scholarly journals Identification of a Novel Nucleobase-Ascorbate Transporter Family Member in Fish and Amphibians

Fishes ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
Diogo Oliveira ◽  
André M. Machado ◽  
Tiago Cardoso ◽  
Mónica Lopes-Marques ◽  
L. Filipe C. Castro ◽  
...  
Keyword(s):  
Uric Acid ◽  
The Novel ◽  
Synteny Analysis ◽  
Transcriptomic Data ◽  
Transporter Family ◽  
Gene Expression Quantification ◽  
Uric Acid Transporters ◽  
Clawed Frog ◽  
The Brain ◽  
Expression Quantification

Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases, and uric acid transporters: With broad evolutionary distribution. In vertebrates, four members have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase transporter Slc23a4 and an orphan transporter Slc23a3. Using phylogenetic and synteny analysis, we identify a fifth member of the vertebrate slc23 complement (slc23a5), present in neopterygians (gars and teleosts) and amphibians, and clarify the evolutionary relationships between the novel gene and known slc23 genes. Further comparative analysis puts forward uric acid as the preferred substrate for Slc23a5. Gene expression quantification, using available transcriptomic data, suggests kidney and testis as major expression sites in Xenopus tropicalis (western clawed frog) and Danio rerio (zebrafish). Additional expression in brain was detected in D. rerio, while in the Neoteleostei Oryzias latipes (medaka) slc23a5 expression is restricted to the brain. The biological relevance of the retention of an extra transporter in fish and amphibians is discussed.

scholarly journals A taxonomically-restricted Uric Acid transporter provides insight into antioxidant equilibrium

2018 ◽  
Author(s):  
Diogo Oliveira ◽  
André Machado ◽  
Tiago Cardoso ◽  
Mónica Lopes-Marques ◽  
L. Filipe C. Castro ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Uric Acid ◽  
Seminal Fluid ◽  
Urogenital System ◽  
The Novel ◽  
Morphological Adaptations ◽  
Gene Expression Quantification ◽  
Uric Acid Transporters ◽  
Clawed Frog

AbstractNucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases and uric acid transporters, with a broad evolutionary distribution. In vertebrates, four members have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase transporter Slc23a4 and an orphan transporter SLC23A3. Here we identify a fifth member of the vertebrateslc23complement (slc23a5), expressed in neopterygians (gars and teleosts) and amphibians, and clarify the evolutionary relationships between the novel gene and knownslc23genes. Further comparative analysis puts forward uric acid as the preferred substrate for Slc23a5. Gene expression quantification suggests kidney and testis as major expression sites inXenopus tropicalis(western clawed frog) andDanio rerio(zebrafish). Additional expression in brain was detected inD. rerio, while in the NeoteleosteiOryzias latipes(medaka)slc23a5expression is restricted to brain. The biological relevance of the retention of an extra transporter in fish and amphibians is examined: with respect to the (1) antioxidant role of uric and ascorbic acid in seminal fluid and brain, (2) the ability to endogenously synthesize ascorbic acid and (3) the morphological adaptations of the male urogenital system.

scholarly journals Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

2021 ◽  
Author(s):  
Antonio Giovannetti ◽  
Gianluca Susi ◽  
Paola Casti ◽  
Arianna Mencattini ◽  
Sandra Pusil ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
Ensemble Classification ◽  
The Novel ◽  
Ensemble Classifiers ◽  
Deep Convolutional Neural Networks ◽  
Early Signs ◽  
Data Representations ◽  
The Brain

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer’s disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships.

scholarly journals Cinematic rendering of a burst sagittal suture caused by an occipito-frontal gunshot wound

2021 ◽  
Author(s):  
Dominic Gascho ◽  
Michael J. Thali ◽  
Rosa M. Martinez ◽  
Stephan A. Bolliger
Keyword(s):  
Gunshot Wound ◽  
Three Dimensional ◽  
The Novel ◽  
Sagittal Suture ◽  
Resonance Imaging ◽  
Cinematic Rendering ◽  
Reconstruction Methods ◽  
Dimensional Reconstruction ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

AbstractThe computed tomography (CT) scan of a 19-year-old man who died from an occipito-frontal gunshot wound presented an impressive radiating fracture line where the entire sagittal suture burst due to the high intracranial pressure that arose from a near-contact shot from a 9 mm bullet fired from a Glock 17 pistol. Photorealistic depictions of the radiating fracture lines along the cranial bones were created using three-dimensional reconstruction methods, such as the novel cinematic rendering technique that simulates the propagation and interaction of light when it passes through volumetric data. Since the brain had collapsed, depiction of soft tissue was insufficient on CT images. An additional magnetic resonance imaging (MRI) examination was performed, which enabled the diagnostic assessment of cerebral injuries.

scholarly journals Uric acid enhances longevity and endurance and protects the brain against ischemia

2019 ◽  
Vol 75 ◽  
pp. 159-168 ◽  
Author(s):  
Roy G. Cutler ◽  
Simonetta Camandola ◽  
Neil H. Feldman ◽  
Jeong Seon Yoon ◽  
James B. Haran ◽  
...  
Keyword(s):  
Uric Acid ◽  
The Brain

scholarly journals Concentration-Dependent Inhibitory Effect of Irbesartan on Renal Uric Acid Transporters

2010 ◽  
Vol 114 (1) ◽  
pp. 115-118 ◽  
Author(s):  
Makiko Nakamura ◽  
Naohiko Anzai ◽  
Promsuk Jutabha ◽  
Hiroyuki Sato ◽  
Hiroyuki Sakurai ◽  
...  
Keyword(s):  
Uric Acid ◽  
Inhibitory Effect ◽  
Uric Acid Transporters

Adaptation of Rehabilitation System Based on User’s Mental Engagement

2015 ◽  
Author(s):  
Ehsan T. Esfahani ◽  
Shrey Pareek ◽  
Pramod Chembrammel ◽  
Mostafa Ghobadi ◽  
Thenkurussi Kesavadas
Keyword(s):  
Brain Activity ◽  
Difficulty Level ◽  
The Novel ◽  
Theta Band ◽  
Robotic Rehabilitation ◽  
Designed Experiments ◽  
Power Spectral ◽  
Rehabilitation System ◽  
Alpha Beta ◽  
The Brain

Recognition of user’s mental engagement is imperative to the success of robotic rehabilitation. The paper explores the novel paradigm in robotic rehabilitation of using Passive BCI as opposed to the conventional Active ones. We have designed experiments to determine a user’s level of mental engagement. In our experimental study, we record the brain activity of 3 healthy subjects during multiple sessions where subjects need to navigate through a maze using a haptic system with variable resistance/assistance. Using the data obtained through the experiments we highlight the drawbacks of using conventional workload metrics as indicators of human engagement, thus asserting that Motor and Cognitive Workloads be differentiated. Additionally we propose a new set of features: differential PSD of Cz-Poz at alpha, Beta and Sigma band, (Mental engagement) and relative C3-C4 at beta (Motor Workload) to distinguish Normal Cases from those instances when haptic where applied with an accuracy of 92.93%. Mental engagement is calculated using the power spectral density of the Theta band (4–7 Hz) in the parietal-midline (Pz) with respect to the central midline (Cz). The above information can be used to adjust robotic rehabilitation parameters I accordance with the user’s needs. The adjustment may be in the force levels, difficulty level of the task or increasing the speed of the task.

scholarly journals Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Zhao ◽  
Yihang Li ◽  
Dahong Yao ◽  
Ran Sun ◽  
Shifang Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Western Blot ◽  
Serum Uric Acid ◽  
Glucose Transporter ◽  
Serum Uric Acid Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
The Novel ◽  
Mice Model ◽  
Protein Levels ◽  
Anti Inflammatory

Background: The prevalence of hyperuricemia is considered high worldwide. Hyperuricemia occurs due to decreased excretion of uric acid, increased synthesis of uric acid, or a combination of both mechanisms. There is growing evidence that hyperuricemia is associated with a decline of renal function.Purpose: This study is aimed at investigating the effects of the novel compound on lowering the serum uric acid level and alleviating renal inflammation induced by high uric acid in hyperuricemic mice.Methods: Hyperuricemic mice model was induced by potassium oxonate and used to evaluate the effects of the novel compound named FxUD. Enzyme-linked immunosorbent assay was used to detect the related biochemical markers. Hematoxylin-eosin (HE) staining was applied to observe pathological changes. The mRNA expression levels were tested by qRT-PCR. The protein levels were determined by Western blot. In parallel, human proximal renal tubular epithelial cells (HK-2) derived from normal kidney was used to further validate the anti-inflammatory effects in vitro.Results: FxUD administration significantly decreased serum uric acid levels, restored the kidney function parameters, and improved the renal pathological injury. Meanwhile, treatment with FxUD effectively inhibited serum and liver xanthine oxidase (XOD) levels. Reversed expression alterations of renal inflammatory cytokines, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were observed in hyperuricemic mice. Western blot results illustrated FxUD down-regulated protein levels of inflammasome components. Further studies showed that FxUD inhibited the activation of NF-κB signaling pathway in the kidney of hyperuricemic mice. In parallel, the anti-inflammatory effect of FxUD was also confirmed in HK-2.Conclusion: Our study reveals that FxUD exhibits the anti-hyperuricemic and anti-inflammatory effects through regulating hepatic XOD and renal urate reabsorption transporters, and suppressing NF-κB/NLRP3 pathway in hyperuricemia. The results provide the evidence that FxUD may be potential for the treatment of hyperuricemia with kidney inflammation.

scholarly journals Preserved representations and decodability of diverse cognitive functions across the cortex, cerebellum, and subcortex

2021 ◽  
Author(s):  
Tomoya Nakai ◽  
Shinji Nishimoto
Keyword(s):  
Cognitive Functions ◽  
Principal Component ◽  
Cognitive Tasks ◽  
Sufficient Information ◽  
The Novel ◽  
Imaging Data ◽  
Functional Representations ◽  
Model Training ◽  
Task Representations ◽  
The Brain

Which part of the brain contributes to our complex cognitive processes? Studies have revealed contributions of the cerebellum and subcortex to higher-order cognitive functions; however it is unclear whether such functional representations are preserved across the cortex, cerebellum, and subcortex. In this study, we used functional magnetic resonance imaging data with 103 cognitive tasks and constructed three voxel-wise encoding and decoding models independently using cortical, cerebellar, and subcortical voxels. Representational similarity analysis revealed that the structure of task representations is preserved across the three brain parts. Principal component analysis visualized distinct organizations of abstract cognitive functions in each part of the cerebellum and subcortex. More than 90% of the cognitive tasks were decodable from the cerebellum and subcortical activities, even for the novel tasks not included in model training. Furthermore, we discovered that the cerebellum and subcortex have sufficient information to reconstruct activity in the cerebral cortex.

scholarly journals Human URAT1/SLC22A12 gene promoter is regulated by 27-hydroxycholesterol through estrogen response elements

2019 ◽  
Author(s):  
Masaya Matsubayashi ◽  
Yoshihiko M. Sakaguchi ◽  
Yoshiki Sahara ◽  
Hitoki Nanaura ◽  
Sotaro Kikuchi ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Cholesterol Metabolism ◽  
Gene Promoter ◽  
Human Kidney ◽  
Response Elements ◽  
Estrogen Response ◽  
Uric Acid Transporters ◽  
Estrogen Response Elements ◽  
Phylogenic Relationship

AbstractElevated levels of uric acid, a metabolite of purine in humans, is related to various diseases, such as gout, atherosclerosis and renal dysfunction. The excretion and reabsorption of uric acid to/from urine is tightly regulated by uric acid transporters. The amino acid sequences of uric acid reabsorption transporters, URAT1/SLC22A12, OAT4/SLC22A11, and OAT10/SLC22A13, share closer phylogenic relationship, whereas the gene promoter sequences are distant phylogenic relationship. Through the single-cell RNA-sequencing analysis of an adult human kidney, we found that only a small number of cells express these transporters, despite their role in the regulation of serum uric acid levels. Transcriptional motif analysis on these transporter genes, revealed that the URAT1/SLC22A12 gene promoter displayed the most conserved estrogen response elements (EREs) among the three transporters. The endogenous selective estrogen receptor modulator (SERM) 27-hydroxycholesterol (27HC) had positive effects on the transcriptional activity of URAT1/SLC22A12. We also found that 27HC increased the protein and gene expression of URAT1/SLC22A12 in mouse kidneys and human kidney organoids, respectively. These results strongly suggest the role of 27HC for URAT1/SLC22A12 expression in renal proximal tubules and upregulation of serum uric acid levels and also show the relationship between cholesterol metabolism and serum uric acid regulation.Significance StatementThe elevated levels of serum uric acid cause various diseases, and the excretion/reabsorption of uric acid to/from urine is tightly regulated by the uric acid transporters. We found that despite the role in serum uric acid regulation, only a small number of cells express URAT1/SLC22A12. We also found that URAT1/SLC22A12 gene promoter region has effective estrogen response elements, and endogenous selective estrogen receptor (ER) modulator 27-hydroxycholesterol (27HC) increased URAT1/SLC22A12 expression in the mice kidneys and human kidney organoids. These suggest that 27HC increases URAT1/SLC22A12 expression and upregulate serum uric acid levels. Since 27HC connects cholesterol metabolism, our study indicates the important link between cholesterol metabolism and serum uric acid regulation, and also provides a novel therapeutic approach to hyperuricemia.

scholarly journals SLC51 family of steroid-derived molecule transporters (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Paul A. Dawson
Keyword(s):  
Enterohepatic Circulation ◽  
Chloride Ions ◽  
Dehydroepiandrosterone Sulphate ◽  
Sodium Potassium ◽  
Transporter Family ◽  
Organic Solute Transporter ◽  
Organic Solute ◽  
Steroidogenic Cells ◽  
Inherited Mutations ◽  
The Brain

The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [2, 4, 1]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to steroid movement [5]. Bile acid transport is suggested to be facilitative and independent of sodium, potassium, chloride ions or protons [4, 2]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate [2, 4, 5]. OSTα/OSTβ-mediated transport of bile salts is inhibited by clofazimine [9]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C-termini [7]. Both proteins function in solute transport [7, 3]. Inherited mutations in OSTα and OSTβ are associated liver disease and congenital diarrhea in children [8, 6].

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