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Sökning: WFRF:(Novikova T)

  • Resultat 1-21 av 21
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  • 2017
  • swepub:Mat__t
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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Tabiri, S, et al. (författare)
  • 2021
  • 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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  • Brachi, B., et al. (författare)
  • Plant genetic effects on microbial hubs impact host fitness in repeated field trials
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200 Arabidopsis thaliana genotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes. 
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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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  • Ivanov, Alexander V., et al. (författare)
  • Adducts of zinc and copper(II) dialkyldithiocarbamate complexes with dialkylamines: Synthesis, EPR, and 13C and 15N CP/MAS NMR
  • 2007
  • Ingår i: Russian Journal of Inorganic Chemistry. - 0036-0236 .- 1531-8613. ; 52:5, s. 691-697
  • Tidskriftsartikel (refereegranskat)abstract
    • Crystalline adducts of zinc and copper(II) dithiocarbamate (Dtc) complexes with dialkylamines [M(NHR′2)(S2CNR2)2] (M = Zn, 63Cu, 65Cu; R = CH3, C2H5, or R2 = (CH2)4O; R′ = C2H5, C3H7) have been preparatively isolated. The structures and spectral properties of the adducts have been studied by EPR and 13C and 15N MAS NMR. Chemisorption of bases on powders of dinuclear dithiocarbamates leads to their dissociation into monomeric adducts. Computer simulation demonstrates that the experimental EPR spectra of isotope-substituted copper(II) adducts have an individual character. The geometry of the copper polyhedra is intermediate between a trigonal bipyramid (TBP) and a tetragonal pyramid (TP). The TBP and TP contributions have been quantified based on EPR data. 13C and 15N MAS NMR data show that the Dtc ligands incorporated into the zinc adduct molecule are structurally nonequivalent. The dependence of the isotropic 15N chemical shifts of the Dtc groups on the alkyl substituents at the nitrogen atom is interpreted based on the concept of joint manifestation of the (+)inductive effect of the alkyl substituents and the mesomeric effect of the Dtc groups.
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  • Orekhova, Elena V, 1967, et al. (författare)
  • Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)
  • 2012
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.
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  • Orekhova, Elena V, 1967, et al. (författare)
  • Auditory Magnetic Response to Clicks in Children and Adults: Its Components, Hemispheric Lateralization and Repetition Suppression Effect
  • 2013
  • Ingår i: Brain Topography. - : Springer Science and Business Media LLC. - 0896-0267 .- 1573-6792. ; 26:3, s. 410-427
  • Tidskriftsartikel (refereegranskat)abstract
    • The auditory magnetic event-related fields (ERF) qualitatively change through the child development, reflecting maturation of auditory cortical areas. Clicks presented with long inter-stimulus interval produce distinct ERF components, and may appear useful to characterize immature EFR morphology in children. The present study is aimed to investigate morphology of the auditory ERFs in school-age children, as well as lateralization and repetition suppression of ERF components evoked by the clicks. School-age children and adults passively listened to pairs of click presented to the right ear, left ear or binaurally, with 8-11 s intervals between the pairs and a 1 s interval within a pair. Adults demonstrated a typical P50m/N100m response. Unlike adults, children had two distinct components preceding the N100m-P50m (at similar to 65 ms) and P100m (at similar to 100 ms). The P100m dominated the child ERF, and was most prominent in response to binaural stimulation. The N100m in children was less developed than in adults and partly overlapped in time with the P100m, especially in response to monaural clicks. Strong repetition suppression was observed for P50m both in children and adults, P100m in children and N100m in adults. Both children and adults demonstrated ERF amplitude and/or latency right hemispheric advantage effects that may reflect right hemisphere dominance for preattentive arousal processes. Our results contribute to the knowledge concerning development of auditory processing and its lateralization in children and have implications for investigation of the auditory evoked fields in developmental disorders.
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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 1-21 av 21

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