29,458 results on '"Physiology"'
Search Results
202. Physiology and Pathologies Linked to Human Splenic Function : Direct and Ex-vivo Perfusion Explorations.
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PHYSIOLOGY ,PERFUSION ,PATHOLOGY ,GENETIC testing ,MOLECULAR biology - Abstract
A clinical trial, NCT06418256, is currently underway to investigate the role of the spleen in various human diseases and its potential to modify the perception of blood cells. The study involves adult patients undergoing splenic interventions, with blood and spleen tissue samples being collected for analysis. The aim is to enhance our understanding of spleen function and explore immunological and clearance mechanisms. The study is recruiting participants and is expected to be completed by October 2031, with Assistance Publique - Hopitaux de Paris and Institut Pasteur as the responsible party and collaborators, respectively. [Extracted from the article]
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- 2024
203. The tricellular junctional protein Ildr2 helps maintain glomerular podocyte architecture.
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CLAUDINS ,KIDNEY physiology ,CELL junctions ,TIGHT junctions ,BASAL lamina ,PROTEINS - Abstract
A recent preprint abstract discusses the role of the tricellular junctional protein Ildr2 in maintaining the architecture of glomerular podocytes, which are specialized cells in the kidney essential for proper kidney function. The study used a conditional knockout mouse model to investigate the effects of Ildr2 deletion in podocytes. The results showed disruptions to podocyte foot process architecture, thickening of the glomerular basement membrane, and accumulation of collagen and glycoproteins. Surprisingly, the knockout mice did not exhibit significant albuminuria, but when subjected to kidney stress, podocyte loss was observed. The findings suggest that tricellular junctions, including Ildr2, play a role in preserving podocyte architecture but may not be necessary for proper filtration in normal physiological states. [Extracted from the article]
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- 2024
204. New Findings Reported from Case Western Reserve University Describe Advances in Blood Proteins (Rapid Measurement of Hemoglobin-oxygen Dissociation By Leveraging Bohr Effect and Soret Band Bathochromic Shift).
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BLOOD proteins ,THERMOPHORESIS ,PHYSIOLOGY ,HEMOGLOBINS - Abstract
Researchers at Case Western Reserve University have developed a new method for rapidly measuring the dissociation of hemoglobin-oxygen (Hb-O2) in blood. The method leverages the Bohr effect, which is a physiological mechanism that affects the affinity of Hb for oxygen based on pH levels. By detecting the optical shift in the Soret band, the researchers were able to reduce the measurement time from hours to minutes. This new approach has the potential to improve the diagnosis and prognosis of Hb disorders, such as sickle cell disease, and could also aid in the development of new therapies. [Extracted from the article]
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- 2024
205. Reports Outline Protein Precursors Study Findings from University Hospital (Proinsulin: Physiology, Measurement, and Interest In Clinical Biology).
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PROTEIN precursors ,PROINSULIN ,UNIVERSITY hospitals ,PEPTIDE hormones ,PHYSIOLOGY - Published
- 2024
206. Selectivity and evolution of Aqp10 in solute permeability influenced by pore molecular weight.
- Abstract
A preprint abstract from biorxiv.org discusses the selectivity and evolution of Aqp10, an aquaglyceroporin that transports water and low-molecular-weight compounds. The study focuses on the weak permeability of Aqp10.2 to urea and boric acid and proposes a novel hypothesis to explain this. Through molecular phylogenetic analysis and site-directed mutagenesis, the researchers deduced the ancestral sequences of Aqp10.1 and Aqp10.2 and identified the importance of specific amino acid sites in the formation of the Aqp10 selectivity filter. The results provide insights into the molecular mechanism by which Aqp10.2 acquired a selectivity filter during evolution. However, it is important to note that this preprint has not been peer-reviewed. [Extracted from the article]
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- 2024
207. Reports Outline Obesity and Diabetes Study Findings from West Bengal (Recent clinical and pharmacological advancements of incretin-based therapy and the effects of incretin on physiology).
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OBESITY ,GLUCAGON-like peptide 1 ,PEPTIDE hormones ,DIABETES ,PHYSIOLOGY - Published
- 2024
208. Expansion of the Genomic Encyclopedia of Bacteria and Archaea
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Woyke, Tanja
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- 2011
209. Enhanced alkali tolerance of rhizobia-inoculated alfalfa correlates with altered proteins and metabolic processes as well as decreased oxidative damage.
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Song, Tingting, Sun, Na, Dong, Li, and Cai, Hua
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ALFALFA , *PROTEOMICS , *PROTEINS , *ORGANIC acids , *ALKALIES - Abstract
Alkaline salt is one of the most devastating environmental factors limiting alfalfa productivity, however, the mechanisms underlying adaptation of alfalfa to alkaline remain unclear. Our aim is to investigate proteomic and metabolomic differences in growth and root of alfalfa under alkaline salt in Rhizobium -alfalfa symbiotic relationships. Rhizobium -inoculated and non-inoculated alfalfa plants were treated with 200 mmol/L NaHCO 3 to investigate physiological, metabolic, and proteomic responses of root-nodule symbiosis under alkaline-induced stress, using an integrated approach combining metabolome and proteome analysis with measurements of physiological parameters. The improved tolerance to alkalinity was observed in RI-plants compared with NI-plants. RI-plants accumulated more proline and MDH, and had higher antioxidant activity and relatively high RWC but low MDA content and low Na+/K+ ratio. The stress-related genes (P5CS, GST13, H + -Ppase, NADP-Me, SDH , and CS) were actively upregulated in RI plants under alkaline stress. In RI-plants, damage caused by alkaline stress was mainly alleviated by decreasing oxidative damage, enhancing the organic acid and amino acid metabolic processes, and scavenging harmful ROS by activating the phenylpropanoid biosynthetic pathway. We revealed distinct proteins and metabolites related to alkali tolerance in RI-plants compared to NI-plants. Alkali tolerance of rhizobia-inoculated alfalfa was enhanced by altered proteins and metabolic processes as well as decreased oxidative damage. • RI alfalfa showed better alkali tolerance than that of NI. • Distinct proteins and metabolites related to alkali tolerance were in RI-plants. • Alkali-responsive mechanisms might be consequence of complex regulatory mechanisms. • An active reprogramming of gene expression, proteome, and metabolome is important. [ABSTRACT FROM AUTHOR]
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- 2021
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210. MicroRNA-210 downregulates TET2 and contributes to inflammatory response in neonatal hypoxic-ischemic brain injury.
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Ma, Qingyi, Dasgupta, Chiranjib, Shen, Guofang, Li, Yong, and Zhang, Lubo
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CEREBRAL anoxia-ischemia , *BRAIN injuries , *INFLAMMATION , *REPORTER genes , *ONE-way analysis of variance , *METHYLCYTOSINE , *PROTEINS , *BIOCHEMISTRY , *ANIMAL populations , *ANIMAL experimentation , *RNA , *PHENOMENOLOGY , *DNA-binding proteins , *RESEARCH funding , *INFLAMMATORY mediators , *CELL lines , *MICE , *PHYSIOLOGY , *CHEMICAL inhibitors - Abstract
Background: Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of acute mortality and chronic disability in newborns. Our previous studies demonstrated that HI insult significantly increased microRNA-210 (miR-210) in the brain of rat pups and inhibition of brain endogenous miR-210 by its inhibitor (LNA) provided neuroprotective effect in HI-induced brain injury. However, the molecular mechanisms underpinning this neuroprotection remain unclear.Methods: We made a neonatal HI brain injury model in mouse pups of postnatal day 7 to uncover the mechanism of miR-210 in targeting the ten eleven translocation (TET) methylcytosine dioxygenase 2 that is a transcriptional suppressor of pro-inflammatory cytokine genes in the neonatal brain. TET2 silencing RNA was used to evaluate the role of TET2 in the neonatal HI-induced pro-inflammatory response and brain injury. MiR-210 mimic and inhibitor (LNA) were delivered into the brain of mouse pups to study the regulation of miR-210 on the expression of TET2. Luciferase reporter gene assay was performed to validate the direct binding of miR-210 to the 3' untranslated region of the TET2 transcript. Furthermore, BV2 mouse microglia cell line was employed to confirm the role of miR-210-TET2 axis in regulating pro-inflammatory response in microglia. Post-assays included chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation, RT-PCR, brain infarct assay, and neurobehavioral test. Student's t test or one-way ANOVA was used for statistical analysis.Results: HI insult significantly upregulated miR-210, downregulated TET2 protein abundance, and increased NF-κB subunit p65 acetylation level and its DNA binding capacity to the interleukin 1 beta (IL-1β) promoter in the brain of mouse pups. Inhibition of miR-210 rescued TET2 protein level from HI insult and miR-210 mimic decreased TET2 protein level in the brain of mouse pups, suggesting that TET2 is a functional target of miR-210. The co-immunoprecipitation was performed to reveal the role of TET2 in HI-induced inflammatory response in the neonatal brain. The result showed that TET2 interacted with NF-κB subunit p65 and histone deacetylase 3 (HDAC3), a co-repressor of gene transcription. Furthermore, TET2 knockdown increased transcriptional activity of acetyl-p65 on IL-1β gene in the neonatal brain and enhanced HI-induced upregulation of acetyl-p65 level and pro-inflammatory cytokine expression. Of importance, TET2 knockdown exacerbated brain infarct size and neurological deficits and counteracted the neuroprotective effect of miR-210 inhibition. Finally, the in vitro results demonstrated that the miR-210-TET2 axis regulated pro-inflammatory response in BV2 mouse microglia cell line.Conclusions: The miR-210-TET2 axis regulates pro-inflammatory cytokine expression in microglia, contributing to neonatal HI brain injury. [ABSTRACT FROM AUTHOR]- Published
- 2021
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211. Effects of taurine levels in feed on blood biochemical parameters and antioxidant indexes of Cynoglossus semilaevis and their responses to fishing stress.
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Xueliang Sun, Hong Yu, Kezhi Xing, Yunchen Tian, Chengxun Chen, Yongjun Guo, Hui Shi1, Shuyuan Yang, Shuqi Chen, and Qingkui Wang
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CYNOGLOSSUS , *TAURINE , *ANTIOXIDANTS , *FISHING , *LYSOZYMES , *PROTEINS - Abstract
Cynoglossus semilaevis blood biochemical parameters and antioxidant indexes that respond to fishing stress were measured under the influence of different feed taurine levels. With taurine levels of 0%, 0.5%, 1% and 1.5%, 4 groups of test feeds were prepared. After 28 days of feeding. Serum was collected before stress and at 0, 4, 12, 24, 48, 96 h after stress to determine the content of total protein, cholesterol, GPT, GOT, nitric oxide, lysozyme, blood sugar and the activity of glutathione (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA) and antioxidant capacity (AOC), the results show: Feeding a feed with a taurine content of 0.5% has a better inhibitory effect on cholesterol and GOT in Cynoglossus semilaevis after fishing stress, and has obvious antistress effect on lysozyme and protein. The 0.5% group had the lowest MDA content 12 h after fishing stress. The results suggested that feeding the feed with a taurine content of 0.5%, the Cynoglossus semilaevis blood biochemical parameters and antioxidant indexes to fishing stress has a better response. [ABSTRACT FROM AUTHOR]
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- 2021
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212. Metallothionein and other cadmium-binding proteins: Recent developments
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Goering, P [Food and Drug Administration, Rockville, MD (USA)]
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- 2020
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213. Advances in the study of heart attack markers
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Xu Yankun, Zang Mingxun, Song Zhenyu, Kong Lingyuan, Zhang Weiping, and Fei Tianyuan
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heart attack ,biomarkers ,clinical diagnosis ,proteins ,enzymes ,Microbiology ,QR1-502 ,Physiology ,QP1-981 ,Zoology ,QL1-991 - Abstract
Heart attacks are a highly prevalent and often life-threatening disease in modern society. Numerous studies have now shown that many biomarkers in blood have been identified as markers for the detection of heart attack and some are widely used in clinical practice, including protein-based and nucleic acid-based markers. With further research into the pathogenesis of heart attacks, new, simpler and earlier biomarkers have been identified. In this paper, we present a comprehensive review of the role of protein, nucleic acid and cytokine markers in the diagnosis of heart attack based on the pathogenesis of heart attack. It is expected that the discovery of markers based on heart attack will help in the clinical diagnosis of acute heart attack and provide some data to support the early detection and treatment of patients with sudden acute heart attack, thus improving the quality of life and long-term outcome of patients.
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- 2022
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214. Physiology: Neutral buoyancy by an insect.
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Woods, H. Arthur
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BUOYANCY , *INSECTS , *PHYSIOLOGY , *DIPTERA , *PROTEINS - Abstract
Larval phantom midges are remarkably adept at maintaining neutral buoyancy in water. A new study reveals that they do so using a previously unknown mechanism — modifying the volumes of internal air sacs using pH-driven changes in a protein embedded in the air-sac walls. [ABSTRACT FROM AUTHOR]
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- 2022
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215. Role of VPS13, a protein with similarity to ATG2, in physiology and disease.
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Ugur, Berrak, Hancock-Cerutti, William, Leonzino, Marianna, and De Camilli, Pietro
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PHYSIOLOGY , *PROTEINS , *NEURODEGENERATION , *ORGANELLES , *AUTOPHAGY - Abstract
The evolutionarily conserved VPS13 family proteins have been implicated in several cellular processes. Mutations in each of the four human VPS13s cause neurodevelopmental or neurodegenerative disorders. Until recently, the molecular function of VPS13 remained elusive. Genetic, functional and structural studies have now revealed that VPS13 acts at contact sites between intracellular organelles to transport lipids by a novel mechanism: direct transfer between bilayers via a hydrophobic channel that spans its entire rod-like N-terminal half. Predicted similarities to the autophagy protein ATG2 suggested a similar role for ATG2 that has now been confirmed by structural and functional studies. Here, after a brief review of this evidence, we discuss what is known of human VPS13 proteins in physiology and disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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216. Emerging links between endoplasmic reticulum stress responses and acute kidney injury
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Aidan W. Porter, Jeffrey L. Brodsky, and Teresa M. Buck
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Physiology ,Unfolded Protein Response ,Humans ,Proteins ,Cell Biology ,Acute Kidney Injury ,Endoplasmic Reticulum Stress ,Endoplasmic Reticulum ,Kidney - Abstract
All cell types must maintain homeostasis under periods of stress. To prevent the catastrophic effects of stress, all cell types also respond to stress by inducing protective pathways. Within the cell, the endoplasmic reticulum (ER) is exquisitely stress-sensitive, primarily because this organelle folds, posttranslationally processes, and sorts one-third of the proteome. In the 1990s, a specialized ER stress response pathway was discovered, the unfolded protein response (UPR), which specifically protects the ER from damaged proteins and toxic chemicals. Not surprisingly, UPR-dependent responses are essential to maintain the function and viability of cells continuously exposed to stress, such as those in the kidney, which have high metabolic demands, produce myriad protein assemblies, continuously filter toxins, and synthesize ammonia. In this mini-review, we highlight recent articles that link ER stress and the UPR with acute kidney injury (AKI), a disease that arises in ∼10% of all hospitalized individuals and nearly half of all people admitted to intensive care units. We conclude with a discussion of prospects for treating AKI with emerging drugs that improve ER function.
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- 2022
217. A Review of Mechanics-Based Mesoscopic Membrane Remodeling Methods: Capturing Both the Physics and the Chemical Diversity
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Gaurav Kumar, Satya Chaithanya Duggisetty, and Anand Srivastava
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Membranes ,general_theoretical_physics ,Physiology ,Physics ,Biophysics ,Proteins ,Cell Biology ,Biophysical Phenomena ,Cytoskeleton - Abstract
Specialized classes of proteins, working together in a tightly orchestrated manner, induce and maintain highly curved cellular and organelles membrane morphology. Due to the various ex- perimental constraints, including the resolution limits of imaging techniques, it is non-trivial to accurately elucidate interactions among the various components involved in membrane deformation. The spatial and temporal scales of the systems also make it formidable to investigate them using simulations with molecular details. Interestingly, mechanics-based mesoscopic models have been used with great success in recapitulating the membrane defor- mations observed in experiments. In this review, we collate together and discuss the various mechanics based mesoscopic models for protein-mediated membrane deformation studies. In particular, we provide an elaborate description of a mesoscopic model where the membrane is modeled as a triangulated sheet and proteins are represented as either nematics or fila- ments. This representation allows us to explore the various aspects of protein-protein and protein-membrane interactions as well as examine the underlying mechanistic pathways for emergent behavior such as curvature-mediated protein localization and membrane deforma- tion. We also put forward current efforts in the field towards back-mapping these mesoscopic models to finer-grained particle based models - a framework that could be used to explore how molecular interactions propagate to physical scales and vice-versa. We end the review with an integrative-modeling based road map where experimental imaging micrograph and biochemical data are combined with mesoscopic and molecular simulations methods in a theoretically consistent manner to faithfully recapitulate the multiple length and time scales in the membrane remodeling processes.
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- 2022
218. CELLS ON FIRE.
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Mehal, Wajahat Z.
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INFLAMMATION , *MACROPHAGES , *MOLECULAR structure , *GOUT , *ALZHEIMER'S disease , *FATTY liver , *IMMUNE response , *CYTOKINES , *PHYSIOLOGY , *ATHEROSCLEROSIS , *CELL physiology , *FOOD , *IMMUNE system , *INGESTION , *PROTEINS , *HYPERPHAGIA - Abstract
The article discusses the role of inflammasomes and inflammation in diseases such as gout, fatty liver disease, and Alzheimer's. The author comments on immune responses, the role of macrophage or white blood cells, and cytokines. Other topics include inflammation as a response to overeating and obesity.
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- 2015
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219. Proteomic Analysis of Atrial Appendages Revealed the Pathophysiological Changes of Atrial Fibrillation
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Ban Liu, Xiang Li, Cuimei Zhao, Yuliang Wang, Mengwei Lv, Xin Shi, Chunyan Han, Pratik Pandey, Chunhua Qian, Changfa Guo, and Yangyang Zhang
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atrial fibrillation ,proteomics ,proteins ,structural remodeling ,mechanism ,Physiology ,QP1-981 - Abstract
Atrial fibrillation (AF), known as the most common arrhythmia in the developed world, affects 1.5–2.0% of the population. Numerous basic studies have been carried out to identify the roles of electric and structural remodeling in the pathophysiological changes of AF, but more explorations are required to further understand the mechanisms of AF development. Proteomics enables researchers to identify protein alterations responsible for the pathological developing progresses of diseases. Compared to the genome, the proteome is closely related to the disease phenotype and can better manifest the progression of diseases. In this study, AF patients proteomically analyzed to identify possible mechanisms. Totally 20 patients undergoing cardiac surgery (10 with paroxysmal AF and 10 with persistent AF) and 10 healthy subjects were recruited. The differentially expressed proteins identified here included AKR1A1, LYZ, H2AFY, DDAH1, FGA, FGB, LAMB1, LAMC1, MYL2, MYBPC3, MYL5, MYH10, HNRNPU, DKK3, COPS7A, YWHAQ, and PAICS. These proteins were mainly involved in the development of structural remodeling. The differently expressed proteins may provide a new perspective for the pathological process of AF, and may enable useful targets for drug interference. Nevertheless, more research in terms of multi-omics is required to investigate possible implicated molecular pathways of AF development.
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- 2020
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220. Mining electron density for functionally relevant protein polysterism in crystal structures
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Fraser, James S and Jackson, Colin J
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Biochemistry and Cell Biology ,Biological Sciences ,Generic health relevance ,Animals ,Catalytic Domain ,Crystallography ,X-Ray ,Electrons ,Evolution ,Molecular ,Humans ,Molecular Conformation ,Proteins ,Polysterism ,Conformational substates ,X-ray crystallography ,NMR ,Evolution ,Protein dynamics ,Catalysis ,Physiology ,Clinical Sciences ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical biochemistry and metabolomics ,Oncology and carcinogenesis - Abstract
This review focuses on conceptual and methodological advances in our understanding and characterization of the conformational heterogeneity of proteins. Focusing on X-ray crystallography, we describe how polysterism, the interconversion of pre-existing conformational substates, has traditionally been analyzed by comparing independent crystal structures or multiple chains within a single crystal asymmetric unit. In contrast, recent studies have focused on mining electron density maps to reveal previously 'hidden' minor conformational substates. Functional tests of the importance of minor states suggest that evolutionary selection shapes the entire conformational landscape, including uniquely configured conformational substates, the relative distribution of these substates, and the speed at which the protein can interconvert between them. An increased focus on polysterism may shape the way protein structure and function is studied in the coming years.
- Published
- 2011
221. Biochemical Composition and Energy Strategy Along the Reproductive Cycle of Female Octopus vulgaris in Galician Waters (NW Spain)
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Pilar Sieiro, Jaime Otero, and Santiago P. Aubourg
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reproduction ,lipids ,fatty acids ,proteins ,glycogen ,energy allocation ,Physiology ,QP1-981 - Abstract
The common octopus, Octopus vulgaris, has a short life cycle, growing rapidly to maturity, spawning once, and characterized by an asynchronic oocyte development and a synchronic ovulation dying after breeding. This species has a protein and amino acid metabolism and it is usually defined as an income breeder. However, most biochemical studies lack an examination of the whole reproductive cycle, in particular the spawning process. We here studied the biochemical changes and determined the energy strategy along reproduction in female O. vulgaris, and found that proteins were the main energy reserve, primarily located in the body muscle when sexually maturing and decreasing during breeding. Lipids were also an important source of energy in the ovary and digestive gland and decreased during breeding too. By contrast, glycogen had a minor contribution to the energy content and was the unique compound that increased in spawning and post-spawning females. Additionally, the most abundant fatty acids (FA) in all tissues were 16:0, 18:0, 20:1n9, 20:4n6 (ARA), 20:5n3 (EPA) and 22:6n3 (DHA), with a clear predominance of long-chain polyunsaturated FA. The FA profile of mature ovaries was compared with other life stages finding similitudes with eggs, hatchlings and juveniles but considerable differences with paralarvae which showed higher DHA/ARA and EPA/ARA ratios. Therefore, we found important biochemical changes along the reproductive cycle that determined the energetic signature in each tissue, though no significant energy trade-offs between tissues were found, suggesting that, on the one hand, female O. vulgaris obtained energy directly from food accumulated simultaneously in the somatic and reproductive tissues during sexual maturation. However, an energy reallocation from somatic to reproductive growth would occur once vitellogenesis has started, so that the rate at which body growths would decrease in favor of ovary growth. On the other hand, during breeding, a general decrease in the energy content occurred in all tissues, so that the ovary would be responsible for the spawning success, whereas muscle tissues and digestive gland would independently supply the energy needed for the body maintenance safeguarding the female survival needed for the maternal care.
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- 2020
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222. Proteomic Profiling and Monitoring of Training Distress and Illness in University Swimmers During a 25-Week Competitive Season
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Amy M. Knab, David C. Nieman, Laura M. Zingaretti, Arnoud J. Groen, and Artyom Pugachev
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swimming ,proteins ,inflammation ,upper respiratory tract infection ,mental stress ,Physiology ,QP1-981 - Abstract
PurposeTo evaluate relationships of proteomics data, athlete-reported illness, athlete training distress (TDS), and coaches’ ratings of distress and performance over the course of the competitive season.MethodsThirty-five NCAA Division II swimmers were recruited to the study (male n = 19, female n = 16; age 19.1 ± 1.6 years). Athletes provided fingerprick dried blood spot (DBS) samples, illness symptoms, and TDS every Monday for 19 of 25 weeks in their season. Coaches monitored performance and rated visual signs of distress. DBS samples were analyzed for a targeted panel of 12 immune-related proteins using liquid chromatography/mass spectrometry (LC/MS).ResultsThirty-two swimmers completed the protocol. The data were grouped in 2–3 weeks segments to facilitate interpretation and analysis of the data. TDS scores varied between athletes, and were highest during the early fall conditioning ramp up period (8.9 ± 1.6 at baseline to a peak of 22.6 ± 2.0). The percent of athletes reporting illness was high throughout the season (50–78%). Analysis of TDS using Principle Component Analysis (PCA) revealed that 40.5% of the variance (PC1) could be attributed to illness prevalence, and TDS scores for the athletes reporting illness and no illness were different across the season (P < 0.001). The coaches’ ratings of swim performance and swimmer’s distress, sex, and racing distance (sprinters, middle distance, long distance) were not correlated with PC1. Linear Discriminant Analysis (LDA) analysis of the data showed a separation of the baseline weeks from exam weeks with or without competitions, and with competitions alone (p < 0.001). Seven of the 12 proteins monitored over the course of training were upregulated, and the addition of the protein data to LDA analysis enhanced the separation between these groups of weeks.ConclusionTDS and illness were related in this group of 32 collegiate swimmers throughout the competitive season, and expression of immune proteins improved the statistical separation of baseline weeks from the most stressful weeks. TDS data provided by the swimmers did not match their coaches’ ratings of distress and swim performance. The importance of the immune system in the reaction to internal and external stress in athletes should be an area of further research.
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- 2020
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223. Circulating S100A8/A9 is potentially a biomarker that could reflect the severity of experimental colitis in rats
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Kohki Okada, Hiroshi Itoh, and Masaki Ikemoto
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Cell biology ,Proteins ,Biochemistry ,Molecular biology ,Gastrointestinal system ,Physiology ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Aims: The clinical significance of circulating S100A8/A9 (calprotectin) in patients with ulcerative colitis (UC) is poorly understood. We examined whether serum S100A8/A9 is a good biomarker for UC, and whether the serum level is a useful index for the severity of the disease. Main methods: Experimental animal (rats) were used to verify clinical significance of serum S100A8/A9 as a biomarker. Rats treated with 5% dextran sulfate sodium (DSS) alone (UCR) or with 5%DSS plus tacrolimus (TMR) were subjected to the experiment. The serum concentrations of rat S100A8/A9 (r-S100A8/A9) and other inflammatory biomarkers, such as C-reactive protein (CRP) and inflammatory cytokines, in the both groups were measured using enzyme-linked immunosorbent assays (ELISAs). The tissue damage in the large intestinal tract was visualized by hematoxylin-eosin staining. The relationship between the serum concetrations of these inflammatory biomarkers and the histological scores of the rectal tissue was statistically analyzed. Principle findings: As determined by the ELISAs, the serum concentration of r-S100A8/A9 in the UCR hardly correlated with those of not only CRP but also some inflammatory cytokines. The deterioration of the rectal tissue, mainly epithelium structure of a large intestine, in the UCR was clearly observed, but was not so severe as that in the TMR. The histological scores of the rectal tissue in the UCR significantly correlated with the serum level of r-S100A8/A9, but not with other inflammatory biomarkers. Furthermore, macrophages actively produced r-S100A8/A9 in response to stimulation with lipopolysaccharide and quickly secreted it in circulation. Therefore, the serum level of r-S100A8/A9 suggestively changes in accordance with the severity of experimental UC. Conclusion: Circulating r-S100A8/A9 is a useful biomarker for experimental UC, and its serum level correlates with the disease severity as judged by histological score.
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- 2020
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224. Findings from University of Vermont Broaden Understanding of Cerebral Blood Flow and Metabolism (Pathogenic soluble tau peptide disrupts endothelial calcium signaling and vasodilation in the brain microvasculature).
- Abstract
A recent study conducted by researchers at the University of Vermont has shed light on the role of tau protein in brain microvascular dysfunction. The accumulation of tau protein around blood vessels has been found to disrupt the stability of microtubules, leading to impaired calcium signaling and vasodilation in endothelial cells. The study used a pathogenic soluble tau peptide model to demonstrate that tau alters cerebrovascular function by attenuating endothelial calcium signaling and endothelium-dependent vasodilation. These findings contribute to a better understanding of cerebral blood flow and metabolism. [Extracted from the article]
- Published
- 2024
225. BMP signaling to pharyngeal muscle in the C. elegans response to a bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping (Updated February 14, 2024).
- Abstract
A recent study investigated the response of the nematode C. elegans to bacterial pathogens and found that the bone morphogenetic protein (BMP) signaling pathway plays a role in this response. The study identified the pharynx as a tissue that responds to BMP signaling and coordinates a systemic response to bacterial pathogens. The researchers also discovered that the expression of certain antimicrobial peptide genes and pharyngeal pumping activity are regulated by BMP signaling. This research provides insights into the host response to pathogens and the role of BMP signaling in infection. However, it is important to note that this study has not yet undergone peer review. [Extracted from the article]
- Published
- 2024
226. Drosophila Undigested Metabolite Profiling reveals age related loss of intestinal amino acid transport regulates longevity (Updated January 25, 2024).
- Abstract
According to a preprint abstract, researchers have developed a method called Drosophila Undigested Metabolite Profiling (D.U.M.P.) to study the impact of intestinal aging on nutrient absorption in fruit flies. The study found that aging leads to an increase in amino acid levels in the feces, which is driven by changes in the microbiota and shortens lifespan. The researchers also discovered that reducing the expression of a specific amino acid transporter in the intestinal epithelium extended lifespan and improved microbial control in aged flies. These findings suggest that age-related changes in the microbiota and the intestinal epithelium can affect nutrient management and have implications for anti-aging nutritional therapies. [Extracted from the article]
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- 2024
227. Research from Department of Physiology Broadens Understanding of Migraine (Evaluating the Interplay between Pentraxin-3 and Cystatin C in Migraine Patients).
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CYSTATIN C ,PRIMARY headache disorders ,MIGRAINE ,NEUROLOGICAL disorders ,PHYSIOLOGY ,MEDICAL periodicals - Abstract
A recent research study conducted at the Department of Physiology at the University of Lahore in Pakistan aimed to evaluate the levels of serum pentraxin-3 and human cystatin C in migraine patients and their relationship to healthy controls. The study found that the mean levels of both pentraxin-3 and cystatin C were significantly higher in migraine patients compared to the control group. The most common symptoms reported by migraine patients were photophobia, followed by phonophobia, nausea, and vomiting. This study provides valuable insights into the interplay between pentraxin-3 and cystatin C in migraine patients. [Extracted from the article]
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- 2024
228. New Physiology Study Findings Have Been Reported from Central South University (The metabolic pathway regulation in kidney injury and repair).
- Abstract
A recent study conducted by researchers at Central South University in China explores the regulation of metabolic pathways in kidney injury and repair. The study highlights the disruptions in various energy production pathways, such as glucose, lipid, amino acid, and ketone body metabolism, that occur during kidney injury. The researchers discuss the impact of these metabolic dysfunctions on renal cell injury, regeneration, and the development of renal fibrosis. They also suggest potential therapeutic strategies that target renal metabolic regulation to ameliorate kidney injury and promote kidney repair. This study provides valuable insights into the complex involvement of metabolic pathways in kidney health and offers potential avenues for future research and treatment. [Extracted from the article]
- Published
- 2024
229. Studies Conducted at Firat University on Melatonin Therapy Recently Published (Modulation of Melatonin Receptors Regulates Reproductive Physiology: The Impact of Agomelatine on the Estrus Cycle, Gestation, Offspring, and Uterine Contractions in...).
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UTERINE contraction ,ESTRUS ,MELATONIN ,PREGNANCY ,PHYSIOLOGY - Abstract
A recent report from Firat University in Elazig, Turkey discusses the use of agomelatine, a pharmaceutical compound that acts as an agonist for melatonin receptors, in regulating reproductive physiology. The study conducted in vivo and in vitro experiments on Wistar Albino rats and found that chronic administration of agomelatine extended the diestrus phase in non-pregnant rats, prolonged the gestational period, increased fetal count in pregnant rats, and reduced plasma oxytocin and prostaglandin-E levels during pregnancy. In vitro experiments showed that agomelatine inhibited myometrial contractions, and this effect was reversed by luzindole, a melatonin receptor antagonist. These findings suggest that agomelatine has the potential to modulate various reproductive parameters during the gestational period. [Extracted from the article]
- Published
- 2024
230. Driving Protein Conformational Cycles in Physiology and Disease: "Frustrated" Amino Acid Interaction Networks Define Dynamic Energy Landscapes: Amino Acid Interaction Networks Change Progressively Along Alpha Tryptophan Synthase's Catalytic Cycle.
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D'Amico, Rebecca N., Murray, Alec M., and Boehr, David D.
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AMINO acids , *PROTEINS , *TRYPTOPHAN , *DISEASE progression , *PHYSIOLOGY , *NUCLEAR magnetic resonance - Abstract
A general framework by which dynamic interactions within a protein will promote the necessary series of structural changes, or "conformational cycle," required for function is proposed. It is suggested that the free‐energy landscape of a protein is biased toward this conformational cycle. Fluctuations into higher energy, although thermally accessible, conformations drive the conformational cycle forward. The amino acid interaction network is defined as those intraprotein interactions that contribute most to the free‐energy landscape. Some network connections are consistent in every structural state, while others periodically change their interaction strength according to the conformational cycle. It is reviewed here that structural transitions change these periodic network connections, which then predisposes the protein toward the next set of network changes, and hence the next structural change. These concepts are illustrated by recent work on tryptophan synthase. Disruption of these dynamic connections may lead to aberrant protein function and disease states. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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231. Regulation of endo‐lysosomal pathway and autophagic flux by broad‐spectrum antipathogen inhibitor ABMA.
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Wu, Yu, Boulogne, Claire, Carle, Stefan, Podinovskaia, Maria, Barth, Holger, Spang, Anne, Cintrat, Jean‐Christophe, Gillet, Daniel, and Barbier, Julien
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LYSOSOMES , *ENDOSOMES , *TOXINS , *ANTITOXINS , *PHYSIOLOGY , *PROTEINS , *RICIN , *BACTERIAL toxins - Abstract
The endo‐lysosome system is involved in endocytosis, protein sorting, and degradation as well as autophagy. Numerous toxins and pathogens exploit this system to enter host cells and exert their deleterious effects. Modulation of host endo‐lysosome pathway may restrict multiple toxins intoxication as well as pathogen infection. ABMA, selected from a high‐throughput screening against the cytotoxicity of ricin toxin, exhibits a broad‐spectrum antitoxin and antipathogen activity. Here, we show that ABMA selectively retains endocytosed protein and toxin to late endosomes and thus delaying their intracellular trafficking. It also impairs the autophagic flux by excessive fusion of late endosomes and autophagosomes. Its exclusive action on late endosomes and corresponding consequences on the endo‐lysosomal pathway and autophagic flux are distinct from known inhibitors such as bafilomycin A1, EGA, or chloroquine. Hence, besides being a broad‐spectrum inhibitor of endocytosed toxins and pathogens, ABMA may serve as a molecular tool to dissect endo‐lysosome system‐related cellular physiology and mechanisms of pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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232. Dual functionality of the amyloid protein TasA in Bacillus physiology and fitness on the phylloplane.
- Author
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Cámara-Almirón, Jesús, Navarro, Yurena, Díaz-Martínez, Luis, Magno-Pérez-Bryan, María Concepción, Molina-Santiago, Carlos, Pearson, John R., de Vicente, Antonio, Pérez-García, Alejandro, and Romero, Diego
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PHYSIOLOGY ,BACILLUS (Bacteria) ,BACILLUS subtilis ,CELL membranes ,PROTEINS ,AMYLOID beta-protein - Abstract
Bacteria can form biofilms that consist of multicellular communities embedded in an extracellular matrix (ECM). In Bacillus subtilis, the main protein component of the ECM is the functional amyloid TasA. Here, we study further the roles played by TasA in B. subtilis physiology and biofilm formation on plant leaves and in vitro. We show that ΔtasA cells exhibit a range of cytological symptoms indicative of excessive cellular stress leading to increased cell death. TasA associates to the detergent-resistant fraction of the cell membrane, and the distribution of the flotillin-like protein FloT is altered in ΔtasA cells. We propose that, in addition to a structural function during ECM assembly and interactions with plants, TasA contributes to the stabilization of membrane dynamics as cells enter stationary phase. The amyloid protein TasA is a main component of the extracellular matrix in Bacillus subtilis biofilms. Here the authors show that, in addition to a structural function during biofilm assembly and interactions with plants, TasA contributes to the stabilization of membrane dynamics during stationary phase. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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233. Compensatory gait deviations in patients with increased outward tibial torsion pre and post tibial derotation osteotomy.
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Alexander, Nathalie, Wegener, Regina, Lengnick, Harald, Payne, Erika, Klima, Harry, Cip, Johannes, and Studer, Kathrin
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GAIT in humans , *TIBIAL arteries , *OSTEOTOMY , *PRINCIPAL components analysis , *POSTOPERATIVE care , *KNEE surgery , *TIBIA surgery , *KNEE diseases , *PROTEINS , *TORSION abnormality (Anatomy) , *FACTOR analysis , *FOOT , *ROTATIONAL motion , *POSTOPERATIVE period , *OSTEOARTHRITIS , *WALKING , *TIBIA , *KINEMATICS , *WEIGHT-bearing (Orthopedics) , *PHYSIOLOGY - Abstract
Background: Tibial torsion describes the rotation between the proximal and distal joint axis along the shaft, which can be, as rotational deformity, pathologically increased or decreased. Some patients might increase hip internal rotation during walking to compensate increased outward tibial torsion.Research Question: The aim of this study was to assess the effect of tibial derotation osteotomy on gait deviations in patients with increased outward tibial torsion.Methods: Thirteen patients (13.5 ± 1.4 yrs, 22 limbs) with increased tibial torsion (CT confirmed 49.2 ± 4.8°) were analyzed pre and post tibial derotation osteotomy and compared with 17 typically developing children (TDC, 13.5 ± 2.3 yrs, 32 limbs). Kinematic and kinetic data were recorded. Subgroup analyses were performed whether patients showed compensatory hip internal rotation (Comp) or not (NoComp). Principal component (PC) analysis was used to achieve data transformation. A linear mixed model was used to estimate the main effect of PC-scores of retained PCs explaining 90% of the cumulative variance.Results: Compensatory hip internal rotation (Comp, present in 45.5% of limbs analyzed) led to a lower external foot progression angle compared to patients without compensatory hip internal rotation (NoComp). In both patient groups foot progression angle was normalized after tibial derotation osteotomy. Post-operative NoComp had normalized frontal plane joint loadings, while Comp showed an increased hip and knee adduction moment.Significance: Future studies should investigate if more time is needed for Comp to normalize gait patterns post-operative or if a pre and post-operative gait training might help. Otherwise the increased knee adduction moment might be clinically relevant due to previous studies reporting a possible association with knee osteoarthritis. [ABSTRACT FROM AUTHOR]- Published
- 2020
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234. Proteogenomic monitoring of Geobacter physiology during stimulated uranium bioremediation
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Abraham, P
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- 2009
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235. Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction.
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Teles, Rosane M. B., Lu, Jing, Tió-Coma, Maria, Goulart, Isabela M. B., Banu, Sayera, Hagge, Deanna, Bobosha, Kidist, Ottenhoff, Tom, Pellegrini, Matteo, Geluk, Annemieke, and Modlin, Robert L.
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HANSEN'S disease , *PROTEIN binding , *MYCOBACTERIUM leprae , *GENE regulatory networks , *CELLULAR immunity - Abstract
Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an 'RR signature' of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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236. Micro-RNA 150-5p predicts overt heart failure in patients with univentricular hearts.
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Abu-Halima, Masood, Meese, Eckart, Saleh, Mohamad Ali, Keller, Andreas, Abdul-Khaliq, Hashim, and Raedle-Hurst, Tanja
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HEART failure patients , *HEART failure , *POLYMERASE chain reaction , *LEFT heart ventricle - Abstract
Background: In patients with left heart failure, micro-RNAs (miRNAs) have been shown to be of diagnostic and prognostic value. The present study aims to identify those miRNAs in patients with univentricular heart (UVH) disease that may be associated with overt heart failure. Methods: A large panel of human miRNA arrays were used to determine miRNA expression profiles in the blood of 48 UVH patients and 32 healthy controls. For further selection, the most abundantly expressed miRNA arrays were related to clinical measures of heart failure and selected miRNAs validated by polymerase chain reaction were used for the prediction of overt heart failure and all-cause mortality. Results: According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-150-5p was best related to heart failure parameters. According to ROC analysis, NT-proBNP levels (AUC 0.940, 95% CI 0.873–1.000; p = 0.001), miR-150-5p (AUC 0.905, 95% CI 0.779–1.000; p = 0.001) and a higher NYHA class ≥ III (AUC 0.893, 95% CI 0.713–1.000; p = 0.002) were the 3 most significant predictors of overt heart failure. Using a combined biomarker model, AUC increased to 0.980 indicating an additive value of miR-150-5p. Moreover, in the multivariate analysis, a higher NYHA class ≥ III (p = 0.005) and miR-150-5p (p = 0.006) turned out to be independent predictors of overt heart failure. Conclusion: In patients with UVH, miR-150-5p is an independent predictor of overt heart failure and thus may be used in the risk assessment of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
237. Effects of dietary intake and nutritional status on cerebral oxygenation in patients with chronic kidney disease not undergoing dialysis: A cross-sectional study.
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Ookawara, Susumu, Kaku, Yoshio, Ito, Kiyonori, Kizukuri, Kanako, Namikawa, Aiko, Nakahara, Shinobu, Horiuchi, Yuko, Inose, Nagisa, Miyahara, Mayako, Shiina, Michiko, Minato, Saori, Shindo, Mitsutoshi, Miyazawa, Haruhisa, Hirai, Keiji, Hoshino, Taro, Murakoshi, Miho, Tabei, Kaoru, and Morishita, Yoshiyuki
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CHRONIC kidney failure , *CHRONICALLY ill , *NUTRITIONAL status , *SERUM albumin , *BODY mass index , *CEREBRAL circulation , *FOOD consumption - Abstract
Background: Dietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited. Methods: This was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection. Results: Multivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p < 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake. Conclusions: Cerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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238. The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model.
- Author
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Šimurda, Jiří, Šimurdová, Milena, and Bébarová, Markéta
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NICOTINE , *PHARMACOLOGY , *POTASSIUM , *HEART cells , *POTASSIUM ions , *DRUG interactions - Abstract
Recent experimental work has revealed unusual features of the effect of certain drugs on cardiac inwardly rectifying potassium currents, including the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current (IKAch). These unusual features have included alternating susceptibility of the current components to activation and inhibition induced by ethanol or nicotine applied at various concentrations, and significant correlation between the drug effect and the current magnitude measured under drug-free conditions. To explain these complex drug effects, we have developed a new type of quantitative model to offer a possible interpretation of the effect of ethanol and nicotine on the IKAch channels. The model is based on a description of IKAch as a sum of particular currents related to the populations of channels formed by identical assemblies of different α-subunits. Assuming two different channel populations in agreement with the two reported functional IKAch-channels (GIRK1/4 and GIRK4), the model was able to simulate all the above-mentioned characteristic features of drug-channel interactions and also the dispersion of the current measured in different cells. The formulation of our model equations allows the model to be incorporated easily into the existing integrative models of electrical activity of cardiac cells involving quantitative description of IKAch. We suppose that the model could also help make sense of certain observations related to the channels that do not show inward rectification. This new ionic channel model, based on a concept we call population type, may allow for the interpretation of complex interactions of drugs with ionic channels of various types, which cannot be done using the ionic channel models available so far. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
239. Interactions of Streptococcus suis serotype 9 with host cells and role of the capsular polysaccharide: Comparison with serotypes 2 and 14.
- Author
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Auger, Jean-Philippe, Payen, Servane, Roy, David, Dumesnil, Audrey, Segura, Mariela, and Gottschalk, Marcelo
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STREPTOCOCCUS suis , *STREPTOCOCCUS , *ACTINOBACILLUS , *SEPTIC shock , *SIALIC acids , *EPITHELIAL cells , *SUDDEN death , *PHAGOCYTOSIS - Abstract
Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent responsible for sudden death, septic shock and meningitis, of which serotype 2 is the most widespread, with serotype 14 also causing infections in humans in South-East Asia. Knowledge of its pathogenesis and virulence are almost exclusively based on these two serotypes. Though serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands and Germany, very little information is currently available regarding this serotype. Of the different virulence factors, the capsular polysaccharide (CPS) is required for S. suis virulence as it promotes resistance to phagocytosis and killing and masks surface components responsible for host cell activation. However, these roles have been described for serotypes 2 and 14, whose CPSs are structurally and compositionally similar, both containing sialic acid. Consequently, we evaluated herein the interactions of serotype 9 with host cells and the role of its CPS, which greatly differs from those of serotypes 2 and 14. Results demonstrated that serotype 9 adhesion to but not invasion of respiratory epithelial cells was greater than that of serotypes 2 and 14. Furthermore serotype 9 was more internalized by macrophages but equally resistant to whole blood killing. Though recognition of serotypes 2, 9 and 14 by DCs required MyD88-dependent signaling, in vitro pro-inflammatory mediator production induced by serotype 9 was much lower. In vivo, however, serotype 9 causes an exacerbated inflammatory response, which combined with persistent bacterial presence, is probably responsible for host death during the systemic infection. Though presence of the serotype 9 CPS masks surface components less efficiently than those of serotypes 2 and 14, the serotype 9 CPS remains critical for virulence as it is required for survival in blood and development of clinical disease, and this regardless of its unique composition and structure. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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240. Optimized bioluminescence analysis of adenosine triphosphate (ATP) released by platelets and its application in the high throughput screening of platelet inhibitors.
- Author
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Wang, Lili, Li, Yunqian, Guo, Ran, Li, Shanshan, Chang, Anqi, Zhu, Zhixiang, and Tu, Pengfei
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ADENOSINE triphosphate analysis , *PLATELET aggregation inhibitors , *BIOLUMINESCENCE , *PHYSIOLOGIC salines , *BLOOD platelet activation - Abstract
Activated platelets release adenosine trisphosphate (ATP) and bioluminescence analysis of ATP release is usually used to monitor activation of platelets induced by various stimulants. However, bioluminescence analysis of ATP possesses poor linearity, the signal is quickly attenuated, and the accuracy of ATP release from platelets is hard to determine accurately enough to be used in a high throughput screening of platelet inhibitors. The present study was designed to optimize bioluminescence analysis of ATP released by platelets and expand its application in high throughput screening of platelet inhibitors. The results showed that accuracy of ATP analysis was significantly improved by adding coenzyme A (CoA) and signal attenuation of ATP analysis was greatly postponed by adding bovine serum albumin (BSA) both in Hank's balanced salt solution (HBSS) and Tyrode's buffer. Furthermore, ATP release of activated platelets and inhibitory effects of Ly294002 and Staurosporine on platelet activation were accurately determined by our optimized bioluminescence analysis of ATP. Thus, we have successfully constructed an optimized bioluminescence analysis of ATP which can be used in high throughput screening of platelet inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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241. A proteomic clock for malignant gliomas: The role of the environment in tumorigenesis at the presymptomatic stage.
- Author
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Zheng, Le, Zhang, Yan, Hao, Shiying, Chen, Lin, Sun, Zhen, Yan, Chi, Whitin, John C., Jang, Taichang, Merchant, Milton, McElhinney, Doff B., Sylvester, Karl G., Cohen, Harvey J., Recht, Lawrence, Yao, Xiaoming, and Ling, Xuefeng B.
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CEREBROSPINAL fluid , *GLIOMAS , *BRAIN tumors , *FALSE discovery rate , *CEREBROSPINAL fluid examination , *NEURAL development , *ECOLOGY - Abstract
Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
242. Anti-inflammatory effects induced by ultralow concentrations of bupivacaine in combination with ultralow concentrations of sildenafil (Viagra) and vitamin D3 on inflammatory reactive brain astrocytes.
- Author
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Hansson, Elisabeth and Skiöldebrand, Eva
- Subjects
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ASTROCYTES , *CHOLECALCIFEROL , *SUBSTANCE P receptors , *TOLL-like receptors , *LOCAL anesthetics , *PHOSPHODIESTERASE-5 inhibitors , *TRANSVERSUS abdominis muscle - Abstract
Network coupled cells, such as astrocytes, regulate their cellular homeostasis via Ca2+ signals spread between the cells through gap junctions. Intracellular Ca2+ release is controlled by different signaling pathways that can be stimulated by ATP, glutamate and serotonin (5-HT). Based on our findings, all these pathways are influenced by inflammatory agents and must be restored to fully recover the Ca2+ signaling network. An ultralow concentration of the local anesthetic agent bupivacaine reduced 5-HT-evoked intracellular Ca2+ release, and an ultralow concentration of the phosphodiesterase-5 inhibitor sildenafil in combination with vitamin D3 reduced ATP-evoked intracellular Ca2+ release. Combinations of these three substances downregulated 5-HT-, glutamate- and ATP-evoked intracellular Ca2+ release to a more normal Ca2+ signaling state. Furthermore, inflammatory Toll-like receptor 4 expression decreased with a combination of these three substances. Substance P receptor neurokinin (NK)-1 expression was reduced by ultralow concentrations of bupivacaine. Here, bupivacaine and sildenafil (at extremely low concentrations) combined with vitamin D3 have potential anti-inflammatory properties. According to the present study, drug combinations at the right concentrations, especially extremely low concentrations of bupivacaine and sildenafil, affect different cellular biochemical mechanisms and represent a potential solution for downregulating inflammatory parameters, thereby restoring cells or networks to normal physiological homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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243. Does rotavirus turn on type 1 diabetes?
- Author
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Harrison, Leonard C., Perrett, Kirsten P., Jachno, Kim, Nolan, Terry M., and Honeyman, Margo C.
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TYPE 1 diabetes , *AUTOANTIBODIES , *CYTOLOGY , *MOLECULAR biology , *VACCINE effectiveness , *LIFE sciences , *ROTAVIRUS vaccines - Abstract
Recently, we observed a 15% decrease in the incidence of type 1 diabetes (T1D) in Australian 0-4-year-old children following the introduction of RV vaccination [[2], [3]], suggesting that RV vaccination could contribute to the primary prevention of this autoimmune disease. Australian surveillance data [[11]] show that the prevalence of RV G3 strains increased slightly along with an increase in strain diversity in the post-RV vaccine era, but G3 remains a minor component of disease-causing RV strains. RV was prevalent in nurseries, and the change to rooming-in would have altered the timing of exposure to RV, delaying it until later in the first year of life when, based on NOD mouse studies [[17]-[19]], RV might promote rather than retard development of diabetes. [Extracted from the article]
- Published
- 2019
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244. Determination of factors affecting medication adherence in type 2 diabetes mellitus patients using a nationwide claim-based database in Japan.
- Author
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Horii, Takeshi, Momo, Kenji, Yasu, Takeo, Kabeya, Yusuke, and Atsuda, Koichiro
- Subjects
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MEDICAL databases , *PATIENT compliance , *TYPE 2 diabetes , *PEOPLE with diabetes , *HYPOGLYCEMIC agents - Abstract
Background: The extent of medication adherence in patients with type 2 diabetes mellitus (T2DM) several years after starting treatment with hypoglycemic agents remains unknown. Most previous work on medication adherence targeting this group of patients has been undertaken across a single year or is questionnaire based. This study aimed to determine medication adherence status and factors affecting adherence 3 years after initiation of hypoglycemic agents, using a nationwide medical claim-based database in Japan. Methods: This retrospective study was conducted on data from 884 subjects with T2DM to better understand medication adherence, the effects of polypharmacy, and other factors. We also investigated the effects of medication nonadherence on hemoglobin A1c levels. Proportion of days covered was defined as the number of days for which a hypoglycemic agent was prescribed and in the patient’s possession to the number of days in the observation period. A proportion of days covered ≥0.8 were considered adherent, and those with a value <0.8 as nonadherence. Polypharmacy was defined as taking ≥5 medications. Results: Of the 884 patients investigated, 440 were considered adherent during the study period. Significant factors related to adherence included number of medications (3 or 4, or ≥5), male sex, age 50–<60 years, and total number of visits ≥17. Medication adherence was also a factor related to patients with hemoglobin A1c values < 7.0% at the end of the observation period. Conclusions: We surveyed medication adherence for 3 years with post medication initiation, and found that subjects aged 50–<60 years, those with ≥3 concomitant medications, and those with a total number of visits ≥17 were more likely to be adherent and persistent, and more likely to continue their hypoglycemic agents. A high degree of medication adherence was found to have a positive influence on hemoglobin A1c levels. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
245. Method comparison for N-glycan profiling: Towards the standardization of glycoanalytical technologies for cell line analysis.
- Author
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Kotsias, Maximilianos, Blanas, Athanasios, van Vliet, Sandra J., Pirro, Martina, Spencer, Daniel I. R., and Kozak, Radoslaw P.
- Subjects
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CELL analysis , *CELL lines , *TECHNOLOGY , *STANDARDIZATION , *ORGANIC chemistry , *BIOPHARMACEUTICS - Abstract
The study of protein N-glycosylation is essential in biological and biopharmaceutical research as N-glycans have been reported to regulate a wide range of physiological and pathological processes. Monitoring glycosylation in diagnosis, prognosis, as well as biopharmaceutical development and quality control are important research areas. A number of techniques for the analysis of protein N-glycosylation are currently available. Here we examine three methodologies routinely used for the release of N-glycans, in the effort to establish and standardize glycoproteomics technologies for quantitative glycan analysis from cultured cell lines. N-glycans from human gamma immunoglobulins (IgG), plasma and a pool of four cancer cell lines were released following three approaches and the performance of each method was evaluated. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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246. Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice.
- Author
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Kato, Hirofumi, Takayama-Ito, Mutsuyo, Iizuka-Shiota, Itoe, Fukushi, Shuetsu, Posadas-Herrera, Guillermo, Horiya, Madoka, Satoh, Masaaki, Yoshikawa, Tomoki, Yamada, Souichi, Harada, Shizuko, Fujii, Hikaru, Shibamura, Miho, Inagaki, Takuya, Morimoto, Kinjiro, Saijo, Masayuki, and Lim, Chang-Kweng
- Subjects
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CORONAVIRUSES , *RABIES virus , *MERS coronavirus , *MIDDLE East respiratory syndrome , *SYMPTOMS , *RABIES , *REVERSE genetics - Abstract
Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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247. Cisd2 is essential to delaying cardiac aging and to maintaining heart functions.
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Yeh, Chi-Hsiao, Shen, Zhao-Qing, Hsiung, Shao-Yu, Wu, Pei-Chun, Teng, Yuan-Chi, Chou, Yi-Ju, Fang, Su-Wen, Chen, Chian-Feng, Yan, Yu-Ting, Kao, Lung-Sen, Kao, Cheng-Heng, and Tsai, Ting-Fen
- Subjects
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IRON-sulfur proteins , *DEVELOPMENTAL biology , *AGING , *CYTOLOGY , *TRANSGENIC mice , *INTRACELLULAR calcium , *CALMODULIN - Abstract
CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart’s electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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248. The developmental Wnt signaling pathway effector β-catenin/TCF mediates hepatic functions of the sex hormone estradiol in regulating lipid metabolism.
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Tian, Lili, Shao, Weijuan, Ip, Wilfred, Song, Zhuolun, Badakhshi, Yasaman, and Jin, Tianru
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SEX hormones , *STEROL regulatory element-binding proteins , *WNT signal transduction , *LIPID metabolism , *GROWTH factors , *WNT proteins , *ESTROGEN receptors , *ESTRADIOL - Abstract
The bipartite transcription factor β-catenin (β-cat)/T cell factor (TCF), formed by free β-cat and a given TCF family member, serves as the effector of the developmental Wnt signaling cascade. β-cat/TCFs also serve as effectors of certain peptide hormones or growth factors during adulthood. We reported that liver-specific expression of dominant-negative Transcription factor 7 like 2 (TCF7L2DN) led to impaired glucose disposal. Here we show that, in this LTCFDN transgenic mouse model, serum and hepatic lipid contents were elevated in male but not in female mice. In hepatocytes, TCF7L2DN adenovirus infection led to stimulated expression of genes that encode lipogenic transcription factors and lipogenic enzymes, while estradiol (E2) treatment attenuated the stimulation, associated with Wnt-target gene activation. Mechanistically, this E2-mediated activation can be attributed to elevated β-cat Ser675 phosphorylation and TCF expression. In wild-type female mice, ovariectomy (OVX) plus high-fat diet (HFD) challenge impaired glucose disposal and insulin tolerance, associated with increased hepatic lipogenic transcription factor sterol regulatory element-binding protein 1-c (SREBP-1c) expression. In wild-type mice with OVX, E2 reconstitution attenuated HFD-induced metabolic defects. Some of the attenuation effects, including insulin intolerance, elevated liver-weight gain, and hepatic SREBP-1c expression, were not affected by E2 reconstitution in HFD-fed LTCFDN mice with OVX. Finally, the effects of E2 in hepatocytes on β-cat/TCF activation can be attenuated by the G-protein-coupled estrogen receptor (GPER) antagonist G15. Our study thus expanded the scope of functions of the Wnt pathway effector β-cat/TCF, as it can also mediate hepatic functions of E2 during adulthood. This study also enriches our mechanistic understanding of gender differences in the risk and pathophysiology of metabolic diseases. [ABSTRACT FROM AUTHOR]
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- 2019
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249. Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells.
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Garcin, Edwige B., Gon, Stéphanie, Sullivan, Meghan R., Brunette, Gregory J., Cian, Anne De, Concordet, Jean-Paul, Giovannangeli, Carine, Dirks, Wilhelm G., Eberth, Sonja, Bernstein, Kara A., Prakash, Rohit, Jasin, Maria, and Modesti, Mauro
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RAD51 recombinase , *GENOMES , *GENETICS , *MITOMYCIN C , *EPITHELIAL cells - Abstract
Deficiency in several of the classical human RAD51 paralogs [RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3] is associated with cancer predisposition and Fanconi anemia. To investigate their functions, isogenic disruption mutants for each were generated in non-transformed MCF10A mammary epithelial cells and in transformed U2OS and HEK293 cells. In U2OS and HEK293 cells, viable ablated clones were readily isolated for each RAD51 paralog; in contrast, with the exception of RAD51B, RAD51 paralogs are cell-essential in MCF10A cells. Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hyper-sensitivity to mitomycin C and olaparib. Altogether these observations underscore the contributions of RAD51 paralogs in diverse DNA repair processes, and demonstrate essential differences in different cell types. Finally, this study will provide useful reagents to analyze patient-derived mutations and to investigate mechanisms of chemotherapeutic resistance deployed by cancers. [ABSTRACT FROM AUTHOR]
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- 2019
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250. Incidence and predictors of retreatment in chronic hepatitis B patients after discontinuation of entecavir or tenofovir treatment.
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Ma, Te-Ling, Hu, Tsung-Hui, Hung, Chao-Hung, Wang, Jing-Houng, Lu, Sheng-Nan, and Chen, Chien-Hung
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CHRONIC hepatitis B , *HEPATITIS associated antigen , *HEPATITIS A - Abstract
Background: This study investigated the incidence and predictors of retreatment after discontinuation of either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment in Taiwan. Methods: A total of 535 non-cirrhotic chronic hepatitis B (CHB) patients undergoing either ETV (n = 358) or TDF (n = 177) treatment were enrolled. Patients were followed for at least 12 months after stopping ETV or TDF treatment. Most patients (86.3%) fulfilled the retreatment criteria of Taiwan's National Health Plan. Results: The 5-year cumulative rates of clinical relapse and retreatment were 52.1% and 47%, respectively, in 160 hepatitis B e antigen (HBeAg)-positive patients, and were 62% and 54.8%, respectively, in 375 HBeAg-negative patients. The median duration from the end of treatment until clinical relapse and retreatment was 40 and 57 weeks, respectively, for all patients. Multivariate Cox regression analysis revealed that discontinuing TDF treatment, old age, male gender, and higher baseline HBsAg levels were independent factors of retreatment in HBeAg-positive patients; old age, HBV genotype B, and higher baseline and end-of-treatment HBsAg levels were independent factors in HBeAg-negative patients. A total of 18.8% of retreated patients satisfied the retreatment criteria of hepatic decompensation according to Taiwan's National Health Plan. Of the 64 patients who had clinical relapse without retreatment, 17 achieved sustained virological remission and 26 did not experience clinical relapse until their last visit after clinical relapse. Four patients developed HBsAg loss. Conclusions: The 5-year retreatment rate was about 50% in HBeAg-positive and HBeAg-negative patients. Discontinuing TDF treatment was an independent factor of retreatment in HBeAg-positive patients. [ABSTRACT FROM AUTHOR]
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- 2019
- Full Text
- View/download PDF
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