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Sökning: WFRF:(Novikova G)

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1.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • 2017
  • swepub:Mat__t
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  • Zaborowski, AM, et al. (författare)
  • Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
  • 2022
  • Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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  • Al Moubayed, Samer, et al. (författare)
  • Human-robot Collaborative Tutoring Using Multiparty Multimodal Spoken Dialogue
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, we describe a project that explores a novel experi-mental setup towards building a spoken, multi-modally rich, and human-like multiparty tutoring robot. A human-robotinteraction setup is designed, and a human-human dialogue corpus is collect-ed. The corpus targets the development of a dialogue system platform to study verbal and nonverbaltutoring strategies in mul-tiparty spoken interactions with robots which are capable of spo-ken dialogue. The dialogue task is centered on two participants involved in a dialogueaiming to solve a card-ordering game. Along with the participants sits a tutor (robot) that helps the par-ticipants perform the task, and organizes and balances their inter-action. Differentmultimodal signals captured and auto-synchronized by different audio-visual capture technologies, such as a microphone array, Kinects, and video cameras, were coupled with manual annotations. These are used build a situated model of the interaction based on the participants personalities, their state of attention, their conversational engagement and verbal domi-nance, and how that is correlated with the verbal and visual feed-back, turn-management, and conversation regulatory actions gen-erated by the tutor. Driven by the analysis of the corpus, we will show also the detailed design methodologies for an affective, and multimodally rich dialogue system that allows the robot to meas-ure incrementally the attention states, and the dominance for each participant, allowing the robot head Furhat to maintain a well-coordinated, balanced, and engaging conversation, that attempts to maximize the agreement and the contribution to solve the task. This project sets the first steps to explore the potential of us-ing multimodal dialogue systems to build interactive robots that can serve in educational, team building, and collaborative task solving applications.
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  • Al Moubayed, Samer, et al. (författare)
  • Tutoring Robots: Multiparty Multimodal Social Dialogue With an Embodied Tutor
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • This project explores a novel experimental setup towards building spoken, multi-modally rich, and human-like multiparty tutoring agent. A setup is developed and a corpus is collected that targets the development of a dialogue system platform to explore verbal and nonverbal tutoring strategies in multiparty spoken interactions with embodied agents. The dialogue task is centered on two participants involved in a dialogue aiming to solve a card-ordering game. With the participants sits a tutor that helps the participants perform the task and organizes and balances their interaction. Different multimodal signals captured and auto-synchronized by different audio-visual capture technologies were coupled with manual annotations to build a situated model of the interaction based on the participants personalities, their temporally-changing state of attention, their conversational engagement and verbal dominance, and the way these are correlated with the verbal and visual feedback, turn-management, and conversation regulatory actions generated by the tutor. At the end of this chapter we discuss the potential areas of research and developments this work opens and some of the challenges that lie in the road ahead.
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11.
  • Alonso-Blanco, Carlos, et al. (författare)
  • 1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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  • Brohlin, Maria, et al. (författare)
  • Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells
  • 2009
  • Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 64:1, s. 41-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.
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  • Kawakatsu, Taiji, et al. (författare)
  • Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
  • 2016
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
  • Tidskriftsartikel (refereegranskat)abstract
    • The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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  • Mårdh, Per-Anders, et al. (författare)
  • Facts and myths on recurrent vulvovaginal candidosis-a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy.
  • 2002
  • Ingår i: International Journal of STD and AIDS. - 0956-4624. ; 13:8, s. 522-539
  • Forskningsöversikt (refereegranskat)abstract
    • Approximately three-quarters of all women will experience an episode of vulvovaginal candidosis at least once in their life and 5-10% of them will have more than one attack. Women suffering from three to four attacks within 12 months will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review covers the large number of proposed aetiological factors for RVVC. The diagnosis of the condition made by conventional means by health providers is often false and is also often misdiagnosed by the affected woman herself. The review covers various methods of diagnosing RVVC and the current knowledge on potential pathogenetic mechanisms proposed for genital candida infections. Treatment of RVVC, including local and systemic antimicrobial therapy and behaviour modification to decrease the risk of recurrences, are discussed. Recent knowledge on drug resistance in candida is also included.
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  • Novikova, G, et al. (författare)
  • Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1610-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (including AP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, and ZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.
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  • Novikova, P. Y., et al. (författare)
  • Sequencing of the genus Arabidopsis identifies a complex history of nonbifurcating speciation and abundant trans-specific polymorphism
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1077-1082
  • Tidskriftsartikel (refereegranskat)abstract
    • The notion of species as reproductively isolated units related through a bifurcating tree implies that gene trees should generally agree with the species tree and that sister taxa should not share polymorphisms unless they diverged recently and should be equally closely related to outgroups. It is now possible to evaluate this model systematically. We sequenced multiple individuals from 27 described taxa representing the entire Arabidopsis genus. Cluster analysis identified seven groups, corresponding to described species that capture the structure of the genus. However, at the level of gene trees, only the separation of Arabidopsis thaliana from the remaining species was universally supported, and, overall, the amount of shared polymorphism demonstrated that reproductive isolation was considerably more recent than the estimated divergence times. We uncovered multiple cases of past gene flow that contradict a bifurcating species tree. Finally, we showed that the pattern of divergence differs between gene ontologies, suggesting a role for selection. © 2016 Nature America, Inc. All rights reserved.
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  • Podlesny-Drabiniok, A, et al. (författare)
  • BHLHE40/41 regulate macrophage/microglia responses associated with Alzheimer's disease and other disorders of lipid-rich tissues
  • 2023
  • Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundGenetic and experimental evidence strongly implicates myeloid cells in the etiology of AD and suggests that AD-associated alleles and genes may modulate disease risk by altering the transcriptional and cellular responses of macrophages (like microglia) to damage of lipid-rich tissues (like the brain). Specifically, recent single-cell/nucleus RNA sequencing (sc/nRNA-seq) studies identified a transcriptionally distinct state of subsets of macrophages in aging or degenerating brains (usually referred to as disease- associated microglia or DAM) and in other diseased lipid-rich tissues (e.g., obese adipose tissue, fatty liver, and atherosclerotic plaques). We collectively refer to these subpopulations as lipid-associated macrophages or LAMs. Importantly, this particular activation state is characterized by increased expression of genes involved in the phagocytic clearance of lipid-rich cellular debris (efferocytosis), including several AD risk genes.MethodsWe used sc/nRNA-seq data from human and mouse microglia from healthy and diseased brains and macrophages from other lipid-rich tissues to reconstruct gene regulatory networks and identify transcriptional regulators whose regulons are enriched for LAM response genes (LAM TFs) across species. We then used gene knock- down/knock-out strategies to validate some of these LAM TFs in human THP-1 macrophages and iPSC-derived microgliain vitro, as well as mouse microgliain vivo.ResultsWe nominate 11 strong candidate LAM TFs shared across human and mouse networks (BHLHE41,HIF1A,ID2,JUNB,MAF,MAFB,MEF2A,MEF2C,NACA, POU2F2andSPI1). We also demonstrate a strong enrichment of AD risk alleles in the cistrome ofBHLHE41(and its close homologBHLHE40), thus implicating its regulon in the modulation of disease susceptibility. Loss or reduction ofBHLHE40/41expression in human THP-1 macrophages and iPSC-derived microglia, as well as loss ofBhlhe40/41in mouse microglia led to increased expression of LAM response genes, specifically those involved in cholesterol clearance and lysosomal processing, with a concomitant increase in cholesterol efflux and storage, as well as lysosomal mass and degradative capacity.ConclusionsTaken together, this study nominates transcriptional regulators of the LAM response, experimentally validates BHLHE40/41 in human and mouse macrophages/microglia, and provides novel targets for therapeutic modulation of macrophage/microglia function in AD and other disorders of lipid-rich tissues.Graphical abstract
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  • Resultat 1-25 av 25

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