-onset CMT that was not associated with additional central nervous system pathology. The disease course was rapidly progressive in the first years and slowed afterwards. We also suggest that single patients with early-onset axonal polyneuropathies should be screened for MFN2 mutations
Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit
No full textThe Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K+ channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown. Because diverse human hereditary deafness syndromes are associated with mutations in K+ channels, we examined auditory function and inner ear structure in mice with a genetically inactivated Kir4.1 K+ channel subunit. Startle response experiments suggest that Kir4.1-/- mice are profoundly deaf, whereas Kir4.1+/- mice react like wild-type mice to acoustic stimuli. In Kir4.1-/- mice, the Reissner membrane is collapsed, the tectorial membrane is swollen, and type I hair cells and spiral ganglion neurons as well as their central processes degenerate over the first postnatal weeks. In the vestibular ganglia, neuronal cell death with apoptotic features is also observed. Immunostaining reveals that Kir4.1 is strongly expressed in stria vascularis of wild-type but not Kir4.1-/- mice. Within the spiral ganglion, Kir4.1 labeling was detected on satellite cells surrounding spiral ganglion neurons and axons. We conclude that Kir4.1 is crucial for normal development of the cochlea and hearing, via two distinct aspects of extracellular K+ homeostasis: (1) in stria vascularis, Kir4.1 helps to generate the cochlear endolymph; and (2) in spiral and vestibular ganglia, Kir4.1 in surrounding glial cells helps to support the spiral and vestibular ganglion neurons and their projecting axons. (C) 2003 Elsevier Science B.V. All rights reserved.NEI NIH HHS [EY12949]; NIGMS NIH HHS [GM-29836
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Severe demyelinating hypertrophic polyneuropathy caused by a de novo frameshift mutation within the intracellular domain of myelin protein zero (MPZ/P-0)
No full textHereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A with an underlying duplication in the gene coding for the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P-0) account for demyelinating CMT1B, Dejerine-Sottas syndrome (DSS), or congenital hypomyelinating neuropathy (CHN). Here, we report a patient with a severe, early-onset hypertrophic and dysmyelmating neuropathy. The patient exhibits a novel frameshift mutation with an insertion of a single T-nucleotide on position c.618_619 of the MPZ gene resulting in a premature stop M207fsX38. (C) 2009 Elsevier B.V. All rights reserved
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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