Abstract:
:Wolfram syndrome (WS) is a recessive multisystem disorder defined by the association of diabetes mellitus and optic atrophy, reminiscent of mitochondrial diseases. The role played by mitochondria remains elusive, with contradictory results on the occurrence of mitochondrial dysfunction. We evaluated 13 recessive WS patients by deep clinical phenotyping, including optical coherence tomography (OCT), serum lactic acid at rest and after standardized exercise, brain Magnetic Resonance Imaging, and brain and muscle Magnetic Resonance Spectroscopy (MRS). Finally, we investigated mitochondrial bioenergetics, network morphology, and calcium handling in patient-derived fibroblasts. Our results do not support a primary mitochondrial dysfunction in WS patients, as suggested by MRS studies, OCT pattern of retinal nerve fiber layer loss, and, in fibroblasts, by mitochondrial bioenergetics and network morphology results. However, we clearly found calcium mishandling between endoplasmic reticulum (ER) and mitochondria, which, under specific metabolic conditions of increased energy requirements and in selected tissue or cell types, may turn into a secondary mitochondrial dysfunction. Critically, we showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria.
journal_name
Sci Repjournal_title
Scientific reportsauthors
La Morgia C,Maresca A,Amore G,Gramegna LL,Carbonelli M,Scimonelli E,Danese A,Patergnani S,Caporali L,Tagliavini F,Del Dotto V,Capristo M,Sadun F,Barboni P,Savini G,Evangelisti S,Bianchini C,Valentino ML,Liguori R,Todoi
10.1038/s41598-020-61735-3subject
Has Abstractpub_date
2020-03-16 00:00:00pages
4785issue
1issn
2045-2322pii
10.1038/s41598-020-61735-3journal_volume
10pub_type
杂志文章abstract::Transition metal oxides potentially present higher specific capacities than the current anodes based on carbon, providing an increasing energy density as compared to commercial Li-ion batteries. However, many parameters could influence the performance of the batteries, which depend on the processing of the electrode m...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-62505-x
更新日期:2020-03-26 00:00:00
abstract::Can humans produce well-timed blink responses to a neutral stimulus voluntarily, without receiving any blink-eliciting, unconditional, stimulus? And if they can, to what degree does classical eyeblink conditioning depend on volition? Here we show that voluntary blink responses learned in two paradigms that did not inv...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03343-2
更新日期:2017-06-13 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer-related death worldwide. Although many molecular-targeted drugs for NSCLC have been developed in recent years, the 5-year survival rate of patients with NSCLC remains low. Therefore, an improved understanding of the molecular mechanisms underlying...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-43355-8
更新日期:2019-05-06 00:00:00
abstract::Enterovirus 71 (EV71) is a major pathogen of hand, foot, and mouth disease (HFMD). To date, no antiviral drug has been approved to treat EV71 infection. Due to the essential role that EV71 3 C protease (3Cpro) plays in the viral life cycle, it is generally considered as a highly appealing target for antiviral drug dev...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10840-x
更新日期:2017-09-04 00:00:00
abstract::Tin selenide has attracted much research interest due to its unprecedentedly high thermoelectric figure of merit (ZT). For real applications, it is desirable to increase the ZT value in the lower-temperature range, as the peak ZT value currently exists near the melting point. It is shown in this paper that the structu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26193
更新日期:2016-05-19 00:00:00
abstract::The origin of (ferro)magnetic ordering in transition metal doped ZnO is a still open question. For applications it is fundamental to establish if it arises from magnetically ordered impurity clusters embedded into the semiconducting matrix or if it originates from ordering of magnetic ions dilute into the host lattice...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-36336-w
更新日期:2019-01-16 00:00:00
abstract::We examined how plant-pollinator interactions were affected by time since habitat restoration and landscape connectivity by comparing plant-pollinator networks in restored, abandoned and continuously grazed semi-natural pastures in south-central Sweden. We measured richness of flowering plants and pollinators, and loc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-51912-4
更新日期:2019-10-29 00:00:00
abstract::RNA interference has had major advances as a developing tool for pest management. In laboratory experiments, double-stranded RNA (dsRNA) is often administered to the insect by genetic modification of the crop, or synthesized in vitro and topically applied to the crop. Here, we engineered genetically modified yeast tha...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep22587
更新日期:2016-03-02 00:00:00
abstract::In the present study, we aimed to explore gender differences in infant mortality and neonatal morbidity in mixed-gender twin pairs. Data were obtained from the US National Center for Health Statistics Linked Birth-Infant Death Cohort. A total of 108,038 pairs of mixed-gender twins were included in this analysis. Among...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-08951-6
更新日期:2017-08-18 00:00:00
abstract::Retinal diseases are frequently characterized by the accumulation of excessive scar tissue found throughout the neural retina. However, the pathophysiology of retinal fibrosis remains poorly understood, and the cell types that contribute to the fibrotic response are incompletely defined. Here, we show that myofibrobla...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72875-x
更新日期:2020-09-25 00:00:00
abstract::Mesenchymal stromal cells (MSCs) are a potential therapy for many chronic inflammatory diseases due to their regenerative, immunologic and anti-inflammatory properties. The two-way dialogue between MSCs and macrophages is crucial to tissue regeneration and repair. Previous research demonstrated that murine adipose-der...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-56835-8
更新日期:2019-12-30 00:00:00
abstract::Functional reactivation of p53 pathway, although arduous, can potentially provide a broad-based strategy for cancer therapy owing to frequent p53 inactivation in human cancer. Using a phosphoprotein-screening array, we found that Benzyl Isothiocynate, (BITC) increases p53 phosphorylation in breast cancer cells and rev...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep40070
更新日期:2017-01-10 00:00:00
abstract::An important step in oxide photochemistry, the loading of electrons into shallow trap states, was studied using infrared (IR) spectroscopy on both, rutile TiO2 powders and single-crystal, r-TiO2(110) oriented samples. After UV-irradiation or n-doping by exposure to H-atoms broad IR absorption lines are observed for th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep03808
更新日期:2014-01-22 00:00:00
abstract::Synapse and dendritic spine loss induced by amyloid-β oligomers is one of the main hallmarks of the early phases of Alzheimer's disease (AD) and is directly correlated with the cognitive decline typical of this pathology. The p75 neurotrophin receptor (p75NTR) binds amyloid-β oligomers in the nM range. While it was sh...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-70153-4
更新日期:2020-08-07 00:00:00
abstract::All-inorganic visibly-transparent energy-harvesting clear laminated glass windows are the most practical solution to boosting building-integrated photovoltaics (BIPV) energy outputs significantly while reducing cooling- and heating-related energy consumption in buildings. By incorporating luminophore materials into la...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06632
更新日期:2014-10-16 00:00:00
abstract::This anatomical study sought to investigate the morphological characteristics and biomechanical properties of the oblique popliteal ligament (OPL). Embalmed cadaveric knees were used for the study. The OPL and its surrounding structures were dissected; its morphology was carefully observed, analyzed and measured; its ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep42698
更新日期:2017-02-16 00:00:00
abstract::There is significant interest in understanding the pathophysiology of Obsessive-Compulsive Disorder (OCD) using resting-state fMRI (rsfMRI). Previous studies acknowledge abnormalities within and beyond the fronto-striato-limbic circuit in OCD that require further clarifications. However, limited information could be i...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-80346-6
更新日期:2021-01-14 00:00:00
abstract::We have studied differentially regulated nuclear proteome of the clinical tissue specimens of glioblastoma (GBM, WHO Grade IV) and lower grades of gliomas (Grade II and III) using high resolution mass spectrometry- based quantitative proteomics approach. The results showed altered expression of many regulatory protein...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-47360-9
更新日期:2019-07-29 00:00:00
abstract::Wrist worn raw-data accelerometers are used increasingly in large-scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. ...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/s41598-018-31266-z
更新日期:2018-08-28 00:00:00
abstract::Soil water retention curve (SWRC) plays an important role in simulating soil water movement and assessing soil water holding capacity and availability. Comparison of fitness between different models to determine the best SWRC model of specific regions is required. In this study, three popular models, van Genuchten, Br...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-54449-8
更新日期:2019-12-05 00:00:00
abstract::Obesity and depression are two common medical problems that pregnant women present with in antenatal care. Overweight and obesity at the beginning of the pregnancy, and excessive weight gain during pregnancy, are independent explanatory variables for fetal birthweight and independent risk factors for giving birth to a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-42360-1
更新日期:2019-04-17 00:00:00
abstract::Due to their convergent evolution, dogs have been suggested as a good model for the evolution of human social skills, such as tolerance and cooperativeness. However, recent studies have revealed that wolves (dogs' closest undomesticated relatives) are more tolerant and cooperative with conspecifics than dogs. It is st...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-40468-y
更新日期:2019-03-07 00:00:00
abstract::Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite genetic and epigenet...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-50735-7
更新日期:2019-10-04 00:00:00
abstract::Multiferroic BiFeO3 exhibits excellent magnetoelectric coupling critical for magnetic information processing with minimal power consumption. However, the degenerate nature of the easy spin axis in the (111) plane presents roadblocks for real world applications. Here, we explore the stabilization and switchability of t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12969
更新日期:2015-08-06 00:00:00
abstract::The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonen...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52814-1
更新日期:2019-11-08 00:00:00
abstract::P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We charac...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71753-w
更新日期:2020-09-24 00:00:00
abstract::We present a detailed experimental and theoretical study of the acoustic phonon modes in rolled-up multilayers with thickness of the layers in the nanometre and diameters in the micrometre range. We compare our results to planar, unrolled multilayers grown by molecular beam epitaxy. For the planar multilayers the expe...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05739-6
更新日期:2017-07-14 00:00:00
abstract::ZnO, aside from TiO2, has been considered as a promising material for purification and disinfection of water and air, and remediation of hazardous waste, owing to its high activity, environment-friendly feature and lower cost. However, their poor visible light utilization greatly limited their practical applications. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep04596
更新日期:2014-04-04 00:00:00
abstract::Caries is associated with shifts of microbiota in dental biofilms and primarily driven by frequent sucrose consumption. Data on environmentally induced in vivo microbiota shifts are scarce therefore we investigated the influence of frequent sucrose consumption on the oral biofilm. Splint systems containing enamel slab...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-32544-6
更新日期:2018-09-21 00:00:00
abstract::Raffinose family oligosaccharides (RFOs) are implicated in plant regulatory mechanisms of abiotic stresses tolerance and, despite their antinutritional proprieties in grain legumes, little information is available about the enzymes involved in RFO metabolism in Fabaceae species. In the present study, the systematic su...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72191-4
更新日期:2020-09-17 00:00:00