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  • Article
    Fatieiev Y, Croissant JG, Julfakyan K, Deng L, Anjum DH, Gurinov A, Khashab NM.
    Nanoscale. 2015 Oct 07;7(37):15046-50.
    We describe biodegradable bridged silsesquioxane (BS) composite nanomaterials with an unusually high organic content (ca. 50%) based on oxamide components mimicking amino acid biocleavable groups. Unlike most bulk BS materials, the design of sub-200 nm nearly monodisperse nanoparticles (NPs) was achieved. These enzymatically degradable BS NPs were further tested as promising imaging nanoprobes.
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  • Article
    Wanger TC, Brook BW, Evans T, Tscharntke T.
    PeerJ. 2023;11:e15046.
    Pesticide use on tropical crops has increased substantially in recent decades, posing a threat to biodiversity and ecosystem services. Amphibians and reptiles are common in tropical agricultural landscapes, but few field studies measure pesticide impacts on these taxa. Here we combine 1-year of correlative data with an experimental field approach from Indonesia. We show that while pesticide application cannot predict amphibian or reptile diversity patterns in cocoa plantations, our experimental exposure to herbicides and insecticides in vegetable gardens eliminated amphibians, whereas reptiles were less impacted by insecticide and not affected by herbicide exposure. The pesticide-driven loss of a common amphibian species known to be a pest-control agent (mainly invertebrate predation) suggests a strong indirect negative effect of pesticides on this service. We recommend landscape-based Integrated Pest Management and additional ecotoxicological studies on amphibians and reptiles to underpin a regulatory framework and to assure recognition and protection of their ecosystem services.
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  • Article
    Matveeva E, Maiorano J, Zhang Q, Eteleeb AM, Convertini P, Chen J, Infantino V, Stamm S, Wang J, Rouchka EC, Fondufe-Mittendorf YN.
    Cell Discov. 2016;2:15046.
    Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that interaction of the chromatin-modifying factor, Poly (ADP) ribose polymerase with nucleosomal structures at exon-intron boundaries, might regulate pre-mRNA splicing. Using genome-wide approaches validated by gene-specific assays, we show that depletion of PARP1 or inhibition of its PARylation activity results in changes in alternative splicing of a specific subset of genes. Furthermore, we observed that PARP1 bound to RNA, splicing factors and chromatin, suggesting that Poly (ADP) ribose polymerase serves as a gene regulatory hub to facilitate co-transcriptional splicing. These studies add another function to the multi-functional protein, Poly (ADP) ribose polymerase, and provide a platform for further investigation of this protein's function in organizing chromatin during gene regulatory processes.
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  • Article
    Zhuang W, Gao Z, Wen L, Huo X, Cai B, Zhang Z.
    Hortic Res. 2015;2:15046.
    Gibberellin (GA4) has a significant effect on promoting dormancy release in flower buds of Japanese apricot (Prunus mume Sieb. et Zucc). The transcriptomic and proteomic changes that occur after GA4 treatment have been reported previously; however, the metabolic changes brought about by GA4 remain unknown. The present study was undertaken to assess changes in metabolites in response to GA4 treatment, as determined using gas chromatography-mass spectrometry and principal component analysis. Fifty-five metabolites that exhibited more than two-fold differences in abundance (P < 0.05) between samples collected over time after a given treatment or between samples exposed to different treatments were studied further. These metabolites were categorized into six main groups: amino acids and their isoforms (10), amino acid derivatives (7), sugars and polyols (14), organic acids (12), fatty acids (4), and others (8). All of these groups are involved in various metabolic pathways, in particular galactose metabolism, glyoxylate and dicarboxylate metabolism, and starch and sucrose metabolism. These results suggested that energy metabolism is important at the metabolic level in dormancy release following GA4 treatment. We also found that more than 10-fold differences in abundance were observed for many metabolites, including sucrose, proline, linoleic acid, and linolenic acid, which might play important roles during the dormancy process. The current research extends our understanding of the mechanisms involved in budburst and dormancy release in response to GA4 and provides a theoretical basis for applying GA4 to release dormancy.
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  • Article
    Kamath S, Ulhaque A, Ali R, Frunzi J.
    Cureus. 2021 May 15;13(5):e15046.
    This case reports a 24-year-old female with prior aortic insufficiency who underwent a mechanical aortic valve replacement with subsequent transient ischemic attacks and documented subtherapeutic international normalized ratio (INR). She presented with pain and bilateral lower extremity pulselessness. Workup showed a supratherapeutic INR, no thrombus on echocardiogram, and computed tomography angiography demonstrating no flow in the bilateral common femoral arteries. Patient failed repeated thrombectomies and had a bilateral above-knee amputation. The patient was suspected to have acute on chronic emboli from the mechanical aortic valve and further testing did not elucidate contributory causes of her critical limb ischemia. We believe this is the first documented case of bilateral lower extremity ischemia due to mechanical valve complications.
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  • Article
    Gouda MNR, Subramanian S.
    Sci Rep. 2024 07 01;14(1):15046.
    The cotton whitefly, Bemisia tabaci, is considered as a species complex with 46 cryptic species, with Asia II-1 being predominant in Asia. This study addresses a significant knowledge gap in the characterization of odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) in Asia II-1. We explored the expression patterns of OBPs and CSPs throughout their developmental stages and compared the motif patterns of these proteins. Significant differences in expression patterns were observed for the 14 OBPs and 14 CSPs of B. tabaci Asia II-1, with OBP8 and CSP4 showing higher expression across the developmental stages. Phylogenetic analysis reveals that OBP8 and CSP4 form distinct clades, with OBP8 appearing to be an ancestral gene, giving rise to the evolution of other odorant-binding proteins in B. tabaci. The genomic distribution of OBPs and CSPs highlights gene clustering on the chromosomes, suggesting functional conservation and evolutionary events following the birth-and-death model. Molecular docking studies indicate strong binding affinities of OBP8 and CSP4 with various odour compounds like β-caryophyllene, α-pinene, β-pinene and limonene, reinforcing their roles in host recognition and reproductive functions. This study elaborates on our understanding of the putative roles of different OBPs and CSPs in B. tabaci Asia II-1, hitherto unexplored. The dynamics of the expression of OBPs and CSPs and their interactions with odour compounds offer scope for developing innovative methods for controlling this global invasive pest.
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  • Article
    Mierzejewski B, Ciemerych MA, Streminska W, Janczyk-Ilach K, Brzoska E.
    Sci Rep. 2023 09 12;13(1):15046.
    Muscle satellite cells (SCs) are stem cells and the main players in skeletal muscle reconstruction. Since satellite cells are located near or in direct contact with blood vessels their niche is formed, inter alia, by endothelial cells. The cross-talk between satellite cells and endothelial cells determines quiescence or proliferation of these cells. However, little is known about the role of miRNA in these interactions. In the present study we identified miRNA that were up-regulated in SC-derived myoblasts treated with stromal derived factor-1 (SDF-1) and/or down-regulated in cells in which the expression of CXCR4 or CXCR7, that is, SDF-1 receptors, was silenced. SDF-1 is one of the important regulators of cell migration, mobilization, skeletal muscle regeneration, and angiogenesis. We hypothesized that selected miRNAs affect SC-derived myoblast fate and interactions with endothelial cells. We showed that miR-126a-3p inhibited both, myoblast migration and fusion. Moreover, the levels of Cxcl12, encoding SDF-1 and Ackr3, encoding CXCR7, were reduced by miR-126a-3p mimic. Interestingly, the miR-126a-3p mimic significantly decreased the level of numerous factors involved in myogenesis and the miR-126a-5p mimic increased the level of Vefga. Importantly, the treatment of endothelial cells with medium conditioned by miR-126-5p mimic transfected SC-derived myoblasts promoted tubulogenesis.
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  • Article
    Wang J, Cao K, Li S, Su B, Jin Z, Pan Z, Tian L, Shi W, Jie Y.
    Heliyon. 2023 Apr;9(4):e15046.
    Introduction: Pterygium is a common multifactorial external eye disease, which causes various ocular symptoms and negatively affects appearance. The aim of this study was to analyze the epidemiological characteristics and the change of surgical methods of pterygium and pseudopterygium in China from 2013 to 2019.
    Materials and methods: This study was a hospital-based nationwide retrospective study to estimate the epidemiologic characteristics and the change of surgical methods of pterygium and pseudopteygium in China from 2013 to 2019. The data was extracted from the Hospital Quality Monitoring System (HQMS) database. The diagnosis was based on the tenth revision of the International Classification of Diseases (ICD-10) code.
    Results: Our study included 1,007,800 pterygium and 2,681 pseudopteygium inpatients. From 2013 to 2019, the proportion of pterygium and pseudopterygium patients who underwent surgery, among all ophthalmology inpatients, increased from 3.3% in 2013 to 7.84% in 2019. The male-female ratio of surgically treated pterygium and pseudopterygium is 1:1.8 and 1.6:1 respectively. Among all age groups, the hospitalized pterygium patients who received surgery were mainly 60-69 years old, accounting for 36.53%. The pseudopterygium patients who received surgery were mostly 50-59 years old, accounting for 24.02%. Among the 31 provinces of mainland China, Yunnan Province has the highest proportion of pterygium patients treated surgically (6.40%), while Shanghai has the highest proportion of pseudopterygium patients treated surgically (12.98%). The most common occupation of participants in the study was farmer, accounting for 47.62% and 28.53%, respectively. During the study period, the application of autologous stem cell transplantation increased year by year, and became the first choice for pterygium and pseudopterygium surgery.
    Discussion: This study was the first to describe the epidemiological characteristics and surgical methods of hospitalized pterygium and pseudopterygium patients in China. This study provides important information for better diagnosis, treatment and prevention of pterygium and pseudopterygium.
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  • Article
    Oikawa T, Nonaka T, Terada M, Tamaoka A, Hisanaga S, Hasegawa M.
    J Biol Chem. 2016 07 15;291(29):15046-56.
    α-Synuclein is the major component of Lewy bodies and Lewy neurites in Parkinson disease and dementia with Lewy bodies and of glial cytoplasmic inclusions in multiple system atrophy. It has been suggested that α-synuclein fibrils or intermediate protofibrils in the process of fibril formation may have a toxic effect on neuronal cells. In this study, we investigated the ability of soluble monomeric α-synuclein to promote microtubule assembly and the effects of conformational changes of α-synuclein on Tau-promoted microtubule assembly. In marked contrast to previous findings, monomeric α-synuclein had no effect on microtubule polymerization. However, both α-synuclein fibrils and protofibrils inhibited Tau-promoted microtubule assembly. The inhibitory effect of α-synuclein fibrils was greater than that of the protofibrils. Dot blot overlay assay and spin-down techniques revealed that α-synuclein fibrils bind to Tau and inhibit microtubule assembly by depleting the Tau available for microtubule polymerization. Using various deletion mutants of α-synuclein and Tau, the acidic C-terminal region of α-synuclein and the basic central region of Tau were identified as regions involved in the binding. Furthermore, introduction of α-synuclein fibrils into cultured cells overexpressing Tau protein induced Tau aggregation. These results raise the possibility that α-synuclein fibrils interact with Tau, inhibit its function to stabilize microtubules, and also promote Tau aggregation, leading to dysfunction of neuronal cells.
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  • Article
    Cheng R, Choudhury D, Liu C, Billet S, Hu T, Bhowmick NA.
    Cell Death Discov. 2015;1:15046.
    Periodontal diseases are classified as inflammation affecting the supporting tissue of teeth, which eventually leads to tooth loss. Mild reversible gingivitis and severe irreversible periodontitis are the most common periodontal diseases. Periodontal pathogens initiate the diseases. The bacterial toxin, lipopolysaccharide (LPS), triggers the inflammatory response and leads to oxidative stress. However, the progress of oxidative stress in periodontal diseases is unknown. The purpose of this study is to examine oxidative stress and cell damage in gingivitis and periodontitis. Our results showed that LPS increases reactive oxygen species (ROS) accumulation in gingival fibroblast (GF). However, oxidative stress resulting from excessive ROS did not influence DNA damage and cell apoptosis within 24 h. The mechanism may be related to the increased expression of DNA repair genes, Ogg1, Neil1 and Rad50. Detection of apoptosis-related proteins also showed anti-apoptotic effects and pro-apoptotic effects were balanced. The earliest damage appeared in DNA when increased γH2AX, an early biomarker for DNA damage, was detected in the LPS group after 48 h. Later, when recurrent inflammation persisted, 8-OHdG, a biomarker for oxidative stress was much higher in periodontitis model compared to the control in vivo. Staining of 8-OHdG in human periodontitis specimens confirmed the results. Furthermore, TUNEL staining of apoptotic cells indicated that the periodontitis model induced more cell apoptosis in gingival tissue. This suggested GF could resist early and acute inflammation (gingivitis), which was regarded as reversible, but recurrent and chronic inflammation (periodontitis) led to permanent cell damage and death.
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  • Article
    Xu J, Ueno H, Xu CY, Chen B, Weissman IL, Xu PX.
    Nat Commun. 2017 05 11;8:15046.
    The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage. These multipotent progenitors originate from Eya1-expressing otic progenitors. Our findings also provide evidence for detectable regenerative potential in the postnatal cochlea beyond 1 week of age.
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  • Article
    Liu X, Kawashima M, Miyagawa T, Otowa T, Latt KZ, Thiri M, Nishida H, Sugiyama T, Tsurusaki Y, Matsumoto N, Mabuchi A, Kato N, Tokunaga K, Sasaki T.
    Hum Genome Var. 2016;3:15046.
    [This corrects the article DOI: 10.1038/hgv.2015.24.][This corrects the article DOI: 10.1038/hgv.2015.24.].
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  • Article
    Ordóñez CD, Lechuga A, Salas M, Redrejo-Rodríguez M.
    Sci Rep. 2020 09 14;10(1):15046.
    The development of whole genome amplification (WGA) and related methods, coupled with the dramatic growth of sequencing capacities, has changed the paradigm of genomic and genetic analyses. This has led to a continual requirement of improved DNA amplification protocols and the elaboration of new tailored methods. As key elements in WGA, identification and engineering of novel, faithful and processive DNA polymerases is a driving force in the field. We have engineered the B-family DNA polymerase of virus Bam35 with a C-terminal fusion of DNA-binding motifs. The new protein, named B35-HhH, shows faithful DNA replication in the presence of magnesium or an optimised combination of magnesium and manganese divalent cofactors, which enhances the replication of damaged DNA substrates. Overall, the newly generated variant displays improved amplification performance, sensitivity, translesion synthesis and resistance to salt, which are of great interest for several applications of isothermal DNA amplification. Further, rolling-circle amplification of abasic site-containing minicircles provides a proof-of-concept for using B35-HhH for processive amplification of damaged DNA samples.
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  • Article
    Gao R, Yu Y, Inoue A, Widodo N, Kaul SC, Wadhwa R.
    J Biol Chem. 2013 May 24;288(21):15046-56.
    Cancer is a leading cause of death and still awaits effective therapies. Rapid industrialization has contributed to increase in incidence of cancer. One of the reasons why most of the cancers fail therapy is due to their metastatic property. Hence identification of factors leading to metastasis is highly important to design effective and novel anti-cancer therapeutics. In our earlier study (Inoue, A., Sawata, S. Y., Taira, K., and Wadhwa, R. (2007) Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. Proc. Natl. Acad. Sci. U.S.A. 104, 8983-8988), we had reported that the involvement of heterogeneous nuclear ribonucleoprotein K (hnRNP-K) in metastasis. Here, we established hnRNP-K-overexpressing and -underexpressing derivative cell lines and examined their proliferation and metastatic properties in vitro and in vivo. Whereas hnRNP-K compromised cells showed delayed tumor growth, its overexpression resulted in enhanced malignancy and metastasis. Molecular basis of the hnRNP-K induced malignant and metastatic phenotypes was dissected by cDNA microarray and pathway analyses. We found that the hnRNP-K regulates extracellular matrix, cell motility, and angiogenesis pathways. Involvement of the selected genes (Cck, Mmp-3, Ptgs2, and Ctgf) and pathways was validated by gene-specific expression analysis. Our results demonstrated that the hnRNP-K is a potential target for metastasis therapy.
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  • Article
    Haridas V, Yadav A, Sharma S, Pandey S.
    Phys Chem Chem Phys. 2016 06 01;18(22):15046-53.
    Pyrene and tryptophan groups judiciously placed on a novel molecular scaffold, namely, bispidine exhibited fluorescence due to the formation of an unprecedented emissive intramolecular complex in polar solvents. Upon protonation, the emission signal from the pyrene unit enhances at the expense of the emission signal from the complex. The probe demonstrates good sensitivity, excellent selectivity, and adequate reversibility towards proton sensing. The present design based on the bispidine scaffold opens up newer opportunities for the design of novel bispidine-peptide sensors.
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  • Article
    Ertl M, Klaus M, Brandt T, Dieterich M, Mast FW.
    Sci Rep. 2019 10 21;9(1):15046.
    A distorted model of a familiar multi-level building with a systematic overestimation of the height was demonstrated earlier in psychophysical and real world navigational tasks. In the current study we further investigated this phenomenon with a tablet-based application. Participants were asked to adjust height and width of the presented buildings to best match their memory of the dimensional ratio. The estimation errors between adjusted and true height-width ratios were analyzed. Additionally, familiarity with respect to in- and outside of the building as well as demographic data were acquired. A total of 142 subjects aged 21 to 90 years from the cities of Bern and Munich were tested. Major results were: (1) a median overestimation of the height of the multi-level buildings of 11%; (2) estimation errors were significantly less if the particular building was unknown to participants; (3) in contrast, the height of tower-like buildings was underestimated; (4) the height of long, flat shaped buildings was overestimated. (5) Further features, such as the architectonical complexity were critical. Overall, our internal models of large multi-level buildings are distorted due to multiple factors including geometric features and memory effects demonstrating that such individual models are not rigid but plastic with consequences for spatial orientation and navigation.
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  • Article
    Vaidya GN, Anaya P, Ignaszewski M, Kolodziej A, Malyala R, Rajagopalan N, Sekela M, Birks E.
    Clin Transplant. 2023 08;37(8):e15046.
    BACKGROUND: Hearts from COVID-19 positive donors (CPD) are being utilized for heart transplantation by some centers; however, this is in the setting of the lack of guidelines or robust evidence. The paucity of evidence is reflected in the recent Organ Procurement and Transplantation Network (OPTN) communication describing CPD utilization as an "unknown risk."
    METHODS AND RESULTS: We analyzed the UNOS database for adult heart transplants performed between January 2021 to December 2022, and CPD comprised of a significant percentage of donors, being used in >10% of recipients in some UNOS regions. Between July 2022 and December 2022, 7.9% of heart transplants were with CPD, and in the same period Hepatitis C positive donors accounted for 7.1% and donation after circulatory death (DCD) accounted for 10.3%.
    CONCLUSION: If the transplant community comes up with a standardized approach and guidance in using CPD hearts, this could provide an effective donor pool expansion strategy.
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  • Article
    Lin Q, Yu S.
    Sci Rep. 2018 10 09;8(1):15046.
    Coastal wetland ecosystems have experienced serious losses of area and ecological function and are currently facing worldwide challenges due to coastal development and global climate change. This study attempted to explore patterns and possible factors driving loss of natural coastal wetlands due to land conversion (permanent loss) and ecological degradation (temporal loss) in three urbanizing coastal city clusters, China in the period of 1990-2015. The natural coastal wetland area was substantially lost due to land conversion highly related to regional economic development. The ecological degradation, assessed as a function of surface water quality, resulted in much greater impairment area of natural coastal wetlands. This impairment was predominantly driven by inbound river pollutants' discharge, rather than local discharge. This study suggests that the ecological degradation should be considered as well as the land conversion loss for conserving the remaining natural coastal wetland ecosystems. The pollutant discharges from the inbound river watersheds need to be mitigated as the local discharges for reducing the functional degradation of the natural coastal wetlands while the regional economic development plan should consider the conservation needs of the remaining natural coastal wetlands worldwide.
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  • Article
    Ellingrod VL, Grove TB, Burghardt KJ, Taylor SF, Dalack G.
    NPJ Schizophr. 2015;1:15046.
    BACKGROUND: Metabolic syndrome may be related to folate's pharmacogenetically regulated metabolism and atypical antipsychotic (AAP) exposure.
    AIMS: We examined folate supplementation on metabolic measures, endothelial functioning (Reactive Hyperemia Index (RHI)), and global methylation in AAP-treated schizophrenia subjects meeting NCEP-ATP-III-a metabolic syndrome criteria.
    METHODS: Subjects were given 5 mg/day open label folate for 3 months. Baseline and end point measurements included RHI, body mass index, fasting metabolic laboratory measures, C-reactive protein, homocysteine, IL-6, and leptin. Subjects were genotyped for methylenetetrahydrofolate reductase (MTHFR) 677C/T and catechol-O-methyltransferase (COMT) 158 Val/Met, as well as global DNA methylation using the LUminometric Methylation Assay (LUMA).
    RESULTS: Thirty-five subjects (mean age 50±9 years and 70% Caucasian) were included. At end point, RHI improved by 20% (P=0.02), homocysteine decreased 14% (P=0.006), and IL-6 decreased 13% (P=0.09). At baseline, 61% met endothelial dysfunction criteria (RHI<1.67), which decreased to 27% (P=0.0006) at end point. The MTHFR 677C/C+COMT 158Met/Met group also showed significant reduction in those meeting endothelial dysfunction (83% baseline and 16% end point (P=0.001)). Global methylation levels increased after supplementation (4.3%, P<0.0001), with subjects receiving olanzapine or clozapine experiencing greater methylation changes after folate supplementation. Folate may reduce AAP-associated metabolic risks.
    CONCLUSIONS: We report significant reductions in the number of subjects meeting endothelial dysfunction. Given that all subjects met metabolic syndrome criteria, this may prove as a useful avenue to reducing cardiovascular disease risk. MTHFR and COMT genotypes may affect response and underlying changes in DNA methylation may help to explain the mechanistic underpinnings of these findings.
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  • Article
    Dehdashti S, Avazzadeh Z, Xu Z, Shen JQ, Mirza B, Wang H.
    Sci Rep. 2017 11 08;7(1):15046.
    In this paper we use spinor transformations under local Lorentz transformations to investigate the curvature effect on the quantum-to-classical transition, described in terms of the decoherence process and of the quantum speed limit. We find that gravitational fields (introduced adopting the Schwarzschild and anti-de Sitter geometries) affect both the decoherence process and the quantum speed limit of a quantum particle with spin-1/2. In addition, as a tangible example, we study the effect of the Earth's gravitational field, characterized by the Rindler space-time, on the same particle. We find that the effect of the Earth's gravitational field on the decoherence process and quantum speed limit is very small, except when the mean speed of the quantum particle is comparable to the speed of light.
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