Abstract:
:The human pyruvate dehydrogenase complex (PDC) comprises four multidomain components, E1, E3, E2 and an E3-binding protein (E3BP), the latter two forming the core as E2·E3BP sub-complex. Pyruvate flux through PDC is regulated via phosphorylation (inactivation) at E1 by four PDC kinases (PDKs), and reactivation by two PDC phosphatases. Up-regulation of PDK isoform gene expression is reported in several forms of cancer, while PDKs may be further activated by PDC by binding to the E2·E3BP core. Hence, the PDK: E2·E3BP interaction provides new therapeutic targets. We carried out both functional kinetic and thermodynamic studies to demonstrate significant differences in the activation of PDK isoforms by binding to the E2·E3BP core: (i) PDK2 needs no activation by E2·E3BP for efficient functioning, while PDK4 was the least effective of the four isoforms, and could not be activated by E2·E3BP. Hence, development of inhibitors to the interaction of PDK2 and PDK4 with E2·E3BP is not promising; (ii) Design of inhibitors to interfere with interaction of E2·E3BP with PDK1 and PDK3 is promising. PDK3 needs E2·E3BP core for activation, an activation best achieved by synergistic combination of E2-derived catalytic domain and tridomain.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Guevara EL,Yang L,Birkaya B,Zhou J,Nemeria NS,Patel MS,Jordan Fdoi
10.1038/srep42760subject
Has Abstractpub_date
2017-02-23 00:00:00pages
42760issn
2045-2322pii
srep42760journal_volume
7pub_type
杂志文章abstract::In this study we uncovered, through targeted ablation, a potential role for corticospinal, cerebello-rubro-spinal, and hypothalamic A11 dopaminergic systems in the development of restless legs syndrome (RLS)-like movements during sleep. Targeted lesions in select basal ganglia (BG) structures also revealed a major rol...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10284-3
更新日期:2017-08-29 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) are immune cells that exert immunosuppression within the tumor, protecting cancer cells from the host's immune system and/or exogenous immunotherapies. While current research has been mostly focused in countering MDSC-driven immunosuppression, little is known about the mechanis...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-57941-8
更新日期:2020-01-27 00:00:00
abstract::Metasurfaces, owing to their attractive features, provide a wide range of potential applications. Electromagnetic absorbers based on metasurfaces have significantly improved responses compared to the earlier absorbers made from composite materials. Active metasurfaces, in contrast to the passive designs, can exhibit m...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-28574-9
更新日期:2018-07-05 00:00:00
abstract::The development of new anode materials having high electrochemical performances and interesting reaction mechanisms is highly required to satisfy the need for long-lasting mobile electronic devices and electric vehicles. Here, we report a layer crystalline structured SnP3 and its unique electrochemical behaviors with ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35980
更新日期:2016-10-24 00:00:00
abstract::The triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12670
更新日期:2015-08-03 00:00:00
abstract::Pulmonary arterial hypertension is a progressive disease that causes the obstruction of precapillary pulmonary arteries and a sustained increase in pulmonary vascular resistance. The aim was to analyze functionally the variants found in the BMPR2 gene and to establish a genotype-phenotype correlation. mRNA expression ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-02074-8
更新日期:2017-05-15 00:00:00
abstract::Both attraction and repulsion from linearly polarized light have been observed in zooplankton. A dichotomous choice experiment, consisting of plankton light traps deployed in natural waters at a depth of 30 m that projected either polarized or unpolarized light of the same intensity, was used to test the hypothesis th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35891
更新日期:2016-10-20 00:00:00
abstract::Although the clinical importance of extragraft bone formation (ExGBF) and bridging (ExGBB) has been reported, few studies have investigated the biomechanical influences of ExGBF on the motion segment. In this study, ExGBF was simulated at the C5-C6 motion segment after anterior cervical discectomy and fusion using a d...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-54785-9
更新日期:2019-12-11 00:00:00
abstract::The physiological, biochemical and functional differences between oxidative and glycolytic muscles play important roles in human metabolic health and in animal meat quality. To explore these differences, we determined the genome-wide landscape of DNA methylomes and their relationship with the mRNA and miRNA transcript...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32186
更新日期:2016-08-26 00:00:00
abstract::Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is mo...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-80776-2
更新日期:2021-01-19 00:00:00
abstract::Routers, switches, and repeaters are essential components of modern information-processing systems. Similar devices will be needed in future superconducting quantum computers. In this work we investigate experimentally the time evolution of Autler-Townes splitting in a superconducting phase qubit under the application...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00645
更新日期:2012-01-01 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06311
更新日期:2014-09-09 00:00:00
abstract::Canalization is a result of intrinsic developmental buffering that ensures phenotypic robustness under genetic variation and environmental perturbation. As a consequence, animal phenotypes are remarkably consistent within a species under a wide range of conditions, a property that seems contradictory to evolutionary c...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16717
更新日期:2015-11-18 00:00:00
abstract::Neurofeedback is a strong direct training method for brain function, wherein brain activity patterns are measured and displayed as feedback, and trainees try to stabilize the feedback signal onto certain desirable states to regulate their own mental states. Here, we introduce a novel neurofeedback method, using the mi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06729
更新日期:2014-10-24 00:00:00
abstract::Network structure has often proven to be important in understanding the decision behavior of individuals or agents in different interdependent situations. Computational studies predict that network structure has a crucial influence on behavior in iterated 2 by 2 asymmetric 'battle of the sexes' games. We test such beh...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-43260-0
更新日期:2019-05-02 00:00:00
abstract::Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05948-z
更新日期:2017-07-20 00:00:00
abstract::The hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinomas and infects approximately 170 million people worldwide. Although several reporter systems have been developed, many shortcomings limit their use in the assessment of HCV infections. Here, we rep...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08865
更新日期:2015-03-09 00:00:00
abstract::Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-st...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep22322
更新日期:2016-02-29 00:00:00
abstract::The largest tsunamis are generated by seafloor uplift resulting from rupture of offshore subduction-zone megathrusts. The rupture of the shallowest part of a megathrust often produces unexpected outsize tsunami relative to their seismic magnitude. These are so called 'tsunami earthquakes', which are difficult to ident...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68097-w
更新日期:2020-07-06 00:00:00
abstract::Quantifying how close two datasets are to each other is a common and necessary undertaking in scientific research. The Pearson product-moment correlation coefficient r is a widely used measure of the degree of linear dependence between two data series, but it gives no indication of how similar the values of these seri...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19401
更新日期:2016-01-14 00:00:00
abstract::Profiling immune repertoires by high throughput sequencing enhances our understanding of immune system complexity and immune-related diseases in humans. Previously, cloning and Sanger sequencing identified limited numbers of T cell receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune repertoir...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10092
更新日期:2015-05-11 00:00:00
abstract::Transcriptomic analysis showed that the central circadian pathway genes had significantly altered expression in fracture calluses from mice fed a low phosphate diet. This led us to hypothesize that phosphate deficiency altered the circadian cycle in peripheral tissues. Analysis of the expression of the central clock g...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-31830-7
更新日期:2018-09-13 00:00:00
abstract::Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, eth...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11923
更新日期:2015-07-06 00:00:00
abstract::STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). STIM1 is a calcium sensor, which oligomerizes and activates Orai channels when calcium levels drop inside the endoplasmic reticulum (ER). The series of molecular rearrangements that STIM1 ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep29634
更新日期:2016-07-27 00:00:00
abstract::The aim of our study was to compare soft tissue measurements with 3D imaging methods in individuals with untreated skeletal and pseudo-Class III malocclusions. The study sample consisted of 75 patients (38 males, 37 females, mean age 12.41 ± 2.35 years) with pseudo- and true skeletal Class III malocclusions and skelet...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71772-7
更新日期:2020-09-07 00:00:00
abstract::The present research relates to a fusion protein comprising a chromogenic blue ultramarine protein (UM) bound to a keratin-based peptide (KP). The KP-UM fusion protein explores UM chromogenic nature together with KP affinity towards hair. For the first time a fusion protein with a chromogenic nature is explored as a h...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-50283-0
更新日期:2019-10-01 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-32119-5
更新日期:2018-09-11 00:00:00
abstract::Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep42942
更新日期:2017-02-22 00:00:00
abstract::The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S. aureus mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicil...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-31098-x
更新日期:2018-08-28 00:00:00
abstract::Carbon nanotubes exhibit mechanical properties ideally suited for reinforced structural composites and surface area and conductivity attractive for electrochemical capacitors. Here we demonstrate the multifunctional synergy between these properties in a composite material exhibiting simultaneous mechanical and energy ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-34963-x
更新日期:2018-12-05 00:00:00