Abstract:
:Channelopathy mutations prove informative on disease causing mechanisms and channel gating dynamics. We have identified a novel heterozygous mutation in the KCNA1 gene of a young proband displaying typical signs and symptoms of Episodic Ataxia type 1 (EA1). This mutation is in the S4 helix of the voltage-sensing domain and results in the substitution of the highly conserved phenylalanine 303 by valine (p.F303V). The contributions of F303 towards K+ channel voltage gating are unclear and here have been assessed biophysically and by performing structural analysis using rat Kv1.2 coordinates. We observed significant positive shifts of voltage-dependence, changes in the activation, deactivation and slow inactivation kinetics, reduced window currents, and decreased current amplitudes of both Kv1.1 and Kv1.1/1.2 channels. Structural analysis revealed altered interactions between F303V and L339 and I335 of the S5 helix of a neighboring subunit. The substitution of an aromatic phenylalanine with an aliphatic valine within the voltage-sensor destabilizes the open state of the channel. Thus, F303 fine-tunes the Kv1.1 gating properties and contributes to the interactions between the S4 segment and neighboring alpha helices. The resulting channel's loss of function validates the clinical relevance of the mutation for EA1 pathogenesis.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Hasan S,Bove C,Silvestri G,Mantuano E,Modoni A,Veneziano L,Macchioni L,Hunter T,Hunter G,Pessia M,D'Adamo MCdoi
10.1038/s41598-017-03041-zsubject
Has Abstractpub_date
2017-07-04 00:00:00pages
4583issue
1issn
2045-2322pii
10.1038/s41598-017-03041-zjournal_volume
7pub_type
杂志文章abstract::Biology is adapted to Earth's gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mut...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-78414-y
更新日期:2020-12-03 00:00:00
abstract::Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of a novel pandemic strain. Antiviral drugs exhibit limited efficacy unless administered early and may induce viral resistance. Thus, targeting the host response directly has been proposed as a nov...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11030
更新日期:2015-06-05 00:00:00
abstract::A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep43588
更新日期:2017-03-02 00:00:00
abstract::Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20911
更新日期:2016-02-12 00:00:00
abstract::The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-78160-1
更新日期:2020-12-04 00:00:00
abstract::Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcripto...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52559-x
更新日期:2019-11-06 00:00:00
abstract::Intraperitoneal administration of antibiotics together with peritoneal dialysis fluids (PDFs) remains the preferable route for treatment of peritoneal dialysis-related peritonitis. For home based therapy, antibiotic-containing PDFs are stored for up to two weeks and warmed up to body-temperature before administration....
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-42854-y
更新日期:2019-04-24 00:00:00
abstract::The newly sequenced mitochondrial genomes of 107 Asian swamp buffalo (Bubalus bubalis carabensis) allowed the reconstruction of the matrilineal divergence since ~900 Kya. Phylogenetic trees and Bayesian skyline plots suggest a role of the glacial periods in the demographic history of swamp buffalo. The ancestral swamp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04830-2
更新日期:2017-07-05 00:00:00
abstract::Dissolved organic carbon (DOC) concentrations and water colour are increasing in many inland waters across northern Europe and northeastern North America. This inland-water "browning" has profound physical, chemical and biological repercussions for aquatic ecosystems affecting water quality, biological community struc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52912-0
更新日期:2019-11-13 00:00:00
abstract::The gist of natural scenes can be extracted very rapidly and even without focal attention. However, it is unclear whether and to what extent the gist of natural scenes can break through the bottleneck of crowding, a phenomenon in which object recognition will be immensely impaired. In the first two experiments, a targ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-32455-6
更新日期:2018-09-19 00:00:00
abstract::Most large herbivores in arid landscapes need to drink which constrains their movements and makes them vulnerable to disturbance. Asiatic wild ass or khulan (Equus hemionus) were widespread and abundant throughout the arid landscapes of Central Asia and Mongolia, but have undergone dramatic population declines and ran...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-59969-2
更新日期:2020-02-19 00:00:00
abstract::Calcitriol, a metabolite of vitamin D, is often used in osteoporosis clinics. However, the material has other bioactivities; for example, it accelerates angiogenesis, has anti-inflammatory properties, and inhibits oxidative stress. We investigated the effects of calcitriol in a random skin flap rat model. "McFarlane f...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep18945
更新日期:2016-01-06 00:00:00
abstract::Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chem...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19995
更新日期:2016-02-05 00:00:00
abstract::Tyrosine hydroxylase (TH), the initial enzyme in the melanin pathway, catalyzes tyrosine conversion into Dopa. Although expression and regulation of TH have been shown to affect cuticle pigmentation in insects, no direct functional studies to date have focused on the specific physiological processes involving the enzy...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep29835
更新日期:2016-07-15 00:00:00
abstract::Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep45648
更新日期:2017-03-31 00:00:00
abstract::Abnormalities in actin cytoskeleton have been linked to Friedreich's ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-62050-7
更新日期:2020-03-23 00:00:00
abstract::Heterogeneous catalysis, which is widely used in the chemical industry, makes a great use of supported late-transition-metal nanoparticles, and bimetallic catalysts often show superior catalytic performances as compared to their single metal counterparts. In order to optimize catalyst efficiency and discover new activ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35226
更新日期:2016-10-14 00:00:00
abstract::Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South Un...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72651-x
更新日期:2020-09-24 00:00:00
abstract::The rainbow trout, a carnivorous fish, displays a 'glucose-intolerant' phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nut...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32187
更新日期:2016-08-26 00:00:00
abstract::Sixty-six million years ago, an asteroid approximately 9 km in diameter hit the hydrocarbon- and sulfur-rich sedimentary rocks in what is now Mexico. Recent studies have shown that this impact at the Yucatan Peninsula heated the hydrocarbon and sulfur in these rocks, forming stratospheric soot and sulfate aerosols and...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-14199-x
更新日期:2017-11-09 00:00:00
abstract::Formamidinium lead iodide (CH(NH2)2PbI3, FAPI) thin films have been deposited on glass substrates at 150 °C using ambient pressure aerosol assisted chemical vapour deposition (AACVD). The films have been analysed by a range of techniques including powder X-ray diffraction (pXRD), scanning electron microscopy (SEM), en...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-79291-1
更新日期:2020-12-17 00:00:00
abstract::Many tissues exhibit subatmospheric interstitial pressures under normal physiologic conditions. The mechanisms by which the lymphatic system extracts fluid from these tissues against the overall pressure gradient are unknown. We address this important physiologic issue by combining experimental measurements of contrac...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11599-x
更新日期:2017-09-21 00:00:00
abstract::In this paper, we propose a real time, ultrahigh accuracy and full-field-of-view (RUF) algorithm for full field of view (FOV) imaging system. The proposed algorithm combines rough matching and precise matching method to stitch multiple images with the whole FOV in short time and high imaging quality. In order to verif...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-69353-9
更新日期:2020-07-24 00:00:00
abstract::Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impa...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32833
更新日期:2016-10-07 00:00:00
abstract::The current theories of antimalarial mechanism of artemisinin are inadequate to fully explain the observed effects. In our study, "organism-like" formation of Schistosoma hemozoin granules by attaching to and utilizing erythrocytes to form new ones was observed. This indicates that heme iron is transferred from erythr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34463
更新日期:2016-10-03 00:00:00
abstract::Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhib...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-17128-0
更新日期:2017-12-08 00:00:00
abstract::Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possib...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-49923-2
更新日期:2019-09-19 00:00:00
abstract::Homogeneously distributed zinc nanoparticles (NPs) on the glass substrate were investigated for the transmittance, mechanical durability, and antibacterial effect. The buffered Ti NPs between Zn NPs and glass substrate were studied for an enhancement of the transmittance and mechanical endurance. The Ti NPs buffered Z...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06271
更新日期:2014-09-03 00:00:00
abstract::Malaria surveillance data provide opportunity to develop forecasting models. Seasonal variability in environmental factors correlate with malaria transmission, thus the identification of transmission patterns is useful in developing prediction models. However, with changing seasonal transmission patterns, either due t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-02560-z
更新日期:2017-06-01 00:00:00
abstract::Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35218
更新日期:2016-10-12 00:00:00